@manuscripts/transform 4.4.1 → 4.4.3

package/src/jats/__tests__/__snapshots__/jats-roundtrip.test.ts.snap

@@ -11,7 +11,7 @@ exports[`JATS roundtrip > jats-import.xml roundtrip 1`] = `
 "<!DOCTYPE article PUBLIC \\"-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD with OASIS Tables with MathML3 v1.2 20190208//EN\\" \\"http://jats.nlm.nih.gov/archiving/1.2/JATS-archive-oasis-article1-mathml3.dtd\\"><article xmlns:xlink=\\"http://www.w3.org/1999/xlink\\" article-type=\\"research-article\\" xml:lang=\\"en\\"><front><article-meta><article-id pub-id-type=\\"doi\\">10.5555/BRB3-2019-12-0787</article-id><title-group><article-title>Blood pressure after follow up in a stroke prevention clinic</article-title><alt-title alt-title-type=\\"running\\">Running title example</alt-title><alt-title alt-title-type=\\"short\\">Short title example</alt-title></title-group><contrib-group content-type=\\"authors\\"><contrib contrib-type=\\"author\\" id=\\"contrib-1\\" corresp=\\"yes\\"><role>author</role><contrib-id contrib-id-type=\\"orcid\\" authenticated=\\"true\\">https://orcid.org/0000-0003-2217-5904</contrib-id><name><surname>Hornnes</surname><given-names>Agnete Hviid</given-names><prefix>Mr</prefix><suffix>Jr.</suffix></name><degrees>RN</degrees><degrees>MPH</degrees><degrees>PhD</degrees><xref ref-type=\\"aff\\" rid=\\"aff-1\\"><sup>1</sup></xref><role vocab-identifier=\\"http://credit.niso.org/\\" vocab=\\"CRediT\\" vocab-term=\\"Writing – original draft\\" vocab-term-identifier=\\"https://credit.niso.org/contributor-roles/writing-original-draft/\\">Writing – original draft</role></contrib><contrib contrib-type=\\"author\\" id=\\"contrib-2\\"><name><surname>Poulsen</surname><given-names>Mai Bang</given-names></name><degrees>MD</degrees><degrees>PhD</degrees><xref ref-type=\\"aff\\" rid=\\"aff-1\\"><sup>1</sup></xref><xref ref-type=\\"fn\\" rid=\\"fn-1\\"><sup>2</sup></xref></contrib><aff id=\\"aff-1\\"><label>1</label><institution content-type=\\"dept\\">Department of
           Neurology</institution>, <institution>Herlev og Gentofte
           Hospital</institution>, <addr-line>Borgmester Ib Juuls Vej 1</addr-line>, <addr-line>2730
-            Herlev</addr-line>, <city>Herlev</city>, <country>Denmark</country>, <postal-code>2730</postal-code></aff></contrib-group><author-notes><fn id=\\"fn-1\\"><p>Mai Bang Poulsen, MD, PhD
Department of Neurology
Nordsjællands Hospital
Dyrehavevej 29
3400 Hillerød
Denmark</p></fn><fn id=\\"fn-2\\"><p>ClinicalTrials.gov NCT03782857.</p></fn><fn fn-type=\\"coi-statement\\"><label>CONFLICT OF INTEREST</label><p id=\\"p-1\\">None.</p></fn></author-notes><supplementary-material id=\\"supplementary-material-1\\" xlink:href=\\"attachment:7d9d686b-5488-44a5-a1c5-46351e7f9312\\" mimetype=\\"application\\" mime-subtype=\\"vnd.openxmlformats-officedocument.wordprocessingml.document\\"><caption><title>final manuscript-hum-huili-dbh-suicide-20200707_figures (9)</title></caption></supplementary-material><history><date date-type=\\"accepted\\"><day>27</day><month>04</month><year>2020</year></date><date date-type=\\"received\\"><day>09</day><month>12</month><year>2019</year></date></history><self-uri content-type=\\"document\\" xlink:href=\\"http://www.harmreductionjournal.com/content/1/1/5\\"/><self-uri content-type=\\"document\\" xlink:href=\\"http://www.harmreductionjournal.com/content/1/1/2\\"/><abstract><sec id=\\"sec-1\\"><title>Objectives</title><p id=\\"p-2\\">In Denmark 25% of hospital admissions with stroke are recurrent strokes. With thrombolytic treatment more patients survive with only minor disability. This promising development should be followed up by intensive secondary prevention. Hypertension is the most important target. We aimed at testing the hypotheses that early follow up in a preventive clinic would result in 1) A higher proportion of patients with blood pressure at target, 2) Time to stroke recurrence, myocardial infarction and death would be longer in the intervention group compared to controls.</p></sec><sec id=\\"sec-2\\" sec-type=\\"methods\\"><title>Materials and Methods</title><p id=\\"p-3\\">Eligible patients admitted to the stroke unit of Herlev Hospital were randomized shortly before discharge to intervention or control group. Of 78 included participants data from 73 was available for follow up nine months after inclusion. Patients in the intervention group were seen in the clinic within one week. In case of hypertension treatment was initiated or supplied with a new drug. We used individual targets for blood pressure according to diagnosis of stroke and patients’ comorbidity. Patients in the intervention group had a median of five visits to the preventive clinic.</p></sec><sec id=\\"sec-3\\" sec-type=\\"results\\"><title>Results</title><p content-type=\\"headshots\\"><graphic xlink:href=\\"headshot.png\\"><caption><title>Jane Doe, Ph.D.</title><p><bold>Editor</bold></p><p>Wiley</p></caption><alt-text>Jane Doe, Ph.D.</alt-text></graphic><graphic xlink:href=\\"headshot2.png\\"><caption><title>Jack Black</title><p><bold>CEO</bold></p><p>Generico</p></caption><alt-text>Headshot of Jack Black</alt-text></graphic></p><p id=\\"p-4\\">In the intervention group blood pressure was treated to target in 25 patients (69%) versus 14 (38%) in the control group (<italic>p</italic> = 0.007). Median time to first event was 44 months (4–49) in the intervention group and 19 months (4–37) in controls (<italic>p</italic> = 0.316).</p></sec><sec id=\\"sec-4\\" sec-type=\\"conclusions\\"><title>Conclusions</title><p id=\\"p-5\\">Treatment of hypertension to individual targets after stroke is feasible. It may postpone recurrent stroke and death in stroke survivors.</p></sec></abstract><abstract abstract-type=\\"graphical\\"><fig id=\\"fig-1\\" fig-type=\\"half-left\\"><graphic xlink:href=\\"demo1.jpg\\"/></fig></abstract><abstract abstract-type=\\"key-image\\"><fig id=\\"fig-2\\" fig-type=\\"half-left\\"><graphic xlink:href=\\"demo2.jpg\\"/></fig></abstract><abstract abstract-type=\\"short\\"><p id=\\"p-6\\">The is the third and last part of the volume devoted to solubility data of rare earth metal chlorides in water and in ternary and quaternary aqueous systems. Compilations of all available experimental data are introduced for each rare earth metal chloride with a corresponding critical evaluation. This part covers chlorides of Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu, with coverage of the literature through the middle of 2008.</p></abstract><trans-abstract xml:lang=\\"fr\\" abstract-type=\\"short\\"><title>Short</title><p id=\\"p-7\\">Il s'agit de la troisième et dernière partie du volume consacrée aux données de solubilité des chlorures de métaux des terres rares dans l'eau et dans les systèmes aqueux ternaires et quaternaires. Une compilation de toutes les données expérimentales disponibles est présentée pour chaque chlorure de métaux des terres rares, accompagnée de l'évaluation critique correspondante. Cette partie couvre les chlorures de Gd, Tb, Dy, Ho, Er, Tm, Yb et Lu, avec une couverture de la littérature jusqu'à mi-2008.</p></trans-abstract><kwd-group kwd-group-type=\\"author\\"><kwd>secondary prevention</kwd><kwd>stroke recurrence</kwd><kwd>blood pressure</kwd><kwd>blood pressure target</kwd><kwd>randomized controlled trial</kwd></kwd-group><funding-group><award-group id=\\"award-group-1\\"><funding-source>National Institutes of Health</funding-source><award-id>GM18458</award-id><principal-award-recipient>Berkeley</principal-award-recipient></award-group><award-group id=\\"award-group-2\\"><funding-source>National Science Foundation</funding-source><award-id>DMS-0204674</award-id><award-id>DMS-0244638</award-id></award-group></funding-group><counts><fig-count count=\\"8\\"/><table-count count=\\"2\\"/><ref-count count=\\"25\\"/><word-count count=\\"3651\\"/></counts></article-meta></front><body><graphic xlink:href=\\"demo1.png\\"><ext-link xlink:href=\\"WLYSP_5_4_Infographic_Nov_11_2022.pdf\\"/><caption><p>simple image</p><p>caption</p></caption></graphic><graphic xlink:href=\\"prodbe.int.aip.org:8080/journal/journal_fs/ 1.2983775.1373315697!/images/1460725790.jpg\\"><alt-text>example of alt text for graphics</alt-text><long-desc>example of long desc</long-desc></graphic><p id=\\"p-8\\">test paragraph</p><disp-quote content-type=\\"quote-with-image\\"><graphic xlink:href=\\"demo1.jpg\\"/><p>It is a far, far better thing that I do now than I have ever done.</p><attrib>Charles Dickens</attrib></disp-quote><sec id=\\"sec-5\\" sec-type=\\"intro\\"><label>1</label><title>INTRODUCTION</title><p id=\\"p-9\\">Over the last two decades continuous development of thrombolytic treatment of acute ischemic stroke (IS) has improved safety and functional outcome in treated patients <xref ref-type=\\"bibr\\" rid=\\"ref-1 ref-2\\"><sup>1,2</sup></xref> thus increasing the possibility of survival with no or only minor disability. With this fact and the ongoing aging of populations in mind <xref ref-type=\\"bibr\\" rid=\\"ref-3\\"><sup>3</sup></xref> the secondary prevention after stroke seems more important than ever. In 1998 the Copenhagen Stroke Study reported a recurrence rate of 23%. <xref ref-type=\\"bibr\\" rid=\\"ref-4\\"><sup>4</sup></xref> According to the Danish Stroke Registry our national recurrence rate was 25% in 2011.<xref ref-type=\\"bibr\\" rid=\\"ref-5\\"><sup>5</sup></xref></p><p id=\\"p-10\\">Hypertension is an important risk factor for stroke recurrence. <xref ref-type=\\"bibr\\" rid=\\"ref-4 ref-6 ref-7 ref-8\\"><sup>4,6–8</sup></xref> Lowering blood pressure (BP) after stroke or transitory ischemic attack (TIA) by 10/5 mm Hg has been associated with reduced risk of stroke recurrence by 24% and myocardial infarction (MI) by 21%. <xref ref-type=\\"bibr\\" rid=\\"ref-9\\"><sup>9</sup></xref></p><p id=\\"p-11\\">Observational studies have demonstrated the difficulties in lowering BP after stroke with rates of BP treated to target ranging from 28% to 73% <xref ref-type=\\"bibr\\" rid=\\"ref-10 ref-11 ref-12 ref-13\\"><sup>10–13</sup></xref> and interventions aimed at control of BP after stroke have not yet found a successful model. <xref ref-type=\\"bibr\\" rid=\\"ref-14 ref-15 ref-16 ref-17 ref-18 ref-19\\"><sup>14–19</sup></xref> Fahey and coworkers have reviewed the literature aimed at improving control of BP in hypertensive subjects. One large study using an organized system of regular visits to a clinic was efficient in producing a large decrease in BP and reduction of all-cause mortality compared to referral to usual primary care. This was achieved by using a stepwise escalation of treatment until target was reached. <xref ref-type=\\"bibr\\" rid=\\"ref-20\\"><sup>20</sup></xref> Other methods had variable or no effect, only nurse or pharmacist led care seemed promising.</p><media id=\\"media-1\\" xlink:show=\\"embed\\" xlink:href=\\"example.mp4\\" mimetype=\\"video\\" mime-subtype=\\"mp4\\"><label>Media 1</label><alt-text>example of alt text for media</alt-text><long-desc>example of long desc</long-desc></media><sec id=\\"sec-6\\"><title>Aims and hypotheses</title><p id=\\"p-12\\">The aim of the present study was to test the hypotheses that follow up after stroke in a specialized nurse led physician supervised clinic with stepwise escalation of BP- and lipid lowering treatment would result in</p><sec id=\\"sec-7\\"><title>Primary endpoint</title><sec id=\\"sec-8\\"><title>A greater proportion of participants with BP at target</title><p id=\\"p-13\\">Secondary endpoints: A greater reduction of BP A greater proportion of participants with LDL-cholesterol treated to target A greater reduction of LDL-cholesterol Longer time to recurrence of stroke, MI and death in the intervention group compared to controls</p></sec></sec><sec id=\\"sec-9\\"><title>BoxedText test</title><boxed-text id=\\"boxed-text-1\\"><label>Box 1</label><sec id=\\"sec-10\\"><title/><p/></sec></boxed-text><boxed-text id=\\"boxed-text-2\\"><label>Box 2</label><caption><title>BoxedTextCaptionTitle</title></caption><sec id=\\"sec-11\\"><title>Key messages</title><list list-type=\\"bullet\\"><list-item><p id=\\"p-14\\">The benefits of geriatric day hospital care have been controversial for many years.</p></list-item><list-item><p id=\\"p-15\\">This systematic review of 12 randomised trials comparing a variety of day hospitals with a range of alternative services found no overall advantage for day hospital care.</p></list-item><list-item><p id=\\"p-16\\">Day hospitals had a possible advantage over no comprehensive care in terms of death or poor outcome, disability, and use of resources.</p></list-item><list-item><p id=\\"p-17\\">The costs of day hospital care may be partly offset by a reduced use of hospital beds and institutional care among survivors.</p></list-item></list><sec id=\\"sec-12\\"><title>testing multiple sections inside a boxed-text element</title><p id=\\"p-18\\">Hello World!</p></sec></sec></boxed-text><boxed-text id=\\"boxed-text-3\\"><label>Box 3</label><sec id=\\"sec-13\\"><title>Key messages</title><list list-type=\\"bullet\\"><list-item><p id=\\"p-19\\">The benefits of geriatric day hospital care have been controversial for many years.</p></list-item><list-item><p id=\\"p-20\\">This systematic review of 12 randomised trials comparing a variety of day hospitals with a range of alternative services found no overall advantage for day hospital care.</p></list-item><list-item><p id=\\"p-21\\">Day hospitals had a possible advantage over no comprehensive care in terms of death or poor outcome, disability, and use of resources.</p></list-item><list-item><p id=\\"p-22\\">The costs of day hospital care may be partly offset by a reduced use of hospital beds and institutional care among survivors.</p></list-item></list></sec></boxed-text></sec></sec></sec><sec id=\\"sec-14\\" sec-type=\\"methods\\"><label>2</label><title>MATERIELS AND METHODS</title><p id=\\"p-23\\">Before the initiation of the study the authors attended a three-day course in treatment of hypertension arranged by the Danish Society of Hypertension. The recommendations of our national guidelines regarding BP targets were in line with those given by the American Stroke Association in force at the time of initiation of the study: “An absolute target BP level and reduction are uncertain and should be individualized.” <xref ref-type=\\"bibr\\" rid=\\"ref-21\\"><sup>21</sup></xref> Following the advice given by the Danish Society of Hypertension we used the following targets: A BP &lt; 140/90 mm Hg was considered at target in non-diabetic patients. In patients aged 80 years or more a BP of 150/90 mm Hg was acceptable if further treatment was not tolerated. In case of severe carotid stenosis or a history of ischemic heart disease BP should not be lower than 130/80 mm Hg. In patients with diabetes or hemorrhagic stroke we aimed at a BP &lt; 130/80 mm Hg. Untreated patients without hypertension were categorized as normotensive, untreated hypertensive patients as having unknown hypertension, treated patients without hypertension as treated to target, and treated patients with hypertension as having untreated hypertension.</p><p id=\\"p-24\\">LDL-cholesterol should be &lt; 2.5 mmol/l in patients with IS or TIA in non-diabetic patients and in case of diabetes &lt; 2.0 mmol/l.</p><p id=\\"p-25\\">A sample size calculation showed that 24 patients in each group were needed to show a difference of 10 mm Hg in the development of systolic BP (80% power).</p><sec id=\\"sec-15\\"><label>2.1</label><title>Study sample and setting</title><p id=\\"p-26\\">From June 2012 to February 2013 all patients diagnosed with a stroke or TIA at the stroke unit of Herlev Gentofte Hospital, University of Copenhagen were considered for inclusion in the study. Patients should be without cognitive deficits that would prevent their active participation and they should be discharged to their own home. The last author used computer-generated block randomization procedures with stratification by hypertension (1:1). The allocation sequence was concealed, and we aimed at equal numbers in the two groups. Shortly before discharge the first author approached eligible patients for oral and written information about the study. Where written informed consent to participation was achieved BP was measured before a concealed envelope administered by a secretary was opened revealing the allocation to either intervention or control group.</p><p id=\\"p-27\\">The research protocol was approved by the ethics committee of the Capital Region of Denmark (H-3-2011–152) and by the Danish Data Protection Agency (2012–41-0429). The study was conducted according to all common ethical standards including the rules given by the Declaration of Helsinki. Patients randomized to the control group had the usual treatment: one visit in the outpatient clinic of the stroke unit three months after discharge. Patients randomized to the intervention group had an appointment with the first author within one week after discharge. The first author undertook all visits in the preventive clinic.</p></sec><sec id=\\"sec-16\\"><label>2.2</label><title>Procedures and intervention</title><p id=\\"p-28\\">BP was measured at every visit after at least five minutes rest in a sitting position in an arm chair. BP was measured simultaneously in both arms followed by two measurements with 10-min intervals using the arm with the highest systolic BP. In case of hypertension the first author would suggest initiation or intensification of antihypertensive treatment. The last author would accept or suggest an alternative and do the prescription. Patients would come to the clinic for control of BP and relevant blood tests every 3–4 weeks until BP was at target. After five weeks on lipid lowering drugs treatment was intensified if needed. Patients who did not tolerate lipid lowering medication were referred to a dietitian. In motivated patients home BP measurements were performed using patients’ own monitor or by lending patients a BP monitor between visits.</p><p id=\\"p-29\\">Patients in the intervention group had a mean of five visits to the clinic with addition of new drugs rather than adding more of the same drug in case of hypertension. Although we used minimum doses to prevent adverse effects, many patients had unacceptable side effects necessitating change to another class of antihypertensive drug.</p><p id=\\"p-30\\">Patients were informed about the importance of life-long adherence with all preventive medication. Those with elevated BP or receiving antihypertensive treatment were advised in salt reduction, smokers were advised to stop smoking and all patients were informed about the benefits of 30 min of moderate physical activity daily. Likewise, information about the risk of an intake of alcohol above seven drinks per week in women and 14 drinks in men was part of the program as well as the benefits of weight reduction in overweight patients with hypertension or diabetes.</p></sec><sec id=\\"sec-17\\"><label>2.3</label><title>Follow up</title><p id=\\"p-31\\">Participants in both groups were invited to the usual follow up visit three months after discharge at the outpatient clinic of the stroke unit as well as a follow up visit in the study a median of 9 (IQR 8–11) months after inclusion.</p><p id=\\"p-32\\">In accordance with the protocol the final follow up visits were performed by nurses in the outpatient clinic with measurement of BP and blood-cholesterols. Patients were asked not to reveal their group allocation but blinding of the nurses was not possible. Patients were interviewed about adherence to all preventive medications as well as their present life style. For practical purposes a minority of visits were performed by the first author. To do intention to treat analyses we used last observation carried forward regarding the endpoints of the study where patients had died or did not respond to the invitation to a follow up visit. Thus, we used the last recorded values in five patients in the intervention group and in seven controls.</p><p id=\\"p-33\\">After a median of 65 months (IQR: 61–66) from inclusion data on vascular events and death were attained from the hospital based medical records covering all hospitals of the region.</p></sec><sec id=\\"sec-18\\"><label>2.4</label><title>Statistics</title><p id=\\"p-34\\">Data were entered into Excel and imported into SAS. Statistical analyses were performed by the first author according to a pre-established statistical analysis plan. We used Chi square test (for the primary outcome) or Fisher’s exact test as appropriate for comparison of proportions, and for change from baseline we used McNemar’s test. For continuous variables we used t-test or Mann-Whitney’s test*. Change from baseline was analyzed by the paired t-test or Wilcoxon signed rank sum test* (*where data were not normally distributed). We used SAS 9.4 for Windows and <italic>p</italic> &lt; 0.05 was considered significant.</p></sec></sec><sec id=\\"sec-19\\" sec-type=\\"results\\"><label>3</label><title>RESULTS</title><p id=\\"p-35\\">We included 78 patients in the study. Due to revision of stroke diagnoses in four participants and as one participant never turned up for the intervention, data on 73 participants were available for follow up (<xref ref-type=\\"fig\\" rid=\\"fig-3\\">Figure 1</xref>). The median stay in hospital was 4 days (IQR: 3–6). As seen from <xref ref-type=\\"table\\" rid=\\"table-wrap-1\\">Table 1</xref> most participants had no or slight disability.</p><fig id=\\"fig-3\\" fig-type=\\"half-left\\"><label>Figure 1</label><caption><p>Flow chart of participants</p></caption><graphic xlink:href=\\"BRB3-2019-12-0787-fig-0001.png\\"><alt-text>example of alt text for graphics inside figures</alt-text><long-desc>example of long desc for graphics inside figures</long-desc></graphic></fig><table-wrap id=\\"table-wrap-1\\" position=\\"anchor\\"><label>Table 1</label><caption><title>Baseline characteristics of 73 patients</title></caption><alt-text>example of alt text for tables</alt-text><long-desc>example of long desc</long-desc><table id=\\"table-1\\"><colgroup><col width=\\"52.14%\\"/><col width=\\"11.92%\\"/><col width=\\"14.9%\\"/><col width=\\"13.1%\\"/><col width=\\"7.94%\\"/></colgroup><thead><tr><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Characteristics</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>All(<italic>n</italic> = 73)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Intervention (<italic>n</italic> = 36)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Control (<italic>n</italic> = 37)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>P</p></th></tr></thead><tbody><tr><td valign=\\"middle\\" align=\\"left\\" scope=\\"row\\" style=\\"border-top: solid 0.50pt\\"><p>Sex, female</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>29 (40)</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>15 (42)</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>14 (38)</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>0.74</p></td></tr><tr><td valign=\\"middle\\" align=\\"left\\" scope=\\"row\\"><p>Age (years), mean ± SD</p></td><td valign=\\"middle\\" align=\\"left\\"><p>66 ± 12</p></td><td valign=\\"middle\\" align=\\"left\\"><p>63 ± 13</p></td><td valign=\\"middle\\" align=\\"left\\"><p>68 ± 11</p></td><td valign=\\"middle\\" align=\\"left\\"><p>0.08</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Length of education&lt; 10 years10 – 12 years&gt; 12 years</p></td><td valign=\\"top\\" align=\\"left\\"><p>12 (17)22 (30)38 (53)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (17)10 (29)19 (54)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (16)12 (33)19 (51)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.95</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diagnosis of strokeIschemic StrokeTIAHemorrhagic stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>63 (87)9 (12)1 (1)</p></td><td valign=\\"top\\" align=\\"left\\"><p>33 (92)3 (8)</p></td><td valign=\\"top\\" align=\\"left\\"><p>30 (81)6 (16)1 (3)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.60<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Recurrent stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (15)</p></td><td valign=\\"top\\" align=\\"left\\"><p>5 (14)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (16)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.00<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Modified Rankin Scale score &gt; 2</p></td><td valign=\\"top\\" align=\\"left\\"><p>5 (6)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1 (3)</p></td><td valign=\\"top\\" align=\\"left\\"><p>4 (11)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.36<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Antihypertensive medication before stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>39 (53)</p></td><td valign=\\"top\\" align=\\"left\\"><p>15 (42)</p></td><td valign=\\"top\\" align=\\"left\\"><p>24 (65)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.047</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Antihypertensive medication at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>46 (63)</p></td><td valign=\\"top\\" align=\\"left\\"><p>20 (56)</p></td><td valign=\\"top\\" align=\\"left\\"><p>26 (70)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.19</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Cholesterol lowering medication before stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>25 (34)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>14 (38)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.51</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Cholesterol lowering medication at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>65 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>35 (97)</p></td><td valign=\\"top\\" align=\\"left\\"><p>30 (81)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.03</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diabetes at baseline</p></td><td valign=\\"top\\" align=\\"left\\"><p>14 (19)</p></td><td valign=\\"top\\" align=\\"left\\"><p>5 (14)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.37<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diabetes at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>16 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (17)</p></td><td valign=\\"top\\" align=\\"left\\"><p>10 (27)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.29</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Atrial fibrillation at baseline</p></td><td valign=\\"top\\" align=\\"left\\"><p>7 (10)</p></td><td valign=\\"top\\" align=\\"left\\"><p>3 (8)</p></td><td valign=\\"top\\" align=\\"left\\"><p>4 (11)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.00<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Atrial fibrillation at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>12 (16)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (16)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (17)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.00</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Unhealthy dieting<sup>b</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>59 (82)</p></td><td valign=\\"top\\" align=\\"left\\"><p>25 (71)</p></td><td valign=\\"top\\" align=\\"left\\"><p>34 (92)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.03</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Current smoking</p></td><td valign=\\"top\\" align=\\"left\\"><p>19 (26)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>8 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.62</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Alcohol above limits<sup>c</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>23 (32)</p></td><td valign=\\"top\\" align=\\"left\\"><p>12 (34)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (30)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.68</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Sedentary lifestyle<sup>d</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>17 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (26)</p></td><td valign=\\"top\\" align=\\"left\\"><p>8 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.68</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>BMI ≥ 25</p></td><td valign=\\"top\\" align=\\"left\\"><p>46 (63)</p></td><td valign=\\"top\\" align=\\"left\\"><p>24 (67)</p></td><td valign=\\"top\\" align=\\"left\\"><p>22 (59)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.52</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\" style=\\"border-bottom: solid 0.50pt\\"><p>Self-rated health: fair, poor, or very poor</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>34 (47)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>15 (43)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>19 (51)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>0.47</p></td></tr></tbody></table><table-wrap-foot><p id=\\"p-36\\">Values are expressed as frequencies (%) or as mean ± standard deviations</p><fn-group id=\\"fn-group-1\\"><fn id=\\"fn-3\\"><p id=\\"p-37\\">Fisher’s exact test. <sup>b</sup> Less than 600 g of fruit and vegetables per day, fish for dinner less than twice per week. <sup>c</sup> More than 7 drinks per week in women/more than 14 drinks per week in men. <sup>d</sup> Less than 30 min of moderate physical activity per day.</p></fn></fn-group></table-wrap-foot></table-wrap><p id=\\"p-38\\">Less than 20% of patients had a baseline BP treated to target (<xref ref-type=\\"fig\\" rid=\\"fig-4\\">Figure 2</xref>). Twenty-eight patients (78%) in the intervention group and 29 patients (78%) in the control group had a 3-month visit in the outpatient clinic. Here 15 patients (42%) in the intervention group had their BP and blood cholesterol measured and so had 23 patients (62%) in the control group. At follow up patients in both groups reported a median of two visits including BP measurement at the general practitioner´s office since discharge from hospital.</p><fig id=\\"fig-4\\" fig-type=\\"half-left\\"><label>Figure 2</label><caption><p>Blood pressure and treatment of hypertension at baseline in 73 patients (%)</p></caption><graphic xlink:href=\\"BRB3-2019-12-0787-fig-0002.png\\"/></fig><sec id=\\"sec-20\\"><label>3.1</label><title>Primary endpoint</title><p id=\\"p-39\\">Follow up visits showed that 25 patients (69%) in the intervention group had a BP at target versus 14 (38%) of controls (<italic>p</italic> = 0.007). In four patients (10%) in the intervention group antihypertensive medication remained unchanged since discharge versus 23 (62%) of controls (<italic>p</italic> &lt; 0.0001) illustrated by the differences in BP treated to target as well as untreated hypertension in <xref ref-type=\\"fig\\" rid=\\"fig-5\\">Figure 3</xref>.</p><fig id=\\"fig-5\\" fig-type=\\"half-left\\"><label>Figure 3</label><caption><p>Blood pressure and treatment of hypertension at follow up in 73 patients (%)</p></caption><graphic xlink:href=\\"BRB3-2019-12-0787-fig-0003.png\\"/></fig></sec><sec id=\\"sec-21\\"><label>3.2</label><title>Secondary endpoints</title><p id=\\"p-40\\">Median reduction in systolic BP was 11 mm Hg (-5-19) with 14 mm Hg (IQR: 5–21) in the intervention group and 3 mm Hg (IQR -11-17) in the control group (<italic>p</italic> = 0.045). Median reduction in diastolic BP was 2 mm Hg (-2-11) with 7 mm Hg (IQR -1-13) in the intervention group and 1 mm Hg (IQR -6-8) in the control group (<italic>p</italic> = 0.04).</p><p id=\\"p-41\\">There was no difference between the groups regarding LDL-cholesterol treated to target with 32 patients (89%) at target in the intervention group versus 29 patients (78%) in the control group (<italic>p</italic> = 0.21). We found significant reductions in LDL-cholesterol in both groups, but no difference between the groups: 1.6 (IQR: 0.4–2.2) mmol/l in the intervention group versus 0.8 (IQR: 0.4–1.8) mmol/l among controls (<italic>p</italic> = 0.18).</p><p id=\\"p-42\\">In 11 patients (31%) in the intervention group cholesterol lowering medication remained unchanged since discharge versus 29 (78%) of controls (<italic>p</italic> &lt; 0.0001).</p><p id=\\"p-43\\">The combined endpoint of both BP and LDL-cholesterol at target was achieved in 22 (61%) of patients in the intervention group and in 10 patients (27%) in the control group (<italic>p</italic> = 0.003). At the end of the study 24 patients (68%) in the intervention group measured their BP at home versus 14 (38%) of controls (<italic>p</italic> = 0.03).</p><p id=\\"p-44\\">The only significant change in lifestyle was a reduction in current smokers by four in the control group (<xref ref-type=\\"table\\" rid=\\"table-wrap-2\\">Table 2</xref>).</p><table-wrap id=\\"table-wrap-2\\" position=\\"anchor\\"><label>Table 2</label><caption><title>Nine months follow up of 73 patients</title></caption><table id=\\"table-2\\"><colgroup><col width=\\"52.91%\\"/><col width=\\"11.06%\\"/><col width=\\"14.16%\\"/><col width=\\"11.5%\\"/><col width=\\"10.37%\\"/></colgroup><thead><tr><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Characteristics</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>All(<italic>n</italic> = 73)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Intervention(<italic>n</italic> = 36)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Control(<italic>n</italic> = 37)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>P</p></th></tr></thead><tbody><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\" style=\\"border-top: solid 0.50pt\\"><p>Systolic BP, mm Hg, mean ± SD</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>134 ± 21</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>130 ± 17</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>137 ± 24</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>0.12</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diastolic BP, mm Hg, mean ± SD</p></td><td valign=\\"top\\" align=\\"left\\"><p>78 ± 11</p></td><td valign=\\"top\\" align=\\"left\\"><p>78 ± 10</p></td><td valign=\\"top\\" align=\\"left\\"><p>78 ± 12.8)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.94</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Antihypertensive medication</p></td><td valign=\\"top\\" align=\\"left\\"><p>55 (75)</p></td><td valign=\\"top\\" align=\\"left\\"><p>29 (81)</p></td><td valign=\\"top\\" align=\\"left\\"><p>26 (70)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.31</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>100% compliance with AHM (<italic>n</italic> = 45)</p></td><td valign=\\"top\\" align=\\"left\\"><p>38 (84)</p></td><td valign=\\"top\\" align=\\"left\\"><p>23 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>15 (79)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.38</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>LDL-cholesterol, mmol/l (<italic>n</italic> = 72), mean ± SD</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.9 ± 0.8</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.9 ± 0.7</p></td><td valign=\\"top\\" align=\\"left\\"><p>2.0 ± 0.8</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.66</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Cholesterol lowering medication</p></td><td valign=\\"top\\" align=\\"left\\"><p>64 (88)</p></td><td valign=\\"top\\" align=\\"left\\"><p>32 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>32 (86)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.76</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>100% compliance with CLM (<italic>n</italic> = 52)</p></td><td valign=\\"top\\" align=\\"left\\"><p>46 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>24 (86)</p></td><td valign=\\"top\\" align=\\"left\\"><p>22 (92)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.50</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Unhealthy dieting<sup>b</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>59 (81)</p></td><td valign=\\"top\\" align=\\"left\\"><p>26 (72)</p></td><td valign=\\"top\\" align=\\"left\\"><p>33 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.76</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Current smoker</p></td><td valign=\\"top\\" align=\\"left\\"><p>15 (21)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>4 (11)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.046<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Alcohol &gt; limits<sup>c</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>20 (27)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.55</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Sedentary lifestyle<sup>d</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>16 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>7 (20)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.66</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\" style=\\"border-bottom: solid 0.50pt\\"><p>BMI ≥ 25</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>43 (59)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>21 (58)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>22 (60)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>0.92</p></td></tr></tbody></table><table-wrap-foot><p id=\\"p-45\\">Values are expressed as frequencies (%) or as mean ± standard deviations.
Abbreviations: AHM, antihypertensive medication; CLM, cholesterol lowering medication.</p><fn-group id=\\"fn-group-2\\"><fn id=\\"fn-4\\"><p id=\\"p-46\\">Fisher’s exact test. <sup>b</sup> Less than 600 g of fruit and vegetables per day, fish for dinner less than twice per week. <sup>c</sup> More than 7 drinks per week in women/more than 14 drinks per week in men. <sup>d</sup> Less than 30 min of moderate physical activity per day.</p></fn></fn-group></table-wrap-foot></table-wrap><p id=\\"p-47\\">Regarding vascular complications and death, we found 32 events in 22 patients after a median of 65 months. Median time to first event was 26 months (IQR: 4–49) with a median of 44 months (IQR: 11–49) in the intervention group and 19 months (IQR: 4–37) in the control group (<italic>p</italic> = 0.32). All in all, we found 11 events in nine patients in the intervention group: two recurrent strokes, three cases of TIA, and six patients died versus 21 events in 13 patients in the control group: seven recurrent strokes, five cases of TIA, one MI, and seven patients died (<italic>p</italic> = 0.49).</p></sec></sec><sec id=\\"sec-22\\" sec-type=\\"discussion\\"><label>4</label><title>DISCUSSION</title><p id=\\"p-48\\">In this randomized clinical trial, a larger proportion of patients in the intervention group compared to controls had BP within the above-mentioned limits and the study fulfilled the aim of the primary endpoint.</p><p id=\\"p-49\\">A systematic review of interventions aimed at modifiable risk factor control for secondary prevention of stroke revealed improvement in achieving BP target. <xref ref-type=\\"bibr\\" rid=\\"ref-22\\"><sup>22</sup></xref> However, as opposed to our study the review showed no significant change in systolic og diastolic BP.</p><p id=\\"p-50\\">In a study of integrated care with five prearranged visits to patients’ general practitioner versus usual care systolic BP at target set to 140 mm Hg was found in 75% versus 58% at 12-month follow up. <xref ref-type=\\"bibr\\" rid=\\"ref-19\\"><sup>19</sup></xref> We set individual targets for BP according to patients’ type of stroke, comorbidities and age. This is well in line with recommendations given by European Society of Hypertension, <xref ref-type=\\"bibr\\" rid=\\"ref-23\\"><sup>23</sup></xref> but as stated by Boan et al., not quite in accordance with international stroke guidelines. <xref ref-type=\\"bibr\\" rid=\\"ref-24\\"><sup>24</sup></xref></p><p id=\\"p-51\\">In a study where patients with minor stroke were randomized to six clinic visits by a pharmacist (intervention) or by a nurse (active control) aiming at treating both BP and LDL-cholesterol to target, 43% of patients in the pharmacist-led clinic met those two targets and so did 31% in the nurse-led clinic. <xref ref-type=\\"bibr\\" rid=\\"ref-25\\"><sup>25</sup></xref> In our study this combined endpoint was met in 22 (61%) of patients in the intervention group. Regarding BP in control 80% of patients in the pharmacist led clinic had systolic BP in control after six months versus 90% in the nurse led clinic. This is a far greater proportion than the 69% in our study. However, almost two thirds of patients had a baseline BP within the limits. The opposite was the case in our study with two thirds presenting with elevated BP. Both studies show that a dedicated follow up with stepwise escalation of preventive medication may be the way to reach the targets of the two important risk factors for recurrent stroke. In both studies five-six visits were needed, which is far beyond our usual treatment. However, despite visits to the outpatient clinic as well as to the general practitioner the proportion of patients with unchanged medication since discharge in the control group illustrate the necessity of frequent visits to a dedicated preventive facility. Considering the preventive effect of BP lowering, and - though insignificant - the difference in time to first event as well as the smaller proportion of events in the intervention group as found in our study, it may be well worth the time and resources for patients, their relatives and society.</p><sec id=\\"sec-23\\"><label>4.1</label><title>Strengths and limitations</title><p id=\\"p-52\\">Our study has some limitations. Most participants had a minor stroke and patients had to be independent and without severe cognitive deficits, which is not representative of a general stroke population. With only 73 participants caution is called for in the drawing of conclusions from the results. Nonetheless, we decided to reorganize the outpatient clinic of our stroke unit as of October 2014 implementing strategies of the present study.</p><p id=\\"p-53\\">The strength of the study is the individual target for BP taking into account the diagnosis of stroke as well as important comorbidity as recommended by Boan et al. <xref ref-type=\\"bibr\\" rid=\\"ref-24\\"><sup>24</sup></xref> Five-year follow up on vascular complications and death is another important advantage.</p></sec></sec><sec id=\\"sec-24\\" sec-type=\\"conclusions\\"><label>5</label><title>CONCLUSIONS</title><p id=\\"p-54\\">In conclusion, the feasibility study has demonstrated that timely follow up of stroke patients in a dedicated preventive outpatient clinic may result in BP and cholesterol treated to target in most patients. To some extent it may postpone time to stroke recurrence, MI and death.</p></sec></body><back><app-group/><ack><title>ACKNOWLEDGMENTS</title><p id=\\"p-55\\">None.<xref ref-type=\\"bibr\\" rid=\\"ref-21\\"><sup>21</sup></xref></p></ack><sec id=\\"sec-25\\" sec-type=\\"availability\\"><title>DATA AVAILABILITY</title><p id=\\"p-56\\">The data that support the findings of this study are not available due to national privacy or ethical restrictions.</p></sec><fn-group><fn fn-type=\\"con\\"><label>Contributor Information</label><p id=\\"p-57\\">Agnete Hviid Hornnes, Email: agnete.hviid.hornnes@regionh.dk <ext-link ext-link-type=\\"uri\\" xlink:href=\\"https://orcid.org/0000-0003-2217-5904\\">https//orcid.org/0000-0003-2217-5904</ext-link>
Mai Bang Poulsen, Email: mai.bang.poulsen.02@regionh.dk</p><p id=\\"p-58\\">Both authors have made substantial contributions to conception and design and acquisitions and analyses  and interpretation of data and have; and been involved in writing the manuscript and given final approval of the version to be published. Both authors have participated sufficiently in the work to take public responsibility for the content; and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.</p></fn></fn-group><ref-list><ref id=\\"ref-1\\"><label>1. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Wahlgren</surname> <given-names>N</given-names></string-name>, <string-name><surname>Ahmed</surname> <given-names>N</given-names></string-name>, <string-name><surname>Eriksson</surname> <given-names>N</given-names></string-name>, et al</person-group>. <article-title>Multivariable analysis of outcome predictors and adjustment</article-title> <source><italic>Stroke</italic></source>. <year>2008</year>;<volume>39</volume>:<fpage>3316</fpage>-<lpage>3322</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1161/STROKEAHA.107.510768</pub-id></mixed-citation></ref><ref id=\\"ref-2\\"><label>2. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Wahlgren</surname> <given-names>N</given-names></string-name></person-group>. <article-title>Systemic thrombolysis in clinical</article-title> <source><italic>Cerebrovascular Diseases (Basel, Switzerland)</italic></source>. <year>2009</year>;<volume>27</volume>:<fpage>168</fpage>-<lpage>176</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1159/000200456</pub-id></mixed-citation></ref><ref id=\\"ref-3\\"><label>3. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Thorvaldsen</surname> <given-names>P</given-names></string-name>, <string-name><surname>Davidsen</surname> <given-names>M</given-names></string-name>, <string-name><surname>Brønnum-Hansen</surname> <given-names>H</given-names></string-name>, <string-name><surname>Schroll</surname> <given-names>M</given-names></string-name></person-group>. <article-title>Stable stroke occurrence despite</article-title> <source><italic>Stroke</italic></source>. <year>1999</year>;<volume>30</volume>:<fpage>2529</fpage>-<lpage>2534</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1161/01.STR.30.12.2529</pub-id></mixed-citation></ref><ref id=\\"ref-4\\"><label>4. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Jørgensen</surname> <given-names>HS</given-names></string-name>, <string-name><surname>Nakayama</surname> <given-names>H</given-names></string-name>, <string-name><surname>Reith</surname> <given-names>J</given-names></string-name>, <string-name><surname>Raaschou</surname> <given-names>HO</given-names></string-name>, <string-name><surname>Olsen</surname> <given-names>TS</given-names></string-name></person-group>. <article-title>Stroke recurrence: Predictors, severity, and prognosis. The</article-title> <source><italic>Neurology</italic></source>. <year>1997</year>;<volume>48</volume>:<fpage>891</fpage>-<lpage>895</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1212/WNL.48.4.891</pub-id></mixed-citation></ref><ref id=\\"ref-5\\"><label>5.</label><mixed-citation specific-use=\\"unstructured-citation\\">Danish Stroke Registry. Danish Stroke
+            Herlev</addr-line>, <city>Herlev</city>, <country>Denmark</country>, <postal-code>2730</postal-code></aff></contrib-group><author-notes><fn id=\\"fn-1\\"><p>Mai Bang Poulsen, MD, PhD
Department of Neurology
Nordsjællands Hospital
Dyrehavevej 29
3400 Hillerød
Denmark</p></fn><fn id=\\"fn-2\\"><p>ClinicalTrials.gov NCT03782857.</p></fn><fn fn-type=\\"coi-statement\\"><label>CONFLICT OF INTEREST</label><p id=\\"p-1\\">None.</p></fn></author-notes><supplementary-material id=\\"supplementary-material-1\\" xlink:href=\\"attachment:7d9d686b-5488-44a5-a1c5-46351e7f9312\\" mimetype=\\"application\\" mime-subtype=\\"vnd.openxmlformats-officedocument.wordprocessingml.document\\"><caption><title>final manuscript-hum-huili-dbh-suicide-20200707_figures (9)</title></caption></supplementary-material><history><date date-type=\\"accepted\\"><day>27</day><month>04</month><year>2020</year></date><date date-type=\\"received\\"><day>09</day><month>12</month><year>2019</year></date></history><self-uri content-type=\\"document\\" xlink:href=\\"http://www.harmreductionjournal.com/content/1/1/5\\"/><self-uri content-type=\\"document\\" xlink:href=\\"http://www.harmreductionjournal.com/content/1/1/2\\"/><abstract><sec id=\\"sec-1\\"><title>Objectives</title><p id=\\"p-2\\">In Denmark 25% of hospital admissions with stroke are recurrent strokes. With thrombolytic treatment more patients survive with only minor disability. This promising development should be followed up by intensive secondary prevention. Hypertension is the most important target. We aimed at testing the hypotheses that early follow up in a preventive clinic would result in 1) A higher proportion of patients with blood pressure at target, 2) Time to stroke recurrence, myocardial infarction and death would be longer in the intervention group compared to controls.</p></sec><sec id=\\"sec-2\\" sec-type=\\"methods\\"><title>Materials and Methods</title><p id=\\"p-3\\">Eligible patients admitted to the stroke unit of Herlev Hospital were randomized shortly before discharge to intervention or control group. Of 78 included participants data from 73 was available for follow up nine months after inclusion. Patients in the intervention group were seen in the clinic within one week. In case of hypertension treatment was initiated or supplied with a new drug. We used individual targets for blood pressure according to diagnosis of stroke and patients’ comorbidity. Patients in the intervention group had a median of five visits to the preventive clinic.</p></sec><sec id=\\"sec-3\\" sec-type=\\"results\\"><title>Results</title><p content-type=\\"headshots\\"><graphic xlink:href=\\"headshot.png\\"><caption><title>Jane Doe, Ph.D.</title><p><bold>Editor</bold></p><p>Wiley</p></caption><alt-text>Jane Doe, Ph.D.</alt-text></graphic><graphic xlink:href=\\"headshot2.png\\"><caption><title>Jack Black</title><p><bold>CEO</bold></p><p>Generico</p></caption><alt-text>Headshot of Jack Black</alt-text></graphic></p><p id=\\"p-4\\">In the intervention group blood pressure was treated to target in 25 patients (69%) versus 14 (38%) in the control group (<italic>p</italic> = 0.007). Median time to first event was 44 months (4–49) in the intervention group and 19 months (4–37) in controls (<italic>p</italic> = 0.316).</p></sec><sec id=\\"sec-4\\" sec-type=\\"conclusions\\"><title>Conclusions</title><p id=\\"p-5\\">Treatment of hypertension to individual targets after stroke is feasible. It may postpone recurrent stroke and death in stroke survivors.</p></sec></abstract><abstract abstract-type=\\"graphical\\"><fig id=\\"fig-1\\" fig-type=\\"half-left\\"><graphic xlink:href=\\"demo1.jpg\\"/></fig></abstract><abstract abstract-type=\\"key-image\\"><fig id=\\"fig-2\\" fig-type=\\"half-left\\"><graphic xlink:href=\\"demo2.jpg\\"/></fig></abstract><abstract abstract-type=\\"short\\"><p id=\\"p-6\\">The is the third and last part of the volume devoted to solubility data of rare earth metal chlorides in water and in ternary and quaternary aqueous systems. Compilations of all available experimental data are introduced for each rare earth metal chloride with a corresponding critical evaluation. This part covers chlorides of Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu, with coverage of the literature through the middle of 2008.</p></abstract><trans-abstract xml:lang=\\"fr\\" abstract-type=\\"short\\"><title>Short</title><p id=\\"p-7\\">Il s'agit de la troisième et dernière partie du volume consacrée aux données de solubilité des chlorures de métaux des terres rares dans l'eau et dans les systèmes aqueux ternaires et quaternaires. Une compilation de toutes les données expérimentales disponibles est présentée pour chaque chlorure de métaux des terres rares, accompagnée de l'évaluation critique correspondante. Cette partie couvre les chlorures de Gd, Tb, Dy, Ho, Er, Tm, Yb et Lu, avec une couverture de la littérature jusqu'à mi-2008.</p></trans-abstract><kwd-group kwd-group-type=\\"author\\"><kwd>secondary prevention</kwd><kwd>stroke recurrence</kwd><kwd>blood pressure</kwd><kwd>blood pressure target</kwd><kwd>randomized controlled trial</kwd></kwd-group><funding-group><award-group id=\\"award-group-1\\"><funding-source>National Institutes of Health</funding-source><award-id>GM18458</award-id><principal-award-recipient>Berkeley</principal-award-recipient></award-group><award-group id=\\"award-group-2\\"><funding-source>National Science Foundation</funding-source><award-id>DMS-0204674</award-id><award-id>DMS-0244638</award-id></award-group></funding-group><counts><fig-count count=\\"8\\"/><table-count count=\\"2\\"/><ref-count count=\\"25\\"/><word-count count=\\"3659\\"/></counts></article-meta></front><body><graphic xlink:href=\\"demo1.png\\"><ext-link xlink:href=\\"WLYSP_5_4_Infographic_Nov_11_2022.pdf\\"/><caption><p>simple image</p><p>caption</p></caption></graphic><graphic xlink:href=\\"prodbe.int.aip.org:8080/journal/journal_fs/ 1.2983775.1373315697!/images/1460725790.jpg\\"><alt-text>example of alt text for graphics</alt-text><long-desc>example of long desc</long-desc></graphic><p id=\\"p-8\\">test paragraph</p><disp-quote content-type=\\"quote-with-image\\"><graphic xlink:href=\\"demo1.jpg\\"/><p>It is a far, far better thing that I do now than I have ever done.</p><attrib>Charles Dickens</attrib></disp-quote><disp-quote content-type=\\"quote\\"><p>A standard pullquote.</p><attrib/></disp-quote><disp-quote content-type=\\"half-left\\"><p>A half-left pullquote.</p><attrib/></disp-quote><disp-quote content-type=\\"half-right\\"><p>A half-right pullquote.</p><attrib/></disp-quote><disp-quote><p>pullquote without content-type</p><attrib/></disp-quote><disp-quote content-type=\\"quote\\"><p>blockquote</p><attrib/></disp-quote><sec id=\\"sec-5\\" sec-type=\\"intro\\"><label>1</label><title>INTRODUCTION</title><p id=\\"p-9\\">Over the last two decades continuous development of thrombolytic treatment of acute ischemic stroke (IS) has improved safety and functional outcome in treated patients <xref ref-type=\\"bibr\\" rid=\\"ref-1 ref-2\\"><sup>1,2</sup></xref> thus increasing the possibility of survival with no or only minor disability. With this fact and the ongoing aging of populations in mind <xref ref-type=\\"bibr\\" rid=\\"ref-3\\"><sup>3</sup></xref> the secondary prevention after stroke seems more important than ever. In 1998 the Copenhagen Stroke Study reported a recurrence rate of 23%. <xref ref-type=\\"bibr\\" rid=\\"ref-4\\"><sup>4</sup></xref> According to the Danish Stroke Registry our national recurrence rate was 25% in 2011.<xref ref-type=\\"bibr\\" rid=\\"ref-5\\"><sup>5</sup></xref></p><p id=\\"p-10\\">Hypertension is an important risk factor for stroke recurrence. <xref ref-type=\\"bibr\\" rid=\\"ref-4 ref-6 ref-7 ref-8\\"><sup>4,6–8</sup></xref> Lowering blood pressure (BP) after stroke or transitory ischemic attack (TIA) by 10/5 mm Hg has been associated with reduced risk of stroke recurrence by 24% and myocardial infarction (MI) by 21%. <xref ref-type=\\"bibr\\" rid=\\"ref-9\\"><sup>9</sup></xref></p><p id=\\"p-11\\">Observational studies have demonstrated the difficulties in lowering BP after stroke with rates of BP treated to target ranging from 28% to 73% <xref ref-type=\\"bibr\\" rid=\\"ref-10 ref-11 ref-12 ref-13\\"><sup>10–13</sup></xref> and interventions aimed at control of BP after stroke have not yet found a successful model. <xref ref-type=\\"bibr\\" rid=\\"ref-14 ref-15 ref-16 ref-17 ref-18 ref-19\\"><sup>14–19</sup></xref> Fahey and coworkers have reviewed the literature aimed at improving control of BP in hypertensive subjects. One large study using an organized system of regular visits to a clinic was efficient in producing a large decrease in BP and reduction of all-cause mortality compared to referral to usual primary care. This was achieved by using a stepwise escalation of treatment until target was reached. <xref ref-type=\\"bibr\\" rid=\\"ref-20\\"><sup>20</sup></xref> Other methods had variable or no effect, only nurse or pharmacist led care seemed promising.</p><media id=\\"media-1\\" xlink:show=\\"embed\\" xlink:href=\\"example.mp4\\" mimetype=\\"video\\" mime-subtype=\\"mp4\\"><label>Media 1</label><alt-text>example of alt text for media</alt-text><long-desc>example of long desc</long-desc></media><sec id=\\"sec-6\\"><title>Aims and hypotheses</title><p id=\\"p-12\\">The aim of the present study was to test the hypotheses that follow up after stroke in a specialized nurse led physician supervised clinic with stepwise escalation of BP- and lipid lowering treatment would result in</p><sec id=\\"sec-7\\"><title>Primary endpoint</title><sec id=\\"sec-8\\"><title>A greater proportion of participants with BP at target</title><p id=\\"p-13\\">Secondary endpoints: A greater reduction of BP A greater proportion of participants with LDL-cholesterol treated to target A greater reduction of LDL-cholesterol Longer time to recurrence of stroke, MI and death in the intervention group compared to controls</p></sec></sec><sec id=\\"sec-9\\"><title>BoxedText test</title><boxed-text id=\\"boxed-text-1\\"><label>Box 1</label><sec id=\\"sec-10\\"><title/><p/></sec></boxed-text><boxed-text id=\\"boxed-text-2\\" content-type=\\"half-left\\"><label>Box 2</label><caption><title>BoxedTextCaptionTitle</title></caption><sec id=\\"sec-11\\"><title>Key messages</title><list list-type=\\"bullet\\"><list-item><p id=\\"p-14\\">The benefits of geriatric day hospital care have been controversial for many years.</p></list-item><list-item><p id=\\"p-15\\">This systematic review of 12 randomised trials comparing a variety of day hospitals with a range of alternative services found no overall advantage for day hospital care.</p></list-item><list-item><p id=\\"p-16\\">Day hospitals had a possible advantage over no comprehensive care in terms of death or poor outcome, disability, and use of resources.</p></list-item><list-item><p id=\\"p-17\\">The costs of day hospital care may be partly offset by a reduced use of hospital beds and institutional care among survivors.</p></list-item></list><sec id=\\"sec-12\\"><title>testing multiple sections inside a boxed-text element</title><p id=\\"p-18\\">Hello World!</p></sec></sec></boxed-text><boxed-text id=\\"boxed-text-3\\"><label>Box 3</label><sec id=\\"sec-13\\"><title>Key messages</title><list list-type=\\"bullet\\"><list-item><p id=\\"p-19\\">The benefits of geriatric day hospital care have been controversial for many years.</p></list-item><list-item><p id=\\"p-20\\">This systematic review of 12 randomised trials comparing a variety of day hospitals with a range of alternative services found no overall advantage for day hospital care.</p></list-item><list-item><p id=\\"p-21\\">Day hospitals had a possible advantage over no comprehensive care in terms of death or poor outcome, disability, and use of resources.</p></list-item><list-item><p id=\\"p-22\\">The costs of day hospital care may be partly offset by a reduced use of hospital beds and institutional care among survivors.</p></list-item></list></sec></boxed-text></sec></sec></sec><sec id=\\"sec-14\\" sec-type=\\"methods\\"><label>2</label><title>MATERIELS AND METHODS</title><p id=\\"p-23\\">Before the initiation of the study the authors attended a three-day course in treatment of hypertension arranged by the Danish Society of Hypertension. The recommendations of our national guidelines regarding BP targets were in line with those given by the American Stroke Association in force at the time of initiation of the study: “An absolute target BP level and reduction are uncertain and should be individualized.” <xref ref-type=\\"bibr\\" rid=\\"ref-21\\"><sup>21</sup></xref> Following the advice given by the Danish Society of Hypertension we used the following targets: A BP &lt; 140/90 mm Hg was considered at target in non-diabetic patients. In patients aged 80 years or more a BP of 150/90 mm Hg was acceptable if further treatment was not tolerated. In case of severe carotid stenosis or a history of ischemic heart disease BP should not be lower than 130/80 mm Hg. In patients with diabetes or hemorrhagic stroke we aimed at a BP &lt; 130/80 mm Hg. Untreated patients without hypertension were categorized as normotensive, untreated hypertensive patients as having unknown hypertension, treated patients without hypertension as treated to target, and treated patients with hypertension as having untreated hypertension.</p><p id=\\"p-24\\">LDL-cholesterol should be &lt; 2.5 mmol/l in patients with IS or TIA in non-diabetic patients and in case of diabetes &lt; 2.0 mmol/l.</p><p id=\\"p-25\\">A sample size calculation showed that 24 patients in each group were needed to show a difference of 10 mm Hg in the development of systolic BP (80% power).</p><sec id=\\"sec-15\\"><label>2.1</label><title>Study sample and setting</title><p id=\\"p-26\\">From June 2012 to February 2013 all patients diagnosed with a stroke or TIA at the stroke unit of Herlev Gentofte Hospital, University of Copenhagen were considered for inclusion in the study. Patients should be without cognitive deficits that would prevent their active participation and they should be discharged to their own home. The last author used computer-generated block randomization procedures with stratification by hypertension (1:1). The allocation sequence was concealed, and we aimed at equal numbers in the two groups. Shortly before discharge the first author approached eligible patients for oral and written information about the study. Where written informed consent to participation was achieved BP was measured before a concealed envelope administered by a secretary was opened revealing the allocation to either intervention or control group.</p><p id=\\"p-27\\">The research protocol was approved by the ethics committee of the Capital Region of Denmark (H-3-2011–152) and by the Danish Data Protection Agency (2012–41-0429). The study was conducted according to all common ethical standards including the rules given by the Declaration of Helsinki. Patients randomized to the control group had the usual treatment: one visit in the outpatient clinic of the stroke unit three months after discharge. Patients randomized to the intervention group had an appointment with the first author within one week after discharge. The first author undertook all visits in the preventive clinic.</p></sec><sec id=\\"sec-16\\"><label>2.2</label><title>Procedures and intervention</title><p id=\\"p-28\\">BP was measured at every visit after at least five minutes rest in a sitting position in an arm chair. BP was measured simultaneously in both arms followed by two measurements with 10-min intervals using the arm with the highest systolic BP. In case of hypertension the first author would suggest initiation or intensification of antihypertensive treatment. The last author would accept or suggest an alternative and do the prescription. Patients would come to the clinic for control of BP and relevant blood tests every 3–4 weeks until BP was at target. After five weeks on lipid lowering drugs treatment was intensified if needed. Patients who did not tolerate lipid lowering medication were referred to a dietitian. In motivated patients home BP measurements were performed using patients’ own monitor or by lending patients a BP monitor between visits.</p><p id=\\"p-29\\">Patients in the intervention group had a mean of five visits to the clinic with addition of new drugs rather than adding more of the same drug in case of hypertension. Although we used minimum doses to prevent adverse effects, many patients had unacceptable side effects necessitating change to another class of antihypertensive drug.</p><p id=\\"p-30\\">Patients were informed about the importance of life-long adherence with all preventive medication. Those with elevated BP or receiving antihypertensive treatment were advised in salt reduction, smokers were advised to stop smoking and all patients were informed about the benefits of 30 min of moderate physical activity daily. Likewise, information about the risk of an intake of alcohol above seven drinks per week in women and 14 drinks in men was part of the program as well as the benefits of weight reduction in overweight patients with hypertension or diabetes.</p></sec><sec id=\\"sec-17\\"><label>2.3</label><title>Follow up</title><p id=\\"p-31\\">Participants in both groups were invited to the usual follow up visit three months after discharge at the outpatient clinic of the stroke unit as well as a follow up visit in the study a median of 9 (IQR 8–11) months after inclusion.</p><p id=\\"p-32\\">In accordance with the protocol the final follow up visits were performed by nurses in the outpatient clinic with measurement of BP and blood-cholesterols. Patients were asked not to reveal their group allocation but blinding of the nurses was not possible. Patients were interviewed about adherence to all preventive medications as well as their present life style. For practical purposes a minority of visits were performed by the first author. To do intention to treat analyses we used last observation carried forward regarding the endpoints of the study where patients had died or did not respond to the invitation to a follow up visit. Thus, we used the last recorded values in five patients in the intervention group and in seven controls.</p><p id=\\"p-33\\">After a median of 65 months (IQR: 61–66) from inclusion data on vascular events and death were attained from the hospital based medical records covering all hospitals of the region.</p></sec><sec id=\\"sec-18\\"><label>2.4</label><title>Statistics</title><p id=\\"p-34\\">Data were entered into Excel and imported into SAS. Statistical analyses were performed by the first author according to a pre-established statistical analysis plan. We used Chi square test (for the primary outcome) or Fisher’s exact test as appropriate for comparison of proportions, and for change from baseline we used McNemar’s test. For continuous variables we used t-test or Mann-Whitney’s test*. Change from baseline was analyzed by the paired t-test or Wilcoxon signed rank sum test* (*where data were not normally distributed). We used SAS 9.4 for Windows and <italic>p</italic> &lt; 0.05 was considered significant.</p></sec></sec><sec id=\\"sec-19\\" sec-type=\\"results\\"><label>3</label><title>RESULTS</title><p id=\\"p-35\\">We included 78 patients in the study. Due to revision of stroke diagnoses in four participants and as one participant never turned up for the intervention, data on 73 participants were available for follow up (<xref ref-type=\\"fig\\" rid=\\"fig-3\\">Figure 1</xref>). The median stay in hospital was 4 days (IQR: 3–6). As seen from <xref ref-type=\\"table\\" rid=\\"table-wrap-1\\">Table 1</xref> most participants had no or slight disability.</p><fig id=\\"fig-3\\" fig-type=\\"half-left\\"><label>Figure 1</label><caption><p>Flow chart of participants</p></caption><graphic xlink:href=\\"BRB3-2019-12-0787-fig-0001.png\\"><alt-text>example of alt text for graphics inside figures</alt-text><long-desc>example of long desc for graphics inside figures</long-desc></graphic></fig><table-wrap id=\\"table-wrap-1\\" position=\\"anchor\\" content-type=\\"half-right\\"><label>Table 1</label><caption><title>Baseline characteristics of 73 patients</title></caption><alt-text>example of alt text for tables</alt-text><long-desc>example of long desc</long-desc><table id=\\"table-1\\"><colgroup><col width=\\"52.14%\\"/><col width=\\"11.92%\\"/><col width=\\"14.9%\\"/><col width=\\"13.1%\\"/><col width=\\"7.94%\\"/></colgroup><thead><tr><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Characteristics</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>All(<italic>n</italic> = 73)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Intervention (<italic>n</italic> = 36)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Control (<italic>n</italic> = 37)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>P</p></th></tr></thead><tbody><tr><td valign=\\"middle\\" align=\\"left\\" scope=\\"row\\" style=\\"border-top: solid 0.50pt\\"><p>Sex, female</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>29 (40)</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>15 (42)</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>14 (38)</p></td><td valign=\\"middle\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>0.74</p></td></tr><tr><td valign=\\"middle\\" align=\\"left\\" scope=\\"row\\"><p>Age (years), mean ± SD</p></td><td valign=\\"middle\\" align=\\"left\\"><p>66 ± 12</p></td><td valign=\\"middle\\" align=\\"left\\"><p>63 ± 13</p></td><td valign=\\"middle\\" align=\\"left\\"><p>68 ± 11</p></td><td valign=\\"middle\\" align=\\"left\\"><p>0.08</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Length of education&lt; 10 years10 – 12 years&gt; 12 years</p></td><td valign=\\"top\\" align=\\"left\\"><p>12 (17)22 (30)38 (53)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (17)10 (29)19 (54)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (16)12 (33)19 (51)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.95</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diagnosis of strokeIschemic StrokeTIAHemorrhagic stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>63 (87)9 (12)1 (1)</p></td><td valign=\\"top\\" align=\\"left\\"><p>33 (92)3 (8)</p></td><td valign=\\"top\\" align=\\"left\\"><p>30 (81)6 (16)1 (3)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.60<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Recurrent stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (15)</p></td><td valign=\\"top\\" align=\\"left\\"><p>5 (14)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (16)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.00<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Modified Rankin Scale score &gt; 2</p></td><td valign=\\"top\\" align=\\"left\\"><p>5 (6)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1 (3)</p></td><td valign=\\"top\\" align=\\"left\\"><p>4 (11)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.36<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Antihypertensive medication before stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>39 (53)</p></td><td valign=\\"top\\" align=\\"left\\"><p>15 (42)</p></td><td valign=\\"top\\" align=\\"left\\"><p>24 (65)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.047</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Antihypertensive medication at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>46 (63)</p></td><td valign=\\"top\\" align=\\"left\\"><p>20 (56)</p></td><td valign=\\"top\\" align=\\"left\\"><p>26 (70)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.19</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Cholesterol lowering medication before stroke</p></td><td valign=\\"top\\" align=\\"left\\"><p>25 (34)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>14 (38)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.51</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Cholesterol lowering medication at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>65 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>35 (97)</p></td><td valign=\\"top\\" align=\\"left\\"><p>30 (81)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.03</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diabetes at baseline</p></td><td valign=\\"top\\" align=\\"left\\"><p>14 (19)</p></td><td valign=\\"top\\" align=\\"left\\"><p>5 (14)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.37<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diabetes at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>16 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (17)</p></td><td valign=\\"top\\" align=\\"left\\"><p>10 (27)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.29</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Atrial fibrillation at baseline</p></td><td valign=\\"top\\" align=\\"left\\"><p>7 (10)</p></td><td valign=\\"top\\" align=\\"left\\"><p>3 (8)</p></td><td valign=\\"top\\" align=\\"left\\"><p>4 (11)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.00<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Atrial fibrillation at discharge</p></td><td valign=\\"top\\" align=\\"left\\"><p>12 (16)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (16)</p></td><td valign=\\"top\\" align=\\"left\\"><p>6 (17)</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.00</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Unhealthy dieting<sup>b</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>59 (82)</p></td><td valign=\\"top\\" align=\\"left\\"><p>25 (71)</p></td><td valign=\\"top\\" align=\\"left\\"><p>34 (92)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.03</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Current smoking</p></td><td valign=\\"top\\" align=\\"left\\"><p>19 (26)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>8 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.62</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Alcohol above limits<sup>c</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>23 (32)</p></td><td valign=\\"top\\" align=\\"left\\"><p>12 (34)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (30)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.68</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Sedentary lifestyle<sup>d</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>17 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (26)</p></td><td valign=\\"top\\" align=\\"left\\"><p>8 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.68</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>BMI ≥ 25</p></td><td valign=\\"top\\" align=\\"left\\"><p>46 (63)</p></td><td valign=\\"top\\" align=\\"left\\"><p>24 (67)</p></td><td valign=\\"top\\" align=\\"left\\"><p>22 (59)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.52</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\" style=\\"border-bottom: solid 0.50pt\\"><p>Self-rated health: fair, poor, or very poor</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>34 (47)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>15 (43)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>19 (51)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>0.47</p></td></tr></tbody></table><table-wrap-foot><p id=\\"p-36\\">Values are expressed as frequencies (%) or as mean ± standard deviations</p><fn-group id=\\"fn-group-1\\"><fn id=\\"fn-3\\"><p id=\\"p-37\\">Fisher’s exact test. <sup>b</sup> Less than 600 g of fruit and vegetables per day, fish for dinner less than twice per week. <sup>c</sup> More than 7 drinks per week in women/more than 14 drinks per week in men. <sup>d</sup> Less than 30 min of moderate physical activity per day.</p></fn></fn-group></table-wrap-foot></table-wrap><p id=\\"p-38\\">Less than 20% of patients had a baseline BP treated to target (<xref ref-type=\\"fig\\" rid=\\"fig-4\\">Figure 2</xref>). Twenty-eight patients (78%) in the intervention group and 29 patients (78%) in the control group had a 3-month visit in the outpatient clinic. Here 15 patients (42%) in the intervention group had their BP and blood cholesterol measured and so had 23 patients (62%) in the control group. At follow up patients in both groups reported a median of two visits including BP measurement at the general practitioner´s office since discharge from hospital.</p><fig id=\\"fig-4\\" fig-type=\\"half-left\\"><label>Figure 2</label><caption><p>Blood pressure and treatment of hypertension at baseline in 73 patients (%)</p></caption><graphic xlink:href=\\"BRB3-2019-12-0787-fig-0002.png\\"/></fig><sec id=\\"sec-20\\"><label>3.1</label><title>Primary endpoint</title><p id=\\"p-39\\">Follow up visits showed that 25 patients (69%) in the intervention group had a BP at target versus 14 (38%) of controls (<italic>p</italic> = 0.007). In four patients (10%) in the intervention group antihypertensive medication remained unchanged since discharge versus 23 (62%) of controls (<italic>p</italic> &lt; 0.0001) illustrated by the differences in BP treated to target as well as untreated hypertension in <xref ref-type=\\"fig\\" rid=\\"fig-5\\">Figure 3</xref>.</p><fig id=\\"fig-5\\" fig-type=\\"half-left\\"><label>Figure 3</label><caption><p>Blood pressure and treatment of hypertension at follow up in 73 patients (%)</p></caption><graphic xlink:href=\\"BRB3-2019-12-0787-fig-0003.png\\"/></fig></sec><sec id=\\"sec-21\\"><label>3.2</label><title>Secondary endpoints</title><p id=\\"p-40\\">Median reduction in systolic BP was 11 mm Hg (-5-19) with 14 mm Hg (IQR: 5–21) in the intervention group and 3 mm Hg (IQR -11-17) in the control group (<italic>p</italic> = 0.045). Median reduction in diastolic BP was 2 mm Hg (-2-11) with 7 mm Hg (IQR -1-13) in the intervention group and 1 mm Hg (IQR -6-8) in the control group (<italic>p</italic> = 0.04).</p><p id=\\"p-41\\">There was no difference between the groups regarding LDL-cholesterol treated to target with 32 patients (89%) at target in the intervention group versus 29 patients (78%) in the control group (<italic>p</italic> = 0.21). We found significant reductions in LDL-cholesterol in both groups, but no difference between the groups: 1.6 (IQR: 0.4–2.2) mmol/l in the intervention group versus 0.8 (IQR: 0.4–1.8) mmol/l among controls (<italic>p</italic> = 0.18).</p><p id=\\"p-42\\">In 11 patients (31%) in the intervention group cholesterol lowering medication remained unchanged since discharge versus 29 (78%) of controls (<italic>p</italic> &lt; 0.0001).</p><p id=\\"p-43\\">The combined endpoint of both BP and LDL-cholesterol at target was achieved in 22 (61%) of patients in the intervention group and in 10 patients (27%) in the control group (<italic>p</italic> = 0.003). At the end of the study 24 patients (68%) in the intervention group measured their BP at home versus 14 (38%) of controls (<italic>p</italic> = 0.03).</p><p id=\\"p-44\\">The only significant change in lifestyle was a reduction in current smokers by four in the control group (<xref ref-type=\\"table\\" rid=\\"table-wrap-2\\">Table 2</xref>).</p><table-wrap id=\\"table-wrap-2\\" position=\\"anchor\\"><label>Table 2</label><caption><title>Nine months follow up of 73 patients</title></caption><table id=\\"table-2\\"><colgroup><col width=\\"52.91%\\"/><col width=\\"11.06%\\"/><col width=\\"14.16%\\"/><col width=\\"11.5%\\"/><col width=\\"10.37%\\"/></colgroup><thead><tr><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Characteristics</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>All(<italic>n</italic> = 73)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Intervention(<italic>n</italic> = 36)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>Control(<italic>n</italic> = 37)</p></th><th valign=\\"top\\" align=\\"left\\" scope=\\"col\\" style=\\"border-top: solid 0.50pt; border-bottom: solid 0.50pt\\"><p>P</p></th></tr></thead><tbody><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\" style=\\"border-top: solid 0.50pt\\"><p>Systolic BP, mm Hg, mean ± SD</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>134 ± 21</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>130 ± 17</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>137 ± 24</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-top: solid 0.50pt\\"><p>0.12</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Diastolic BP, mm Hg, mean ± SD</p></td><td valign=\\"top\\" align=\\"left\\"><p>78 ± 11</p></td><td valign=\\"top\\" align=\\"left\\"><p>78 ± 10</p></td><td valign=\\"top\\" align=\\"left\\"><p>78 ± 12.8)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.94</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Antihypertensive medication</p></td><td valign=\\"top\\" align=\\"left\\"><p>55 (75)</p></td><td valign=\\"top\\" align=\\"left\\"><p>29 (81)</p></td><td valign=\\"top\\" align=\\"left\\"><p>26 (70)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.31</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>100% compliance with AHM (<italic>n</italic> = 45)</p></td><td valign=\\"top\\" align=\\"left\\"><p>38 (84)</p></td><td valign=\\"top\\" align=\\"left\\"><p>23 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>15 (79)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.38</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>LDL-cholesterol, mmol/l (<italic>n</italic> = 72), mean ± SD</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.9 ± 0.8</p></td><td valign=\\"top\\" align=\\"left\\"><p>1.9 ± 0.7</p></td><td valign=\\"top\\" align=\\"left\\"><p>2.0 ± 0.8</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.66</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Cholesterol lowering medication</p></td><td valign=\\"top\\" align=\\"left\\"><p>64 (88)</p></td><td valign=\\"top\\" align=\\"left\\"><p>32 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>32 (86)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.76</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>100% compliance with CLM (<italic>n</italic> = 52)</p></td><td valign=\\"top\\" align=\\"left\\"><p>46 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>24 (86)</p></td><td valign=\\"top\\" align=\\"left\\"><p>22 (92)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.50</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Unhealthy dieting<sup>b</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>59 (81)</p></td><td valign=\\"top\\" align=\\"left\\"><p>26 (72)</p></td><td valign=\\"top\\" align=\\"left\\"><p>33 (89)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.76</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Current smoker</p></td><td valign=\\"top\\" align=\\"left\\"><p>15 (21)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>4 (11)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.046<sup>a</sup></p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Alcohol &gt; limits<sup>c</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>20 (27)</p></td><td valign=\\"top\\" align=\\"left\\"><p>11 (31)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.55</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\"><p>Sedentary lifestyle<sup>d</sup></p></td><td valign=\\"top\\" align=\\"left\\"><p>16 (22)</p></td><td valign=\\"top\\" align=\\"left\\"><p>7 (20)</p></td><td valign=\\"top\\" align=\\"left\\"><p>9 (24)</p></td><td valign=\\"top\\" align=\\"left\\"><p>0.66</p></td></tr><tr><td valign=\\"top\\" align=\\"left\\" scope=\\"row\\" style=\\"border-bottom: solid 0.50pt\\"><p>BMI ≥ 25</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>43 (59)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>21 (58)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>22 (60)</p></td><td valign=\\"top\\" align=\\"left\\" style=\\"border-bottom: solid 0.50pt\\"><p>0.92</p></td></tr></tbody></table><table-wrap-foot><p id=\\"p-45\\">Values are expressed as frequencies (%) or as mean ± standard deviations.
Abbreviations: AHM, antihypertensive medication; CLM, cholesterol lowering medication.</p><fn-group id=\\"fn-group-2\\"><fn id=\\"fn-4\\"><p id=\\"p-46\\">Fisher’s exact test. <sup>b</sup> Less than 600 g of fruit and vegetables per day, fish for dinner less than twice per week. <sup>c</sup> More than 7 drinks per week in women/more than 14 drinks per week in men. <sup>d</sup> Less than 30 min of moderate physical activity per day.</p></fn></fn-group></table-wrap-foot></table-wrap><p id=\\"p-47\\">Regarding vascular complications and death, we found 32 events in 22 patients after a median of 65 months. Median time to first event was 26 months (IQR: 4–49) with a median of 44 months (IQR: 11–49) in the intervention group and 19 months (IQR: 4–37) in the control group (<italic>p</italic> = 0.32). All in all, we found 11 events in nine patients in the intervention group: two recurrent strokes, three cases of TIA, and six patients died versus 21 events in 13 patients in the control group: seven recurrent strokes, five cases of TIA, one MI, and seven patients died (<italic>p</italic> = 0.49).</p></sec></sec><sec id=\\"sec-22\\" sec-type=\\"discussion\\"><label>4</label><title>DISCUSSION</title><p id=\\"p-48\\">In this randomized clinical trial, a larger proportion of patients in the intervention group compared to controls had BP within the above-mentioned limits and the study fulfilled the aim of the primary endpoint.</p><p id=\\"p-49\\">A systematic review of interventions aimed at modifiable risk factor control for secondary prevention of stroke revealed improvement in achieving BP target. <xref ref-type=\\"bibr\\" rid=\\"ref-22\\"><sup>22</sup></xref> However, as opposed to our study the review showed no significant change in systolic og diastolic BP.</p><p id=\\"p-50\\">In a study of integrated care with five prearranged visits to patients’ general practitioner versus usual care systolic BP at target set to 140 mm Hg was found in 75% versus 58% at 12-month follow up. <xref ref-type=\\"bibr\\" rid=\\"ref-19\\"><sup>19</sup></xref> We set individual targets for BP according to patients’ type of stroke, comorbidities and age. This is well in line with recommendations given by European Society of Hypertension, <xref ref-type=\\"bibr\\" rid=\\"ref-23\\"><sup>23</sup></xref> but as stated by Boan et al., not quite in accordance with international stroke guidelines. <xref ref-type=\\"bibr\\" rid=\\"ref-24\\"><sup>24</sup></xref></p><p id=\\"p-51\\">In a study where patients with minor stroke were randomized to six clinic visits by a pharmacist (intervention) or by a nurse (active control) aiming at treating both BP and LDL-cholesterol to target, 43% of patients in the pharmacist-led clinic met those two targets and so did 31% in the nurse-led clinic. <xref ref-type=\\"bibr\\" rid=\\"ref-25\\"><sup>25</sup></xref> In our study this combined endpoint was met in 22 (61%) of patients in the intervention group. Regarding BP in control 80% of patients in the pharmacist led clinic had systolic BP in control after six months versus 90% in the nurse led clinic. This is a far greater proportion than the 69% in our study. However, almost two thirds of patients had a baseline BP within the limits. The opposite was the case in our study with two thirds presenting with elevated BP. Both studies show that a dedicated follow up with stepwise escalation of preventive medication may be the way to reach the targets of the two important risk factors for recurrent stroke. In both studies five-six visits were needed, which is far beyond our usual treatment. However, despite visits to the outpatient clinic as well as to the general practitioner the proportion of patients with unchanged medication since discharge in the control group illustrate the necessity of frequent visits to a dedicated preventive facility. Considering the preventive effect of BP lowering, and - though insignificant - the difference in time to first event as well as the smaller proportion of events in the intervention group as found in our study, it may be well worth the time and resources for patients, their relatives and society.</p><sec id=\\"sec-23\\"><label>4.1</label><title>Strengths and limitations</title><p id=\\"p-52\\">Our study has some limitations. Most participants had a minor stroke and patients had to be independent and without severe cognitive deficits, which is not representative of a general stroke population. With only 73 participants caution is called for in the drawing of conclusions from the results. Nonetheless, we decided to reorganize the outpatient clinic of our stroke unit as of October 2014 implementing strategies of the present study.</p><p id=\\"p-53\\">The strength of the study is the individual target for BP taking into account the diagnosis of stroke as well as important comorbidity as recommended by Boan et al. <xref ref-type=\\"bibr\\" rid=\\"ref-24\\"><sup>24</sup></xref> Five-year follow up on vascular complications and death is another important advantage.</p></sec></sec><sec id=\\"sec-24\\" sec-type=\\"conclusions\\"><label>5</label><title>CONCLUSIONS</title><p id=\\"p-54\\">In conclusion, the feasibility study has demonstrated that timely follow up of stroke patients in a dedicated preventive outpatient clinic may result in BP and cholesterol treated to target in most patients. To some extent it may postpone time to stroke recurrence, MI and death.</p></sec></body><back><app-group/><ack><title>ACKNOWLEDGMENTS</title><p id=\\"p-55\\">None.<xref ref-type=\\"bibr\\" rid=\\"ref-21\\"><sup>21</sup></xref></p></ack><sec id=\\"sec-25\\" sec-type=\\"availability\\"><title>DATA AVAILABILITY</title><p id=\\"p-56\\">The data that support the findings of this study are not available due to national privacy or ethical restrictions.</p></sec><fn-group><fn fn-type=\\"con\\"><label>Contributor Information</label><p id=\\"p-57\\">Agnete Hviid Hornnes, Email: agnete.hviid.hornnes@regionh.dk <ext-link ext-link-type=\\"uri\\" xlink:href=\\"https://orcid.org/0000-0003-2217-5904\\">https//orcid.org/0000-0003-2217-5904</ext-link>
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<given-names>G</given-names></string-name></person-group>. <article-title>Blood pressure 1 year after stroke: The</article-title> <source><italic>Journal of Stroke and Cerebrovascular Diseases</italic></source>. <year>2011</year>;<volume>20</volume>:<fpage>16</fpage>-<lpage>23</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1016/j.jstrokecerebrovasdis.2009.10.002</pub-id></mixed-citation></ref><ref id=\\"ref-18\\"><label>18. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Johnston</surname> <given-names>SC</given-names></string-name>, <string-name><surname>Sidney</surname> <given-names>S</given-names></string-name>, <string-name><surname>Hills</surname> <given-names>NK</given-names></string-name>, et al</person-group>. <article-title>Standardized discharge orders after</article-title> <source><italic>Annals of Neurology</italic></source>. 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publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Fahey</surname> <given-names>T</given-names></string-name>, <string-name><surname>Schroeder</surname> <given-names>K</given-names></string-name>, <string-name><surname>Ebrahim</surname> <given-names>S</given-names></string-name></person-group>. <article-title>Interventions used to improve control of</article-title> <source><italic>Cochrane Database of Systematic Reviews</italic></source>. <year>2006</year>.</mixed-citation></ref><ref id=\\"ref-21\\"><label>21. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Furie</surname> <given-names>KL</given-names></string-name>, <string-name><surname>Kasner</surname> <given-names>SE</given-names></string-name>, <string-name><surname>Adams</surname> <given-names>RJ</given-names></string-name>, et al</person-group>. <article-title>Guidelines for the prevention of 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Database of Systematic Reviews</italic></source>. <year>2018</year>;<volume>5</volume>.</mixed-citation></ref><ref id=\\"ref-23\\"><label>23. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Mancia</surname> <given-names>G</given-names></string-name>, <string-name><surname>Fagard</surname> <given-names>R</given-names></string-name>, <string-name><surname>Narkiewicz</surname> <given-names>K</given-names></string-name>, et al</person-group>. <article-title>2013 Practice guidelines for the management of arterial</article-title> <source><italic>Journal of Hypertension</italic></source>. <year>2013</year>;<volume>31</volume>:<fpage>1925</fpage>-<lpage>1938</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1097/HJH.0b013e328364ca4c</pub-id></mixed-citation></ref><ref id=\\"ref-24\\"><label>24. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>Boan</surname> <given-names>AD</given-names></string-name>, <string-name><surname>Lackland</surname> <given-names>DT</given-names></string-name>, <string-name><surname>Ovbiagele</surname> <given-names>B</given-names></string-name></person-group>. <article-title>Lowering of blood pressure for recurrent</article-title> <source><italic>Stroke</italic></source>. <year>2014</year>;<volume>45</volume>:<fpage>2506</fpage>-<lpage>2513</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1161/STROKEAHA.114.003666</pub-id></mixed-citation></ref><ref id=\\"ref-25\\"><label>25. </label><mixed-citation publication-type=\\"journal\\"><person-group person-group-type=\\"author\\"><string-name><surname>McAlister</surname> <given-names>FA</given-names></string-name>, <string-name><surname>Majumdar</surname> <given-names>SR</given-names></string-name>, <string-name><surname>Padwal</surname> <given-names>RS</given-names></string-name>, et al</person-group>. <article-title>Case management for blood pressure and</article-title> <source><italic>Canadian Medical Association Journal</italic></source>. <year>2014</year>;<volume>186</volume>:<fpage>577</fpage>-<lpage>584</lpage>. doi:<pub-id pub-id-type=\\"doi\\">https://doi.org/10.1503/cmaj.140053</pub-id></mixed-citation></ref></ref-list></back><floats-group><graphic xlink:href=\\"fig1.png\\" content-type=\\"leading\\"><alt-text>example of alt text for hero-image</alt-text><long-desc>example of long desc for hero image</long-desc></graphic></floats-group></article>"
 `;
 

package/src/jats/exporter/jats-exporter.ts

@@ -990,11 +990,11 @@ export class JATSExporter {
         return this.createElement('boxed-text')
       },
       pullquote_element: (node) => {
-        let type = 'pullquote'
-        if (node.firstChild?.type === schema.nodes.quote_image) {
-          type = 'quote-with-image'
+        const attrs: { [key: string]: string } = {}
+        if (node.attrs.type) {
+          attrs['content-type'] = node.attrs.type
         }
-        return ['disp-quote', { 'content-type': type }, 0]
+        return ['disp-quote', attrs, 0]
       },
       quote_image: (node) => {
         const img = node as QuoteImageNode
@@ -1030,6 +1030,9 @@ export class JATSExporter {
       table_element: (node) => {
         const element = createTableElement(node)
         element.setAttribute('position', 'anchor')
+        if (node.attrs.type) {
+          element.setAttribute('content-type', node.attrs.type)
+        }
         return element
       },
       table_cell: (node) => [
@@ -1160,6 +1163,9 @@ export class JATSExporter {
     }
     const createBoxElement = (node: ManuscriptNode) => {
       const element = createElement(node, 'boxed-text')
+      if (node.attrs.type) {
+        element.setAttribute('content-type', node.attrs.type)
+      }
       appendLabels(element, node)
       const child = node.firstChild
       if (child?.type === schema.nodes.caption_title) {
@@ -1186,6 +1192,14 @@ export class JATSExporter {
       })
     }
 
+    const findParentHeroImage = (targetID: string) => {
+      const heroes = this.getChildrenOfType(schema.nodes.hero_image)
+      return heroes.find(
+        (hero) =>
+          !!findChildrenByAttr(hero, (attrs) => attrs.id === targetID)[0]
+      )
+    }
+
     const createImage = (node: ManuscriptNode) => {
       const graphicNode = node.content.firstChild
       if (!graphicNode) {
@@ -1206,8 +1220,9 @@ export class JATSExporter {
       const graphic = this.createElement('graphic')
       graphic.setAttributeNS(XLINK_NAMESPACE, 'xlink:href', node.attrs.src)
 
-      if (isChildOfNodeType(node.attrs.id, schema.nodes.hero_image)) {
-        graphic.setAttribute('content-type', 'leading')
+      const hero = findParentHeroImage(node.attrs.id)
+      if (hero) {
+        graphic.setAttribute('content-type', hero.attrs.type || 'leading')
       } else if (
         !isChildOfNodeType(node.attrs.id, schema.nodes.figure_element) &&
         node.attrs.type

package/src/jats/importer/jats-dom-parser.ts

@@ -718,7 +718,6 @@ export class JATSDOMParser {
       node: 'blockquote_element',
       getAttrs: (node) => {
         const element = node as HTMLElement
-
         return {
           id: element.getAttribute('id'),
         }
@@ -732,6 +731,7 @@ export class JATSDOMParser {
 
         return {
           id: element.getAttribute('id'),
+          type: element.getAttribute('content-type'),
         }
       },
     },
@@ -842,8 +842,14 @@ export class JATSDOMParser {
       },
     },
     {
-      tag: 'graphic[content-type=leading]',
+      tag: 'graphic[content-type^=leading]',
       node: 'hero_image',
+      getAttrs: (node) => {
+        const element = node as HTMLElement
+        return {
+          type: element.getAttribute('content-type'),
+        }
+      },
       getContent: this.getFigContent,
     },
     {
@@ -1067,6 +1073,7 @@ export class JATSDOMParser {
         const element = node as HTMLElement
         return {
           id: element.getAttribute('id'),
+          type: element.getAttribute('content-type') ?? '',
         }
       },
     },
@@ -1162,6 +1169,7 @@ export class JATSDOMParser {
         const element = node as HTMLElement
         return {
           id: element.getAttribute('id'),
+          type: element.getAttribute('content-type') ?? '',
         }
       },
     },

package/src/jats/importer/jats-transformations.ts

@@ -171,7 +171,7 @@ export const moveAbstracts = (
 }
 
 export const moveHeroImage = (doc: Document) => {
-  const heroImage = doc.querySelector('graphic[content-type="leading"]')
+  const heroImage = doc.querySelector('graphic[content-type^="leading"]')
   if (!heroImage) {
     return
   }

package/src/schema/migration/migration-scripts/4.4.2.ts

@@ -0,0 +1,60 @@
+/*!
+ * © 2026 Atypon Systems LLC
+ *
+ * Licensed under the Apache License, Version 2.0 (the "License");
+ * you may not use this file except in compliance with the License.
+ * You may obtain a copy of the License at
+ *
+ *    http://www.apache.org/licenses/LICENSE-2.0
+ *
+ * Unless required by applicable law or agreed to in writing, software
+ * distributed under the License is distributed on an "AS IS" BASIS,
+ * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+ * See the License for the specific language governing permissions and
+ * limitations under the License.
+ */
+import { JSONProsemirrorNode } from '../../../types'
+import { MigrationScript } from '../migration-script'
+
+class Migration442 implements MigrationScript {
+  fromVersion = '4.4.1'
+  toVersion = '4.4.2'
+
+  migrateNode(node: JSONProsemirrorNode): JSONProsemirrorNode {
+    switch (node.type) {
+      case 'hero_image':
+        if (!node.attrs || node.attrs.type === undefined) {
+          return {
+            ...node,
+            attrs: { ...(node.attrs ?? {}), type: 'leading' },
+          }
+        }
+        return node
+      case 'pullquote_element':
+        if (!node.attrs || node.attrs.type === undefined) {
+          const hasImage = node.content?.[0]?.type === 'quote_image'
+          return {
+            ...node,
+            attrs: {
+              ...(node.attrs ?? {}),
+              type: hasImage ? 'quote-with-image' : 'pullquote',
+            },
+          }
+        }
+        return node
+      case 'box_element':
+      case 'table_element':
+        if (!node.attrs || node.attrs.type === undefined) {
+          return {
+            ...node,
+            attrs: { ...(node.attrs ?? {}), type: '' },
+          }
+        }
+        return node
+      default:
+        return node
+    }
+  }
+}
+
+export default Migration442

package/src/schema/migration/migration-scripts/index.ts

@@ -28,6 +28,7 @@ import Migration4215 from './4.2.15'
 import Migration4323 from './4.3.23'
 import Migration4334 from './4.3.34'
 import Migration4335 from './4.3.35'
+import Migration442 from './4.4.2'
 
 const migrations = [
   new Migration125(),
@@ -44,6 +45,7 @@ const migrations = [
   new Migration4323(),
   new Migration4334(),
   new Migration4335(),
+  new Migration442(),
 ]
 
 export default migrations

package/src/schema/nodes/blockquote_element.ts

@@ -18,13 +18,13 @@ import { NodeSpec } from 'prosemirror-model'
 
 import { ManuscriptNode } from '../types'
 
-interface Attrs {
+export interface BlockquoteElementAttrs {
   id: string
   placeholder: string
 }
 
 export interface BlockquoteElementNode extends ManuscriptNode {
-  attrs: Attrs
+  attrs: BlockquoteElementAttrs
 }
 
 export const blockquoteElement: NodeSpec = {
@@ -42,7 +42,7 @@ export const blockquoteElement: NodeSpec = {
       getAttrs: (blockquote) => {
         const dom = blockquote as HTMLQuoteElement
 
-        const attrs: Partial<Attrs> = {
+        const attrs: Partial<BlockquoteElementAttrs> = {
           id: dom.getAttribute('id') || undefined,
         }