Effectiveness of needle and syringe Programmes in people who inject drugs - An overview of systematic reviews.

BACKGROUND: Needle and syringe programmes (NSP) are a critical component of harm reduction interventions among people who inject drugs (PWID). Our primary objective was to summarize the evidence on the effectiveness of NSP for PWID in reducing blood-borne infection transmission and injecting risk behaviours (IRB). METHODS: We conducted an overview of systematic reviews that included PWID (excluding prisons and consumption rooms), addressed community-based NSP, and provided estimates of the effect regarding incidence/prevalence of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV), Hepatitis B virus (HBV) and bacteremia/sepsis, and/or measures of IRB. Systematic literature searches were undertaken on relevant databases, including EMBASE, MEDLINE, and PsychINFO (up to May 2015). For each review we identified relevant studies and extracted data on methods, and findings, including risk of bias and quality of evidence assessed by review authors. We evaluated the risk of bias of each systematic review using the ROBIS tool. We categorized reviews by reported outcomes and use of meta-analysis; no additional statistical analysis was performed. RESULTS: We included thirteen systematic reviews with 133 relevant unique studies published between 1989 and 2012. Reported outcomes related to HIV (n = 9), HCV (n = 8) and IRB (n = 6). Methods used varied at all levels of design and conduct, with four reviews performing meta-analysis. Only two reviews were considered to have low risk of bias using the ROBIS tool, and most included studies were evaluated as having low methodological quality by review authors. We found that NSP was effective in reducing HIV transmission and IRB among PWID, while there were mixed results regarding a reduction of HCV infection. Full harm reduction interventions provided at structural level and in multi-component programmes, as well as high level of coverage, were more beneficial. CONCLUSIONS: The heterogeneity and the overall low quality of evidence highlights the need for future community-level studies of adequate design to support these results. TRIAL REGISTRATION: The protocol of this systematic review was registered in Prospective Register of Systematic Reviews (PROSPERO 2015: CRD42015026145 ).

Clinical trials in palliative care: a systematic review of their methodological characteristics and of the quality of their reporting.

BACKGROUND: Over the past decades there has been a significant increase in the number of published clinical trials in palliative care. However, empirical evidence suggests that there are methodological problems in the design and conduct of studies, which raises questions about the validity and generalisability of the results and of the strength of the available evidence. We sought to evaluate the methodological characteristics and assess the quality of reporting of clinical trials in palliative care. METHODS: We performed a systematic review of published clinical trials assessing therapeutic interventions in palliative care. Trials were identified using MEDLINE (from its inception to February 2015). We assessed methodological characteristics and describe the quality of reporting using the Cochrane Risk of Bias tool. RESULTS: We retrieved 107 studies. The most common medical field studied was oncology, and 43.9% of trials evaluated pharmacological interventions. Symptom control and physical dimensions (e.g. intervention on pain, breathlessness, nausea) were the palliative care-specific issues most studied. We found under-reporting of key information in particular on random sequence generation, allocation concealment, and blinding. CONCLUSIONS: While the number of clinical trials in palliative care has increased over time, methodological quality remains suboptimal. This compromises the quality of studies. Therefore, a greater effort is needed to enable the appropriate performance of future studies and increase the robustness of evidence-based medicine in this important field.

Stroke and Transient Ischemic Attack in Takayasu's Arteritis: A Systematic Review and Meta-analysis.

BACKGROUND: Cerebrovascular disease is one of the possible consequences of Takayasu's arteritis (TA). However, little is known about the prevalence of stroke/transient ischemic attack (TIA) or its related clinical features among these patients. We have performed a systematic review and meta-analysis to estimate the rate and risk factors of stroke/TIA in TA as well as to explore associations with poorer outcomes. METHODS: MEDLINE and Embase were searched (October 2014) for observational studies of any design reporting prevalence rates of stroke/TIA among TA patients. Study selection, data collection, and quality assessment were done independently. Studies' results were pooled through random-effect meta-analysis. Heterogeneity was assessed with the I(2) test. RESULTS: Twenty-one studies (16 studies were of cohort design) were included (n = 3269). The pooled stroke/TIA prevalence rate estimate was 15.8% (95% confidence interval [CI]: 10.7%-22.6%, I(2) = 94%). Sensitivity analysis, excluding 8 studies with poorer TA diagnostic criteria, yielded a similar estimate but without statistical heterogeneity (15.7%; 95% CI: 13.6%-18.1%, I(2) = 5.5%). Data were unavailable to explore possible associations between patients' characteristics and stroke/TIA prevalence. CONCLUSION: Our results document a high prevalence of stroke/TIA among TA patients. However, there is scarce information on the type of stroke, the characteristics of the affected individuals, and stroke-associated morbidity and mortality. Future studies should aim to further explore this disabling complication to find the best treatment and prevention strategies.

Tapentadol for chronic musculoskeletal pain in adults.

BACKGROUND: Chronic musculoskeletal pain is a prevalent condition and a major cause of disability and absence from the workplace worldwide. Opioids are frequently used to treat chronic pain, although adverse effects often restrict their long-term benefits. Tapentadol is an opioid and norepinephrine re-uptake inhibitor, which may cause a lower incidence (and severity) of adverse effects compared to other strong opioids. OBJECTIVES: To determine the efficacy, safety and tolerability of tapentadol extended release for moderate-to-severe pain for at least three months for any musculoskeletal cause. SEARCH METHODS: We searched electronic databases (CENTRAL, MEDLINE, EMBASE, Web of Science) to March 2014, unrestricted by language, as well as trials registers and reference lists from retrieved studies. We contacted drug manufacturers for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs) of tapentadol in people with chronic musculoskeletal pain, compared to placebo or active control. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed risk of bias of included studies and extracted data. We performed two meta-analyses for the comparisons tapentadol extended release vs. placebo, and tapentadol extended release vs. active-control (oxycodone). We used random-effects and fixed-effect models according to the presence or not of heterogeneity, respectively. Also, we performed subgroup analyses. The primary efficacy outcome was pain control assessed by change in pain intensity scores and responder's rate (at least 50% pain relief). Primary safety outcome was withdrawal rate due to adverse effects. MAIN RESULTS: Four parallel-design RCTs of moderate quality including 4094 patients with osteoarthritis or back pain, or both, met the inclusion criteria. Three trials were phase III studies with 12-weeks follow-up and the fourth trial was an open-label safety study of 52-weeks follow-up. All trials were oxycodone-controlled and three were also placebo-controlled. Two trials included patients with knee osteoarthritis, one evaluated patients with low back pain and one enrolled both. All studies reported last-observation-carried-forward (LOCF) as imputation method. We requested baseline-observation-carried-forward (BOCF) imputed analyses and any unpublished data from the manufacturer but the manufacturers denied the request. Two out of the four oxycodone-controlled studies and one out of the three placebo-controlled studies did not provided data on responder's rate. Two studies were considered to be of high risk of bias.In comparison to placebo, tapentadol was associated with a mean reduction of 0.56 points (95% confidence interval (CI) 0.92 to 0.20) in the 11-point numerical rating scale (NRS) at 12 weeks and with a 1.36 increase (95% CI 1.13 to 1.64) in the risk of responding to treatment (number needed to treat for an additional beneficial outcome (NNTB) 16; 95% CI 9 to 57, for 12-weeks). Moderate-to-high heterogeneity was found for the efficacy outcome estimates. Tapentadol was associated with a 2.7 fold increase (95% CI 2.05 to 3.52) in the risk of discontinuing treatment due to adverse effects number needed to treat for an additional harmful outcome (NNTH) 10; 95%CI 7 to 12, for 12 weeks).In comparison to oxycodone, pooled data showed a 0.24 points (95%CI 0.43 to 0.05) reduction in pain intensity from baseline in the 11-point NRS. The two studies that evaluated responder's rate showed a non-significant 1.46 increase (95% CI 0.92 to 2.32) in the risk of responding to treatment among tapentadol treated patients. Tapentadol was associated with a 50% risk reduction (95% CI 42% to 60%) of discontinuing treatment due to adverse effects (NNTB 6; 95% CI 5 to 7, for 12 weeks). Tapentadol was also associated with a 9% reduction (95% CI 4 to 15) in the overall risk of adverse effects (NNTH 18; 95% CI 12 to 35, for 12 weeks) and with a non-significant 43% reduction (95% CI 33 to 76) in the risk of serious adverse effects. Moderate to high heterogeneity was found for most efficacy (except for the primary outcome) and safety outcome estimates. Subgroup analysis showed a higher improvement with tapentadol among patients with knee osteoarthritis and among pooled results from studies of higher quality and shorter follow-up period, although there were no statistical significant differences in the effect size between these subgroups. AUTHORS' CONCLUSIONS: Tapentadol extended release is associated with a reduction in pain intensity in comparison to placebo and oxycodone. However, the clinical significance of the results is uncertain due to the following reasons: modest difference between interventions in efficacy outcomes, high heterogeneity in some comparisons and outcomes, high withdrawals rates, lack of data for the primary outcome in some studies and impossibility to use BOCF as imputation method. Tapentadol is associated with a more favourable safety profile and tolerability than oxycodone.

Frequency of dementia in Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: There is a considerable variation in the reported frequency of dementia in Parkinson's disease (PDD). The aim of this study was to evaluate the frequency of PDD reported in published studies and to examine the different methodological, clinical, and demographic factors that may contribute to this variation. METHODS: We conducted a systematic review, searching EMBASE and MEDLINE databases for relevant articles on PDD frequency published before May 2019. A global estimation of PDD was calculated. Different subgroup analyses were performed for methodological, clinical, and demographic characteristics. Meta-regression was also conducted to identify any significant differences within the subgroups. RESULTS: We included 295 studies. The global pooled dementia frequency was 26.3%. These estimations varied according to methodological (14%-55%), clinical (18%-46%), and demographic (21%-43%) variables. The declared primary objective of the studies (to study PDD), the follow-up length (≥7 years), the age of the participants (≥75 years), Parkinson's disease (PD) duration (>10 years), and the Hoehn & Yahr (H&Y) stage (>3) were important factors affecting reported dementia frequency. CONCLUSIONS: This systematic review found that approximately one-quarter of the PD patients were diagnosed with PDD. Dementia frequency varied according to methodological, clinical and demographic variables. We cannot examine PDD frequency without considering all these variables that have an impact on it.

Cognitive testing in late-stage Parkinson's disease: A critical appraisal of available instruments.

OBJECTIVE: For patients with Parkinson's disease (PD), cognitive impairment is one of the most disabling non-motor symptoms, particularly in the late disease stages (LSPD). Without a common cognitive assessment battery, it is difficult to estimate its prevalence and limits comparisons across studies. In addition, some instruments traditionally used in PD may not be adequate for use in LSPD. We sought to identify instruments used to assess cognition in LSPD and to investigate their global characteristics and psychometric properties to recommend a cognitive battery for the LSPD population. METHOD: We conducted a literature search of EMBASE and MEDLINE for articles reporting the use of cognitive tests in LSPD. The global characteristics and psychometric properties of the four most used cognitive tests in each cognitive domain were verified to recommend a cognitive assessment battery. RESULTS: Of 60 included studies, 71.7% used screening scales to assess cognition. Of the 53 reported instruments, the Montreal Cognitive Assessment, the Digit Span, the Trail Making Test, the Semantic Fluency test, the Rey Auditory Verbal Learning Test, the Brief Visuospatial Memory Test-Revised, the Boston Naming Test, the Judgment of Line Orientation, and the Clock Drawing Test corresponded best overall to the requirements considered important for selecting instruments in LSPD. CONCLUSION: Screening scales are frequently used to assess cognition in LSPD. We recommend a cognitive assessment battery that considers the special characteristics of the LSPD population, including being quick and easy to use, with minimized motor demands, and covering all relevant cognitive domains.

Atherosclerosis in the primary health care setting: A real-word data study.

INTRODUCTION AND OBJECTIVES: To characterize patients with atherosclerosis, a disease with a high socioeconomic impact, in the Lisbon and Tagus Valley Health Region. METHODS: A cross-sectional observational study was carried out through the Lisbon and Tagus Valley Regional Health Administration primary health care database, extracting data on the clinical and demographic characteristics and resource use of adult primary health care users with atherosclerosis during 2016. Different criteria were used to define atherosclerosis (presence of clinical manifestations, atherothrombotic risk factors and/or consumption of drugs related to atherosclerosis). Comparisons between different subpopulations were performed using parametric tests. RESULTS: A total of 318 692 users were identified, most of whom (n=224 845 users; 71%) had no recorded clinical manifestations. The subpopulation with clinical manifestations were older (72.0±11.5 vs. 71.3±11.0 years), with a higher proportion of men (58.0% vs. 45.9%), recorded hypertension (78.3% vs. 73.5%) and dyslipidemia (55.8% vs. 53.5%), and a lower proportion of recorded obesity (18.2% vs. 20.8%), compared to those without clinical manifestations (p<0.001). Mean blood pressure, LDL-C and glycated hemoglobin values were lower in the subpopulation with manifestations (142/74 vs. 146/76 mmHg, 101 vs. 108 mg/dl, and 6.80 vs. 6.84%, respectively; p<0.001). Each user with atherosclerosis attended 4.1±2.9 face-to-face medical consultations and underwent 8.6±10.0 laboratory test panels, with differences in subpopulations with and without clinical manifestations (4.4±3.2 vs. 4.0±2.8 and 8.3±10.3 vs. 8.7±9.8, respectively; p<0.001). CONCLUSIONS: About one in three adult primary health care users with atherosclerosis have clinical manifestations. The results suggest that control of cardiovascular risk factors is suboptimal in patients with atherosclerosis.

The burden of atherosclerosis in Portugal.

AIMS: This article sought to estimate the burden of disease attributable to atherosclerosis in mainland Portugal in 2016. METHODS AND RESULTS: The burden of atherosclerosis was measured in disability-adjusted life years following the latest 2010 Global Burden of Disease (GBD) methodology. Disability-adjusted life years were estimated as the sum of years of life lost (YLL) with years lived with disability (YLD). The following clinical manifestations of atherosclerosis were included: ischaemic heart disease (IHD) (including acute myocardial infarction, stable angina, and ischaemic heart failure), ischaemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD). Years of life lost were estimated based on all-cause mortality data for the Portuguese population and mortality due to IHD, ICVD, and PAD for the year 2016 sourced from national statistics. Standard life expectancy was sourced from the GBD study. Years lived with disability corresponded to the product of the number of prevalent cases by an average disability weight for all possible combinations of disease. Prevalence data for the different clinical manifestations of atherosclerosis were sourced from epidemiological studies. Disability weights were sourced from the published literature. In 2016, 15 123 deaths were attributable to atherosclerosis, which corresponded to 14.3% of overall mortality in mainland Portugal. Disability-adjusted life years totalled 260 943, 75% due to premature death (196 438 YLL) and 25% due to disability (64 505 YLD). CONCLUSION: Atherosclerosis entails a high disease burden to society. A large part of this burden would be avoidable if evidence-based effective and cost-effective interventions targeting known risk factors, from prevention to treatment, were implemented.

Atherosclerosis: The cost of illness in Portugal.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease is the leading cause of death in Portugal and atherosclerosis is the most common underlying pathophysiological process. The aim of this study was to quantify the economic impact of atherosclerosis in Portugal by estimating disease-related costs. METHODS: Costs were estimated based on a prevalence approach and following a societal perspective. Three national epidemiological sources were used to estimate the prevalence of the main clinical manifestations of atherosclerosis. The annual costs of atherosclerosis included both direct costs (resource consumption) and indirect costs (impact on population productivity). These costs were estimated for 2016, based on data from the Hospital Morbidity Database, the health care database (SIARS) of the Regional Health Administration of Lisbon and Tagus Valley including real-world data from primary care, the 2014 National Health Interview Survey, and expert opinion. RESULTS: The total cost of atherosclerosis in 2016 reached 1.9 billion euros (58% and 42% of which was direct and indirect costs, respectively). Most of the direct costs were associated with primary care (55%), followed by hospital outpatient care (27%) and hospitalizations (18%). Indirect costs were mainly driven by early exit from the labor force (91%). CONCLUSIONS: Atherosclerosis has a major economic impact, being responsible for health expenditure equivalent to 1% of Portuguese gross domestic product and 11% of current health expenditure in 2016.

Cost-effectiveness of sacubitril/valsartan for the treatment of patients with heart failure with reduced ejection fraction in Portugal.

Objectives: This study assesses the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with symptomatic heart failure with reduced ejection fraction (HFrEF).Methods: We used a previously developed Markov model calibrated with patient-level data from the PARADIGM-HF trial, adapted to the Portuguese setting. The model considers two health states (alive or dead) and uses regression analyzes to estimate hospitalizations and deaths over time. A panel of experts estimated resource consumption in the outpatient setting. To estimate resource consumption with hospitalizations, the National Health Service Diagnosis Related Groups database was used. Unit costs were based on national legislation, and on the Infomed database. The model considers a societal perspective, a time horizon of 30-years, and a 5% annual discount rate. Sensitivity analyses assessed the robustness of results.Results: Sacubitril/valsartan increases life expectancy by 0.5 life-years, corresponding to 0.4 incremental quality adjusted life-years (QALY) versus enalapril. The estimated incremental cost-effectiveness ratio (ICER) is 22,702€/QALY. Sensitivity analysis shows that results are robust, but sensitive to the parameter estimates of the cardiovascular survival curve.Conclusion: Sacubitril/valsartan is a cost-effective therapeutic option in the treatment of Portuguese patients with HFrEF and translate into significant health gains and increased life expectancy versus the current standard of care.

Measurement Instruments to Assess Functional Mobility in Parkinson's Disease: A Systematic Review.

BACKGROUND: Functional mobility (FM) is a person's ability to move to accomplish activities of daily living; it bridges the concepts of mobility and functional ability. There is frequently a loss of FM in Parkinson's disease (PD). Several instruments have been used to assess this concept in PD; however, there is no consensus on which are the most appropriate. OBJECTIVE: We aimed to identify and critically appraise which measurement instruments have been used to assess FM. METHODS: A systematic review was conducted using the databases CENTRAL, MEDLINE, Embase, and PEDro from their inception to January 2019 to identify all observational and experimental studies conducted in PD or atypical parkinsonism that included an FM assessment. Two reviewers independently screened citations, extracted data, and assessed clinimetric properties. RESULTS: We included 95 studies that assessed FM in PD. Fifty-five (57.9%) studies mentioned FM in the article, and 39 (41.1%) specified the measurement tools used to evaluate FM. FM was the primary outcome in 12 (12.6%) studies. The Timed Up and Go test was the most frequently used measurement tool. Only one study presented a definition of FM. Several overlapping terms were used, the most common being mobility. CONCLUSION: Several studies reported the use of FM measurement tools in PD, though with frequent misconceptions, an inadequate context of use, or suboptimal assessment. We propose the establishment of the concept of FM applied to PD, followed by the adequate clinimetric validation of existing measurement tools to provide a comprehensive and reliable evaluation of FM in PD.

Intensive Monitoring Studies for Assessing Medicines: A Systematic Review.

Introduction: Intensive monitoring (IM) is one of the methods of post-marketing active surveillance based upon event monitoring, which has received interest in the current medicines regulatory landscape. For a specific period of time, IM involves primary data collection and is actively focused on gathering longitudinal information, mainly safety, since the first day of drug use. Objectives: To describe IM systems and studies' data published over 11-years period (2006-2016). Specifically, we reviewed study population/event surveillance, methodological approaches, limitations, and its applications in the real-world evidence generation data. Methods: We completed a systematic search of MEDLINE and EMBASE to identify studies published from 2006 to 2016, that used IM methodology. We extracted data using a standardized form and results were analyzed descriptively. The methodological quality of selected studies was assessed using the modified Downs and Black checklist. Results: From 1,400 screened citations, we identified 86 papers, corresponding to 69 different studies. Seventy percent of reviewed studies corresponded to established IM systems, of which, more than half were prescription event monitoring (PEM) and modified-PEM. Among non-established IM systems, vaccines were the most common studied drugs (n = 14). The median cohort size ranged from 488 (hospitals) to 10,479 (PEM) patients. Patients and caregivers were the event data source in 39.1% of studies. The mean overall quality score was similar between established and non-established IM. Conclusions: Over the study period, IM studies were implemented in 26 countries with different maturity levels of post-marketing surveillance systems. We identified two major limitations: only 20% of studies were conducted at hospital-level, which is a matter of concern, insofar as healthcare systems are facing a lack of access to new medicines at ambulatory care level. Additionally, IM access to data of drug exposure cohorts, either at identification or at follow-up stages, could somehow constitute a barrier, given the complexity of managerial, linkable, and privacy data issues.

Burden of disease and cost of illness of atrial fibrillation in Portugal.

INTRODUCTION AND OBJECTIVES: Atrial fibrillation is the most prevalent sustained arrhythmia. This paper estimates the burden and cost of illness attributable to atrial fibrillation in Portugal based on demographic and health statistics. METHODS: Mortality data by cause of death came from the European Detailed Mortality Database of the World Health Organization (WHO). Hospital data were taken from the Portuguese diagnosis-related groups database. The burden of disease was measured using DALYs (disability-adjusted life years), a metric adopted by the WHO. Costs studied included resource use and lost productivity. The burden and cost of illness are those attributable to atrial fibrillation and its main complication, ischemic stroke. RESULTS: In Portugal, 4070 deaths were attributable to atrial fibrillation in 2010, corresponding to 3.8% of all deaths. In total, the burden of disease attributable to atrial fibrillation was estimated at 23,084 DALYs: 10,521 resulting from premature deaths (1.7% of the total DALYs due to death in 2010 in Portugal), and 12,563 resulting from disability. The total estimated direct costs attributable to atrial fibrillation at 2013 prices were €115 million: €34 million for inpatient care and €81 million for outpatient care. Indirect costs resulting from lost production due to disability were estimated at €25 million. CONCLUSIONS: Atrial fibrillation has an important social impact in Portugal due to its associated mortality and morbidity, and was responsible in 2013 for a total cost of €140 million, about 0.08% of gross domestic product.

[Off-label prescribing: scientific analysis taking the use of bevacizumab in ophthalmology as an example]. / Prescrição off-label: análise científica tendo como exemplo a utilização de bevacizumab em oftalmologia.

Off-label prescribing poses specific technical/scientific, professional and ethical problems. In this study we carry out a technical and scientific analysis of the off-label prescribing using a current, clinical and economically relevant example: the paradigmatic case of the use of bevacizumab in ophthalmologic pathologies for which it has no formal indication. We conducted a systematic review of the literature on the efficacy and safety of this drug, as well as ranibizumab - which has approved ophthalmologic indications, in order to qualitatively analyze the available evidence on the two interventions. This is a typical case for technical and scientific analysis of the off-label prescribing problems. According to the results of the systematic review, the use of bevacizumab in this context has in fact scientific evidence of appreciable size, including clinical trials head-to-head with ranibizumab. However, the identified safety issues raise the question of the use of this drug in ophthalmologic pathologies. The different players involved in the treatment decisions (physicians, patients and institutional decision makers) should be adequately informed about the existing evidence that supports off-label prescribing which, by definition, must always be on an exceptional basis and properly justified.

A prescrição off-label levanta problemas técnicos/científicos, profissionais e éticos específicos. No presente trabalho, procurámos realizar uma análise técnico-científica da prescrição off-label recorrendo a um exemplo atual, clinica e economicamente relevante: o caso paradigmático da utilização de bevacizumab em patologias do foro oftalmológico para as quais não tem indicação formal aprovada. Para tal realizámos uma revisão sistemática da literatura sobre a eficácia e segurança deste medicamento, assim como de ranibizumab­ o qual tem indicações oftalmológicas aprovadas, no sentido de analisar qualitativamente a evidência científica disponível sobreas duas intervenções. Este caso é exemplar para análise técnico-científica dos problemas da prescrição off-label, já que, de acordo com os resultados da revisão sistemática realizada, o uso do bevacizumab neste contexto possui, de facto, evidência científica de dimensão apreciável, incluindo ensaios clínicos head-to-head com ranibizumab. No entanto, os problemas de segurança identificados levantam a questão da utilização deste fármaco nas patologias oftalmológicas. Os diferentes agentes que participam no processo de decisão terapêutica (médicos, doentes e decisores institucionais) devem estar adequadamente informados sobre a evidência existente que suporta a prescrição off-label, a qual, por definição, deve ser sempre de caracter excecional e devidamente justificada.

Infliximab reduces hospitalizations and surgery interventions in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: We systematically reviewed infliximab benefit in reducing hospitalizations and/or major surgery rates in patients with inflammatory bowel disease (IBD). METHODS: A literature search to May 2012 was performed to identify all studies (experimental and observational) evaluating patients with IBD treated with infliximab and providing data on hospitalizations and/or major surgery rates. Three reviewers independently performed studies' selection, quality assessment, and data extraction. Analyses were carried according to study design (randomized clinical trials [RCTs] and observational studies) and IBD type (Crohn's disease [CD] and ulcerative colitis [UC]). Random-effects meta-analysis was used to derive pooled and 95% confidence intervals (CIs) estimates of odds ratios (OR). Heterogeneity was assessed with I test. RESULTS: Twenty-seven eligible studies were included (9 RCTs and 18 observational studies). Infliximab reduced hospitalization risk, both in pooled RCTs (OR, 0.51; 95% CI 0.40-0.65; I = 0%) and results of observational studies (OR, 0.29, 95% CI, 0.19-0.43; I = 87%), without differences between CD and UC. Infliximab reduced surgery risk in pooled RCTs results, both in CD (OR, 0.31; 95% CI, 0.15-0.64; I = 0%) and UC (OR, 0.57; 95% CI, 0.37-0.88; I = 0%). Pooled estimate from observational studies favored infliximab for patients with CD (OR, 0.32; 95% CI, 0.21-0.49; I = 77%), but not for patients with UC. CONCLUSIONS: The best evidence available points toward a reduction of the risk of hospitalization and major surgery requirement in patients with IBD treated with infliximab. This impact is clinically and economically relevant because hospitalization and surgery are considered to be markers of disease severity and significantly contribute to the total direct costs associated with IBD.

Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis.

OBJECTIVE: To systematically review longitudinal studies evaluating use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and risk of pneumonia. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline through PubMed, Web of Science with conference proceedings (inception to June 2011), and US Food and Drug Administration website (June 2011). Systematic reviews and references of retrieved articles were also searched. STUDY SELECTION: Two reviewers independently selected randomised controlled trials and cohort and case-control studies evaluating the use of ACE inhibitors or ARBs and risk of pneumonia and retrieved characteristics of the studies and data estimates. DATA SYNTHESIS: The primary outcome was incidence of pneumonia and the secondary outcome was pneumonia related mortality. Subgroup analyses were carried according to baseline morbidities (stroke, heart failure, and chronic kidney disease) and patients' characteristics (Asian and non-Asian). Pooled estimates of odds ratios and 95% confidence intervals were derived by random effects meta-analysis. Adjusted frequentist indirect comparisons between ACE inhibitors and ARBs were estimated and combined with direct evidence whenever available. Heterogeneity was assessed using the I(2) test. RESULTS: 37 eligible studies were included. ACE inhibitors were associated with a significantly reduced risk of pneumonia compared with control treatment (19 studies: odds ratio 0.66, 95% confidence interval 0.55 to 0.80; I(2) = 79%) and ARBs (combined direct and indirect odds ratio estimate 0.69, 0.56 to 0.85). In patients with stroke, the risk of pneumonia was also lower in those treated with ACE inhibitors compared with control treatment (odds ratio 0.46, 0.34 to 0.62) and ARBs (0.42, 0.22 to 0.80). ACE inhibitors were associated with a significantly reduced risk of pneumonia among Asian patients (0.43, 0.34 to 0.54) compared with non-Asian patients (0.82, 0.67 to 1.00; P<0.001). Compared with control treatments, both ACE inhibitors (seven studies: odds ratio 0.73, 0.58 to 0.92; I(2)=51%) and ARBs (one randomised controlled trial: 0.63, 0.40 to 1.00) were associated with a decrease in pneumonia related mortality, without differences between interventions. CONCLUSIONS: The best evidence available points towards a putative protective role of ACE inhibitors but not ARBs in risk of pneumonia. Patient populations that may benefit most are those with previous stroke and Asian patients. ACE inhibitors were also associated with a decrease in pneumonia related mortality, but the data lacked strength.