Real-world evaluation of osteoporotic fractures using the Japan Medical Data Vision database.

In Japanese patients who experienced an osteoporotic fracture, 10.8% and 18.6% had a subsequent fracture within 1 and 2 years of follow-up, respectively. Although the burden of hip and vertebral fractures has been reported widely, we found that patients with non-hip non-vertebral (NHNV) fractures had a 26% higher risk of subsequent fracture than patients with hip fractures; therefore, NHNV fractures should also be considered an important risk factor for subsequent fracture. INTRODUCTION: To investigate imminent risk and odds of subsequent osteoporotic fractures and associated risk factors in patients who experienced an initial osteoporotic fracture. METHODS: Patients aged ≥ 50 years with ≥ 1 osteoporotic fracture were analyzed from Japan's Medical Data Vision (MDV) database of claims from acute-care hospitals (January 2012-January 2017). Multivariable models were constructed to explore the impact of key comorbidities and medications on the subsequent fracture risk: Cox proportional hazards model for time to subsequent fracture and logistic regression models for odds of subsequent fracture within 1 and 2 years from index fracture. RESULTS: In total, 32,926 patients were eligible with a median follow-up duration of 12.3 months. The percentage of patients experiencing subsequent fractures was 14.1% across the study duration, and 10.8% and 18.6% in patients with 1 and 2 years of follow-up, respectively. In the Cox proportional hazards model, patients with vertebral or NHNV index fractures had a higher subsequent fracture risk than patients with a hip index fracture (adjusted hazard ratio [aHR] 1.11 and 1.26, respectively); subsequent fracture risk was lower in males than females (aHR 0.89). Patients with baseline claims for tranquilizers and glucocorticoids had a higher subsequent fracture risk than those without (aHR 1.14 and 1.08, respectively). Additionally, baseline claims for anti-Parkinson's medications, alcoholism, and stage 4/5 chronic kidney disease were significantly associated with higher odds of subsequent fracture in the logistic regression models. CONCLUSION: Several clinical and demographic factors were associated with a higher risk and odds of subsequent fracture. This may help to identify patients who should be prioritized for osteoporosis treatment.

Residual Disease Associated with Suboptimal Treatment Response in Patients with Psoriatic Arthritis: A Systematic Review of Real-World Evidence.

OBJECTIVE: This systematic literature review aimed to identify and summarise real-world observational studies reporting the type, prevalence and/or severity of residual symptoms and disease in adults with psoriatic arthritis (PsA) who have received treatment and been assessed against remission or low disease activity targets. METHODS: Patients had received treatment and been assessed with treat-to-target metrics, including minimal disease activity (MDA), Disease Activity Index in PsA (DAPSA) and others. MEDLINE, Embase® and the Cochrane Database of Systematic Reviews (CDSR) were searched using search terms for PsA, treatment targets and observational studies. Screening of search results was completed by two independent reviewers; studies were included if they reported relevant residual disease outcomes in adults with PsA who had received one or more pharmacological treatments for PsA in a real-world setting. Non-observational studies were excluded. Information from included studies was extracted into a prespecified grid by a single reviewer and checked by a second reviewer. RESULTS: Database searching yielded 2328 articles, of which 42 publications (27 unique studies) were included in this systematic literature review. Twenty-three studies reported outcomes for MDA-assessed patients, and 14 studies reported outcomes for DAPSA-assessed patients. Physician- and patient-reported residual disease was less frequent and/or severe in patients reaching targets, but often not absent, including when patients achieved very low disease activity (VLDA) or remission. For example, studies reported that 0-8% patients in remission according to DAPSA (or clinical DAPSA) had > 1 tender joint, 25-39% had Psoriasis Area and Severity Index (PASI) score > 1 and 0-10% had patient-reported pain > 15. Residual disease was usually less frequent and/or severe among patients achieving MDA-assessed targets versus DAPSA--assessed targets, especially for skin outcomes. CONCLUSION: The findings demonstrate a need for further optimisation of care for patients with PsA.

Antipsychotic-Related Stigma and the Impact on Treatment Choices: A Systematic Review and Framework Synthesis.

BACKGROUND: Antipsychotics are a class of medications primarily used to treat individuals with psychotic disorders. They have also been indicated for patients with other psychiatric conditions, such as post-traumatic stress disorder and major depressive disorder. Non-adherence is prominent amongst individuals prescribed antipsychotics, with medication-related self-stigma and social stigma identified as major factors. No previous reviews have focused on stigma associated specifically with antipsychotic medication. This systematic literature review aimed to synthesise evidence on the prevalence of stigmatising attitudes and behaviours related to antipsychotic treatment and understand their impact on antipsychotic treatment initiation and continuation. METHODS: Two independent reviewers screened studies from databases, congress proceedings, ClinicalTrials.gov, and PsychU.org; relevant studies reported quantitative or qualitative data on antipsychotic-related stigma in adults with psychotic disorders, mood disorders, borderline personality disorder or anxiety disorders, or healthcare providers or caregivers of these patients, and any impact on treatment. Framework synthesis facilitated extraction and synthesis of relevant information; quantitative and qualitative data were coded and indexed against a pre-specified thematic framework by two independent reviewers. RESULTS: Forty-five articles reporting on 40 unique studies were included; 22 reported quantitative data, 16 reported qualitative data, and two reported quantitative and qualitative data relating to antipsychotic-related stigma. Framework synthesis identified four themes: 1) impact of antipsychotic treatment on a) social stigma or b) self-stigma; 2) impact of side effects of antipsychotic treatment on a) social stigma or b) self-stigma; 3) impact of route of administration of antipsychotic treatment on stigma; 4) impact of stigma on the use of antipsychotics. CONCLUSION: This systematic literature review found that antipsychotic-related social and self-stigma is a factor in non-adherence to antipsychotics. Further research should examine stigma in a wider range of patients and the extent to which clinicians' treatment decisions are impacted by the potential stigma associated with antipsychotic medications.

Comorbidities and healthcare costs and resource use of patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in the Japan medical data vision database.

BACKGROUND: This study examined demographics, comorbidities and healthcare resource use (HCRU) and costs among Japanese patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). METHODS: We conducted a repeated cross-sectional analysis of the Medical Data Vision (MDV) claims database, from January 2011 to March 2018. Demographics were described at index date and by calendar year; a "NASH" subpopulation included patients with ≥ 1 claim for NASH at any time. Prevalence of pre-specified comorbidities of interest and data-emergent top comorbidities were estimated. All-cause HCRU and costs were quantified by calendar year. Outcomes were compared between 2011 and 2017 using partially overlapping t tests. RESULTS: 58,958 patients (mean age 61.6 years; 55.5% male) were included. 1139 patients (2%) were in the NASH subpopulation. At baseline, comorbid cardiovascular disease (69.4%), diabetes (62.1%) and hyperlipidaemia (54.4%) were most prevalent; comorbidity prevalence increased with age. Mean outpatient visits decreased from 9.36 per patient in 2011 to 7.80 in 2017; mean inpatient admissions increased (both p < 0.001 for 2011 vs 2017). Mean total all-cause healthcare costs ranged from ¥322,206 to ¥340,399 per patient per year between 2011 and 2017. Although total all-cause healthcare costs did not change significantly (p = 0.552), cost burden shifted from the outpatient to inpatient setting between 2011 and 2017. All-cause healthcare resource use/costs were generally higher for the NASH subgroup compared with the overall population. CONCLUSIONS: There is a high burden of disease among Japanese NAFLD/NASH patients, including a high prevalence of comorbidities which generally increase with age. Accordingly, substantial all-cause HCRU and costs were incurred.

Carcinoid Heart Disease: Prognostic Value of 5-Hydroxyindoleacetic Acid Levels and Impact on Survival: A Systematic Literature Review.

BACKGROUND: Carcinoid heart disease (CHD) can develop in patients with carcinoid syndrome (CS), itself caused by overproduction of hormones and other products from some neuroendocrine tumours. The most common hormone is serotonin, detected as high 5-hydroxyindoleacetic acid (5-HIAA). This systematic literature review summarises current literature on the impact of CHD on survival, and the relationship between 5-HIAA levels and CHD development, progression, and mortality. METHODS: MEDLINE, Embase, Cochrane databases, and grey literature were searched using terms for CHD, 5-HIAA, disease progression, and mortality/survival. Eligible articles were non-interventional and included patients with CS and predefined CHD and 5-HIAA outcomes. RESULTS: Publications reporting on 31 studies were included. The number and disease states of patients varied between studies. Estimates of CHD prevalence and incidence among patients with a diagnosis/symptoms indicative of CS were 3-65% and 3-42%, respectively. Most studies evaluating survival found significantly higher mortality rates among patients with versus without CHD. Patients with CHD reportedly had higher 5-HIAA levels; median urinary levels in patients with versus without CHD were 266-1,381 versus 67.5-575 µmol/24 h. Higher 5-HIAA levels were also found to correlate with disease progression (median progression/worsening-associated levels: 791-2,247 µmol/24 h) and increased odds of death (7% with every 100 nmol/L increase). CONCLUSIONS: Despite the heterogeneity of studies, the data indicate that CHD reduces survival, and higher 5-HIAA levels are associated with CHD development, disease progression, and increased risk of mortality; 5-HIAA levels should be carefully managed in these patients.

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review.

BACKGROUND: Approximately 20% of patients with neuroendocrine tumours (NETs) develop carcinoid syndrome (CS), characterised by flushing and diarrhoea. Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion. Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs (GEP-NETs), other causes to consider include pancreatic enzyme insufficiency (PEI), bile acid malabsorption and small intestinal bacterial overgrowth. If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea, these treatments may be ineffective against the diarrhoea, risking detrimental effects to patient quality of life. AIM: To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs. METHODS: Electronic databases (MEDLINE, Embase and the Cochrane Library) were searched from inception to September 12, 2018 using terms for NETs and diarrhoea. Congresses, systematic literature review bibliographies and included articles were also hand-searched. Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported. Studies were screened by two independent reviewers at abstract and full-text stages. Framework synthesis was adapted to synthesise quantitative and qualitative data. The definition of qualitative data was expanded to include all textual data in any section of relevant publications. RESULTS: Forty-seven publications (44 studies) were included, comprising a variety of publication types, including observational studies, reviews, guidelines, case reports, interventional studies, and opinion pieces. Most reported on PEI on/after treatment with somatostatin analogs; 9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI. Where reported, 14.3%-50.7% of patients received pancreatic enzyme replacement therapy. Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption (80%), small intestinal bacterial overgrowth (23.6%-62%), colitis (20%) and infection (7.1%). Diagnostic approaches included faecal elastase, breath tests, tauroselcholic (selenium-75) acid (SeHCAT) scan and stool culture, although evidence on the effectiveness or diagnostic accuracy of these approaches was limited. Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation. From the identified evidence, if diarrhoea is assumed to be CS diarrhoea, consequences include uncontrolled diarrhoea, malnutrition, and perceived ineffectiveness of CS treatment. Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team, including gastroenterologists. CONCLUSION: Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use. This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches, to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.

Velamentous cord insertion: results from a rapid review of incidence, risk factors, adverse outcomes and screening.

BACKGROUND: Velamentous cord insertion (VCI) is an umbilical cord attachment to the membranes surrounding the placenta instead of the central mass. VCI is strongly associated with vasa praevia (VP), where umbilical vessels lie in close proximity to the internal cervical os. VP leaves the vessels vulnerable to rupture, which can lead to fatal fetal exsanguination. Screening for VP using second-trimester transabdominal sonography (TAS) to detect VCI has been proposed. We conducted a rapid review investigating the quality, quantity and direction of evidence available on the epidemiology, screening test accuracy and post-screening management pathways for VCI. METHODS: MEDLINE, Embase and the Cochrane Library were searched on 5 July 2016 and again on 11 October 2019, using general search terms for VP and VCI. Only peer-reviewed articles reporting on the epidemiology of VCI, the accuracy of the screening test and/or downstream management pathways for VCI pregnancies were included. Quality and risk of bias of each included study were assessed using pre-specified tools. RESULTS: Forty-one relevant publications were identified; all but one were based on non-UK pregnancy cohorts, and most included relatively few VCI cases. The estimated incidence of VCI was 0.4-11% in singleton pregnancies, with higher incidence in twin pregnancies (1.6-40%). VCI incidence was also increased among pregnancies with one or more other risk factors, including in vitro fertilisation pregnancies or nulliparity. VCI incidence among women without any known risk factors was unclear. VCI was associated with adverse perinatal outcomes, most notably pre-term birth and emergency caesarean section in singleton pregnancies, and perinatal mortality in twins; however, associations varied across studies and the increased risk was typically low or moderate compared with pregnancies without VCI. In studies on limited numbers of cases, screening for VCI using TAS had good overall accuracy, driven by high specificity. No studies on post-screening management of VCI were identified. CONCLUSIONS: Literature on VCI epidemiology and outcomes is limited and low-quality. The accuracy of second-trimester TAS and the benefits and harms of screening cannot be determined without prospective studies in large cohorts. Modelling studies may indicate the feasibility and value of studying the epidemiology of VCI and the potential impact of detecting VCI as part of a population screening programme for VP.

Case report: a rapid review approach used by the UK National Screening Committee to inform recommendations on general population screening for vasa praevia.

BACKGROUND: The UK National Screening Committee (UK NSC) reviews evidence about existing or potential population screening programmes using rapid review products called evidence summaries. We provide a case report as an example of how rapid reviews are developed within the UK NSC's process, consider how the quality of rapid reviews should be assessed and ask whether the rapid review was an appropriate tool to inform the UK NSC's decision-making process. METHODS: We present the rapid review approach taken by the commissioner and the reviewers to develop an evidence summary for vasa praevia (VP), which the UK NSC reappraised as part of its 3-yearly cycle for conditions where screening is currently not recommended. We apply the AMSTAR 2 quality appraisal checklist for systematic reviews, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and a published checklist of items to consider with a rapid review approach. As UK NSC evidence summaries do not include meta-analyses, any related AMSTAR 2 or PRISMA checklist items were considered inapplicable. RESULTS: The evidence summary was available within the required timelines and highlighted little change from the previous review in terms of key evidence gaps relating to the epidemiology of VP, the screening test and the management pathway. Therefore, the UK NSC concluded that there was insufficient evidence to support a change in its previous recommendation against screening. The evidence summary scored moderately against the applicable AMSTAR 2 and PRISMA checklist items. Against the published checklist of items to consider with a rapid review approach, the evidence summary performed well. CONCLUSIONS: In this case report, the use of a rapid review as part of the UK NSC's process enabled a pragmatic approach to assessing the overall volume, quality and direction of literature on key questions relating to the viability of a population screening programme for VP. Based on our assessments of this single evidence summary, systematic review quality appraisal tools may undervalue rapid reviews. The validity of the methods used in this case report, as well as the wider generalisability of our insights relating to rapid review practice, reporting and quality assessment, requires analysis of a larger sample of rapid reviews.

Evidence in support of hyperkalaemia management strategies: A systematic literature review.

BACKGROUND: Hyperkalaemia is a potentially life-threatening condition that can be managed with pharmacological and non-pharmacological approaches. With the recent development of new hyperkalaemia treatments, new information on safe and effective management of hyperkalaemia has emerged. OBJECTIVES: This systematic literature review (SLR) aimed to identify all relevant comparative and non-comparative clinical data on management of hyperkalaemia in adults. Our secondary aim was to assess the feasibility of quantitatively comparing randomised controlled trial (RCT) data on the novel treatment sodium zirconium cyclosilicate (ZS) and established pharmacological treatments for the non-emergency management of hyperkalaemia, such as the cation-exchangers sodium/calcium polystyrene sulphonate (SPS/CPS). METHODS: MEDLINE, Embase and the Cochrane Library were searched on 3rd April 2017, with additional hand-searches of key congresses and previous SLRs. Articles were screened by two independent reviewers. Eligible records reported interventional or observational studies of pharmacological or non-pharmacological management of hyperkalaemia in adults. RESULTS: Database searches identified 2,073 unique records. Two hundred and one publications were included, reporting 30 RCTs, 29 interventional non-RCTs and 43 observational studies. Interventions investigated in RCTs included ZS (3), SPS/CPS (3), patiromer (4) and combinations of temporising agents (6 RCTs). A robust and meaningful indirect treatment comparison between ZS and long-established cation-binding agents (SPS/CPS) was infeasible because of heterogeneity between studies (including time points and dosing) and small sample size in SPS/CPS studies. CONCLUSIONS: Despite hyperkalaemia being associated with several chronic diseases, there is a paucity of high-quality randomised evidence on long-established treatment options (SPS and CPS) and a limited evidence base for hyperkalaemia management with these agents.

Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. METHODS: MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. FINDINGS: We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). INTERPRETATION: AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.