Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: systematic review and meta-analysis of complex interventions.

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (> 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database's inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I2 = 96%; European QOL-5 dimensions: MD 0.01, 95% CI [- 0.01, 0.02], 15 RCTs, 6628 participants, I2 = 25%; St George's Respiratory Questionnaire: MD - 2.12, 95% CI [- 3.72, - 0.51] 44 12 RCTs, 2893 participants, I2 = 44%). KT interventions improved QOC (OR 1.55, 95% CI [1.29, 1.85], 12 RCTS, 5271 participants, I2 = 21%). CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

Community based intervention to optimize osteoporosis management: randomized controlled trial.

BACKGROUND: Osteoporosis-related fractures are a significant public health concern. Interventions that increase detection and treatment of osteoporosis are underutilized. This pragmatic randomised study was done to evaluate the impact of a multifaceted community-based care program aimed at optimizing evidence-based management in patients at risk for osteoporosis and fractures. METHODS: This was a 12-month randomized trial performed in Ontario, Canada. Eligible patients were community-dwelling, aged ≥55 years, and identified to be at risk for osteoporosis-related fractures. Two hundred and one patients were allocated to the intervention group or to usual care. Components of the intervention were directed towards primary care physicians and patients and included facilitated bone mineral density testing, patient education and patient-specific recommendations for osteoporosis treatment. The primary outcome was the implementation of appropriate osteoporosis management. RESULTS: 101 patients were allocated to intervention and 100 to control. Mean age of participants was 71.9 ± 7.2 years and 94% were women. Pharmacological treatment (alendronate, risedronate, or raloxifene) for osteoporosis was increased by 29% compared to usual care (56% [29/52] vs. 27% [16/60]; relative risk [RR] 2.09, 95% confidence interval [CI] 1.29 to 3.40). More individuals in the intervention group were taking calcium (54% [54/101] vs. 20% [20/100]; RR 2.67, 95% CI 1.74 to 4.12) and vitamin D (33% [33/101] vs. 20% [20/100]; RR 1.63, 95% CI 1.01 to 2.65). CONCLUSIONS: A multi-faceted community-based intervention improved management of osteoporosis in high risk patients compared with usual care. TRIAL REGISTRATION: This trial has been registered with clinicaltrials.gov (ID: NCT00465387).

Prevention of Clostridium difficile infection with Saccharomyces boulardii: a systematic review.

BACKGROUND: Clostridium difficile is a major cause of antibiotic-associated diarrhea within the hospital setting. The yeast Saccharomyces boulardii has been found to have some effect in reducing the risk of C difficile infection (CDI); however, its role in preventive therapy has yet to be firmly established. OBJECTIVE: To review the effectiveness of S boulardii in the prevention of primary and recurrent CDI. Benefit was defined as a reduction of diarrhea associated with C difficile. Risk was defined as any adverse effects of S boulardii. METHODS: A literature search in MEDLINE, EMBASE, CINAHL and the Cochrane Library was performed. Included studies were English language, randomized, double-blind placebo controlled trials evaluating S boulardii in CDI prevention. RESULTS: Four studies were reviewed. Two studies investigated the prevention of recurrence in populations that were experiencing CDI at baseline. One trial showed a reduction of relapses in patients experiencing recurrent CDI (RR=0.53; P<0.05). The other demonstrated a trend toward reduction of CDI relapse in the recurrent treatment group of patients receiving high-dose vancomycin (RR=0.33; P=0.05). Two other studies examined primary prevention of CDI in populations that had been recently prescribed antibiotics. These studies lacked the power to detect statistically significant differences. Patients on treatment experienced increased risk for thirst and constipation. CONCLUSION: S boulardii seems to be well tolerated and may be effective for secondary prevention in some specific patient populations with particular concurrent antibiotic treatment. Its role in primary prevention is poorly defined and more research is required before changes in practice are recommended.

Sustaining knowledge translation interventions for chronic disease management in older adults: protocol for a systematic review and network meta-analysis.

BACKGROUND: Failure to sustain knowledge translation (KT) interventions impacts patients and health systems, diminishing confidence in future implementation. Sustaining KT interventions used to implement chronic disease management (CDM) interventions is of critical importance given the proportion of older adults with chronic diseases and their need for ongoing care. Our objectives are to (1) complete a systematic review and network meta-analysis of the effectiveness and cost-effectiveness of sustainability of KT interventions that target CDM for end-users including older patients, clinicians, public health officials, health services managers and policy-makers on health care outcomes beyond 1 year after implementation or the termination of initial project funding and (2) use the results of this review to complete an economic analysis of the interventions identified to be effective. METHODS: For objective 1, comprehensive searches of relevant electronic databases (e.g. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials), websites of health care provider organisations and funding agencies will be conducted. We will include randomised controlled trials (RCTs) examining the impact of a KT intervention targeting CDM in adults aged 65 years and older. To examine cost, economic studies (e.g. cost, cost-effectiveness analyses) will be included. Our primary outcome will be the sustainability of the delivery of the KT intervention beyond 1 year after implementation or termination of study funding. Secondary outcomes will include behaviour changes at the level of the patient (e.g. symptom management) and clinician (e.g. physician test ordering) and health system (e.g. cost, hospital admissions). Article screening, data abstraction and risk of bias assessment will be completed independently by two reviewers. Using established methods, if the assumption of transitivity is valid and the evidence forms a connected network, Bayesian random-effects pairwise and network meta-analysis will be conducted. For objective 2, we will build a decision analytic model comparing effective interventions to estimate an incremental cost-effectiveness ratio. DISCUSSION: Our results will inform knowledge users (e.g. patients, clinicians, policy-makers) regarding the sustainability of KT interventions for CDM. Dissemination plan of our results will be tailored to end-users and include passive (e.g. publications, website posting) and interactive (e.g. knowledge exchange events with stakeholders) strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810.

The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs.

OBJECTIVE: To estimate the effect of reference pricing (RP) of nonsteroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures on analgesic drugs. DATA SOURCES/STUDY SETTING: Monthly claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada, over the period of February 1993 to June 2001. STUDY DESIGN: RP limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. Pharmacare introduced two different forms of RP to the NSAIDs, Type 1 in April 1994 and Type 2 in November 1995. Under Type 1 RP, generic and brand versions of the same NSAID are considered interchangeable, whereas under Type 2 RP different NSAIDs are considered interchangeable. We extrapolated average reimbursement per day of NSAID therapy over the months before RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared with actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the postpolicy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes. PRINCIPAL FINDINGS: After Type 2 RP, program expenditures declined by $22.7 million (CAN), or $4 million (CAN), annually cutting expenditure by about half. Most savings accrued from the substitution of low-cost NSAIDs for more costly alternatives. About 20 percent of savings represented expenditures by seniors who elected to pay for partially reimbursed drugs. Type 1 RP produced one-quarter the savings of type 2 RP. CONCLUSIONS: Type 2 RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than Type 1 RP. The effects of RP on patient health and associated health care costs remain to be investigated.

The perception of continuity of care from the perspective of patients with diabetes.

BACKGROUND AND OBJECTIVES: Traditional indices of continuity of care typically capture frequency of physician visits but lack information regarding how patients themselves perceive continuity of care. The present study's objectives were (1) to examine the meaning of continuity of care from the perspective of patients with diabetes and (2) to understand the factors that enhance or detract from continuity of care. METHODS: Seven focus groups with 46 adult patients were held at a health service organization in Northern Ontario. All focus group interviews were tape recorded, transcribed verbatim, and analyzed using a phenomenological approach. Triangulation occurred through participant feedback of transcript summaries and consensus of themes by the multidisciplinary research team. RESULTS: Patients conceptualized continuity of care in a broad and multifaceted manner that was comprised of five components: (1) access to services, (2) interactions with physician, (3) interactions with other health care providers, (4) personal self responsibility, and (5) communication. CONCLUSIONS: Continuity of care was perceived by patients to include a wider range of components than what is traditionally associated with continuity of care. The emphasis on personal self responsibility by some patients provides a deeper understanding of what patients feel encompass continuity of care.

The Diabetes Continuity of Care Scale: the development and initial evaluation of a questionnaire that measures continuity of care from the patient perspective.

The purpose of the present study was to develop and pilot test a questionnaire to assess continuity of care from the perspective of patients with diabetes. Seven patient and two healthcare-provider focus groups were conducted. These focus groups generated 777 potential items. This number was reduced to 56 items after item reduction, face validity testing and readability analysis, and to 47 items after a preliminary factor analysis. Readability was assessed as requiring 7-8 years of schooling. Sixty adult patients with diabetes completed the draft Diabetes Continuity of Care Scale (DCCS) at a single point in time to assess the validity of the instrument. Patients completed the draft DCCS again 2 weeks later to assess test-retest reliability. A provisional factor analysis and grouping according to clinical sense yielded five domains: access and getting care, care by doctor, care by other healthcare professionals, communication between healthcare professionals, and self-care. The internal consistency (Cronbach's alpha) for the whole scale was 0.89. The test-retest reliability was r = 0.73. The DCCS total score was moderately correlated with some of the measures used to establish construct validity. The DCCS could differentiate between patients who did and did not achieve specific process and clinical indicators of good diabetes care (e.g. Hba1c tested within 6 months). The development of the DCCS was centred on the patient's perspective and revealed that the patient perspective regarding continuity of care extends beyond the concept of seeing one doctor. Initial testing of this instrument demonstrates that it has promise as a reliable and valid measure in this area.

The effectiveness of integrated health information technologies across the phases of medication management: a systematic review of randomized controlled trials.

OBJECTIVE: The US Agency for Healthcare Research and Quality funded an evidence report to address seven questions on multiple aspects of the effectiveness of medication management information technology (MMIT) and its components (prescribing, order communication, dispensing, administering, and monitoring). MATERIALS AND METHODS: Medline and 11 other databases without language or date limitations to mid-2010. Randomized controlled trials (RCTs) assessing integrated MMIT were selected by two independent reviewers. Reviewers assessed study quality and extracted data. Senior staff checked accuracy. RESULTS: Most of the 87 RCTs focused on clinical decision support and computerized provider order entry systems, were performed in hospitals and clinics, included primarily physicians and sometimes nurses but not other health professionals, and studied process changes related to prescribing and monitoring medication. Processes of care improved for prescribing and monitoring mostly in hospital settings, but the few studies measuring clinical outcomes showed small or no improvements. Studies were performed most frequently in the USA (n=63), Europe (n=16), and Canada (n=6). DISCUSSION: Many studies had limited description of systems, installations, institutions, and targets of the intervention. Problems with methods and analyses were also found. Few studies addressed order communication, dispensing, or administering, non-physician prescribers or pharmacists and their MMIT tools, or patients and caregivers. Other study methods are also needed to completely understand the effects of MMIT. CONCLUSIONS: Almost half of MMIT interventions improved the process of care, but few studies measured clinical outcomes. This large body of literature, although instructive, is not uniformly distributed across settings, people, medication phases, or outcomes.

Enabling medication management through health information technology (Health IT).

OBJECTIVES: The objective of the report was to review the evidence on the impact of health information technology (IT) on all phases of the medication management process (prescribing and ordering, order communication, dispensing, administration and monitoring as well as education and reconciliation), to identify the gaps in the literature and to make recommendations for future research. DATA SOURCES: We searched peer-reviewed electronic databases, grey literature, and performed hand searches. Databases searched included MEDLINE®, Embase, CINAHL (Cumulated Index to Nursing and Allied Health Literature), Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, Compendex, Inspec (which includes IEEE Xplore), Library and Information Science Abstracts, E-Prints in Library and Information Science, PsycINFO, Sociological Abstracts, and Business Source Complete. Grey literature searching involved Internet searching, reviewing relevant Web sites, and searching electronic databases of grey literatures. AHRQ also provided all references in their e-Prescribing, bar coding, and CPOE knowledge libraries. METHODS: Paired reviewers looked at citations to identify studies on a range of health IT used to assist in the medication management process (MMIT) during multiple levels of screening (titles and abstracts, full text and final review for assignment of questions and data abstrction). Randomized controlled trials and cohort, case-control, and case series studies were independently assessed for quality. All data were abstracted by one reviewer and examined by one of two different reviewers with content and methods expertise. RESULTS: 40,582 articles were retrieved. After duplicates were removed, 32,785 articles were screened at the title and abstract phase. 4,578 full text articles were assessed and 789 articles were included in the final report. Of these, 361 met only content criteria and were listed without further abstraction. The final report included data from 428 articles across the seven key questions. Study quality varied according to phase of medication management. Substantially more studies, and studies with stronger comparative methods, evaluated prescribing and monitoring. Clinical decision support systems (CDSS) and computerized provider order entry (CPOE) systems were studied more than any other application of MMIT. Physicians were more often the subject of evaluation than other participants. Other health care professionals, patients, and families are important but not studied as thoroughly as physicians. These nonphysicians groups often value different aspects of MMIT, have diverse needs, and use systems differently. Hospitals and ambulatory clinics were well-represented in the literature with less emphasis placed on long-term care facilities, communities, homes, and nonhospital pharmacies. Most studies evaluated changes in process and outcomes of use, usability, and knowledge, skills, and attitudes. Most showed moderate to substantial improvement with implementation of MMIT. Economics studies and those with clinical outcomes were less frequently studied. Those articles that did address economics and clinical outcomes often showed equivocal findings on the effectiveness and cost-effectiveness of MMIT systems. Qualitative studies provided evidence of strong perceptions, both positive and negative, of the effects of MMIT and unintended consequences. We found little data on the effects of forms of medications, conformity, standards, and open source status. Much descriptive literature discusses implementation issues but little strong evidence exists. Interest is strong in MMIT and more groups and institutions will implement systems in the next decades, especially with the Federal Government's push toward more health IT to support better and more cost-effective health care. CONCLUSIONS: MMIT is well-studied, although on closer examination of the literature the evidence is not uniform across phases of medication management, groups of people involved, or types of MMIT. MMIT holds the promise of improved processes; clinical and economics studies and the understanding of sustainability issues are lacking.

Adverse events associated with pyrazinamide and levofloxacin in the treatment of latent multidrug-resistant tuberculosis.

BACKGROUND: The current Canadian and US guidelines for the treatment of multidrug-resistant latent tuberculosis infection advocate the use of pyrazinamide and a fluoroquinolone as a first-line treatment option. However, there is very little information in the literature that describes the use of these agents together. This case series describes the probable association between multiple adverse events and the use of pyrazinamide and levofloxacin in the treatment of individuals with suspected latent multidrug-resistant tuberculosis infection. METHODS: We studied a case series of 17 individuals with suspected latent multidrug-resistant tuberculosis infection in Hamilton, Ont., who were being treated with pyrazinamide and levofloxacin. The Naranjo scale was used to assess patients for musculoskeletal, central nervous system, gastrointestinal and dermatological adverse events. Hepatocellular events were assessed and defined using criteria established by the Council for International Organizations of Medical Sciences. Laboratory abnormalities and adverse events that were documented during combination drug therapy were evaluated to determine the likelihood of an association. RESULTS: Fourteen individuals developed musculoskeletal adverse effects (11 were deemed to be probably related to combination therapy). There were 8 reports of central nervous system effects (5 of which were assessed as being probably associated with therapy). Hyperuricemia and gastrointestinal and dermatological effects were also common; the use of pyrazinamide and levofloxacin was believed to be probably responsible for the emergence of these adverse effects. There were 5 cases of hepatocellular injury. Therapy was discontinued in all individuals. INTERPRETATION: The combination of pyrazinamide and levofloxacin appears to be a poorly tolerated regimen. The mechanism of a possible interaction is not yet understood. Given the severity of some of the adverse events, a better understanding of dosing and clearer guidelines for monitoring therapy are imperative if these drugs are to be prescribed together.

Impact of reference-based pricing for histamine-2 receptor antagonists and restricted access for proton pump inhibitors in British Columbia.

BACKGROUND: Two programs to reduce expenditures for common gastrointestinal drugs were introduced simultaneously by British Columbia (BC) Pharmacare in 1995. Reference-based pricing restricted reimbursement for all histamine-2 receptor antagonists (H2RAs) to the cost of the least expensive H2RA available, generic cimetidine. Special authority restricted reimbursement for proton pump inhibitors (PPIs) to patients who met certain eligibility criteria. We evaluated the effect of reference-based pricing for H2RAs and special authority for PPIs on dispensing and reimbursement for senior citizen beneficiaries of BC Pharmacare. METHODS: Itemized monthly claims data for upper gastrointestinal drugs were obtained from BC Pharmacare for all beneficiaries 65 years of age or older. Periods before and after implementation of reference-based pricing and special authority were compared with respect to defined daily doses dispensed per 100,000 beneficiaries, BC Pharmacare reimbursement per 100,000 beneficiaries, BC Pharmacare reimbursement per defined daily dose and beneficiary contributions per defined daily dose. We used regression models to project forward trends in expenditures observed before implementation of the new policies and hence to estimate accrued cost savings. RESULTS: Before reference-based pricing and special authority, the numbers of defined daily doses that were dispensed and total BC Pharmacare reimbursements for H2RAs appeared to be declining gradually, whereas those for PPIs were rising. With reference-based pricing, the monthly defined daily dose of cimetidine dispensed increased more than 4-fold, to 116,257 per 100,000 beneficiaries, while those of other restricted H2RAs decreased by more than half, to 50,927 per 100,000 beneficiaries. Special authority immediately reduced the dispensed volumes of PPIs by one-fourth, but growth in volume then appeared to resume at its previous rate. The estimated annualized cost savings achieved by reference-based pricing and special authority were $1.8 million to $3.2 million for H2RAs (depending on the estimation method used) and $5.5 million for PPIs. However, beneficiary contributions for H2RAs increased from negligible amounts to approximately 16% of total drug expenditures. INTERPRETATION: Reference-based pricing and special authority appear to have been successful in altering prescribing habits and reducing provincial expenditures for upper gastrointestinal drugs, but they have increased the financial burden on senior citizen beneficiaries.