Absorptive capacity in the adoption of innovations in health: a scoping review.

OBJECTIVE: The objective of this scoping review was to explore how absorptive capacity has been conceptualized and measured in studies of innovation adoption in health care organizations. INTRODUCTION: Current literature highlights the need to incorporate knowledge translation processes at the organizational and system level to enhance the adoption of new knowledge into practice. Absorptive capacity is a set of routines and processes characterized by knowledge acquisition, assimilation, transformation, and application. A key concept in organizational learning theory, absorptive capacity is thought to be critical to the adoption of new knowledge and innovations in organizations. To understand how absorptive capacity was conceptualized and measured in health care organizations, it was appropriate to conduct a scoping review to answer our research question. INCLUSION CRITERIA: This scoping review included published and unpublished primary studies (ie, experimental, quasi-experimental, observational, and qualitative study designs), as well as reviews that broadly focused on the adoption of innovations at the organizational level in health care, and framed innovation adoption as processes that rely on organizational learning and absorptive or learning capacity. METHODS: Searches included electronic databases (ie, MEDLINE, Embase, PsycINFO, CINAHL, and Scopus) and gray literature, as well as reference scanning of relevant studies. Study abstracts and full texts were screened for eligibility by two independent reviewers. Data extraction of relevant studies was also done independently by two reviewers. All discrepancies were addressed through discussion or adjudicated by a third reviewer. Synthesis of the extracted data focused on descriptive frequencies and counts of the results. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). RESULTS: The search strategies identified a total of 7433 citations. Sixteen papers were identified for inclusion, including a set of two companion papers, and data were extracted from 15 studies. We synthesized the objectives of the included studies and identified that researchers focused on at least one of the following aspects: i) exploring pre-existing capacity that affects improvement and innovation in health care settings; ii) describing factors influencing the spread and sustainability of organizations; iii) identifying measures and testing the knowledge application process; and iv) providing construct clarity. No new definitions were identified within this review; instead existing definitions were refined to suit the local context of the health care organization in which they were used. CONCLUSIONS: Given the rapidly changing and evolving nature of health care, it is important to understand both current best practices and an organization's ability to acquire, assimilate, transform, and apply these practices to their specific organization. While much research has gone into developing ways to implement knowledge translation, understanding an organization's internal structures and framework for seeking out and implementing new evidence as it relates to absorptive capacity is still a relatively novel concept.

Comparative safety and efficacy of cognitive enhancers for Alzheimer's dementia: a systematic review with individual patient data network meta-analysis.

OBJECTIVE: To examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer's dementia (AD). DESIGN: Systematic review and individual patient data (IPD) network meta-analysis (NMA) based on our previously published systematic review and aggregate data NMA. DATA SOURCES: MEDLINE, Embase, Cochrane Methodology Register, CINAHL, AgeLine and Cochrane Central Register of Controlled Trials up to March 2016. PARTICIPANTS: 80 randomised controlled trials (RCTs) including 21 138 adults with AD, and 12 RCTs with IPD including 6906 patients. INTERVENTIONS: Cognitive enhancers (donepezil, rivastigmine, galantamine and memantine) alone or in any combination against other cognitive enhancers or placebo. DATA EXTRACTION AND SYNTHESIS: We requested IPD from authors, sponsors and data sharing platforms. When IPD were not available, we used aggregate data. We appraised study quality with the Cochrane risk-of-bias. We conducted a two-stage random-effects IPD-NMA, and assessed their findings using CINeMA (Confidence in Network Meta-Analysis). PRIMARY AND SECONDARY OUTCOMES: We included trials assessing cognition with the Mini-Mental State Examination (MMSE), and adverse events. RESULTS: Our IPD-NMA compared nine treatments (including placebo). Donepezil (mean difference (MD)=1.41, 95% CI: 0.51 to 2.32) and donepezil +memantine (MD=2.57, 95% CI: 0.07 to 5.07) improved MMSE score (56 RCTs, 11 619 participants; CINeMA score: moderate) compared with placebo. According to P-score, oral rivastigmine (OR=1.26, 95% CI: 0.82 to 1.94, P-score=16%) and donepezil (OR=1.08, 95% CI: 0.87 to 1.35, P-score=30%) had the least favourable safety profile, but none of the estimated treatment effects were sufficiently precise when compared with placebo (45 RCTs, 15 649 patients; CINeMA score: moderate to high). For moderate-to-severe impairment, donepezil, memantine and their combination performed best, but for mild-to-moderate impairment donepezil and transdermal rivastigmine ranked best. Adjusting for MMSE baseline differences, oral rivastigmine and galantamine improved MMSE score, whereas when adjusting for comorbidities only oral rivastigmine was effective. CONCLUSIONS: The choice among the different cognitive enhancers may depend on patient's characteristics. The MDs of all cognitive enhancer regimens except for single-agent oral rivastigmine, galantamine and memantine, against placebo were clinically important for cognition (MD larger than 1.40 MMSE points), but results were quite imprecise. However, two-thirds of the published RCTs were associated with high risk of bias for incomplete outcome data, and IPD were only available for 15% of the included RCTs. PROSPERO REGISTRATION NUMBER: CRD42015023507.

The Cost-Effectiveness of Intermediate-Acting, Long-Acting, Ultralong-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: A Systematic Review.

OBJECTIVES: The incidence of type 1 diabetes mellitus is increasing every year requiring substantial expenditure on treatment and complications. A systematic review was conducted on the cost-effectiveness of insulin formulations, including ultralong-, long-, or intermediate-acting insulin, and their biosimilar insulin equivalents. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, HTA, and NHS EED were searched from inception to June 11, 2021. Cost-effectiveness and cost-utility analyses were included if insulin formulations in adults (≥ 16 years) with type 1 diabetes mellitus were evaluated. Two reviewers independently screened titles, abstracts, and full-text articles, extracted study data, and appraised their quality using the Drummond 10-item checklist. Costs were converted to 2020 US dollars adjusting for inflation and purchasing power parity across currencies. RESULTS: A total of 27 studies were included. Incremental cost-effectiveness ratios ranged widely across the studies. All pairwise comparisons (11 of 11, 100%) found that ultralong-acting insulin was cost-effective compared with other long-acting insulins, including a long-acting biosimilar. Most pairwise comparisons (24 of 27, 89%) concluded that long-acting insulin was cost-effective compared with intermediate-acting insulin. Few studies compared long-acting insulins with one another. CONCLUSIONS: Long-acting insulin may be cost-effective compared with intermediate-acting insulin. Future studies should directly compare biosimilar options and long-acting insulin options and evaluate the long-term consequences of ultralong-acting insulins.

Comparative Efficacy and Safety of Ultra-Long-Acting, Long-Acting, Intermediate-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: a Systematic Review and Network Meta-Analysis.

BACKGROUND: Increasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM). METHODS: MEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR). RESULTS: We included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12). CONCLUSIONS: Our results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction. PROSPERO REGISTRATION: CRD42017077051.

Absorptive capacity in the adoption of innovations in health care: a scoping review protocol.

OBJECTIVE: To explore how absorptive capacity has been conceptualized and measured in studies of innovation adoption in health care organizations. INTRODUCTION: Current literature highlights the need to incorporate knowledge translation processes at the organizational and system level to enhance the adoption of new knowledge into practice. Absorptive capacity is a set of routines and processes characterized by knowledge acquisition, assimilation, transformation, and application. Absorptive capacity, a key concept in organizational learning theory, is thought to be critical to the adoption of new knowledge and innovations in organizations. INCLUSION CRITERIA: This scoping review will include primary studies (ie, experimental, quasi-experimental, observational, and qualitative study designs) and gray literature that broadly focus on the adoption of innovations at the organizational level in health care, and frame innovation adoption as processes that rely on organizational learning and absorptive or learning capacity. METHODS: Data sources will include comprehensive searches of electronic databases (eg, MEDLINE, Embase, PsycINFO, CINAHL, and Scopus), gray literature, and reference scanning of relevant studies. Study abstracts and full texts will be screened for eligibility by two reviewers, independently. Data extraction of relevant studies will also be done independently by two reviewers. All discrepancies will be addressed through further discussion or adjudicated by a third reviewer. Synthesis of the extracted data will focus on descriptive frequencies, counts, and thematic analysis and the results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR).

Retrieval of individual patient data depended on study characteristics: a randomized controlled trial.

OBJECTIVES: The aim of the study was to examine the effect of providing a financial incentive to authors of randomized clinical trials (RCTs) to obtain individual patient data (IPD). STUDY DESIGN AND SETTING: Parallel-group RCT with authors identified in the RCTs eligible for two systematic reviews. The authors were randomly allocated to the intervention (financial incentive with several contact approaches) or control group (using the same contact approaches). Studied outcomes are proportion of authors who provided IPD, time to obtain IPD, and completeness of IPD received. RESULTS: Of the 129 authors contacted, 37 authors suggested or contacted a person or funder providing relevant details or showed interest to collaborate, whereas 45 authors directed us to contact a person or funder, lacked resources or time, did not have ownership or approval to share the IPD, or claimed IPD was too old. None of the authors shared their IPD. We contacted 17 sponsors and received two complete IPD datasets from one sponsor. The time to obtain IPD was >1 year after a sponsor's positive response. Common barriers included study identification, data ownership, limited data access, and required IPD licenses. CONCLUSION: IPD sharing may depend on study characteristics, including funding type, study size, study risk of bias, and treatment effect, but not on providing a financial incentive.

Variability in the validity and reliability of outcome measures identified in a systematic review to assess treatment efficacy of cognitive enhancers for Alzheimer's Dementia.

INTRODUCTION: Selection of optimal outcome measures is a critical step in a systematic review; inclusion of uncommon or non-validated outcome measures can impact the uptake of systematic review findings. Our goals were to identify the validity and reliability of outcome measures used in primary studies to assess cognition, function, behaviour and global status; and, to use these data to select outcomes for a systematic review (SR) on treatment efficacy of cognitive enhancers for Alzheimer's Dementia (AD). METHODS: Articles fulfilling the eligibility criteria of the SR were included in a charting exercise to catalogue outcome measures reported. Outcome measures were then assessed for validity and reliability. Two independent reviewers abstracted data on outcome measures and validity and reliability reported for cognition, function, behaviour and global status. RESULTS: 129 studies were included in the charting exercise; 57 outcome measures were identified for cognition, 21 for function, 13 for behaviour and 10 for global status. A total of 35 (61%) cognition measures, 10 (48%) functional measures, 8 (61%) behavioural measures and four (40%) of global status measures were only used once in the literature. Validity and reliability information was found for 51% of cognition measures, 90% of function and global status measures and 100% of behavioural measures. CONCLUSIONS: While a large number of outcome measures were used in primary studies, many of these were used only once. Reporting of validity and reliability varied in AD studies of cognitive enhancers. Core outcome sets should be used when available; when they are not available researchers need to balance frequency of reported outcome measures, their respective validity and reliability, and preferences of knowledge users. SYSTEMATIC REVIEW REGISTRATION: CRD#42012001948.

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

BACKGROUND: Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analysis (NMA) was to evaluate the comparative safety and effectiveness of ART drugs in children exposed to maternal HIV and ART (or no ART/placebo) across different study designs. METHODS: We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception until December 7, 2015). Primary outcomes were any congenital malformations (CMs; safety), including overall major and minor CMs, and mother-to-child transmission (MTCT; effectiveness). Random-effects Bayesian pairwise meta-analyses and NMAs were conducted. After screening 6,468 citations and 1,373 full-text articles, 90 studies of various study designs and 90,563 patients were included. RESULTS: The NMA on CMs (20 studies, 7,503 children, 16 drugs) found that none of the ART drugs examined here were associated with a significant increase in CMs. However, zidovudine administered with lamivudine and indinavir was associated with increased risk of preterm births, zidovudine administered with nevirapine was associated with increased risk of stillbirths, and lamivudine administered with stavudine and efavirenz was associated with increased risk of low birth weight. A NMA on MTCT (11 studies, 10,786 patients, 6 drugs) found that zidovudine administered once (odds ratio [OR] = 0.39, 95% credible interval [CrI]: 0.19-0.83) or twice (OR = 0.43, 95% CrI: 0.21-0.68) was associated with significantly reduced risk of MTCT. CONCLUSIONS: Our findings suggest that ART drugs are not associated with an increased risk of CMs, yet some may increase adverse birth events. Some ART drugs (e.g., zidovudine) effectively reduce MTCT.

Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis.

BACKGROUND/OBJECTIVES: To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD). DESIGN: Systematic review and Bayesian network metaanalysis (NMA). SETTING: MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception-March 2016). PARTICIPANTS: Individuals with AD in randomized controlled trials (RCTs), quasi-RCTs, and nonrandomized studies. INTERVENTION: Any combination of donepezil, rivastigmine, galantamine, or memantine. MEASUREMENTS: Two reviewers independently screened titles, abstracts, and full-texts; abstracted data; and appraised risk of bias. RESULTS: Twenty thousand three hundred forty-three citations were screened, and 142 studies were included (110 RCTs, 21 non-RCTs, 11 cohort studies). NMA found that donepezil (Mini-Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53-2.24), donepezil+memantine (2.59, 95% CrI = 0.12-4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02-4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale-cognitive: MD = -3.29, 95% CrI = -4.57 to -1.99) and galantamine (MD = -2.13, 95% CrI = -3.91 to -0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = -5.23, 95% CrI = -8.72 to -1.56) improved behavior more than placebo. NMA found that donepezil (MD = -0.32, 95% CrI = -0.46 to -0.19), donepezil+memantine (MD = -0.57, 95% CrI = -0.95 to -0.21), oral rivastigmine (MD = -0.38, 95% CrI = -0.56 to -0.17), and galantamine (MD = -3.79, 95% CrI = -6.98 to -0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36-0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). CONCLUSION: An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.

Effectiveness of different compression-to-ventilation methods for cardiopulmonary resuscitation: A systematic review.

AIM: To compare the effectiveness of different compression-to-ventilation methods during cardiopulmonary resuscitation (CPR) in patients with cardiac arrest. METHODS: We searched MEDLINE and Cochrane Central Register of Controlled Trials from inception until January 2016. We included experimental, quasi-experimental, and observational studies that compared different chest compression-to-ventilation ratios during CPR for all patients and assessed at least one of the following outcomes: favourable neurological outcomes, survival, return of spontaneous circulation (ROSC), and quality of life. Two reviewers independently screened literature search results, abstracted data, and appraised the risk of bias. Random-effects meta-analyses were conducted separately for randomised and non-randomised studies, as well as study characteristics, such as CPR provider. RESULTS: After screening 5703 titles and abstracts and 229 full-text articles, we included 41 studies, of which 13 were companion reports. For adults receiving bystander or dispatcher-instructed CPR, no significant differences were observed across all comparisons and outcomes. Significantly less adults receiving bystander-initiated or plus dispatcher-instructed compression-only CPR experienced favourable neurological outcomes, survival, and ROSC compared to CPR 30:2 (compression-to-ventilation) in un-adjusted analyses in a large cohort study. Evidence from emergency medical service (EMS) CPR providers showed significantly more adults receiving CPR 30:2 experiencing improved favourable neurological outcomes and survival versus those receiving CPR 15:2. Significantly more children receiving CPR 15:2 or 30:2 experienced favourable neurological outcomes, survival, and greater ROSC compared to compression-only CPR. However, for children <1 years of age, no significant differences were observed between CPR 15:2 or 30:2 and compression-only CPR. CONCLUSIONS: Our results demonstrated that for adults, CPR 30:2 is associated with better survival and favourable neurological outcomes when compared to CPR 15:2. For children, more patients receiving CPR with either 15:2 or 30:2 compression-to ventilation ratio experienced favourable neurological function, survival, and ROSC when compared to CO-CPR for children of all ages, but for children <1years of age, no statistically significant differences were observed.

Sustainability of knowledge translation interventions in healthcare decision-making: a scoping review.

BACKGROUND: Knowledge translation (KT, also known as research utilization, and sometimes referring to implementation science) is a dynamic and iterative process that includes the synthesis, dissemination, exchange, and ethically sound application of knowledge to improve health. A KT intervention is one which facilitates the uptake of research. The long-term sustainability of KT interventions is unclear. We aimed to characterize KT interventions to manage chronic diseases that have been used for healthcare outcomes beyond 1 year or beyond the termination of initial grant funding. METHODS: We conducted a scoping review by searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Campbell from inception until February 2013. We included experimental, quasi-experimental, and observational studies providing information on the sustainability of KT interventions for managing chronic diseases in adults and focusing on end-users including patients, clinicians, public health officials, health service managers, and policy-makers. Articles were screened and abstracted by two reviewers, independently. The data were charted and results described narratively. RESULTS: We included 62 studies reported in 103 publications (total 260,688 patients) plus 41 companion reports after screening 12,328 titles and abstracts and 464 full-text articles. More than half of the studies were randomized controlled trials (RCTs). The duration of the KT intervention ranged from 61 to 522 weeks. Nine chronic conditions were examined across the studies, such as diabetes (34 %), cardiovascular disease (28 %), and hypertension (16 %). Thirteen KT interventions were reported across the studies. Patient education was the most commonly examined (20 %), followed by self-management (17 %). Most studies (61 %) focused on patient-level outcomes (e.g. disease severity), while 31 % included system-level outcomes (e.g. number of eye examinations), and 8 % used both. The interventions were aimed at the patient (58 %), health system (28 %), and healthcare personnel (14 %) levels. CONCLUSIONS: We found few studies focusing on the sustainability of KT interventions. Most of the included studies focused on patient-level outcomes and patient-level KT interventions. A future systematic review can be conducted of the RCTs to examine the impact of sustainable KT interventions on health outcomes.

Comparative safety and effectiveness of cognitive enhancers for Alzheimer's dementia: protocol for a systematic review and individual patient data network meta-analysis.

INTRODUCTION: Alzheimer's dementia (AD) is the most common cause of dementia, and several organisations, such as the National Institute for Health and Care Excellence, suggest that management of patients with AD should be tailored to their needs. To date, little research has been conducted on the treatment effect in different subgroups of patients with AD. The aim of this study is to examine the comparative effectiveness and safety of cognitive enhancers for different patient characteristics. METHODS AND ANALYSIS: We will update our previous literature search from January 2015 forward, using the same terms and electronic databases (eg, MEDLINE) from our previous review. We will additionally search grey literature and scan the reference lists of the included studies. Randomised clinical trials of any duration conducted at any time comparing cognitive enhancers alone or in any combination against other cognitive enhancers, or placebo in adults with AD will be eligible. The outcomes of interest are cognition according to the Mini-Mental State Examination, and overall serious adverse events. For each outcome and treatment comparison, we will perform a Bayesian hierarchical random-effects meta-analysis combining the individual patient data (IPD) from each eligible study. If the identified treatment comparisons form a connected network diagram, we will perform an IPD network meta-analysis (NMA) to estimate subgroup effects for patients with different characteristics, such as AD severity and sex. We will combine aggregated data from studies that we will not be able to obtain IPD, with the IPD provided by the original authors, in a single model. We will use the PRISMA-IPD and PRISMA-NMA statements to report our findings. ETHICS AND DISSEMINATION: The findings of this study will be of interest to stakeholders, including decision makers, guideline developers, clinicians, methodologists and patients, and they will help to improve guidelines for the management of patients with AD. TRIAL REGISTRATION NUMBER: CRD42015023507.

Safety and effectiveness of long-acting versus intermediate-acting insulin for patients with type 1 diabetes: protocol for a systematic review and individual patient data network meta-analysis.

INTRODUCTION: The choice of a basal insulin regimen to manage type 1 diabetes mellitus (T1DM) may have different risks of adverse events and effectiveness, due to the difference in the effectiveness of these agents across patient characteristics (eg, baseline glycosylated haemoglobin; A1C). Currently, there is a lack of high quality evidence to support the tailoring of insulin regimens according to an individual's needs. The aim of this study is to update our previous systematic review and perform an individual patient data network meta-analysis (IPD-NMA) to evaluate the comparative safety and effectiveness of long-acting versus intermediate-acting insulin in different subgroups of patients with T1DM. METHODS AND ANALYSIS: We will update our previous literature search from January 2013 onwards searching relevant electronic databases (eg, MEDLINE), as well as perform grey literature search through relevant society/association websites, and conference abstracts, and scan reference lists of the eligible studies. We will include randomised clinical trials of any duration examining long-acting versus intermediate-acting insulin preparations for adult patients with T1DM. We will focus on A1C and severe hypoglycaemia outcomes. For each pairwise treatment comparison, we will combine all IPD from all studies in a single multilevel model, where each study is a different cluster. For a connected network of trials, we will perform an IPD-NMA to identify potential effect modifiers, and estimate the most effective and safe treatments for patients with different characteristics. If we are not successful in obtaining IPD for at least one study, we will include aggregated data (AD) abstracted from the included RCTs in our analysis, combining IPD and AD into a single model. We will report our results using the PRISMA-IPD statement. ETHICS AND DISSEMINATION: The results of this systematic review and IPD-NMA will be of interest to stakeholders and will help in improving existing guideline recommendations. PROSPERO REGISTRY NUMBER: CRD42015023511.

Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis.

OBJECTIVE: To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013. STUDY SELECTION: Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included. RESULTS: 39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference -0.39%, 95% confidence interval -0.59% to -0.19%; -0.26%, -0.48% to -0.03%; and -0.36%, -0.65% to -0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: -5.51 kg, -6.56 to -4.46 kg; glargine once daily versus NPH once daily: -5.14 kg, -6.07 to -4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses. CONCLUSIONS: Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013003610.

Effectiveness of quality improvement strategies for coordination of care to reduce use of health care services: a systematic review and meta-analysis.

BACKGROUND: Frequent users of health care services are a relatively small group of patients who account for a disproportionately large amount of health care utilization. We conducted a meta-analysis of the effectiveness of interventions to improve the coordination of care to reduce health care utilization in this patient group. METHODS: We searched MEDLINE, Embase and the Cochrane Library from inception until May 2014 for randomized clinical trials (RCTs) assessing quality improvement strategies for the coordination of care of frequent users of the health care system. Articles were screened, and data abstracted and appraised for quality by 2 reviewers, independently. Random effects meta-analyses were conducted. RESULTS: We identified 36 RCTs and 14 companion reports (total 7494 patients). Significantly fewer patients in the intervention group than in the control group were admitted to hospital (relative risk [RR] 0.81, 95% confidence interval [CI] 0.72-0.91). In subgroup analyses, a similar effect was observed among patients with chronic medical conditions other than mental illness, but not among patients with mental illness. In addition, significantly fewer patients 65 years and older in the intervention group than in the control group visited emergency departments (RR 0.69, 95% CI 0.54-0.89). INTERPRETATION: We found that quality improvement strategies for coordination of care reduced hospital admissions among patients with chronic conditions other than mental illness and reduced emergency department visits among older patients. Our results may help clinicians and policy-makers reduce utilization through the use of strategies that target the system (team changes, case management) and the patient (promotion of self-management).

Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We conducted a systematic review to examine the efficacy and safety of cognitive enhancers for mild cognitive impairment. METHODS: Our eligibility criteria were studies of the effects of donepezil, rivastigmine, galantamine or memantine on mild cognitive impairment reporting cognition, function, behaviour, global status, and mortality or harms. We identified relevant material by searching electronic databases (e.g., MEDLINE, Embase), the references of included studies, trial registries and conference proceedings, and by contacting experts. Two reviewers independently screened the results of the literature search, abstracted data and appraised risk of bias using the Cochrane risk-of-bias tool. RESULTS: We screened 15,554 titles and abstracts and 1384 full-text articles. Eight randomized clinical trials and 3 companion reports met our inclusion criteria. We found no significant effects of cognitive enhancers on cognition (Mini-Mental State Examination: 3 randomized clinical trials [RCTs], mean difference [MD] 0.14, 95% confidence interval [CI] -0.22 to 0.50; Alzheimer's Disease Assessment Scale - cognition subscale: 3 RCTs, standardized MD -0.07, 95% CI-0.16 to 0.01]) or function (Alzheimer's Disease Cooperative Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI -0.26 to 0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea and vomiting than placebo. INTERPRETATION: Cognitive enhancers did not improve cognition or function among patients with mild cognitive impairment and were associated with a greater risk of gastrointestinal harms. Our findings do not support the use of cognitive enhancers for mild cognitive impairment.

Safety, effectiveness, and cost of long-acting versus intermediate-acting insulin for type 1 diabetes: protocol for a systematic review and network meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) causes progressive destruction of pancreatic beta cells leading to absolute insulin deficiency. Treatment of T1DM requires insulin, and some evidence suggests that longer acting insulin analogues might have a higher effectiveness and greater safety profile compared to intermediate-acting insulin. Our objective is to evaluate the comparative effectiveness, safety, and cost of long-acting insulin versus intermediate-acting insulin through a systematic review and network meta-analysis. DESIGN/METHODS: Studies examining long-acting versus intermediate-acting insulin or placebo preparations for adult T1DM patients will be included. The primary outcome is glycosylated hemoglobin (A1C), and secondary outcomes include emergency department and physician visits, hospital admissions, weight gain, quality of life, microvascular complications (e.g., retinopathy), macrovascular complications (e.g., cardiovascular disease), all-cause mortality, incident cancers, and cost. We will include experimental [randomized clinical trials (RCTs), quasi-RCTs, non-RCTs], quasi-experimental (controlled before-after, interrupted time series), observational (cohort), and cost studies, of any duration of follow-up, conducted during all time periods, and disseminated in any language.We will conduct comprehensive searches of electronic databases from inception onwards, including MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. We will also search for difficult to locate and unpublished literature by searching dissertation databases, public health organization websites, and trial registries. After a calibration exercise using our eligibility criteria and data abstraction forms, two reviewers will screen all citations, full-text articles, and abstract data in duplicate. Conflicts will be resolved by team discussion. Using a similar process, the Cochrane Effective Practice and Organization of Care Risk of Bias tool will be used to appraise the risk of bias of experimental and quasi-experimental studies, while the Newcastle Ottawa Scale will be used to assess the methodological quality of cohort studies. If feasible and appropriate, we will conduct a random effects meta-analysis, as well as a network meta-analysis. DISCUSSION: Our systematic review will be of utility to healthcare providers, policy-makers, T1DM patients and family members regarding treatment options of long-acting versus intermediate-acting insulin preparations. TRIAL REGISTRATION: PROSPERO registry number: CRD42013003610.