Integration of evidence into Theory of Change frameworks in the healthcare sector: A rapid systematic review.

BACKGROUND: Theory of Change (ToC) has become an established approach to design and evaluate interventions. While ToC should-in line with the growing international focus on evidence-informed health decision-making-consider explicit approaches to incorporate evidence, there is limited guidance on how this should be done. This rapid review aims to identify and synthesize the available literature on how to systematically use research evidence when developing or adapting ToCs in the health sector. METHODS: A rapid review methodology using a systematic approach, was designed. Eight electronic databases were consulted to search for peer-reviewed and gray publications detailing tools, methods, and recommendations promoting the systematic integration of research evidence in ToCs. The included studies were compared, and the findings summarized qualitatively into themes to identify key principles, stages, and procedures, guiding the systematic integration of research evidence when developing or revising a ToC. RESULTS: This review included 18 studies. The main sources from which evidence was retrieved in the ToC development process were institutional data, literature searches, and stakeholder consultation. There was a variety of ways of finding and using evidence in ToC. Firstly, the review provided an overview of existing definitions of ToC, methods applied in ToC development and the related ToC stages. Secondly, a typology of 7 stages relevant for evidence integration into ToCs was developed, outlining the types of evidence and research methods the included studies applied for each of the proposed stages. CONCLUSION: This rapid review adds to the existing literature in two ways. First, it provides an up-to-date and comprehensive review of the existing methods for incorporating evidence into ToC development in the health sector. Second, it offers a new typology guiding any future endeavors of incorporating evidence into ToCs.

Ultrafiltration for acute heart failure.

BACKGROUND: Pharmacotherapies such as loop diuretics are the cornerstone treatment for acute heart failure (AHF), but resistance and poor response can occur. Ultrafiltration (UF) is an alternative therapy to reduce congestion, however its benefits, efficacy and safety are unclear. OBJECTIVES: To assess the effects of UF compared to diuretic therapy on clinical outcomes such as mortality and rehospitalisation rates. SEARCH METHODS: We undertook a systematic search in June 2021 of the following databases: CENTRAL, MEDLINE, Embase, Web of Science CPCI-S and ClinicalTrials.gov. We also searched the WHO ICTRP platform in October 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared UF to diuretics in adults with AHF. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors for any further information, and language interpreters to translate texts. We assessed risk of bias in included studies using Risk of Bias 2 (RoB2) tool and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 14 trials involving 1190 people. We included people who had clinical signs of acute hypervolaemia. We excluded critically unwell people such as those with ischaemia or haemodynamic instability. Mean age ranged from 57.5 to 75 years, and the setting was a mix of single and multi-centre. Two trials researched UF as a complimentary therapy to diuretics, while the remaining trials withheld diuretic use during UF. There was high risk of bias in some studies, particularly with deviations from the intended protocols from high cross-overs as well as missing outcome data for long-term follow-up.  We are uncertain about the effect of UF on all-cause mortality at 30 days or less (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.13 to 2.85; 3 studies, 286 participants; very low-certainty evidence). UF may have little to no effect on all-cause mortality at the longest available follow-up (RR 1.00, 95% CI 0.73 to 1.36; 9 studies, 987 participants; low-certainty evidence). UF may reduce all-cause rehospitalisation at 30 days or less (RR 0.76, 95% CI 0.53 to 1.09; 3 studies, 337 participants; low-certainty evidence). UF may slightly reduce all-cause rehospitalisation at longest available follow-up (RR 0.91, 95% CI 0.79 to 1.05; 6 studies, 612 participants; low-certainty evidence). UF may reduce heart failure-related rehospitalisation at 30 days or less (RR 0.62, 95% CI 0.37 to 1.04; 2 studies, 395 participants; low-certainty evidence). UF probably reduces heart failure-related rehospitalisation at longest available follow-up, with a number needed to treat for an additional beneficial effect (NNTB) of 10 (RR 0.69, 95% CI 0.53 to 0.90; 4 studies, 636 participants; moderate-certainty evidence).  No studies measured need for mechanical ventilation.  UF may have little or no effect on serum creatinine change at 30 days since discharge (mean difference (MD) 14%, 95% CI -12% to 40%; 1 study, 221 participants; low-certainty evidence). UF may increase the risk of new initiation of renal replacement therapy at longest available follow-up (RR 1.42, 95% CI 0.42 to 4.75; 4 studies, 332 participants; low-certainty evidence).  There is an uncertain effect of UF on the risk of complications from central line insertion in hospital (RR 4.16, 95% CI 1.30 to 13.30; 6 studies, 779 participants; very low-certainty evidence).  AUTHORS' CONCLUSIONS: This review summarises the latest evidence on UF in AHF. Moderate-certainty evidence shows UF probably reduces heart failure-related rehospitalisation in the long term, with an NNTB of 10. UF may reduce all-cause rehospitalisation at 30 days or less and at longest available follow-up. The effect of UF on all-cause mortality at 30 days or less is unclear, and it may have little effect on all-cause mortality in the long-term.  While UF may have little or no effect on serum creatinine change at 30 days, it may increase the risk of new initiation of renal replacement therapy in the long term. The effect on complications from central line insertion is unclear.  There is insufficient evidence to determine the true impact of UF on AHF. Future research should evaluate UF as an adjunct therapy, focusing on outcomes such as heart failure-related rehospitalisation, cardiac mortality and renal outcomes at medium- to long-term follow-up.

Prehabilitation exercise therapy before elective abdominal aortic aneurysm repair.

BACKGROUND: An abdominal aortic aneurysm (AAA) is an abnormal dilation in the diameter of the abdominal aorta of 50% or more of the normal diameter or greater than 3 cm in total. The risk of rupture increases with the diameter of the aneurysm, particularly above a diameter of approximately 5.5 cm. Perioperative and postoperative morbidity is common following elective repair in people with AAA. Prehabilitation or preoperative exercise is the process of enhancing an individual's functional capacity before surgery to improve postoperative outcomes. Studies have evaluated exercise interventions for people waiting for AAA repair, but the results of these studies are conflicting. OBJECTIVES: To assess the effects of exercise programmes on perioperative and postoperative morbidity and mortality associated with elective abdominal aortic aneurysm repair. SEARCH METHODS: We searched the Cochrane Vascular Specialised register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Physiotherapy Evidence Database (PEDro) databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 6 July 2020. We also examined the included study reports' bibliographies to identify other relevant articles. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) examining exercise interventions compared with usual care (no exercise; participants maintained normal physical activity) for people waiting for AAA repair. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed the included studies, extracted data and resolved disagreements by discussion. We assessed the methodological quality of studies using the Cochrane risk of bias tool and collected results related to the outcomes of interest: post-AAA repair mortality; perioperative and postoperative complications; length of intensive care unit (ICU) stay; length of hospital stay; number of days on a ventilator; change in aneurysm size pre- and post-exercise; and quality of life. We used GRADE to evaluate certainty of the evidence. For dichotomous outcomes, we calculated the risk ratio (RR) with the corresponding 95% confidence interval (CI). MAIN RESULTS: This review identified four RCTs with a total of 232 participants with clinically diagnosed AAA deemed suitable for elective intervention, comparing prehabilitation exercise therapy with usual care (no exercise). The prehabilitation exercise therapy was supervised and hospital-based in three of the four included trials, and in the remaining trial the first session was supervised in hospital, but subsequent sessions were completed unsupervised in the participants' homes. The dose and schedule of the prehabilitation exercise therapy varied across the trials with three to six sessions per week and a duration of one hour per session for a period of one to six weeks. The types of exercise therapy included circuit training, moderate-intensity continuous exercise and high-intensity interval training. All trials were at a high risk of bias. The certainty of the evidence for each of our outcomes was low to very low. We downgraded the certainty of the evidence because of risk of bias and imprecision (small sample sizes). Overall, we are uncertain whether prehabilitation exercise compared to usual care (no exercise) reduces the occurrence of 30-day (or longer if reported) mortality post-AAA repair (RR 1.33, 95% CI 0.31 to 5.77; 3 trials, 192 participants; very low-certainty evidence). Compared to usual care (no exercise), prehabilitation exercise may decrease the occurrence of cardiac complications (RR 0.36, 95% CI 0.14 to 0.92; 1 trial, 124 participants; low-certainty evidence) and the occurrence of renal complications (RR 0.31, 95% CI 0.11 to 0.88; 1 trial, 124 participants; low-certainty evidence). We are uncertain whether prehabilitation exercise, compared to usual care (no exercise), decreases the occurrence of pulmonary complications (RR 0.49, 95% 0.26 to 0.92; 2 trials, 144 participants; very low-certainty evidence), decreases the need for re-intervention (RR 1.29, 95% 0.33 to 4.96; 2 trials, 144 participants; very low-certainty evidence) or decreases postoperative bleeding (RR 0.57, 95% CI 0.18 to 1.80; 1 trial, 124 participants; very low-certainty evidence). There was little or no difference between the exercise and usual care (no exercise) groups in length of ICU stay, length of hospital stay and quality of life. None of the studies reported data for the number of days on a ventilator and change in aneurysm size pre- and post-exercise outcomes. AUTHORS' CONCLUSIONS: Due to very low-certainty evidence, we are uncertain whether prehabilitation exercise therapy reduces 30-day mortality, pulmonary complications, need for re-intervention or postoperative bleeding. Prehabilitation exercise therapy might slightly reduce cardiac and renal complications compared with usual care (no exercise). More RCTs of high methodological quality, with large sample sizes and long-term follow-up, are needed. Important questions should include the type and cost-effectiveness of exercise programmes, the minimum number of sessions and programme duration needed to effect clinically important benefits, and which groups of participants and types of repair benefit most.

Non-vitamin K antagonist oral anticoagulants (NOACs) post-percutaneous coronary intervention: a network meta-analysis.

BACKGROUND: Clinicians must balance the risks of bleeding and thrombosis after percutaneous coronary intervention (PCI) in people with an indication for anticoagulation. The potential of non-vitamin K antagonists (NOACs) to prevent bleeding complications is promising, but evidence remains limited. OBJECTIVES: To review the evidence from randomised controlled trials assessing the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared to vitamin K antagonists post-percutaneous coronary intervention (PCI) in people with an indication for anticoagulation. SEARCH METHODS: We identified studies by searching CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science and two clinical trials registers in February 2019. We checked bibliographies of identified studies and applied no language restrictions. SELECTION CRITERIA: We searched for randomised controlled trials (RCT) that compared NOACs and vitamin K antagonists for people with an indication for anticoagulation who underwent PCI. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects, pairwise analyses using Review Manager 5 and network meta-analyses (NMA) using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons, and allow ranking of treatments on a continuous 0 to 1 scale. MAIN RESULTS: We identified nine RCTs that met the inclusion criteria, but four were ongoing trials, and were not included in this analysis. We included five RCTs, with 8373 participants, in the NMA (two RCTs compared apixaban to a vitamin K antagonist, two RCTs compared rivaroxaban to a vitamin K antagonist, and one RCT compared dabigatran to a vitamin K antagonist). Very low- to moderate-certainty evidence suggests little or no difference between NOACs and vitamin K antagonists in death from cardiovascular causes (not reported in the dabigatran trial), myocardial infarction, stroke, death from any cause, and stent thrombosis. Apixaban (RR 0.85, 95% CI 0.77 to 0.95), high dose rivaroxaban (RR 0.86, 95% CI 0.74 to 1.00), and low dose rivaroxaban (RR 0.80, 95% CI 0.68 to 0.92) probably reduce the risk of recurrent hospitalisation compared with vitamin K antagonists. No studies looked at health-related quality of life. Very low- to moderate-certainty evidence suggests that NOACs may be safer than vitamin K antagonists in terms of bleeding. Both high dose dabigatran (RR 0.53, 95% CI 0.29 to 0.97), and low dose dabigatran (RR 0.38, 95% CI 0.21 to 0.70) may reduce major bleeding more than vitamin K antagonists. High dose dabigatran (RR 0.83, 95% CI 0.72 to 0.96), low dose dabigatran (RR 0.66, 95% CI 0.58 to 0.75), apixaban (RR 0,67 , 95% Cl 0.51 to 0.88), high dose rivaroxaban (RR 0.66, 95% CI 0.52 to 0.83), and low dose rivaroxaban (RR 0.71, 95% CI 0.57 to 0.88) probably reduce non-major bleeding more than vitamin K antagonists. The results from the NMA were inconclusive between the different NOACs for all primary and secondary outcomes. AUTHORS' CONCLUSIONS: Very low- to moderate-certainty evidence suggests no meaningful difference in efficacy outcomes between non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonists following percutaneous coronary interventions (PCI) in people with non-valvular atrial fibrillation. NOACs probably reduce the risk of recurrent hospitalisation for adverse events compared with vitamin K antagonists. Low- to moderate-certainty evidence suggests that dabigatran may reduce the rates of major and non-major bleeding, and apixaban and rivaroxaban probably reduce the rates of non-major bleeding compared with vitamin K antagonists. Our network meta-analysis did not show superiority of one NOAC over another for any of the outcomes. Head to head trials, directly comparing NOACs against each other, are required to provide more certain evidence.