Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials: a meta-epidemiological study.

BACKGROUND: Researchers and decision-makers often use evidence from randomised controlled trials (RCTs) to determine the efficacy or effectiveness of a treatment or intervention. Studies with observational designs are often used to measure the effectiveness of an intervention in 'real world' scenarios. Numerous study designs and their modifications (including both randomised and observational designs) are used for comparative effectiveness research in an attempt to give an unbiased estimate of whether one treatment is more effective or safer than another for a particular population. An up-to-date systematic analysis is needed to identify differences in effect estimates from RCTs and observational studies. This updated review summarises the results of methodological reviews that compared the effect estimates of observational studies with RCTs from evidence syntheses that addressed the same health research question. OBJECTIVES: To assess and compare synthesised effect estimates by study type, contrasting RCTs with observational studies. To explore factors that might explain differences in synthesised effect estimates from RCTs versus observational studies (e.g. heterogeneity, type of observational study design, type of intervention, and use of propensity score adjustment). To identify gaps in the existing research comparing effect estimates across different study types. SEARCH METHODS: We searched MEDLINE, the Cochrane Database of Systematic Reviews, Web of Science databases, and Epistemonikos to May 2022. We checked references, conducted citation searches, and contacted review authors to identify additional reviews. SELECTION CRITERIA: We included systematic methodological reviews that compared quantitative effect estimates measuring the efficacy or effectiveness of interventions tested in RCTs versus in observational studies. The included reviews compared RCTs to observational studies (including retrospective and prospective cohort, case-control and cross-sectional designs). Reviews were not eligible if they compared RCTs with studies that had used some form of concurrent allocation. DATA COLLECTION AND ANALYSIS: Using results from observational studies as the reference group, we examined the relative summary effect estimates (risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), mean differences (MDs), and standardised mean differences (SMDs)) to evaluate whether there was a relatively larger or smaller effect in the ratio of odds ratios (ROR) or ratio of risk ratios (RRR), ratio of hazard ratios (RHR), and difference in (standardised) mean differences (D(S)MD). If an included review did not provide an estimate comparing results from RCTs with observational studies, we generated one by pooling the estimates for observational studies and RCTs, respectively. Across all reviews, we synthesised these ratios to produce a pooled ratio of ratios comparing effect estimates from RCTs with those from observational studies. In overviews of reviews, we estimated the ROR or RRR for each overview using observational studies as the reference category. We appraised the risk of bias in the included reviews (using nine criteria in total). To receive an overall low risk of bias rating, an included review needed: explicit criteria for study selection, a complete sample of studies, and to have controlled for study methodological differences and study heterogeneity. We assessed reviews/overviews not meeting these four criteria as having an overall high risk of bias. We assessed the certainty of the evidence, consisting of multiple evidence syntheses, with the GRADE approach. MAIN RESULTS: We included 39 systematic reviews and eight overviews of reviews, for a total of 47. Thirty-four of these contributed data to our primary analysis. Based on the available data, we found that the reviews/overviews included 2869 RCTs involving 3,882,115 participants, and 3924 observational studies with 19,499,970 participants. We rated 11 reviews/overviews as having an overall low risk of bias, and 36 as having an unclear or high risk of bias. Our main concerns with the included reviews/overviews were that some did not assess the quality of their included studies, and some failed to account appropriately for differences between study designs - for example, they conducted aggregate analyses of all observational studies rather than separate analyses of cohort and case-control studies. When pooling RORs and RRRs, the ratio of ratios indicated no difference or a very small difference between the effect estimates from RCTs versus from observational studies (ratio of ratios 1.08, 95% confidence interval (CI) 1.01 to 1.15). We rated the certainty of the evidence as low. Twenty-three of 34 reviews reported effect estimates of RCTs and observational studies that were on average in agreement. In a number of subgroup analyses, small differences in the effect estimates were detected: - pharmaceutical interventions only (ratio of ratios 1.12, 95% CI 1.04 to 1.21); - RCTs and observational studies with substantial or high heterogeneity; that is, I2 ≥ 50% (ratio of ratios 1.11, 95% CI 1.04 to 1.18); - no use (ratio of ratios 1.07, 95% CI 1.03 to 1.11) or unclear use (ratio of ratios 1.13, 95% CI 1.03 to 1.25) of propensity score adjustment in observational studies; and - observational studies without further specification of the study design (ratio of ratios 1.06, 95% CI 0.96 to 1.18). We detected no clear difference in other subgroup analyses. AUTHORS' CONCLUSIONS: We found no difference or a very small difference between effect estimates from RCTs and observational studies. These findings are largely consistent with findings from recently published research. Factors other than study design need to be considered when exploring reasons for a lack of agreement between results of RCTs and observational studies, such as differences in the population, intervention, comparator, and outcomes investigated in the respective studies. Our results underscore that it is important for review authors to consider not only study design, but the level of heterogeneity in meta-analyses of RCTs or observational studies. A better understanding is needed of how these factors might yield estimates reflective of true effectiveness.

Preoperative combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery.

BACKGROUND: The success of elective colorectal surgery is mainly influenced by the surgical procedure and postoperative complications. The most serious complications include anastomotic leakages and surgical site infections (SSI)s, which can lead to prolonged recovery with impaired long-term health.  Compared with other abdominal procedures, colorectal resections have an increased risk of adverse events due to the physiological bacterial colonisation of the large bowel. Preoperative bowel preparation is used to remove faeces from the bowel lumen and reduce bacterial colonisation. This bowel preparation can be performed mechanically and/or with oral antibiotics. While mechanical bowel preparation alone is not beneficial, the benefits and harms of combined mechanical and oral antibiotic bowel preparation is still unclear. OBJECTIVES: To assess the evidence for the use of combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL and trial registries on 15 December 2021. In addition, we searched reference lists and contacted colorectal surgery organisations. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adult participants undergoing elective colorectal surgery comparing combined mechanical and oral antibiotic bowel preparation (MBP+oAB) with either MBP alone, oAB alone, or no bowel preparation (nBP). We excluded studies in which no perioperative intravenous antibiotic prophylaxis was given. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. Pooled results were reported as mean difference (MD) or risk ratio (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel method. The certainty of the evidence was assessed with GRADE. MAIN RESULTS: We included 21 RCTs analysing 5264 participants who underwent elective colorectal surgery. None of the included studies had a high risk of bias, but two-thirds of the included studies raised some concerns. This was mainly due to the lack of a predefined analysis plan or missing information about the randomisation process. Most included studies investigated both colon and rectal resections due to malignant and benign surgical indications. For MBP as well as oAB, the included studies used different regimens in terms of agent(s), dosage and timing.  Data for all predefined outcomes could be extracted from the included studies. However, only four studies reported on side effects of bowel preparation, and none recorded the occurrence of adverse effects such as dehydration, electrolyte imbalances or the need to discontinue the intervention due to side effects. Seventeen trials compared MBP+oAB with sole MBP. The incidence of SSI could be reduced through MBP+oAB by 44% (RR 0.56, 95% CI 0.42 to 0.74; 3917 participants from 16 studies; moderate-certainty evidence) and the risk of anastomotic leakage could be reduced by 40% (RR 0.60, 95% CI 0.36 to 0.99; 2356 participants from 10 studies; moderate-certainty evidence). No difference between the two comparison groups was found with regard to mortality (RR 0.87, 95% CI 0.27 to 2.82; 639 participants from 3 studies; moderate-certainty evidence), the incidence of postoperative ileus (RR 0.89, 95% CI 0.59 to 1.32; 2013 participants from 6 studies, low-certainty of evidence) and length of hospital stay (MD -0.19, 95% CI -1.81 to 1.44; 621 participants from 3 studies; moderate-certainty evidence). Three trials compared MBP+oAB with sole oAB. No difference was demonstrated between the two treatment alternatives in terms of SSI (RR 0.87, 95% CI 0.34 to 2.21; 960 participants from 3 studies; very low-certainty evidence), anastomotic leakage (RR 0.84, 95% CI 0.21 to 3.45; 960 participants from 3 studies; low-certainty evidence), mortality (RR 1.02, 95% CI 0.30 to 3.50; 709 participants from 2 studies; low-certainty evidence), incidence of postoperative ileus (RR 1.25, 95% CI 0.68 to 2.33; 709 participants from 2 studies; low-certainty evidence) or length of hospital stay (MD 0.1 respectively 0.2, 95% CI -0.68 to 1.08; data from 2 studies; moderate-certainty evidence). One trial (396 participants) compared MBP+oAB versus nBP. The evidence is uncertain about the effect of MBP+oAB on the incidence of SSI as well as mortality (RR 0.63, 95% CI 0.33 to 1.23 respectively RR 0.20, 95% CI 0.01 to 4.22; low-certainty evidence), while no effect on the risk of anastomotic leakages (RR 0.89, 95% CI 0.33 to 2.42; low-certainty evidence), the incidence of postoperative ileus (RR 1.18, 95% CI 0.77 to 1.81; low-certainty evidence) or the length of hospital stay (MD 0.1, 95% CI -0.8 to 1; low-certainty evidence) could be demonstrated. AUTHORS' CONCLUSIONS: Based on moderate-certainty evidence, our results suggest that MBP+oAB is probably more effective than MBP alone in preventing postoperative complications. In particular, with respect to our primary outcomes, SSI and anastomotic leakage, a lower incidence was demonstrated using MBP+oAB. Whether oAB alone is actually equivalent to MBP+oAB, or leads to a reduction or increase in the risk of postoperative complications, cannot be clarified in light of the low- to very low-certainty evidence. Similarly, it remains unclear whether omitting preoperative bowel preparation leads to an increase in the risk of postoperative complications due to limited evidence. Additional RCTs, particularly on the comparisons of MBP+oAB versus oAB alone or nBP, are needed to assess the impact of oAB alone or nBP compared with MBP+oAB on postoperative complications and to improve confidence in the estimated effect. In addition, RCTs focusing on subgroups (e.g. in relation to type and location of colon resections) or reporting side effects of the intervention are needed to determine the most effective approach of preoperative bowel preparation.

Models of integrated care for multi-morbidity assessed in systematic reviews: a scoping review.

BACKGROUND: The prevalence of multi-morbidity is increasing globally. Integrated models of care present a potential intervention to improve patient and health system outcomes. However, the intervention components and concepts within different models of care vary widely and their effectiveness remains unclear. We aimed to describe and map the definitions, characteristics, components, and reported effects of integrated models of care in systematic reviews (SRs). METHODS: We conducted a scoping review of SRs according to pre-specified methods (PROSPERO 2019 CRD42019119265). Eligible SRs assessed integrated models of care at primary health care level for adults and children with multi-morbidity. We searched in PubMed (MEDLINE), Embase, Cochrane Database of Systematic Reviews, Epistemonikos, and Health Systems Evidence up to 3 May 2022. Two authors independently assessed eligibility of SRs and extracted data. We identified and described common components of integrated care across SRs. We extracted findings of the SRs as presented in the conclusions and reported on these verbatim. RESULTS: We included 22 SRs, examining data from randomised controlled trials and observational studies conducted across the world. Definitions and descriptions of models of integrated care varied considerably. However, across SRs, we identified and described six common components of integrated care: (1) chronic conditions addressed, (2) where services were provided, (3) the type of services provided, (4) healthcare professionals involved in care, (5) coordination and organisation of care and (6) patient involvement in care. We observed differences in the components of integrated care according to the income setting of the included studies. Some SRs reported that integrated care was beneficial for health and process outcomes, while others found no difference in effect when comparing integrated care to other models of care. CONCLUSIONS: Integrated models of care were heterogeneous within and across SRs. Information that allows the identification of effective components of integrated care was lacking. Detailed, standardised and transparent reporting of the intervention components and their effectiveness on health and process outcomes is needed.

Fluvoxamine for the treatment of COVID-19.

BACKGROUND: Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been approved for the treatment of depression, obsessive-compulsive disorder, and a variety of anxiety disorders; it is available as an oral preparation. Fluvoxamine has not been approved for the treatment of infections, but has been used in the early treatment of people with mild to moderate COVID-19. As there are only a few effective therapies for people with COVID-19 in the community, a thorough understanding of the current evidence regarding the efficacy and safety of fluvoxamine as an anti-inflammatory and possible anti-viral treatment for COVID-19, based on randomised controlled trials (RCTs), is needed. OBJECTIVES: To assess the efficacy and safety of fluvoxamine in addition to standard care, compared to standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy for the treatment of COVID-19 outpatients and inpatients. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv), Web of Science and WHO COVID-19 Global literature on COVID-19 to identify completed and ongoing studies up to 1 February 2022. SELECTION CRITERIA: We included RCTs that compared fluvoxamine in addition to standard care (also including no intervention), with standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy in clinical trials for the treatment of people with confirmed COVID-19, irrespective of disease severity, in both inpatients and outpatients. Co-interventions needed to be the same in both study arms. We excluded studies comparing fluvoxamine to other pharmacological interventions with unproven efficacy. DATA COLLECTION AND ANALYSIS: We assessed risk of bias of primary outcomes using the Cochrane Risk of Bias 2 tool for RCTs. We used GRADE to rate the certainty of evidence to treat people with asymptomatic to severe COVID-19 for the primary outcomes including mortality, clinical deterioration, clinical improvement, quality of life, serious adverse events, adverse events of any grade, and suicide or suicide attempt. MAIN RESULTS: We identified two completed studies with a total of 1649 symptomatic participants. One study was conducted in the USA (study with 152 participants, 80 and 72 participants per study arm) and the other study in Brazil (study with 1497 high-risk participants for progression to severe disease, 741 and 756 participants per study arm) among outpatients with mild COVID-19. Both studies were double-blind, placebo-controlled trials in which participants were prescribed 100 mg fluvoxamine two or three times daily for a maximum of 15 days. We identified five ongoing studies and two studies awaiting classification (due to translation issues, and due to missing published data). We found no published studies comparing fluvoxamine to other pharmacological interventions of proven efficacy. We assessed both included studies to have an overall high risk of bias. Fluvoxamine for the treatment of COVID-19 in inpatients We did not identify any completed studies of inpatients. Fluvoxamine for the treatment of COVID-19 in outpatients Fluvoxamine in addition to standard care may slightly reduce all-cause mortality at day 28 (RR 0.69, 95% CI 0.38 to 1.27; risk difference (RD) 9 per 1000; 2 studies, 1649 participants; low-certainty evidence), and may reduce clinical deterioration defined as all-cause hospital admission or death before hospital admission (RR 0.55, 95% CI 0.16 to 1.89; RD 57 per 1000; 2 studies, 1649 participants; low-certainty evidence). We are very uncertain regarding the effect of fluvoxamine on serious adverse events (RR 0.56, 95% CI 0.15 to 2.03; RD 54 per 1000; 2 studies, 1649 participants; very low-certainty evidence) or adverse events of any grade (RR 1.06, 95% CI 0.82 to 1.37; RD 7 per 1000; 2 studies, 1649 participants; very low-certainty evidence). Neither of the studies reported on symptom resolution (clinical improvement), quality of life or suicide/suicide attempt. AUTHORS' CONCLUSIONS: Based on a low-certainty evidence, fluvoxamine may slightly reduce all-cause mortality at day 28, and may reduce the risk of admission to hospital or death in outpatients with mild COVID-19. However, we are very uncertain regarding the effect of fluvoxamine on serious adverse events, or any adverse events. In accordance with the living approach of this review, we will continually update our search and include eligible trials as they arise, to complete any gaps in the evidence.

Mixed method evaluation of the CEBHA+ integrated knowledge translation approach: a protocol.

BACKGROUND: The Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA+) is a research consortium concerned with the prevention, diagnosis and treatment of non-communicable diseases. CEBHA+ seeks to engage policymakers and practitioners throughout the research process in order to build lasting relationships, enhance evidence uptake, and create long-term capacity among partner institutions in Ethiopia, Malawi, Rwanda, South Africa and Uganda in collaboration with two German universities. This integrated knowledge translation (IKT) approach includes the formal development, implementation and evaluation of country specific IKT strategies. METHODS: We have conceptualised the CEBHA+ IKT approach as a complex intervention in a complex system. We will employ a comparative case study (CCS) design and mixed methods to facilitate an in-depth evaluation. We will use quantitative surveys, qualitative interviews, quarterly updates, and a policy document analysis to capture the process and outcomes of IKT across the African CEBHA+ partner sites. We will conduct an early stage (early 2020) and a late-stage evaluation (early 2022), triangulate the data collected with various methods at each site and subsequently compare our findings across the five sites. DISCUSSION: Evaluating a complex intervention such as the CEBHA+ IKT approach is complicated, even more so when undertaken across five diverse countries. Despite conceptual, methodological and practical challenges, our comparative case study addresses important evidence gaps: While involving decision-makers in the research process is gaining traction worldwide, we still know very little regarding (i) whether this approach really makes a difference to evidence uptake, (ii) the mechanisms that make IKT successful, and (iii) relevant differences across socio-cultural contexts. The evaluation described here is intended to provide relevant insights on all of these aspects, notably in countries in Sub-Saharan Africa, and is expected to contribute to the science of IKT overall.

Non-nutritive sweeteners for diabetes mellitus.

BACKGROUND: Products sweetened with non-nutritive sweeteners (NNS) are widely available. Many people with type 1 or type 2 diabetes use NNS as a replacement for nutritive sweeteners to control their carbohydrate and energy intake. Health outcomes associated with NNS use in diabetes are unknown. OBJECTIVES: To assess the effects of non-nutritive sweeteners in people with diabetes mellitus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Scopus, the WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases (except for Scopus) was May 2019. We last searched Scopus in January 2019. We did not apply any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of four weeks or more comparing any type of NNS with usual diet, no intervention, placebo, water, a different NNS, or a nutritive sweetener in individuals with type 1 or type 2 diabetes. Trials with concomitant behaviour-changing interventions, such as diet, exercise, or both, were eligible for inclusion, given that the concomitant interventions were the same in the intervention and comparator groups. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, full texts, and records retrieved from trials registries, assessed the certainty of the evidence, and extracted data. We used a random-effects model to perform meta-analysis, and calculated effect estimates as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane 'Risk of bias' tool and the certainty of evidence using the GRADE approach. MAIN RESULTS: We included nine RCTs that randomised a total of 979 people with type 1 or type 2 diabetes. The intervention duration ranged from 4 to 10 months. We judged none of these trials as at low risk of bias for all 'Risk of bias' domains; most of the included trials did not report the method of randomisation. Three trials compared the effects of a dietary supplement containing NNS with sugar: glycosylated haemoglobin A1c (HbA1c) was 0.4% higher in the NNS group (95% CI -0.5 to 1.2; P = 0.44; 3 trials; 72 participants; very low-certainty evidence). The MD in weight change was -0.1 kg (95% CI -2.7 to 2.6; P = 0.96; 3 trials; 72 participants; very low-certainty evidence). None of the trials with sugar as comparator reported on adverse events. Five trials compared NNS with placebo. The MD for HbA1c was 0%, 95% CI -0.1 to 0.1; P = 0.99; 4 trials; 360 participants; very low-certainty evidence. The 95% prediction interval ranged between -0.3% and 0.3%. The comparison of NNS versus placebo showed a MD in body weight of -0.2 kg, 95% CI -1 to 0.6; P = 0.64; 2 trials; 184 participants; very low-certainty evidence. Three trials reported the numbers of participants experiencing at least one non-serious adverse event: 36/113 participants (31.9%) in the NNS group versus 42/118 participants (35.6%) in the placebo group (RR 0.78, 95% CI 0.39 to 1.56; P = 0.48; 3 trials; 231 participants; very low-certainty evidence). One trial compared NNS with a nutritive low-calorie sweetener (tagatose). HbA1c was 0.3% higher in the NNS group (95% CI 0.1 to 0.4; P = 0.01; 1 trial; 354 participants; very low-certainty evidence). This trial did not report body weight data and adverse events. The included trials did not report data on health-related quality of life, diabetes complications, all-cause mortality, or socioeconomic effects. AUTHORS' CONCLUSIONS: There is inconclusive evidence of very low certainty regarding the effects of NNS consumption compared with either sugar, placebo, or nutritive low-calorie sweetener consumption on clinically relevant benefit or harm for HbA1c, body weight, and adverse events in people with type 1 or type 2 diabetes. Data on health-related quality of life, diabetes complications, all-cause mortality, and socioeconomic effects are lacking.

Screening strategies for hypertension.

BACKGROUND: Hypertension is a major public health challenge affecting more than one billion people worldwide; it disproportionately affects populations in low- and middle-income countries (LMICs), where health systems are generally weak. The increasing prevalence of hypertension is associated with population growth, ageing, genetic factors, and behavioural risk factors, such as excessive salt and fat consumption, physical inactivity, being overweight and obese, harmful alcohol consumption, and poor management of stress. Over the long term, hypertension leads to risk for cardiovascular events, such as heart disease, stroke, kidney failure, disability, and premature mortality. Cardiovascular events can be preventable when high-risk populations are targeted, for example, through population-wide screening strategies. When available resources are limited, taking a total risk approach whereby several risk factors of hypertension are taken into consideration (e.g. age, gender, lifestyle factors, diabetes, blood cholesterol) can enable more accurate targeting of high-risk groups. Targeting of high-risk groups can help reduce costs in that resources are not spent on the entire population. Early detection in the form of screening for hypertension (and associated risk factors) can help identify high-risk groups, which can result in timely treatment and management of risk factors. Ultimately, early detection can help reduce morbidity and mortality linked to it and can help contain health-related costs, for example, those associated with hospitalisation due to severe illness and poorly managed risk factors and comorbidities. OBJECTIVES: To assess the effectiveness of different screening strategies for hypertension (mass, targeted, or opportunistic) to reduce morbidity and mortality associated with hypertension. SEARCH METHODS: An Information Specialist searched the Cochrane Register of Studies (CRS-Web), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS) Bireme, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) without language, publication year, or publication status restrictions. The searches were conducted from inception until 9 April 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) and non-RCTs (NRCTs), that is, controlled before and after (CBA), interrupted time series (ITS), and prospective analytic cohort studies of healthy adolescents, adults, and elderly people participating in mass, targeted, or opportunistic screening of hypertension. DATA COLLECTION AND ANALYSIS: Screening of all retrieved studies was done in Covidence. A team of reviewers, in pairs, independently assessed titles and abstracts of identified studies and acquired full texts for studies that were potentially eligible. Studies were deemed to be eligible for full-text screening if two review authors agreed, or if consensus was reached through discussion with a third review author. It was planned that at least two review authors would independently extract data from included studies, assess risk of bias using pre-specified Cochrane criteria, and conduct a meta-analysis of sufficiently similar studies or present a narrative synthesis of the results. MAIN RESULTS: We screened 9335 titles and abstracts. We identified 54 potentially eligible studies for full-text screening. However, no studies met the eligibility criteria. AUTHORS' CONCLUSIONS: There is an implicit assumption that early detection of hypertension through screening can reduce the burden of morbidity and mortality, but this assumption has not been tested in rigorous research studies. High-quality evidence from RCTs or programmatic evidence from NRCTs on the effectiveness and costs or harms of different screening strategies for hypertension (mass, targeted, or opportunistic) to reduce hypertension-related morbidity and mortality is lacking.

Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units.

BACKGROUND: Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress-induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator-associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding. OBJECTIVES: To assess the effect and risk-benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs. SEARCH METHODS: We searched the following databases up to 23 August 2017, using relevant search terms: MEDLINE; Embase; the Cochrane Central Register of Controlled Trials; Latin American Caribbean Health Sciences Literature; and the Cochrane Upper Gastrointestinal and Pancreatic Disease Group Specialised Register, as published in the Cochrane Library (2017, Issue 8). We searched the reference lists of all included studies and those from relevant systematic reviews and meta-analyses to identify additional studies. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and contacted individual researchers working in this field, as well as organisations and pharmaceutical companies, to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs with participants of any age and gender admitted to ICUs for longer than 48 hours. We excluded studies in which participants were admitted to ICUs primarily for the management of GI bleeding and studies that compared different doses, routes, and regimens of one drug in the same class because we were not interested in intraclass effects of drugs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. MAIN RESULTS: We identified 2292 unique records.We included 129 records reporting on 121 studies, including 12 ongoing studies and two studies awaiting classification.We judged the overall risk of bias of two studies as low. Selection bias was the most relevant risk of bias domain across the included studies, with 78 studies not clearly reporting the method used for random sequence generation. Reporting bias was the domain with least risk of bias, with 12 studies not reporting all outcomes that researchers intended to investigate.Any intervention versus placebo or no prophylaxisIn comparison with placebo, any intervention seems to have a beneficial effect on the occurrence of upper GI bleeding (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.57; moderate certainty of evidence). The use of any intervention reduced the risk of upper GI bleeding by 10% (95% CI -12.0% to -7%). The effect estimate of any intervention versus placebo or no prophylaxis with respect to the occurrence of nosocomial pneumonia, all-cause mortality in the ICU, duration of ICU stay, duration of intubation (all with low certainty of evidence), the number of participants requiring blood transfusions (moderate certainty of evidence), and the units of blood transfused was consistent with benefits and harms. None of the included studies explicitly reported on serious adverse events.Individual interventions versus placebo or no prophylaxisIn comparison with placebo or no prophylaxis, antacids, H2 receptor antagonists, and sucralfate were effective in preventing upper GI bleeding in ICU patients. Researchers found that with H2 receptor antagonists compared with placebo or no prophylaxis, 11% less developed upper GI bleeding (95% CI -0.16 to -0.06; RR 0.50, 95% CI 0.36 to 0.70; 24 studies; 2149 participants; moderate certainty of evidence). Of ICU patients taking antacids versus placebo or no prophylaxis, 9% less developed upper GI bleeding (95% CI -0.17 to -0.00; RR 0.49, 95% CI 0.25 to 0.99; eight studies; 774 participants; low certainty of evidence). Among ICU patients taking sucralfate versus placebo or no prophylaxis, 5% less had upper GI bleeding (95% CI -0.10 to -0.01; RR 0.53, 95% CI 0.32 to 0.88; seven studies; 598 participants; moderate certainty of evidence). The remaining interventions including proton pump inhibitors did not show a significant effect in preventing upper GI bleeding in ICU patients when compared with placebo or no prophylaxis.Regarding the occurrence of nosocomial pneumonia, the effects of H2 receptor antagonists (RR 1.12, 95% CI 0.85 to 1.48; eight studies; 945 participants; low certainty of evidence) and of sucralfate (RR 1.33, 95% CI 0.86 to 2.04; four studies; 450 participants; low certainty of evidence) were consistent with benefits and harms when compared with placebo or no prophylaxis. None of the studies comparing antacids versus placebo or no prophylaxis provided data regarding nosocomial pneumonia.H2 receptor antagonists versus proton pump inhibitorsH2 receptor antagonists and proton pump inhibitors are most commonly used in practice to prevent upper GI bleeding in ICU patients. Proton pump inhibitors significantly more often prevented upper GI bleeding in ICU patients compared with H2 receptor antagonists (RR 2.90, 95% CI 1.83 to 4.58; 18 studies; 1636 participants; low certainty of evidence). When taking H2 receptor antagonists, 4.8% more patients might experience upper GI bleeding (95% CI 2.1% to 9%). Nosocomial pneumonia occurred in similar proportions of participants taking H2 receptor antagonists and participants taking proton pump inhibitors (RR 1.02, 95% CI 0.77 to 1.35; 10 studies; 1256 participants; low certainty of evidence). AUTHORS' CONCLUSIONS: This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient-relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high-quality RCTs to confirm the results of previously conducted, smaller, and older studies.

Health outcomes of non-nutritive sweeteners: analysis of the research landscape.

BACKGROUND: Food products containing non-nutritive sweeteners (NNSs) instead of sugar have become increasingly popular in the last decades. Their appeal is obviously related to their calorie-free sweet taste. However, with the dramatic increase in their consumption, it is reasonable and timely to evaluate their potential health benefits and, more importantly, potential adverse effects. The main aim of this scoping review was to map the evidence about health outcomes possibly associated with regular NNS consumption by examining the extent, range, and nature of research activity in this area. METHODS: We systematically searched Ovid MEDLINE, EMBASE and the Cochrane CENTRAL databases for studies on NNSs (artificial sweeteners or natural, non-caloric sweeteners, either used individually or in combination) using text terms with appropriate truncation and relevant indexing terms. All human studies investigating any health outcomes of a NNS intervention or exposure were eligible for inclusion. No studies were excluded based on language, study design or methodological quality. Data for each health outcome were summarized in tabular form and were discussed narratively. RESULTS: Finally, we included 372 studies in our scoping review, comprising 15 systematic reviews, 155 randomized controlled trials (RCTs), 23 non-randomized controlled trials, 57 cohort studies, 52 case-control studies, 28 cross sectional studies and 42 case series/case reports. In healthy subjects, appetite and short term food intake, risk of cancer, risk of diabetes, risk of dental caries, weight gain and risk of obesity are the most investigated health outcomes. Overall there is no conclusive evidence for beneficial and harmful effects on those outcomes. Numerous health outcomes including headaches, depression, behavioral and cognitive effects, neurological effects, risk of preterm delivery, cardiovascular effects or risk of chronic kidney disease were investigated in fewer studies and further research is needed. In subjects with diabetes and hypertension, the evidence regarding health outcomes of NNS use is also inconsistent. CONCLUSIONS: This scoping review identifies the needs for future research to address the numerous evidence gaps related to health effects of NNSs use.It also specifies the research questions and areas where a systematic review with meta-analyses is required for the proper evaluation of health outcomes associated to regular NNSs consumption.

Acceptability and feasibility of tuberculosis and diabetes mellitus bidirectional screening and joint treatment services in Malawi: a cross-sectional study and a policy document review.

OBJECTIVES: A cross-sectional and a policy document review study was performed to investigate perceived acceptability and feasibility to implementing different integration measures for tuberculosis (TB) and diabetes mellitus (DM) healthcare among healthcare workers (HCWs) and health managers, and to describe policy influence through a policy documents review in Malawi. SETTING: The survey was performed at eight hospitals, ministry of health offices and 10 non-governmental organisations. We collected data in March and April 2021. PARTICIPANTS: Of 95 HCWs and health managers invited; 92 participated. 21/92 (23%) were female, and 17/92 (18%) participants were from clinics that piloted the integrated care for TB and DM. OUTCOME MEASURES: We described awareness levels on TB/DM comorbidity, perceptions and experiences in TB/DM care. Furthermore, development processes and contents of included documents were analysed. RESULTS: 16/17 (94%) of HCWs from clinics piloting integrated care and 65/75 (86%) HCWs from hospitals that do not use integrated care for TB and DM responded that integrated care was acceptable and feasible. In qualitative data, shortage of resources, inadequate information sharing were common themes. We included seven relevant documents for the analysis. On development process and content, six of seven documents were scored ≥70%. In these documents, DM is a recognised risk factor for TB, and integration of healthcare services for infectious diseases and non-communicable diseases is recommended, however, these documents lacked information specifically on integrated care for TB and DM. CONCLUSION: In this study, we identified inadequate information sharing, and lack of resources as major factors impeding implementation of integration of services, however, awareness on TB/DM comorbidity was high.

Willingness to participate in, support or carry out scientific studies for benefit assessment of available medical interventions: A stakeholder survey.

BACKGROUND: Post-entry studies are a key element in managed entry agreements and aim at generating evidence about the additional benefit of new medical interventions before reimbursement decisions are made. This study evaluates the willingness of different stakeholder groups to engage post-entry in studies for benefit assessment and to assess differences in their willingness by study type, i.e. randomised controlled trial or observational study. METHODS: We conducted a cross-sectional, web-based survey with a self-administrated questionnaire in German language. We disseminated invitations to patients, patient representatives, healthcare providers, trialists & scientists and representatives of the medical private sector, using a snowball system, public contact details of German associations and organisations, and social media. We analysed quantitative data descriptively and qualitative data inductively. RESULTS: Data of 154 respondents were available for analysis. The majority (>85%) was willing to engage in the studies in general, and regarding different study types. Scientists reported a higher willingness to conduct and support RCTs (p = 0.01) as compared to observational studies. Representatives of the private sector were mainly willing to support, but not to carry out post-entry studies. Stakeholders frequently mentioned that potential personal benefit and altruistic motives were relevant for their decision to engage in studies. Practical inconveniences, poor integration into daily life, high demand for time and personnel, and lack of resources were commonly mentioned barriers. DISCUSSION AND CONCLUSION: Stakeholders clearly reported to be willing to engage in post-entry studies for benefit assessment. Self-reported willingness to participate in and support for studies seems higher than practical recruitment rates. The survey might be subject to survey error and self-enhancement of participants. Inquiring about the willingness of hypothetical studies might have caused participants to report higher willingness. Motives for and against participation may be possible starting points for approaches to overcome recruitment difficulties and facilitate successful study conduct.

Subsequent full publication of qualitative studies presented at United Kingdom Royal College of Nursing Research Conference 2015 and 2016: A follow-up study.

A considerable proportion of quantitative research remains unpublished once completed. Little research has documented non-dissemination and dissemination bias in qualitative research. This study aimed to generate evidence on the extent of non-dissemination in qualitative research. We followed a cohort of qualitative studies presented as conference abstracts to ascertain their subsequent publication status. We searched for subsequent full publication in MEDLINE, in the Cumulative Index to Nursing & Allied Health Literature and in Google Scholar. We matched abstracts to subsequent publications according to authors, method of data collection and phenomenon of interest. Fisher's exact test was calculated to examine associations between study characteristics and publication. Factors potentially associated with time to publication were evaluated with Cox regression analysis. For 91 of 270 included abstracts (33.70%; 95% CI 28.09%-39.68%), no full publication was identified. Factors that were found to be associated with subsequent full publication were oral presentation (OR 4.62; 95% CI 2.43-8.94) and university affiliation (OR 1.96; 95% CI 1.05-3.66). Compared to oral presentations, studies presented as posters took longer time to reach full publication (hazard ratio 0.35, 95% CI 0.21-0.58). This study shows that it was not possible to retrieve a full publication for over one-third of abstracts. Our findings suggest that where this non-dissemination is systematic, it may lead to distortions of the qualitative evidence-base for decision-making through dissemination bias. Our findings are congruent with those of other studies. Further research might investigate non-dissemination of qualitative studies in other disciplines to consolidate our findings.

Evidence-based guidelines for hypertension and diabetes in sub-Saharan Africa: a scoping review.

OBJECTIVE: The Collaboration for Evidence-Based Healthcare and Public Health in sub-Saharan Africa (CEBHA+), a research network, aims to build capacities for evidence-based healthcare. Hypertension (HTN) and diabetes mellitus (DM) are two priority areas of the network, both are major causes of burden of disease in this region. This review aimed to: (1) identify existing evidence-based guidelines for HTN and DM, (2) map their recommendations and (3) assess their quality. SETTING: Sub-Saharan Africa. DESIGN: Scoping review. METHODS: Systematic searches for evidence-based guidelines, developed with systematic review of evidence and certainty of evidence assessment, were undertaken in electronic databases and grey literature, and ministries of health of all countries in this region were contacted. Included guidelines were assessed with the Appraisal of Guidelines for research and evaluation II (AGREE-II) tool. Searches were conducted between 7 December 2021 and 14 January 2022. Results are presented descriptively. RESULTS: 66 potentially relevant guidelines were identified, developed in 23, out of 49 sub-Saharan African countries. Of these, only two guidelines (on DM) reported the use of systematic review of evidence and certainty of evidence assessment. Their quality appraisal showed that both have relatively similar scores on domains of AGREE-II, with higher scores on Scope and Purpose and Clarity and Presentation domains, and lower on Stakeholder Involvement, Applicability, Rigour of Development and Editorial independence domains. The overall scores of both guidelines were 50% and 58%, respectively. CONCLUSIONS: Less than half of the countries in sub-Saharan Africa developed and published their own guidelines for HTN or DM. The quality appraisal showed that the two included guidelines scored relatively low in several crucial domains of AGREE-II. Countries in this region could consider adopting or adapting already published high-quality recommendations, in order to facilitate a more efficient and faster development of much needed trustworthy evidence-based guidance.

Effects of integrated models of care for diabetes and hypertension in low-income and middle-income countries: a systematic review and meta-analysis.

OBJECTIVES: To assess the effects of integrated models of care for people with multimorbidity including at least diabetes or hypertension in low-income and middle-income countries (LMICs) on health and process outcomes. DESIGN: Systematic review. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, LILACS, Africa-Wide, CINAHL and Web of Science up to 12 December 2019. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs), non-RCTs, controlled before-and-after studies and interrupted time series (ITS) studies of people with diabetes and/or hypertension plus any other disease, in LMICs; assessing the effects of integrated care. DATA EXTRACTION AND SYNTHESIS: Two authors independently screened retrieved records; extracted data and assessed risk of bias. We conducted meta-analysis where possible and assessed certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Of 7568 records, we included five studies-two ITS studies and three cluster RCTs. Studies were conducted in South Africa (n=3), Uganda/Kenya (n=1) and India (n=1). Integrated models of care compared with usual care may make little or no difference to mortality (very low certainty), the number of people achieving blood pressure (BP) or diabetes control (very low certainty) and access to care (very low certainty); may increase the number of people who achieve both HIV and BP/diabetes control (very low certainty); and may have a very small effect on achieving HIV control (very low certainty). Interventions to promote integrated delivery of care compared with usual care may make little or no difference to mortality (very low certainty), depression (very low certainty) and quality of life (very low certainty); and may have little or no effect on glycated haemoglobin (low certainty), systolic BP (low certainty) and total cholesterol levels (low certainty). CONCLUSIONS: Current evidence on the effects of integrated care on health outcomes is very uncertain. Programmes and policies on integrated care must consider context-specific factors related to health systems and populations. PROSPERO REGISTRATION NUMBER: CRD42018099314.

[Relevance of different study types in benefit assessment: Results from expert interviews]. / Bedeutung verschiedener Studientypen in der Nutzenbewertung: Ergebnisse aus Experteninterviews.

BACKGROUND: Careful evaluation of new interventions is essential. Randomized controlled trials (RCTs) and systematic reviews of RCTs provide the most reliable evidence base in comparative evaluations of treatments and interventions. Observational study designs are found at the lower levels of the classical evidence hierarchy. In light of policy efforts to accelerate the availability of innovations, the use of evidence from non-randomized studies for reimbursement decisions is being discussed. The present study addresses the question of the value and feasibility of RCTs and observational studies for benefit assessment after an intervention has been introduced into practice. METHODS: Experts from German-speaking countries were interviewed using qualitative, semi-structured interviews. Participants included experts in health economics, health services and health services research, health communication, ethics, and health policy. The interviews were conducted by one researcher and then analyzed using a deductive approach. Main categories and subcategories were extracted. RESULTS: Twenty-six experts were invited to participate, and 15 agreed to be interviewed. The duration of the individual interviews varied between 35 and 80minutes. The interviewed experts considered it possible and necessary to conduct RCTs when an intervention is already available in care in order to demonstrate that an intervention is more effective than existing alternatives. Experts considered good study design, methodological knowledge of those conducting the study, infrastructure, and funding as underlying conditions. They emphasized that the benefit of an intervention cannot be conclusively clarified on the basis of observational studies and that RCTs can therefore only be dispensed with in exceptional cases. Therefore, observational studies do not represent an alternative to RCTs in benefit assessment in general. In the opinion of the experts, the requirements for observational studies included sensible criteria and quality assurance measures. As alternatives to RCTs, the experts named studies based on routine data or high-quality, prospective, comparative cohort studies. Individual experts were very critical of studies based on data from registries. DISCUSSION AND CONCLUSION: The results of the interviews are underlined by findings from the scientific literature. For example, international scientists advocate for conducting RCTs instead of observational studies and for a reduction in hurdles and barriers for conducting RCTs. In international methodological standards for the preparation of health technology assessments, RCTs are also generally preferred for benefit assessment. Nevertheless, there is still a need for research about the optimal use of observational studies, alternative RCT designs and the use of data from routine care or registries, as policy makers, among others, believe that observational studies should be used for benefit assessment. The results show that experts still adhere to the established principles of clinical epidemiology. Observational studies should only be used as an alternative to RCTs in exceptional cases to examine whether one intervention is more effective than existing alternatives.

Use of GRADE in evidence syntheses published in high-impact-factor nutrition journals: A methodological survey.

OBJECTIVE: To identify and describe the use of the GRADE approach for rating the certainty of evidence in nutrition systematic reviews (SRs). STUDY DESIGN AND SETTING: We systematically searched for SRs using GRADE that were published between 2015 and 2019 in the 10 "nutrition" journals with the highest impact factor according to the JCR 2018. RESULTS: Out of 800 SRs, 55 SRs of randomized control trials (RCTs) and/or nonrandomized studies (NRSs) used GRADE. Forty-seven SRs (5.9%) rated the outcome specific certainty of evidence (n = 36 in 2018/2019). We identified a total of 465 certainty of evidence outcome ratings (n = 335 RCT ratings), ranging from very-low (28.8%) to low (41%), moderate (26.5%), and high (3.7%). Very-low and high certainty of evidence ratings accounted for 61.4% and 0.8% of ratings in SRs of NRSs, compared to 16.1% and 4.8% in SRs of RCTs. Certainty of evidence was downgraded mostly for risk of bias (37.8%) and imprecision (33%) in SRs of RCTs and for imprecision (32.7%), risk of bias (29.4%) and inconsistency (29%) in SRs of NRSs. CONCLUSION: Our study suggests a need for directing more attention toward strengthening acceptance of GRADE as well as building knowledge of the GRADE methodology in nutrition evidence synthesis.

[GRADE guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence]. / GRADE-Leitlinien: 18. Wie ROBINS-I und andere Instrumente zur Einschätzung des Risikos für Bias von nicht-randomisierten Studien verwendet werden sollten, um die Vertrauenswürdigkeit eines Evidenzkörpers zu bewerten.

OBJECTIVE: To provide guidance on how systematic review authors, guideline developers, and health technology assessment practitioners should approach the use of the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool as a part of GRADE's certainty rating process. STUDY DESIGN AND SETTING: The study design and setting comprised iterative discussions, testing in systematic reviews, and presentation at GRADE working group meetings with feedback from the GRADE working group. RESULTS: We describe where to start the initial assessment of a body of evidence with the use of ROBINS-I and where one would anticipate the final rating would end up. The GRADE accounted for issues that mitigate concerns about confounding and selection bias by introducing the upgrading domains: large effects, dose-effect relations, and when plausible residual confounders or other biases increase certainty. They will need to be considered in an assessment of a body of evidence when using ROBINS-I. CONCLUSION: The use of ROBINS-I in GRADE assessments may allow for a better comparison of evidence from randomized controlled trials (RCTs) and nonrandomized studies (NRSs) because they are placed on a common metric for risk of bias. Challenges remain, including appropriate presentation of evidence from RCTs and NRSs for decision-making and how to optimally integrate RCTs and NRSs in an evidence assessment.

Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies.

OBJECTIVE: To assess the association between intake of non-sugar sweeteners (NSS) and important health outcomes in generally healthy or overweight/obese adults and children. DESIGN: Systematic review following standard Cochrane review methodology. DATA SOURCES: Medline (Ovid), Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and reference lists of relevant publications. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies including generally healthy adults or children with or without overweight or obesity were eligible. Included study designs allowed for a direct comparison of no intake or lower intake of NSS with higher NSS intake. NSSs had to be clearly named, the dose had to be within the acceptable daily intake, and the intervention duration had to be at least seven days. MAIN OUTCOME MEASURES: Body weight or body mass index, glycaemic control, oral health, eating behaviour, preference for sweet taste, cancer, cardiovascular disease, kidney disease, mood, behaviour, neurocognition, and adverse effects. RESULTS: The search resulted in 13 941 unique records. Of 56 individual studies that provided data for this review, 35 were observational studies. In adults, evidence of very low and low certainty from a limited number of small studies indicated a small beneficial effect of NSSs on body mass index (mean difference -0.6, 95% confidence interval -1.19 to -0.01; two studies, n=174) and fasting blood glucose (-0.16 mmol/L, -0.26 to -0.06; two, n=52). Lower doses of NSSs were associated with lower weight gain (-0.09 kg, -0.13 to -0.05; one, n=17 934) compared with higher doses of NSSs (very low certainty of evidence). For all other outcomes, no differences were detected between the use and non-use of NSSs, or between different doses of NSSs. No evidence of any effect of NSSs was seen on overweight or obese adults or children actively trying to lose weight (very low to moderate certainty). In children, a smaller increase in body mass index z score was observed with NSS intake compared with sugar intake (-0.15, -0.17 to -0.12; two, n=528, moderate certainty of evidence), but no significant differences were observed in body weight (-0.60 kg, -1.33 to 0.14; two, n=467, low certainty of evidence), or between different doses of NSSs (very low to moderate certainty). CONCLUSIONS: Most health outcomes did not seem to have differences between the NSS exposed and unexposed groups. Of the few studies identified for each outcome, most had few participants, were of short duration, and their methodological and reporting quality was limited; therefore, confidence in the reported results is limited. Future studies should assess the effects of NSSs with an appropriate intervention duration. Detailed descriptions of interventions, comparators, and outcomes should be included in all reports. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42017047668.

Screening strategies for hypertension: a systematic review protocol.

INTRODUCTION: It is unclear whether early detection of hypertension, through screening, leads to healthier behaviours and better control of blood pressure levels. There is a need to learn from studies that have assessed the impact of different screening approaches on patient important outcomes. This systematic review protocol outlines the methods that will be used to assess the comparative effectiveness of different screening strategies (mass, targeted or opportunistic) for hypertension to reduce morbidity and mortality associated with hypertension. METHODS AND ANALYSIS: We will primarily search Cochrane Central Register of Controlled Trials, Medline, Embase and Latin American and Caribbean Health Sciences Literature (LILACS). Relevant randomised controlled trials, controlled before and after, interrupted time series and prospective analytic cohort studies regardless of publication date, language and geographic location, will be included. We are interested in clinical, adverse event and health system outcomes. Two reviewers will independently screen titles, abstracts and full-text articles against inclusion criteria; perform data extraction and assess risk of bias in included studies. We will assess the certainty of the overall evidence using the Grading of Recommendations Assessment, Development and Evaluation approach and report findings accordingly. ETHICS AND DISSEMINATION: No ethics approval will be sought, as only secondary studies will be used. Findings will be disseminated through peer-reviewed publication and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42018093046.