PhD thesis assessing the role of non-randomized studies with randomized in evidence syntheses of health interventions. / Randomized studies (RS) are considered the best source of evidence for knowledge syntheses (e.g., systematic reviews, health technology assessments, health guidelines, among others) about healthcare interventions. Historically, non-randomized studies (NRS) have been usually discarded from knowledge syntheses of interventions due to their intrinsic risk of bias and confounding, and they are used only when RS are considered unfeasible or unethical to conduct. With better research methods in observational studies and new tools for the evaluation of risk of bias, NRS are more likely to be a helpful source of information when used as replacement, sequential, or complementary evidence. This, together with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, provide an opportunity for guiding decisions about using RS and NRS in knowledge synthesis and increasing our certainty in a body of evidence. This work aims to improve research synthesis methods by assessing the role and use of RS and NRS in knowledge syntheses using GRADE. This can help health professionals, researchers, guideline developers, and policy-makers build better and more complete healthcare recommendations. / Thesis / Doctor of Philosophy (PhD) / All recommendations about healthcare interventions (from common medicines to strategies to prevent diseases) should ideally come from an adequate synthesis (e.g., systematic reviews) of the least biased studies. Many researchers and authors of health syntheses consider randomized studies (RS), the ‘gold standard’ to demonstrate if an intervention is truly effective. Unfortunately, they are not always available, feasible, or ethical to conduct. Non-randomized studies (NRS), also called observational studies, can potentially provide complementary evidence for a research question. Unfortunately, they are usually considered of poorer quality because of their intrinsic nature of being prone to bias and confounding. In most circumstances, authors of syntheses discard these types of studies from the outset, without considering their potential for providing evidence that could complement or even replace that from randomized studies. This work aims to improve this situation by offering methods for evaluating the appropriateness of integrating both RS and NRS, guiding authors and researchers in cases where this is possible, hence increasing the certainty in a body of evidence and help all stakeholders reach decisions.

This thesis investigates stress and coping in high performance squash coaching from the perspectives of both the coach and the player. An introduction to the thesis (chapter 1), a discussion of key concepts and theories from the general stress and coping literature (chapter 2), and a systematic review of the stress and coping in sport literature (chapter 3) are presented. The empirical work is reported in two phases. Phase one (chapters 4, 5 & 6) documents an in-depth study of 18 high performance squash coaches. Retrospective interviews were used to collect both qualitative and quantitative data. Inductive content analysis (Patton, 1980) revealed 223 raw data themes for stress, which collapsed into 12 general dimensions, and 415 raw data themes for coping, from which 13 general dimensions emerged. Descriptive statistics on stress source characteristics revealed a number of interesting trends that required further investigation. Further, general ('multi-purpose') and specific coping strategies were identified. Coping effectiveness and frequency data detailed the analysis. Phase two (chapters 7, 8 & 9) investigates stress and coping experiences of elite squash players during coaching activities via two studies. In study one, data were collected through telephone interviews, and analysed using inductive content analysis (QSR NUDIST), revealing 227 raw data themes for stress and coping from which 9 stress and 8 coping general dimensions emerged. These results were used to develop a postal questionnaire (study two) administered to 84 elite squash players on the England Squash World Class Performance Programme (Jan. 1999). A response rate of 60% was obtained, data was input into SPSS, and various statistical tests revealed significant contributions to 5 major investigative themes detennined at the outset. An overall picture of the landscape in stress and coping in high performance squash coaching is offered, and conclusions and future directions are presented (chapter 10).

Bakgrund: Smittsamma sjukdomar är ett ökande problem för världen med ständig utveckling av bland annat antibiotikaresistenta bakterier, vilket kan göra att patienter med smittsam sjukdom blir komplicerade att vårda. För att minska smittspridning vårdas patienter i isolering, vilket kan medföra negativa upplevelser. Problem: När patienter vårdas i isolering blir de begränsade i sin livssituation. Deras möjlighet till att socialisera och interagera med andra människor försvåras, vilket kan ge upphov till ohälsa och eventuellt lidande. Isoleringsvård innebär även tillämpning av skydds- och försiktighetsåtgärder som orsakar ökad arbetsbelastning för sjukvårdspersonal, vilket kan leda till sämre omvårdnadskvalitet för patienter som vårdas i isolering. Syfte: Beskriva patienters upplevelser av isoleringsvård vid smittsam sjukdom. Metod: Kvalitativ systematisk litteraturstudie med beskrivande syntes, där tio analyserade vetenskapliga artiklar användes i resultatet. Resultat: Det framkom både negativa och positiva upplevelser hos patienter som vårdas i isolering. Dessa delades in i två övergripande teman; Vårdas i ensamhet med tre tillhörande subteman och Behov av att förstå med två tillhörande subteman. Slutsats: Sjukvårdspersonal behöver anpassa den vård som ges med hänsyn till patienters omvårdnadsbehov. Genom att sjukvårdspersonal får utökade kunskaper om patienters positiva och negativa upplevelser av isoleringsvård kan sjukvårdspersonal anpassa vårdandet. / Background: Communicable diseases is an increasing problem world-wide due to the ongoing increase of antibiotic-resistant bacteria, which makes the diseases hard to treat. Patients are forcibly being treated in isolation due to the risk of spreading the infection to other people, this can cause negative experiences for these patients. Problem: Patients who are being treated in isolation are forced into a limited situation in their lives. Their possibilities of socializing and interacting with other people are reduced which could cause unhealthiness and suffering. Isolation care means that healthcare professionals have to apply precautionary methods with protective equipment when treating these patients. This could cause an increased workload for healthcare professionals and lead to poor quality of care for patients in isolation. Aim: To describe patients’ experience of isolation care due to communicable diseases. Method: A systematic review with a descriptive synthesis, and ten articles were analyzed for the result. Result: Both negative and positive experiences were identified of patient treated in isolation. These experiences were divided into two major themes; To receive care in loneliness with three included sub-themes and The need to understand with two included sub-themes. Conclusion: Healthcare professionals have to adapt the care to the needs of the unique patient. If healthcare professionals had more knowledge of caring for patients in isolation some of the negative experiences could be eliminated and lead to better quality of care.

Objectives: The EZSCAN is a non-invasive device that, by evaluating sweat gland function, may detect subjects with type 2 diabetes mellitus (T2DM). The aim of the study was to conduct a systematic review and meta-analysis including studies assessing the performance of the EZSCAN for detecting cases of undiagnosed T2DM. Methodology/Principal findings: We searched for observational studies including diagnostic accuracy and performance results assessing EZSCAN for detecting cases of undiagnosed T2DM. OVID (Medline, Embase, Global Health), CINAHL and SCOPUS databases, plus secondary resources, were searched until March 29, 2017. The following keywords were utilized for the systematic searching: type 2 diabetes mellitus, hyperglycemia, EZSCAN, SUDOSCAN, and sudomotor function. Two investigators extracted the information for meta-analysis and assessed the quality of the data using the Revised Version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Pooled estimates were obtained by fitting the logistic-normal random-effects model without covariates but random intercepts and using the Freeman-Tukey Arcsine Transformation to stabilize variances. Heterogeneity was also assessed using the I2 measure. Four studies (n = 7,720) were included, three of them used oral glucose tolerance test as the gold standard. Using Hierarchical Summary Receiver Operating Characteristic model, summary sensitivity was 72.0% (95%CI: 60.0%– 83.0%), whereas specificity was 56.0% (95%CI: 38.0%– 74.0%). Studies were very heterogeneous (I2 for sensitivity: 79.2% and for specificity: 99.1%) regarding the inclusion criteria and bias was present mainly due to participants selection. Conclusions: The sensitivity of EZSCAN for detecting cases of undiagnosed T2DM seems to be acceptable, but evidence of high heterogeneity and participant selection bias was detected in most of the studies included. More studies are needed to evaluate the performance of the EZSCAN for undiagnosed T2DM screening, especially at the population level.

Ensuring the objectivity of systematic reviews and meta-analyses (SRMA) begins with comprehensive searches into diverse resources mining primary studies. Guidelines for systematic reviews recommend authors to routinely search of trial registries to identify unpublished studies. In this dissertation, I investigated the utilization of ClinicalTrials.gov (CTG), the world’s largest clinical trial registry that contains data from clinical trials of products that are subject to United States Food and Drug Administration (FDA) regulation, as an information resource in SRMAs. First, I examined the use of various information resources including CTG in SRMAs published from 2005-2016, and identified the factors associated with their use. Thereafter, to determine the accuracy of trial safety data reported at CTG, I compared the data at CTG with that in corresponding journal articles and FDA drug reviews. I found that trial safety data at both CTG and articles differed frequently from FDA drug reviews, but the differences were modest in magnitude. Finally, I repeated published meta-analysis (conducted using data from primary study articles) with data at CTG to find that most meta-analysis results were reproduced using CTG data. Taken together, this work suggests that CTG should not only be searched more often to find primary research for systematic reviews, but that data at CTG can also be used to conduct quantitative data synthesis.

Background and Objectives: HIV in a major public health problem in many countries of the world. Recent advances in care for people living with HIV such as the use of antiretroviral medication have reduced the mortality and morbidity associated with HIV infection. However, many people receiving antiretroviral therapy do not take it as prescribed and still experience sub-optimal health outcomes. Mobile phone text messaging is emerging as an important tool in health care, and HIV in particular. Our objectives were to explore the determining factors for adherence to antiretroviral therapy, test text messaging as an adherence enhancement tool, develop a framework for community ownership of a text messaging program and describe strategies for transfer of evidence in HIV to other conditions. Methods: This research is primarily based in Yaoundé, Cameroon, and employs a variety of methodologies, including a systematic review, two cross- sectional surveys, a randomized controlled trial, an individual patient data meta-analysis, a mixed methods study and a systematic review of systematic reviews. Results and Conclusions: Two-way weekly text messaging is an effective strategy in improving adherence to antiretroviral therapy and enhancing provider-client communication. People living with HIV in Yaoundé, Cameroon like receiving text messages, and are willing to own and run a text messaging program. Text messaging interventions may be transferred to other conditions by integrating services or by copying what works in HIV. Further research on potential harms, cost effectiveness and text messaging for other chronic conditions is warranted. / Thesis / Doctor of Philosophy (PhD)

yes / We read with interest the review written by Evans and Allen, and published in the Journal of Optometry, in July, 2016.

Systematische Übersichtsarbeiten klinischer Studien spielen bei der Beurteilung der Wirksamkeit prophylaktischer und therapeutischer Interventionen eine zentrale Rolle. Übersichtsarbeiten (im folgenden synonym mit der Bezeichnung Review gebraucht) werden dann als systematisch bezeichnet, wenn sie vordefinierte und transparente Methoden bzgl. Literatursuche, Studienselektion und Studienbewertung verwenden. Systematische Übersichtsarbeiten, bei denen die einbezogenen Studien (Primärstudien) in einer integrierenden statistischen Analyse wie eine einzige große Studie ausgewertet (gepoolt) werden, bezeichnet man als Meta-Analysen. Die vorliegende Monographie präsentiert 1. zwei größere eigene systematische Übersichtsarbeiten als Anwendungsbeispiele (Kapitel 2), 2. drei empirisch-methodische Untersuchungen zum Thema Studienqualität und deren Auswirkung auf das Ergebnis (Kapitel 3) und 3. eine Analyse der vorliegenden systematischen Übersichtsarbeiten in den Bereichen Akupunktur, Phytotherapie und Homöopathie (Kapitel 4). Sie versteht sich als Beitrag zur methodischen Diskussion und Entwicklung von systematischen Übersichtsarbeiten. Im ersten Anwendungsbeispiel wurde untersucht, ob Propranolol, Metoprolol und Flunarizin bei der prophylaktischen Behandlung der Migräne wirksamer sind als Placebo, ob die einzelnen Substanzen ähnlich wirksam sind bzw. wie wirksam sie im Vergleich zu anderen Medikamenten sind. Eingeschlossen wurden randomisierte klinische Studien an erwachsenen Migränepatienten mit mindestens 4 Wochen Dauer, in denen eine oder mehrere der genannten Substanzen mit Placebo oder einem anderen Medikament verglichen wurden. Die Literatursuche erfolgte in Medline und der Cochrane Library sowie über das Durchsuchen von Literaturverzeichnissen. Informationen zu Patienten, Interventionen und Ergebnissen wurden mit Hilfe eines vorgetesteten Formulars extrahiert. Die Qualität der Studien wurde mit drei Skalen beurteilt. Soweit möglich erfolgten Effektstärkeberechnungen für Therapieerfolg, Attackenhäufigkeit und Zahl der Patienten mit Nebenwirkungen. Eine quantitative Meta-Analyse wurde aufgrund der inkonsistenten und häufig inadäquaten Ergebnispräsentation in den Primärstudien nicht durchgeführt. Insgesamt entsprachen 57 Studien zu Propranolol (mit 25 Vergleichen vs. Placebo und 46 Vergleichen mit anderen Medikamenten), 16 zu Metoprolol (mit 4 Vergleichen vs. Placebo und 17 vs. andere) und 40 zu Flunarizin (mit 10 Vergleichen vs. Placebo und 36 vs. andere) den Einschlusskriterien. Die Qualität der Studien war in vielen Fällen unbefriedigend. Hauptproblem war die unzureichende Beschreibung von Studienabbrüchen und -ausschlüssen bzw. deren Berücksichtigung in der Analyse. Alle drei Substanzen waren in Bezug auf Therapieerfolg und Attackenzahl Placebo überlegen. Langzeiteffekte über 6 Monate hinaus und nach Absetzen können nicht sicher beurteilt werden. Mit wenigen Ausnahmen ergaben sich in Vergleichen mit anderen Substanzen keine signifikanten Unterschiede; die meisten Studien hatten jedoch zu geringe Fallzahlen, um potenziell relevante Unterschiede ausschließen zu können. Insgesamt kann die Wirksamkeit von Propranolol, Metoprolol und Flunarizin in der Migräneprophylaxe aufgrund der Konsistenz der Ergebnisse trotz der häufig unbefriedigenden Studienqualität als belegt angesehen werden. Im zweiten Anwendungsbeispiel wurde untersucht, ob Hypericumextrakte (Hypericum perforatum, Johanniskraut) bei der Behandlung von Depressionen (a) wirksamer sind als Placebo, (b) ähnlich wirksam sind wie synthetische Antidepressiva und (c) nebenwirkungsärmer sind als synthetische Antidepressiva. Eingeschlossen wurden randomisierte Studien an depressiven Patienten mit einer Therapiedauer von mindestens 4 Wochen, in denen ein Hypericummonoextrakt mit Placebo oder einem anderen Antidepressivum verglichen wurde. Die Literatursuche erfolgte in verschiedenen Datenbanken, über das Prüfen von Literaturverzeichnissen und über Kontakte mit Experten und Herstellern. Hauptzielkriterium für die Beurteilung der Wirksamkeit war der Responderanteil (meist definiert als ein Rückgang um 50% oder auf einen Wert von max. 10 auf der Hamilton Rating Scale for Depression). 33 Studien (23 Vergleiche mit Placebo, 12 mit anderen Antidepressiva) entsprachen den Einschlusskriterien. Im Vergleich zu Placebo erwiesen sich die Hypericumextrakte als deutlich überlegen, allerdings war der Effekt in neueren Studien und in Studien mit schwerer depressiven Patienten geringer ausgeprägt. Im Vergleich zu älteren und neueren Antidepressiva waren Hypericumextrakte ähnlich effektiv; Nebenwirkungen waren jedoch signifikant seltener. Aufgrund der vorliegenden Daten kann die Wirksamkeit von Hypericumextrakten bei leichten bis mittleren Depressionen als nachgewiesen gelten. Die Heterogenität in den Ergebnissen der einzelnen Studien deutet jedoch darauf hin, dass verschiedene Faktoren (möglicherweise Extraktwahl, Dosierung, Patientenklientel) die Effektivität beeinflussen. Die erste der drei empirisch-methodischen Analysen in Kapitel 3 untersucht die methodische Qualität randomisierter Studien zu Akupunktur, Phytotherapie und Homöopathie. Insgesamt 207 randomisierte Studien wurden einbezogen; diese waren im Rahmen von 5 systematischen Übersichtsarbeiten gesammelt und bewertet worden. Die Beurteilung der methodischen Qualität erfolgte mithilfe einer validierten Skala (Jadadscore) und Einzelitems. Die methodische Qualität der bewerteten Studien war in hohem Maße variabel, die Mehrzahl der Studien hatte relevante Schwächen. Hauptprobleme waren die Beschreibung der Verblindung der Gruppenzuteilung sowie von Studienabbrüchen und -ausschlüssen. Phytotherapiestudien hatten im Mittel bessere Qualität als Homöopathie- und Akupunkturstudien. Publikationen in einer Medline-gelisteten Zeitschrift, in jüngerer Vergangenheit und in englischer Sprache hatten im Mittel bessere Qualität als ältere, nicht in gelisteten Zeitschriften und in anderen Sprachen veröffentlichte Arbeiten. Die Qualitätsscores der komplementärmedizinischen Studien waren im Schnitt ähnlich wie diejenigen von Studien zu konventionellen Interventionen, die in ähnlichen Analysen bewertet worden waren. In der zweiten empirisch-methodischen Untersuchung wurde geprüft, ob ein Zusammenhang zwischen methodischer Qualität und Studienergebnis in 89 placebokontrollierten Studien zur Homöopathie besteht. Die Beurteilung der methodischen Qualität erfolgte mit zwei Skalen und Einzelkriterien. Ein potenzieller Zusammenhang zwischen methodischer Qualität wurde mit drei Methoden untersucht: Prüfung eines Zusammenhangs zwischen einzelnen Qualitätskomponenten und Studienergebnis (Komponentenanalyse), Vergleich von Studien, die eine bestimmte Minimumpunktzahl auf den Qualitätsskalen erreichten bzw. nicht erreichten (Mindestscoreanalyse), und konsekutiver Einschluss von Studien in die Meta-Analyse entsprechend den erreichten Qualitätsscores (kumulative Meta-Analyse). Mit allen drei Methoden ergab sich, dass bessere Studien weniger optimistische Ergebnisse erbracht hatten. In der dritten empirisch-methodischen Untersuchung wurde am Beispiel der klinischen Studien zu Akupunktur bei Kopfschmerzen die zuletzt angesprochene Thematik auch auf nichtkontrollierte Studien ausgeweitet. Es wurde geprüft, inwieweit sich randomisierte und nichtrandomisierte Studien in Bezug auf Patienten, Interventionen, design-unabhängige Qualitätsaspekte und Ergebnisse unterscheiden. 59 Studien (24 randomisierte und 35 nichtrandomisierte) konnten in die Analyse einbezogen werden. Randomisierte und nichtrandomisierte Studien unterschieden sich bzgl. Patienten und Interventionen zum Teil deutlich. Nichtrandomisierte Studien hatten im Schnitt schlechtere Qualität, jedoch gab es unter den randomisierten Studien sehr schlechte und unter den nichtrandomisierten auch gute Studien. Ein Randomisationsdesign und bessere Qualität waren mit weniger positiven Ergebnissen assoziiert. Die nichtrandomisierten Studien nutzten potenzielle Vorteile (bzgl. Fallzahl, Langzeitbeobachtung, Repräsentativität und Untersuchung prognostischer Faktoren) kaum. Der Einbezug nichtrandomisierter Studien in einen systematischen Review zur Evidenz für die Wirksamkeit der Akupunktur bei Kopfschmerzen hätte daher die Schlussfolgerungen kaum beeinflusst. In Kapitel 4 wurden die bis Frühjahr 2001 verfügbaren systematischen Übersichtsarbeiten zu Akupunktur, Phytotherapie und Homöopathie zusammengestellt. Die Suche erfolgte primär über die Datenbank des Bereichs Komplementärmedizin der Cochrane Collaboration und in Medline. Um als systematisch klassifiziert zu werden, mußte ein Review mindestens eines der folgenden drei Kriterien erfüllen: explizite Beschreibung von Literatursuche und Einschlusskriterien und/oder formale Beurteilung der methodischen Qualität der eingeschlossenen Studien und/oder Beschreibung und Durchführung einer quantitativen Meta-Analyse. 39 Reviews zur Akupunktur, 58 zur Phytotherapie und 18 zur Homöopathie entsprachen den Einschlusskriterien. Positive Schlussfolgerungen waren im Bereich Phytotherapie am häufigsten, bei der Akupunktur am seltensten. Die Qualität der Reviews war variabel, viele hatten jedoch relevante methodische Schwächen. Siebzehn Fragestellungen wurden von mehr als einer systematischen Übersicht bearbeitet. Die Zahl der eingeschlossenen Primärstudien variierte bei 10 von 17 Vergleichen um mehr als 50%. Unterschiede in den Einschlusskriterien und der Literatursuche erschienen als wahrscheinlichste Ursache für die Diskrepanzen, Unterschiede in der methodischen Qualität der Reviews schienen dagegen eine geringe Rolle zu spielen. Die Schlussfolgerungen waren trotz der Diskrepanzen häufig ähnlich. Die vorgelegten Anwendungsbeispiele, empirisch-methodischen Untersuchungen und die Zusammenstellung zu Akupunktur, Phytotherapie und Homöopathie demonstrieren Stärken und Schwächen von systematischen Reviews. Trotz der zu erwartenden methodischen Weiterentwicklungen werden derartige Übersichtsarbeiten auch in Zukunft mit Sorgfalt und Zurückhaltung interpretiert werden müssen. / Systematic reviews of randomized controlled trials have a central role in the assessment of the effectiveness of health care interventions. Reviews are considered systematic if they describe and use adequate methods for literature search, study selection, quality assessment and summary of study results. Meta-analyses are systematic reviews if the results of the included primary studies are pooled to calculate an overall effect size measure. This monograph reports 1) two major own systematic reviews as examples (chapter 2); 2) three empirical studies on the issue of study quality and its effect on outcome (chapter 3); and 3) an analysis of the available systematic reviews on acupuncture, herbal medicines, and homeopathy (chapter 4). The reported work aims to contribute to the further development of the methodology of systematic reviews. The first systematic review in chapter 2 investigates whether there is evidence that the prophylactic treatment of migraine with propranolol, metoprolol and flunarizine is more effective than placebo and how these drugs compare to each other and to other drugs for migraine prophylaxis. To be included studies had to be randomized trials of at least 4 weeks duration in adult migraine patients comparing one of the three drugs with placebo or another drug treatment. Studies were identified through the database Medline, the Cochrane Library, and screening of bibliographies. Information on patients, interventions, methods and results was extracted in a standardized manner. Methodological quality was assessed with three checklists. As far as possible effect size estimates were calculated for single trials for the outcomes response, frequency of attacks, and number of patients with side effects. A pooled effect size estimate was not calculated due to the inconsistent and often insufficient presentation of results in the primary studies. A total of 57 trials on propranolol (with 25 comparisons vs. placebo and 46 comparisons vs. other drugs), 16 on metoprolol (4 vs. placebo and 17 vs. other drugs), and 40 on flunarizine (10 vs. placebo and 36 vs. other drugs) met the inclusion criteria. The majority of trials had relevant methodological shortcomings. The major problems were the description of drop-outs and withdrawals and the lack of intention to treat analyses. All three drugs have been shown to be superior to placebo in respect to response rates and frequency of attacks. There is insuccifient data to assess long-term effects and duration of the treatment effects after stopping prophylaxis. Apart from few exceptions there were no statistically significant differences in effectiveness in comparisons with other drugs. However, most trials had insufficient power to rule out potentially relevant differences. Overall, despite considerable methodological shortcomings the short-term effectiveness of propranolol, metoprolol and flunarizine for migraine prophylaxis has been proven beyond reasonable doubt. The second systematic review in chapter 2 investigates whether extracts from St. John s wort (Hypericum perforatum L.) are a) more effective than placebo, b) similarly effective as synthetic drugs, and c) have less side effects than synthetic drugs in the treatment of patients suffering from depression. Randomized trials in depressed patients were included if treatment with a hypericum mono-preparation for at least 4 weeks was compared with placebo or a synthetic antidepressant. Trials were identified from a variety of databases, by screening bibliographies, and through contacts with manufacturers and experts in the field. Main outcomes measure to assess effectiveness was the proportion of responders (mostly defined as patients with a 50% reduction vs. baseline or less than 10 points on the Hamilton Rating Scale for Depression). 33 trials (with 23 comparisons with placebo, and 12 with synthetic antidepressants) met the inclusion criteria. Hypericum extracts were markedly superior to placebo; however, the effect was smaller in more recent trials and in trials with patients suffering from more severe depression. The available trials indicate that hypericum extracts are similarly effective as both older and newer synthetic antidepressants in patients with mild and moderate depression and have less side effects. The heterogeneity of the observed effects suggests that a number of variables (mainly patient characteristics and quality of trials) influences outcomes. The first of the three empirical studies on review methodology in chapter 3 investigates the quality of randomized trials of acupuncture, herbal medicines, and homeopathy. A total of 207 studies originally collected for 5 systematic reviews were included in the analyses. Methodological quality was assessed with the validated scale by Jadad et al. and a number of single quality criteria. The quality of the included trials was highly variable but the majority of trials had relevant shortcomings. Major problems were the description of concealment of randomisation, and of drop-outs and withdrawals. In average, trials on herbal remdies had better quality than acupuncture and homeopathy trials. Publication in a Medline-listed journal, in more recent years and in English language was associated with better quality ratings. Compared to a sample of studies form conventional medicine from a similar analysis the average quality of trials in the three complementary medicine areas was very similar. The second study on methodology investigates whether there is an association between methodological quality and results in 89 placebo-controlled trials on homeopathy. Methodological quality was assessed with two score systems and single quality criteria. A potential association of quality and outcome was investigated with three approaches: 1) Testing whether the fulfillment of single criteria had impact on the pooled effect estimate (component analysis); 2) whether results of trials scoring a minimal number of points were different from those of trials with lower scores (minimal score analysis); 3) entering studies consecutively into the meta-analysis depending on the number of score points achieved (cumulative meta-analysis). With all three methods trials with better methodological quality were shown to yield less optimistic results. In the third study on methodology it was investigated whether randomized and non-randomized trials of acupuncture for chronic headache differ in regard to patients, interventions, design-independent quality aspects and results. 59 studies (24 randomized and 35 non-randomized) met the inclusion criteria. Randomized and non-randomized differed significantly regarding patient characteristics and interventions. In average, non-randomized studies had lower quality; however, there were also good quality non-randomized studies and randomized trials with very low quality. Studies with random assignment and better quality in general yielded less optimistic results. The non-randomized studies rarely took advantage of the possible strengths of such designs (in respect to sample size, long-term observation, representative sampling and investigation of prognostic factors). In the case of acupuncture for chronic headache the inclusion of non-randomized studies would not have altered the conclusions of a systematic review on effectiveness. In chapter 4 the systematic reviews on acupuncture, herbal medicines and homeopathy available until spring 2001 have been summarized. Eligible reviews were identified mainly through searches in the database of the Cochrane Collaboration s Complementary Medicine Field and in Medline. To be included a review had to meet at least one of the following criteria: explicit description of literature search and inclusion criteria; formal assessment of the methodological quality of the included primary studies; performance of a quantitative meta-analysis. 39 reviews on acupuncture, 58 on herbal medicines and 18 on homeopathy met the inclusion criteria. Positive conclusions were most frequent in herbal medicine, and rare in acupuncture. The quality of reviews was variable, but many had relevant shortcomings. 17 topics were adressed by more than one systematic reviews. In 10 of these 17 topics the number of included primary studies varied by more than 50%. Differencs in selection criteria and the literature search were the most likely cause for discrepancies. Differences in methodological quality had little impact. Conclusions were often similar despite discrepanices in methods and results. The examples and empirical studies on methodology presented in this monograph demonstrate the strengths and limitations of systematic reviews. Although it can be expected that the methods of systematic reviews will be improved in the future this kind of research will still have to be interpreted with great caution.

The increased number of international immigrants and associated global problems of health deterioration and vitamin D (vitD) deficiency/insufficiency may lead to significant burdens for host countries. This thesis investigated immigrants’ health deterioration and vitD status through a comprehensive analysis of Canadian national vitD data, systematic evaluation of the quality/content of clinical practice guidelines, and global systematic review of vitD status and determinants among first-generation immigrants. Immigrants had lower serum 25-hydroxyvitamin D (S-25(OH)D) and higher melanin levels than non-immigrants. S-25(OH)D levels improved over time, with ethnicity the main factor explaining variations. The longer immigrants lived in Canada, the higher the prevalence of chronic diseases (CDs), potentially reflecting health deterioration. Low levels of accumulated S-25(OH)D may impact CD-related biomarkers, partially explaining immigrants’ health deterioration over time. Local and international guidance regarding immigrants’ vitD deficiency/insufficiency was lacking. Improving immigrants’ vitD status requires prevention and intervention programs (e.g., vitD supplementation/screening), relevant national/international guidelines, and longitudinal research clarifying the complex bidirectional association between S-25(OH)D and CDs.

OBJECTIVE: The purpose of this study was to determine the association between baseline patient recovery expectations and outcomes following physical therapy care. METHODS: PubMed, CINAHL Complete, PEDro, SPORTDiscus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and PsycINFO were searched from inception to February 2021. Concepts represented in the search included physical therapy, patient expectations, patient outcomes, and their relevant synonyms. Two reviewers independently screened studies of article abstracts and full texts. Eligibility criteria included English language studies that evaluated adults seeking physical therapist intervention for any health condition where both patient outcome (recovery) expectations and functional or other outcome measures were reported. Methodologic standards were assessed using the Critical Appraisal Skills Program criteria. Data were extracted using a custom template for this review with planned descriptive reporting of results. Vote counting was used to measure reported outcomes. RESULTS: Twenty-one studies were included in this review, representing 4879 individuals. Studies were most commonly prospective cohort studies or secondary analyses of controlled trials. Varied expectation, outcome, and statistical measures that generally link patient recovery expectations with self-reported outcomes in musculoskeletal practice were used. CONCLUSION: Patient recovery expectations are commonly associated with patient outcomes in musculoskeletal physical therapy. IMPACT: Evidence supports measuring baseline patient expectations as part of a holistic examination process.