Tools and tactics for postdischarge medication management interventions.

PURPOSE: To identify interventions for organizational pharmacist-leaders and frontline pharmacy staff to optimize peri- and postdischarge medication management. SUMMARY: An evidence-based toolkit was systematically constructed on the basis of findings of 3 systematic overviews of systematic reviews. The interventions were reviewed by a technical expert panel and categorized as either tools or tactics. The identified tools are instruments such as diagrams, flow charts, lists, tables, and templates used in performing a distinct operation, whereas identified tactics reflect broader methods (eg, reduced dosing frequency). Tools and tactics were chosen on the basis of their potential to improve postdischarge medication management, with a focus on interventions led by pharmacy staff that may reduce hospital readmissions among older, sicker patients. Overall, 23 tools and 2 tactics were identified. The identified tools include items such as education, text messaging, and phone calls. The tactics identified are dose simplification and monetary incentives. Practical information has also been provided to facilitate implementation. CONCLUSION: Several tools and tactics are available to optimize peri- and postdischarge medication management. Organizational pharmacist-leaders and frontline pharmacy staff can implement these interventions to improve patient outcomes.

A systematic overview of systematic reviews evaluating medication adherence interventions.

PURPOSE: To systematically summarize evidence from multiple systematic reviews (SRs) examining interventions addressing medication nonadherence and to discern differences in effectiveness by intervention, patient, and study characteristics. SUMMARY: MEDLINE, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects were searched for papers published from January 2004 to February 2017. English-language SRs examining benefits of medication adherence interventions were eligible. Inclusion was limited to adult patients prescribed medication for 1 of the following disease conditions: diabetes and prediabetes, heart conditions, hypertension and prehypertension, stroke, and cognitive impairment. Non-disease-specific SRs that considered medication adherence interventions for older adults, adults with chronic illness, and adults with known medication adherence problems were also included. Two researchers independently screened titles, abstracts, and full-text articles. They then extracted key variables from eligible SRs, reconciling discrepancies via discussion. A MeaSurement Tool to Assess systematic Reviews (AMSTAR) was used to assess SRs; those with scores below 8 were excluded. Conclusions regarding intervention effectiveness were extracted. Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was applied to assess evidence quality. RESULTS: Of 390 SRs, 25 met the inclusion criteria and assessed adherence as a primary outcome. Intervention types most consistently found to be effective were dose simplification, patient education, electronic reminders to patients, and reduced patient cost sharing or incentives. Of 50 conclusions drawn by the SRs, the underlying evidence was low or very low quality for 45 SRs. CONCLUSION: Despite an abundance of primary studies and despite only examining high-quality SRs, the vast majority of primary studies supporting SR authors' conclusions were of low or very low quality. Nonetheless, health system leaders seeking to improve medication adherence should prioritize interventions that have been studied and found to be effective at improving patient adherence, including dose simplification, education, reminders, and financial incentives.

Effect of medication reconciliation interventions on outcomes: A systematic overview of systematic reviews.

PURPOSE: To evaluate and summarize published evidence from systematic reviews examining medication reconciliation. METHODS: MEDLINE, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects were searched for English-language systematic reviews published from January 2004 to March 2019. Reviewers independently extracted information and scored review quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. For reviews with AMSTAR scores above 7, Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess evidence quality, with evidence summarized and conclusions compared across reviews. RESULTS: Eleven reviews met the inclusion criteria, 5 of which used meta-analytic pooling. Most systematic reviews included primary studies of comprehensive bundled interventions that featured medication reconciliation as a central component. Reviews largely focused on transitions into and out of hospital settings. Five reviews focused exclusively on pharmacist-led interventions. Of the 5 reviews that considered all types of medication discrepancies, 3 reviews found very low-quality evidence that interventions reduced medication discrepancies. Neither of the 2 reviews that examined clinically significant medication discrepancies found any intervention effect. Of the 5 reviews that examined healthcare utilization outcomes, only 1 found any intervention effect, and that finding was based on low- to very low-quality evidence. Four reviews considered clinical outcomes, but none found any intervention effect. CONCLUSION: An overview of systematic reviews of medication reconciliation interventions found 9 high-quality systematic reviews. A minority of those reviews' conclusions were consistent with medication reconciliation alone having a measurable impact, and such conclusions were almost all based on very low-quality evidence.

A systematic overview of systematic reviews evaluating interventions addressing polypharmacy.

PURPOSE: To systematically evaluate and summarize evidence across multiple systematic reviews (SRs) examining interventions addressing polypharmacy. SUMMARY: MEDLINE, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (DARE) were searched for SRs evaluating interventions addressing polypharmacy in adults published from January 2004 to February 2017. Two authors independently screened, appraised, and extracted information. SRs with Assessment of Multiple Systematic Reviews (AMSTAR) scores below 8 were excluded. After extraction of relevant conclusions from each SR, evidence was summarized and conclusions compared. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess evidence quality. Six SRs met the inclusion criteria, 4 of which used meta-analytic pooling. Five SRs focused on older adults. Four were not restricted to any specific disease type, whereas 1 focused on proton pump inhibitors and another focused on patients with severe dementia. Care settings and measured outcomes varied widely. SRs examining the impact on patient-centered outcomes, including morbidity, mortality, patient satisfaction, and utilization, found inconsistent evidence regarding the benefit of polypharmacy interventions, but most concluded that interventions had either null or uncertain impact. Two SRs assessing medication appropriateness found very low-quality evidence of modest improvements with polypharmacy interventions. CONCLUSION: An overview of SRs of interventions to address polypharmacy found 6 recent and high-quality SRs, mostly focused on older adults, in which both process and outcome measures were used to evaluate interventions. Despite the low quality of evidence in the underlying primary studies, both SRs that assessed medication appropriateness found evidence that polypharmacy interventions improved it. However, there was no consistent evidence of any impact on downstream patient-centered outcomes such as healthcare utilization, morbidity, or mortality.

Economic Evaluation of Quality Improvement Interventions Designed to Improve Glycemic Control in Diabetes: A Systematic Review and Weighted Regression Analysis.

OBJECTIVE: Quality improvement (QI) interventions can improve glycemic control, but little is known about their value. We systematically reviewed economic evaluations of QI interventions for glycemic control among adults with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: We used English-language studies from high-income countries that evaluated organizational changes and reported program and utilization-related costs, chosen from PubMed, EconLit, Centre for Reviews and Dissemination, New York Academy of Medicine's Grey Literature Report, and WorldCat (January 2004 to August 2016). We extracted data regarding intervention, study design, change in HbA1c, time horizon, perspective, incremental net cost (studies lasting ≤3 years), incremental cost-effectiveness ratio (ICER) (studies lasting ≥20 years), and study quality. Weighted least-squares regression analysis was used to estimate mean changes in HbA1c and incremental net cost. RESULTS: Of 3,646 records, 46 unique studies were eligible. Across 19 randomized controlled trials (RCTs), HbA1c declined by 0.26% (95% CI 0.17-0.35) or 3 mmol/mol (2 to 4) relative to usual care. In 8 RCTs lasting ≤3 years, incremental net costs were $116 (95% CI -$612 to $843) per patient annually. Long-term ICERs were $100,000-$115,000/quality-adjusted life year (QALY) in 3 RCTs, $50,000-$99,999/QALY in 1 RCT, $0-$49,999/QALY in 4 RCTs, and dominant in 1 RCT. Results were more favorable in non-RCTs. Our limitations include the fact that the studies had diverse designs and involved moderate risk of bias. CONCLUSIONS: Diverse multifaceted QI interventions that lower HbA1c appear to be a fair-to-good value relative to usual care, depending on society's willingness to pay for improvements in health.

The Cost of Interventions to Increase Influenza Vaccination: A Systematic Review.

CONTEXT: Influenza vaccination rates remain below Healthy People 2020 goals. This project sought to systematically review economic evaluations of healthcare-based quality improvement interventions for improving influenza vaccination uptake among general populations and healthcare workers. EVIDENCE ACQUISITION: The databases MEDLINE, Econlit, Centre for Reviews & Dissemination, Greylit, and Worldcat were searched in July 2016 for papers published from January 2004 to July 2016. Eligible studies evaluated efforts by bodies within the healthcare system to encourage influenza vaccination by means of an organizational or structural change. For each study, program costs per enrollee and per additional enrollee vaccinated were derived (excluding vaccine costs, standardized to 2017 U.S. dollars). Complete economic evaluations were examined when available. EVIDENCE SYNTHESIS: Of 2,350 records, 18 articles were eligible and described 29 unique interventions. Most interventions improved vaccine uptake. Among 23 interventions in general populations, the median program cost was $3.27 (interquartile range, $0.82-$11.53) per enrollee and $50.78 (interquartile range, $27.85-$124.84) per additional enrollee vaccinated. Among ten complete economic evaluations in general populations, three studies reported net cost savings, four reported costs <$50,000 per quality-adjusted life year, and three reported costs <$60,000 per life saved. Among six interventions in healthcare workers, the median program cost was $8.09 (interquartile range, $5.03-$10.31) per worker enrolled and $125.24 (interquartile range, $96.06-$171.38) per additional worker vaccinated (there were no complete economic analyses). CONCLUSIONS: Quality improvement interventions for influenza vaccination involve per-enrollee costs that are similar to the cost of the vaccine itself ($11.78-$36.08/dose). Based on limited available evidence in general populations, quality improvement interventions may be cost saving to cost effective for the health system.

Comparative Evaluation of 2 Nucleic Acid Amplification Tests for the Detection of Chlamydia trachomatis and Neisseria gonorrhoeae at Extragenital Sites.

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are frequently asymptomatic, requiring highly accurate diagnostic tests and proper management to prevent further transmission. We compared two nucleic acid tests, Xpert® CT/NG (Cepheid, Sunnyvale, CA) point-of-care platform and at an offsite clinical laboratory with Aptima Combo 2® (Hologic, Inc., San Diego, CA) assay, for the detection of extragenital infection in patients at an STI clinic in Hollywood, CA.We calculated concordance between the two assays and used the exact binomial method to calculate 95% confidence intervals (CIs) for each specimen type and pathogen.The concordance between the two assays was 97.7% (95% CI: 95.7%,99.0%) for 393 paired CT rectal results, 98.2% (95% CI: 96.4%,99.3%) for 391 paired NG rectal results and 98.4% (95% CI: 96.8%,99.4%) for 448 paired NG pharyngeal results.The performance of Xpert® CT/NG assay in point-of-care testing in extragenital specimens was highly similar to the laboratory-based platform.

Chronic disease self-management support for persons with dementia, in a clinical setting.

The burden of chronic disease is greater in individuals with dementia, a patient group that is growing as the population is aging. The cornerstone of optimal management of chronic disease requires effective patient self-management. However, this is particularly challenging in older persons with a comorbid diagnosis of dementia. The impact of dementia on a person's ability to self-manage his/her chronic disease (eg, diabetes mellitus or heart failure) varies according to the cognitive domain(s) affected, severity of impairment and complexity of self-care tasks. A framework is presented that describes how impairment in cognitive domains (attention and information processing, language, visuospatial ability and praxis, learning and memory and executive function) impacts on the five key processes of chronic disease self-management. Recognizing the presence of dementia in a patient with chronic disease may lead to better outcomes. Patients with dementia require individually tailored strategies that accommodate and adjust to the individual and the cognitive domains that are impaired, to optimize their capacity for self-management. Management strategies for clinicians to counter poor self-management due to differentially impaired cognitive domains are also detailed in the presented framework. Clinicians should work in collaboration with patients and care givers to assess a patient's current capabilities, identify potential barriers to successful self-management and make efforts to adjust the provision of information according to the patient's skill set. The increasing prevalence of age-related chronic illness along with a decline in the availability of informal caregivers calls for innovative programs to support self-management at a primary care level.

Cost-effectiveness of HIV and syphilis antenatal screening: a modelling study.

OBJECTIVES: The WHO called for the elimination of maternal-to-child transmission (MTCT) of HIV and syphilis, a harmonised approach for the improvement of health outcomes for mothers and children. Testing early in pregnancy, treating seropositive pregnant women and preventing syphilis reinfection can prevent MTCT of HIV and syphilis. We assessed the health and economic outcomes of a dual testing strategy in a simulated cohort of 100 000 antenatal care patients in Malawi. METHODS: We compared four screening algorithms: (1) HIV rapid test only, (2) dual HIV and syphilis rapid tests, (3) single rapid tests for HIV and syphilis and (4) HIV rapid and syphilis laboratory tests. We calculated the expected number of adverse pregnancy outcomes, the expected costs and the expected newborn disability-adjusted life years (DALYs) for each screening algorithm. The estimated costs and DALYs for each screening algorithm were assessed from a societal perspective using Markov progression models. Additionally, we conducted a Monte Carlo multiway sensitivity analysis, allowing for ranges of inputs. RESULTS: Our cohort decision model predicted the lowest number of adverse pregnancy outcomes in the dual HIV and syphilis rapid test strategy. Additionally, from the societal perspective, the costs of prevention and care using a dual HIV and syphilis rapid testing strategy was both the least costly ($226.92 per pregnancy) and resulted in the fewest DALYs (116 639) per 100 000 pregnancies. In the Monte Carlo simulation the dual HIV and syphilis algorithm was always cost saving and almost always reduced DALYs compared with HIV testing alone. CONCLUSIONS: The results of the cost-effectiveness analysis showed that a dual HIV and syphilis test was cost saving compared with all other screening strategies. Updating existing prevention of mother-to-child HIV transmission programmes in Malawi and similar countries to include dual rapid testing for HIV and syphilis is likely to be advantageous.

Sexually transmitted infections among incarcerated women: findings from a decade of screening in a Los Angeles County Jail, 2002-2012.

OBJECTIVES: We describe and report findings from a screening program to identify sexually transmitted infections (STIs) and HIV among female inmates in Los Angeles County Jail. METHODS: Chlamydia and gonorrhea screening was offered to entering female inmates. Women were eligible if they were (1) aged 30 years or younger, or (2) pregnant or possibly pregnant, or (3) booked on prostitution or sex-related charges. Voluntary syphilis and HIV testing was offered to all women between 2006 and 2009. This analysis reports on data collected from 2002 through 2012. RESULTS: A total of 76,207 women participated in the program. Chlamydia prevalence was 11.4% and gonorrhea was 3.1%. Early syphilis was identified in 1.4% (141 of 9733) and the overall prevalence of HIV was 1.1% (83 of 7448). Treatment levels for early syphilis and HIV were high (99% and 100%, respectively), but only 56% of chlamydia and 58% of gonorrhea cases were treated. CONCLUSIONS: Screening incarcerated women in Los Angeles County revealed a high prevalence of STIs and HIV. These inmates represent a unique opportunity for the identification of STIs and HIV, although strategies to improve chlamydia and gonorrhea treatment rates are needed.

The effectiveness of computerized order entry at reducing preventable adverse drug events and medication errors in hospital settings: a systematic review and meta-analysis.

BACKGROUND: The Health Information Technology for Economic and Clinical Health (HITECH) Act subsidizes implementation by hospitals of electronic health records with computerized provider order entry (CPOE), which may reduce patient injuries caused by medication errors (preventable adverse drug events, pADEs). Effects on pADEs have not been rigorously quantified, and effects on medication errors have been variable. The objectives of this analysis were to assess the effectiveness of CPOE at reducing pADEs in hospital-related settings, and examine reasons for heterogeneous effects on medication errors. METHODS: Articles were identified using MEDLINE, Cochrane Library, Econlit, web-based databases, and bibliographies of previous systematic reviews (September 2013). Eligible studies compared CPOE with paper-order entry in acute care hospitals, and examined diverse pADEs or medication errors. Studies on children or with limited event-detection methods were excluded. Two investigators extracted data on events and factors potentially associated with effectiveness. We used random effects models to pool data. RESULTS: Sixteen studies addressing medication errors met pooling criteria; six also addressed pADEs. Thirteen studies used pre-post designs. Compared with paper-order entry, CPOE was associated with half as many pADEs (pooled risk ratio (RR) = 0.47, 95% CI 0.31 to 0.71) and medication errors (RR = 0.46, 95% CI 0.35 to 0.60). Regarding reasons for heterogeneous effects on medication errors, five intervention factors and two contextual factors were sufficiently reported to support subgroup analyses or meta-regression. Differences between commercial versus homegrown systems, presence and sophistication of clinical decision support, hospital-wide versus limited implementation, and US versus non-US studies were not significant, nor was timing of publication. Higher baseline rates of medication errors predicted greater reductions (P < 0.001). Other context and implementation variables were seldom reported. CONCLUSIONS: In hospital-related settings, implementing CPOE is associated with a greater than 50% decline in pADEs, although the studies used weak designs. Decreases in medication errors are similar and robust to variations in important aspects of intervention design and context. This suggests that CPOE implementation, as subsidized under the HITECH Act, may benefit public health. More detailed reporting of the context and process of implementation could shed light on factors associated with greater effectiveness.

Chaperone signalling complexes in Alzheimer's disease.

Molecular chaperones and heat shock proteins (Hsp) have emerged as critical regulators of proteins associated with neurodegenerative disease pathologies. The very nature of the chaperone system, which is to maintain protein quality control, means that most nascent proteins come in contact with chaperone proteins. Thus, amyloid precursor protein (APP), members of the gamma-secretase complex (presenilin 1 [PS1] collectively), the microtubule-associated protein tau (MAPT) as well as a number of neuroinflammatory components are all in contact with chaperones from the moment of their production. Chaperones are often grouped together as one machine presenting abnormal or mutant proteins to the proteasome for degradation, but this is not at all the case. In fact, the chaperone family consists of more than 100 proteins in mammalian cells, and the primary role for most of these proteins is to protect clients following synthesis and during stress; only as a last resort do they facilitate protein degradation. To the best of our current knowledge, the chaperone system in eukaryotic cells revolves around the ATPase activities of Hsp70 and Hsp90, the two primary chaperone scaffolds. Other chaperones and co-chaperones manipulate the ATPase activities of Hsp70 and Hsp90, facilitating either folding of the client or its degradation. In the case of Alzheimer's disease (AD), a number of studies have recently emerged describing the impact that these chaperones have on the proteotoxic effects of tau and amyloid- beta accumulation. Here, we present the current understandings of chaperone biology and examine the literature investigating these proteins in the context of AD.