Do proton pump inhibitors increase mortality? A systematic review and in-depth analysis of the evidence.

Proton pump inhibitors (PPIs) were primarily approved for short-term use (2 to 8 weeks). However, PPI use continues to expand. Widely believed to be safe, we reviewed emerging evidence on increased mortality with PPI long-term use. Our 2016 systematic PPI drug class review found that mortality was not reported as an outcome in randomized controlled trials (RCTs) that directly compared different PPIs. We sought more recent and comprehensive data on PPI harm outcomes from research syntheses as a follow-on. A search was conducted from January 2014 to January 2020. We searched MEDLINE, EMBASE, and Cochrane Central for evidence from systematic reviews (SRs) and primary studies reporting all-cause mortality in adults treated with a PPI for any indication (duration >12 weeks) compared to patients without PPI treatment (no use, placebo, or H2RA use). Two independent investigators assessed study eligibility, synthesized evidence, and assessed the quality of the included studies. Data on all-cause mortality were sought, analyzed, critically examined, and interpreted herein. From 1304 articles, one SR was identified that reported on all-cause mortality. The SRs pooled three observational studies with data to 1 year: odds ratio, 95% confidence interval (CI) 1.53-1.84. A RCT, the COMPASS (Cardiovascular Outcomes for People Using Anticoagulant Strategies) RCT with data to 3 years: hazard ratio (HR) 1.03, 95% CI 0.92-1.15. The US Veterans Affairs cohort study using a large national dataset with data to 10 years found a HR of 1.17, 95% CI (1.10-1.24) and (NNH) of 22. The most common causes of death were from cardiovascular and chronic kidney diseases, with an excess death of 15 and 4 per 1000 patients, respectively, over the 10-year period. Harms arising from real-world medication use are best evaluated using a pharmacovigilance "convergence of proof" approach using data from a variety of sources and various study designs. Given that most PPI indications for use recommended a treatment duration of less than 12 weeks, it seems clear that PPIs were significantly overused in older patients. The median exposure time to PPI ranged from 1 to 4.6 years. Signals of serious harms including increased mortality with long-term PPI use are reported in observational studies. The COMPASS trial findings are not inconsistent with contemporaneous findings from observational studies. The COMPASS RCT was unlikely to detect an increase in mortality given the trial was not powered to detect this outcome. The potential increase in mortality in older patients associated with prolonged PPI exposure needs to be conveyed to health professionals. Clinicians and patients may be able to reverse the relentless expansion of long-term PPI exposure by reviewing indications and considering potential harms as well as benefits.

Will This Hospitalized Patient Develop Severe Alcohol Withdrawal Syndrome?: The Rational Clinical Examination Systematic Review.

Importance: Although severe alcohol withdrawal syndrome (SAWS) is associated with substantial morbidity and mortality, most at-risk patients will not develop this syndrome. Predicting its occurrence is important because the mortality rate is high when untreated. Objective: To assess the accuracy and predictive value of symptoms and signs for identifying hospitalized patients at risk of SAWS, defined as delirium tremens, withdrawal seizure, or clinically diagnosed severe withdrawal. Data Sources: MEDLINE and EMBASE (1946-January 2018) were searched for articles investigating symptoms and signs predictive of SAWS in adults. Reference lists of retrieved articles were also searched. Study Selection: Original studies that were included compared symptoms, signs, and risk assessment tools among patients who developed SAWS and patients who did not. Data Extraction and Synthesis: Data were extracted and used to calculate likelihood ratios (LRs), sensitivity, and specificity. A meta-analysis was performed to calculate summary LR. Results: Of 530 identified studies, 14 high-quality studies that included 71 295 patients and 1355 relevant cases of SAWS (1051 cases), seizure (53 cases), or delirium tremens (251 cases) were analyzed. A history of delirium tremens (LR, 2.9 [95% CI 1.7-5.2]) and baseline systolic blood pressure 140 mm Hg or higher (LR, 1.7 [95% CI, 1.3-2.3) were associated with an increased likelihood of SAWS. No single symptom or sign was associated with exclusion of SAWS. Six high-quality studies evaluated combinations of clinical findings and were useful for identifying patients in acute care facilities at high risk of developing SAWS. Of these combinations, the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) was most useful, with an LR of 174 (95% CI, 43-696; specificity, 0.93) when patients had 4 or more individual findings and an LR of 0.07 (95% CI, 0.02-0.26; sensitivity, 0.99) when there were 3 or fewer findings. Conclusions and Relevance: Assessment tools that use a combination of symptoms and signs are useful for identifying patients at risk of developing severe alcohol withdrawal syndrome. Most studies of these tools were not fully validated, limiting their generalizability.

Pharmaceutical policies: effects of restrictions on reimbursement.

BACKGROUND: Public policy makers and benefit plan managers need to restrain rising pharmaceutical drug costs while preserving access and optimizing health benefits. OBJECTIVES: To determine the effects of a pharmaceutical policy restricting the reimbursement of selected medications on drug use, health care utilization, health outcomes and costs (expenditures). SEARCH STRATEGY: We searched the 14 major bibliographic databases and websites (to January 2009). SELECTION CRITERIA: Included were studies of pharmaceutical policies that restrict coverage and reimbursement of selected drugs or drug classes, often using additional patient specific information related to health status or need. We included randomised controlled trials, non-randomised controlled trials, interrupted time series (ITS) analyses, repeated measures studies and controlled before-after studies set in large care systems or jurisdictions. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study limitations. Quantitative re-analysis of time series data was undertaken for studies with sufficient data. MAIN RESULTS: We included 29 ITS analyses (12 were controlled) investigating policies targeting 11 drug classes for restriction. Participants were most often senior citizens or low income adult populations, or both, in publically subsidized or administered pharmaceutical benefit plans. Impact of policies varied by drug class and whether restrictions were implemented or relaxed. When policies targeted gastric-acid suppressant and non-steroidal anti-inflammatory drug classes, decreased drug use and substantial savings on drugs occurred immediately and for up to two years afterwards, with no increase in the use of other health services (6 studies). Targeting second generation antipsychotic drugs increased treatment discontinuity and the use of other health services without reducing overall drug expenditures (2 studies). Relaxing restrictions for reimbursement of antihypertensives and statins increased appropriate use and decreased overall drug expenditures. Two studies which measured health outcomes directly were inconclusive. AUTHORS' CONCLUSIONS: Implementing restrictions to coverage and reimbursement of selected medications can decrease third-party drug spending without increasing the use of other health services (6 studies). Relaxing reimbursement rules for drugs used for secondary prevention can also remove barriers to access. Policy design, however, needs to be based on research quantifying the harm and benefit profiles of target and alternative drugs to avoid unwanted health system and health effects. Health impact evaluation should be conducted where drugs are not interchangeable. Impacts on health equity, relating to the fair and just distribution of health benefits in society (sustainable access to publically financed drug benefits for seniors and low income populations, for example), also require explicit measurement.

Information system support as a critical success factor for chronic disease management: Necessary but not sufficient.

UNLABELLED: Improvement of chronic disease management in primary care entails monitoring indicators of quality over time and across patients and practices. Informatics tools are needed, yet implementing them remains challenging. OBJECTIVE: To identify critical success factors enabling the translation of clinical and operational knowledge about effective and efficient chronic care management into primary care practice. DESIGN: A prospective case study of positive deviants using key informant interviews, process observation, and document review. SETTING: A chronic disease management (CDM) collaborative of primary care physicians with documented improvement in adherence to clinical practice guidelines using a web-based patient registry system with CDM guideline-based flow sheet. PARTICIPANTS: Thirty community-based physician participants using predominantly paper records, plus a project management team including the physician lead, project manager, evaluator and support team. ANALYSIS: A critical success factor (CSF) analysis of necessary and sufficient pathways to the translation of knowledge into clinical practice. RESULTS: A web-based CDM 'toolkit' was found to be a direct CSF that allowed this group of physicians to improve their practice by tracking patient care processes using evidence-based clinical practice guideline-based flow sheets. Moreover, the information and communication technology 'factor' was sufficient for success only as part of a set of seven direct CSF components including: health delivery system enhancements, organizational partnerships, funding mechanisms, project management, practice models, and formal knowledge translation practices. Indirect factors that orchestrated success through the direct factor components were also identified. A central insight of this analysis is that a comprehensive quality improvement model was the CSF that drew this set of factors into a functional framework for successful knowledge translation. CONCLUSIONS: In complex primary care settings environment where physicians have low adoption rates of electronic tools to support the care of patients with chronic conditions, successful implementation may require a set of interrelated system and technology factors.

Improving population health or the population itself? Health technology assessment and our genetic future.

The province of British Columbia (BC), Canada is developing its first population-wide prenatal genetic screening program, known as triple-marker screening (TMS). TMS, initiated with a simple blood test, is most commonly used to screen for fetuses with the chromosomal abnormality known as Down syndrome or neural tube disorders. Women testing TMS-positive are offered diagnostic amniocentesis and, if the diagnosis is confirmed, selective second-trimester abortion. The project described in this study was initiated to address the broad range of issues arising from this testing technology and provides an example of the new type of health technology assessment (HTA) contribution emerging (and likely to become increasing necessary) in health policy development. With the advent of prenatal genetic screening programs, would-be parents gain the promise of identifying target conditions and, hence, the option of selective abortion of affected fetuses. There is considerable awareness that these developments pose challenges in every dimension (ethical, political, economic, and clinical) of the health-care environment. In the effort to construct an appropriate prenatal screening policy, therefore, administrators have understandably sought guidance from within the field of HTA. The report authors concluded that, within the restricted path open to it, the role of government is relatively clear. It has the responsibility to maintain equal access to prenatal testing, as to any other health service. It should also require maintenance of medical standards and evaluation of program performance. At the same time, policy-makers need actively to support those individuals born with disabilities and their families.

Systematic review of the role of gender as a health determinant of hospitalization for depression.

OBJECTIVES: To conduct a systematic review of selected health determinants, including gender, and their impact on hospitalization rates for depression. Depression includes both depressive and bipolar disorders. Selected health determinants were gender, age, sex, family structure, education, and socioeconomic status. METHODS: Systematic search of conventional and fugitive literature sources. All reports of primary data, systematic reviews, and meta-analysis of primary data were included if they focused on hospitalization for depression and reported data by one or more of the selected health determinants. Two researchers independently evaluated each citation for inclusion and extracted data from the included studies. RESULTS: There is an important underreporting of health determinants data in studies of hospitalization for depression. No studies examined the role of gender. Age and sex were reported in 83 percent and 80 percent of the 110 included studies. Women showed a higher rate of hospitalization for depression than men (p < .05). Age and diagnosis had different effects in men and women. Adult women were significantly more likely than men to report a depressive disorder, whereas men were more likely to report a bipolar disorder (p < .05). Little can be concluded on the other health determinants. CONCLUSIONS: The importance of reporting hospitalization data and conducting hospital utilization analysis by sex and health determinants, including gender, must be emphasized.

Informing, advising, or persuading? An assessment of bone mineral density testing information from consumer health websites.

UNLABELLED: Greater access to web-based information on health-care interventions might result in greater participation by patients in care and self-care decisions, but only improve health outcomes if the indicated actions produce the intended benefits. Unbiased research on benefits and harms of health information can provide a basis for evidence-based patient information systems. OBJECTIVES: To evaluate the quality of the information content on bone-mineral density (BMD) testing posted on consumer health websites (CHWS). METHODS: Five popular engines (Yahoo, MSN, AOL, Lycos, and Go.com) were used to search for patient information on bone densitometry. The fifteen websites that supplied relevant content and were identified by three of the five search engines were selected in order of popularity of the search engine and primacy of placement. Six BMD reports from health technology assessment (HTA) organizations were used as a standard of scientific quality. These were identified from the HTA Database at York University United Kingdom and published between 1996 and 2001. Content was extracted from both document types, and these sets were compared independently by two reviewers. RESULTS: The majority of CHWS identified by popular search engines do not disclose the limited capacity of BMD to discriminate between low-risk individuals and those who will suffer future fractures. CHWS generally present BMD testing as quick, painless, noninvasive, and as being recommended, based on risk factors that are widespread among the general public. BMD testing information is prominently paired on CHWS sites with information on osteoporosis, with an emphasis on "silent disease" and the devastating consequences of advanced disease. Sponsors of CHWS sites are frequently either providers of BMD testing or companion drugs, and consequently in a position of conflict of interest with regard to decisions to undergo BMD testing. HTA organizations have no documented conflict of interest, nor do they invoke emotional arguments. Their approach is to emphasize the effects of testing on populations, on the basis of referenced research findings. CONCLUSIONS: Content analysis demonstrates the omissions and divergence of information on BMD testing available to consumers on the Internet, as compared with HTA reports. The content of HTA reports has undergone rigorous systematic and peer review; therefore, their findings may be useful to consumers. This information is not generally accessible to patients using the most popular Internet search engines. Inaccurate and incomplete information may cause harm by deflecting patients from optimal decisions.

Introducing a technology-enabled problem-based learning approach into a health informatics curriculum.

PURPOSE: To investigate the effect on learner satisfaction of introducing a technology-enabled problem-based learning (PBL) approach into a health informatics curriculum. Course redesign was undertaken to prepare students for three 4-month work terms and a rapidly changing professional environment upon graduation. METHODS: Twenty-six Canadian undergraduate students of a redesigned course in biomedical fundamentals completed a midterm questionnaire in 2002. Eight of these students participated in a focus group. RESULTS: Students agreed that seven of nine functions provided by the web-based online course management system enhanced their learning: private email (92.3%), calendaring (88.5%), course notes (88.5%), discussion forums (84.5%), online grades (84.5%) assignment descriptions (80.8%) and online quizzes (80.8%). Although students agreed that two PBL activities enhanced learning (learning to present information) (84.5%) and learning to identify information needed (73.1%), the majority of students (69.2%) expressed a preference for the traditional lecture approach over the PBL approach. Students reported feeling uncertain of what was required of them and related anxiety accounted for most of the negative feedback. CONCLUSION: These findings give us clear goals for improvement in the course beginning with a comprehensive, carefully guided introduction to the processes of PBL. The positive trends are encouraging for the use of web-enabled courseware and for the further development of the PBL approach.

Beyond Medline: reducing bias through extended systematic review search.

OBJECTIVE: To evaluate the sensitivity and precision of various extended search methods in identifying randomized controlled trials (RCTs) for systematic reviews. METHOD: Prospective analysis of extended search methods (specialized databases or trial registries, reference lists, hand-searching, personal communication, and Internet) used in two systematic reviews of RCTs. The gold standard was the total number of RCTs identified by major databases (MEDLINE, EMBASE, etc.) and extended search strategies combined. Sensitivity was the proportion of all known RCTs identified by any extended search method. Precision reflected the proportion of all items uncovered by any extended search method that actually were RCTs. RESULTS: The extended search identified 94 additional RCTs for the systematic reviews beyond those identified with the major databases. Specialized databases and trial registries had the highest sensitivity and precision for the lipid-lowering project (13.6% and 52.7%, respectively; p < .05) followed by scanning of reference lists (7.2% sensitivity and 41.9% precision; p <.05). Hand-searching was more effective than personal communication and Internet searching (1.7% sensitivity and 12.2% precision; p < .05). The acupuncture project had slightly different results, with the specialized databases and trial registries tied with the review of reference lists for highest sensitivity (14.2%). The precision followed the same trend as the lipid-lowering project (17.6% specialized databases; 8.3% reference lists; p < .05). A post-hoc analysis showed that 75 of the 94 RCTs were indexed in the major databases but missed by the major database search. CONCLUSIONS: Extended searching identified additional RCTs for the systematic reviews beyond those found in major databases. Specialized databases and trial registries were most effective. An important number of RCTs were missed by the major database search. Timing and accuracy of indexing may explain this finding. The definitive measure, whether there is an association between the method used to uncover RCTs, the quality of the items uncovered and their impact on systematic review results, is yet to be determined.

Decision support for governing boards of integrated delivery networks: explicating versus eliciting knowledge.

The everyday knowledge work of members of one governing health board was mapped using institutional ethnography. Our objective was to identify opportunities to improve the effective use of information and communication technologies for decision support. The dynamic interplay of work processes, professional discourse, institutional complexes and dominant ideology was explicated, that is, made visible in relation to the actualities of work practices.

Beyond effectiveness: the evaluation of information systems using A Comprehensive Health Technology Assessment Framework.

A Comprehensive Health Technology Assessment Framework is presented as a conceptual tool for decision-making about health technologies, including information technologies. The aim of the model is to provide an empirical, evidence-based foundation for health technology decisions. The major framework dimensions are (1) population at risk, (2) population impact, (3) economic concerns, (4) social context (including ethical, legal, and political concerns), and (5) technology assessment information. This multi-disciplinary approach provides guidelines on use of appropriate information in aligning 'stakeholder wants' and 'population needs'.