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Objectives: To evaluate and compare medication adherence and persistence for patients newly initiating single-inhaler triple therapy (SITT) and multiple-inhaler triple therapy (MITT) for chronic obstructive pulmonary disease (COPD) in Japan., Design: Retrospective, new-user, active comparator, observational cohort study using inverse probability of treatment weighting., Setting: Health insurance claims data from the Medical Data Vision Co., Ltd, hospital claims database., Participants: Adults diagnosed with COPD at age ≥40 years newly initiating MITT or SITT (fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or formoterol fumarate/budesonide/glycopyrronium) from 1 September 2019 to 31 July 2021., Primary and Secondary Outcome Measures: The primary outcome was medication adherence compared between patients using SITT and MITT, assessed by the proportion of days covered ≥80%. Secondary outcomes included medication persistence (time from index treatment initiation to discontinuation) compared between patients using SITT and MITT and medication adherence compared before and after the switch in a subgroup of patients switching from MITT to SITT., Results: We included 2575 MITT and 2962 SITT users with similar baseline characteristics following weighting. The proportion of adherent patients was significantly greater for SITT versus MITT users at 6 months (19.7% vs 10.2%, p<0.0001), 12 months (6.0% vs 3.8%, p=0.0009) and 18 months (3.8% vs 1.4%, p<0.0001) post-index. Median persistence was also significantly higher for SITT versus MITT users (2.0 vs 1.0 months, p<0.001). Comparing specific SITT versus MITT, the proportion of adherent patients at each time point and median persistence was greater for FF/UMEC/VI. In patients switching from MITT to SITT (n=688), the proportion of adherent patients increased postswitch at the class level and for FF/UMEC/VI specifically., Conclusions: Patients with COPD in Japan who were newly initiating SITT had greater medication adherence and persistence compared with those on MITT up to 18 months following initiation., Competing Interests: Competing interests: SJ, AI, AM, CC, MY, KH and KJR are employees of and/or hold stocks/shares in GSK. AI is also an unpaid part-time professor at McMaster University, Hamilton, ON, Canada. RW, LC, OM, RS and TJ are employees of Adelphi Real World; Adelphi Real World received funds from GSK to complete the study. AC and TI were employees of GSK at the time of the study. Current affiliation details for AM and MY: Real World Data Analytics, Japan Development, GSK, Tokyo, Japan., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England., Methods: Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics data sets. The study included patients <18 years old with varicella diagnosed during 2014-2018 and 3-month follow-up available. We determined varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3 months after diagnosis., Results: We identified 114 578 children with a primary varicella diagnosis. Of these, 7.7% (n = 8814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1% [n = 3271]). In all, 25.9% (n = 29 706 of 114 578) were prescribed antibiotics. A higher proportion of patients with complications than without complications were prescribed antibiotics (64.3% [n = 5668 of 8814] vs 22.7% [n = 24 038 of 105 764]). Mean annualized varicella-related costs were £2 231 481 for the study cohort. Overall, antibiotic prescriptions cost approximately £262 007., Conclusions: This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs., Competing Interests: Potential conflicts of interest. S. A. K. and M. P. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. V. B. was an employee of Adelphi Real World at the time of study design and initiation and is currently employed by and owns stocks/shares in Bayer. C. S. C. was an employee of Adelphi Real World during study completion. S. B. D. has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD, and Sanofi, with fees paid to St George's, University of London. S. B. D. is a member of the UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) RSV subcommittee and a member of the Medicines and Healthcare products Regulatory Agency's (MHRA’s) Paediatric Medicine Expert Advisory Group (PMEAG), but the reviews expressed herein do not necessarily represent those of DHSC, JCVI, MHRA, or PMEAG. A. P., O. M., and T. H. are employees of Adelphi Real World; the company received funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA to conduct the study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Evaluate real-world epidemiologic trends and treatment patterns in newly diagnosed patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in Japan., Methods: This retrospective analysis included adults with newly diagnosed la/mUC in Japan (January 2015-December 2019) from a nationwide-linked electronic medical record Diagnostic Procedure Combination claims dataset. Outcomes included epidemiologic trends (incidence and prevalence), baseline demographics, clinical characteristics, and treatment patterns in newly diagnosed patients with la/mUC before (2015-2017) and after (2018-2019) approval of pembrolizumab in Japan., Results: Of 975 patients included, 76.4% were men; 71.6% were aged 70 years or older. Most cases (70.5%) were of the bladder. Between 2015 and 2019, the annual age-adjusted incidence increased from 6.8 to 12.4 per 100 000; the annual age-adjusted period prevalence increased from 13.0 to 25.2 per 100 000; and 307 (31.5%) and 668 (68.5%) patients were diagnosed from 2015 to 2017 and 2018 to 2019, respectively. Overall, 731 (75%) patients received systemic anticancer therapy; all received 1 line and 50.2% received 2 lines of therapy; 78.3% of patients received gemcitabine plus platinum-based therapy and 2.2% received pembrolizumab as first-line treatment. First-line treatment rates increased from 69.4% to 77.5% after pembrolizumab approval. Of 367 patients who received second-line treatment, 22.3% received gemcitabine plus platinum-based therapy; 14.7% received pembrolizumab., Conclusions: In the Japanese regions considered, incidence and prevalence of newly diagnosed la/mUC increased over time and first-line treatment with pembrolizumab increased after approval., (© 2024 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Background: Triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite dual therapy. The optimal timing of triple therapy following an exacerbation of COPD is unknown. The outcomes of prompt (≤ 30 days) vs. delayed (31-180 days) initiation of single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) following an exacerbation of COPD were examined., Methods: This was a retrospective cohort study of linked English primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Patients aged ≥ 35 years with COPD were indexed on the first and/or earliest date of exacerbation between November 15, 2017 and March 31, 2019 with subsequent FF/UMEC/VI initiation within 180 days. Patients were required to be continuously registered with a general practitioner for ≥ 12 months prior to and following index. Subsequent exacerbations, direct medical costs, and hospital readmissions were compared between prompt and delayed initiators. Inverse probability of treatment weighting was used to adjust for measured confounders between cohorts., Results: Overall, 1599 patients were included (prompt: 393, delayed: 1206). After weighting, prompt initiators had numerically lower moderate/severe exacerbations compared with delayed initiators (rate ratio: 0.87, 95% confidence interval [CI]: 0.76-1.01, p = 0.0587). Both all-cause and COPD-related 30-day hospital readmissions were significantly lower among patients with prompt initiation compared with delayed initiators (all-cause: 23.6% vs. 34.6%, odds ratio [95% CI]: 0.58 [0.36-0.95], p = 0.0293; COPD-related: 20.3% vs. 30.6%, odds ratio [95% CI]: 0.58 [0.35-0.96], p = 0.0347). Prompt initiators also had numerically lower all-cause total costs and significantly lower COPD-related costs per-person-per year compared with delayed initiators (COPD-related: £742 vs. £801, p = 0.0016)., Conclusion: Prompt initiation of FF/UMEC/VI following a moderate/severe exacerbation was associated with fewer subsequent exacerbations, fewer hospital readmissions, and lower COPD-related medical costs compared with delayed initiation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Triple therapy comprising a long-acting muscarinic antagonist, long-acting β 2 -agonist and inhaled corticosteroid is recommended for patients with chronic obstructive pulmonary disease (COPD) who continue to experience frequent exacerbations or symptoms whilst receiving dual therapy. Adherence and persistence to multiple-inhaler triple therapy (MITT) is known to be poor. This study assessed comparative adherence to single-inhaler triple therapy (SITT) versus MITT in a real-world setting in England., Patients and Methods: This was a retrospective cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics [HES] Admitted Patient Care) data to identify patients with COPD who were newly initiated on SITT or MITT between November 2017 and June 2019. Eligible patients were aged ≥35 years and had a forced expiratory volume in 1 second/forced vital capacity <0.7, linkage to HES and continuous registration with a general practitioner for 12 months pre- and 6 months post-initiation. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Adherence was measured using the proportion of days covered by days' supply of SITT or MITT prescriptions. Persistence was measured with a gap of >30 days between the end of a prescription and the following refill used to determine non-persistence., Results: Overall, 4080 SITT and 6579 MITT users comprised the study cohort. After weighting, the baseline characteristics between the cohorts were comparable (absolute standardized mean difference <10%). SITT users had significantly higher adherence than MITT users at 6, 12, and 18 months post-initiation (p<0.001 for all comparisons). Median persistence was higher among SITT users than MITT users (5.09 months vs 0.99 months)., Conclusion: Patients with COPD in England initiating SITT had significantly better adherence and persistence compared with MITT initiators. These improvements continued at least 18 months following treatment initiation., Competing Interests: Kieran J Rothnie, Alexandrosz Czira, Chris Compton, Kirill Nikitin, Raj Sharma, and Afisi S Ismaila are employees of and/or hold stocks/shares in GSK. Neil Snowise is a previous employee of GSK and holds GSK stocks/shares. Victoria Banks, Robert Wood, Theo Tritton, Olivia Massey, and Rosie Wild are employees of Adelphi Real World. Adelphi Real World received funding from GSK to conduct the study. David MG Halpin reports personal fees from AstraZeneca, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Aerogen, Chiesi, CSL Behring, and GSK, personal fees and non-financial support from Novartis, and personal fees from Pfizer and Sanofi. Claus F Vogelmeier has received research grants from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, and Grifols, and has given presentations at symposia and/or served on scientific advisory boards sponsored by Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, Grifols, Menarini, Novartis, and Nuvaira. The authors report no other conflicts of interest in this work., (© 2022 Halpin et al.)

Objective: To identify discrete clusters of systemic lupus erythematosus (SLE) patients based on symptoms and investigate differences across clusters., Methods: Data were collected in the US and 5 European countries via the Adelphi Real World Lupus Disease Specific Programme, a cross-sectional survey. Rheumatologists provided data for 5 consecutively consulting adult patients with SLE, who were invited to participate. Identified SLE symptoms were reduced to factors based on commonly concurrent symptoms, using principal-component factor analysis. Factors were used as covariates in a latent-class cluster analysis to identify discrete patient clusters. Patient-reported outcomes and physician-reported data were compared across clusters., Results: Among 1,376 patients, 87% were female and 74% were White. We identified 4 patient clusters (very mild, mild, moderate, and severe) based on 39 signs/symptoms. Physician-reported symptom burden, organ involvement, disease activity, and the number of flares increased with increasing cluster severity (P < 0.0001). Patient-reported impact (health status, fatigue, work productivity impairment, anxiety/depression, and emotional impact) increased with increasing cluster severity (P < 0.0001). Glucocorticoid and immunosuppressant use increased, and antimalarial use decreased, with increasing cluster severity. In all clusters, <20% of patients received biologics; >15% of patients not receiving biologics were considered eligible for treatment by their physician. The proportion of physicians and patients satisfied with treatment decreased with increasing cluster severity (P < 0.0001)., Conclusion: Our large, international, real-world survey of SLE patients and physicians demonstrated strong associations between increased impairment, organ involvement, and humanistic burden in SLE, highlighting an unmet need for effective treatment options in patients with high disease activity., (© 2020 American College of Rheumatology.)

Aims: To determine the proportion of UK patients with type 2 diabetes (T2D) who meet the cardiovascular (CV) or combined CV/core eligibility criteria used for the CV outcome trials (CVOTs) of UK-marketed glucagon-like peptide-1 receptor agonists (GLP-1RAs) showing CV benefit (dulaglutide in REWIND, liraglutide in LEADER and injectable semaglutide in SUSTAIN-6)., Materials and Methods: Adults with T2D on/before June 2018 were identified from the UK Clinical Practice Research Datalink GOLD primary care database and linked to Hospital Episode Statistics data (Protocol 19&#95;262). Patient CV and clinical data were evaluated against the CVOT eligibility criteria. Data were analysed descriptively., Results: The study cohort (N = 33 118 patients with T2D) had a mean (standard deviation) age of 66.0 (13.3) years and 56.6% were male. Almost two-thirds (64.5%) of the study cohort met the CV criteria for REWIND, versus 43.0% for both LEADER and SUSTAIN-6. The proportions of the study cohort who met the CVOT criteria of "established CV disease" and "CV risk factors only" for REWIND were 22.4% and 42.1%, respectively, versus 38.7% and 4.3%, respectively, for both LEADER and SUSTAIN-6. The proportions of patients satisfying both CV and core criteria were 44.4% for REWIND, 13.3% for LEADER and 13.5% for SUSTAIN-6. Study findings remained consistent when restricted to GLP-1RA users., Conclusions: REWIND captured a trial population more representative of the real-world T2D population in the United Kingdom than LEADER or SUSTAIN-6 with regard to both CV and combined CV/core eligibility criteria., (© 2021 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The IL-4 and IL-13 cytokine pathways play integral roles in stimulating IgE inflammation, with the IL-4 cytokine being a major cytokine in the etiology of thunderstorm asthma, atopic dermatitis, and allergic rhinitis. The increasing prevalence of thunderstorm asthma in the younger population and the lessening efficacy of corticosteroids and other anti-inflammatories has created a need for more effective pharmaceuticals. This review summarizes the IL-4 and IL-13 pathways while highlighting and discussing the current pathway inhibitors aimed at treating thunderstorm asthma and atopic dermatitis, as well as the potential efficacy of peptide therapeutics in this field.

The debilitating effects of muscle damage, either through ischemic injury or volumetric muscle loss (VML), can have significant impacts on patients, and yet there are few effective treatments. This challenge arises when function is degraded due to significant amounts of skeletal muscle loss, beyond the regenerative ability of endogenous repair mechanisms. Currently available surgical interventions for VML are quite invasive and cannot typically restore function adequately. In response to this, many new bioengineering studies implicate 3D bioprinting as a viable option. Bioprinting for VML repair includes three distinct phases: printing and seeding, growth and maturation, and implantation and application. Although this 3D bioprinting technology has existed for several decades, the advent of more advanced and novel printing techniques has brought us closer to clinical applications. Recent studies have overcome previous limitations in diffusion distance with novel microchannel construct architectures and improved myotubule alignment with highly biomimetic nanostructures. These structures may also enhance angiogenic and nervous ingrowth post-implantation, though further research to improve these parameters has been limited. Inclusion of neural cells has also shown to improve myoblast maturation and development of neuromuscular junctions, bringing us one step closer to functional, implantable skeletal muscle constructs. Given the current state of skeletal muscle 3D bioprinting, the most pressing future avenues of research include furthering our understanding of the physical and biochemical mechanisms of myotube development and expanding our control over macroscopic and microscopic construct structures. Further to this, current investigation needs to be expanded from immunocompromised rodent and murine myoblast models to more clinically applicable human cell lines as we move closer to viable therapeutic implementation., (© 2021 Author(s).)

Background: Major depressive disorder (MDD) is a chronic recurrent or episodic psychiatric illness that can be successfully treated with oral antidepressants, yet one-in-three patients do not respond to currently-available treatments. According to the FDA and EMA, patients are considered to have treatment-resistant depression (TRD) when their MDD fails to respond adequately to ≥2 successive antidepressants in a single episode., Aims: To describe current clinical management of patients with MDD and TRD in England, including treatment strategies and referral to secondary mental healthcare., Method: A retrospective cohort study of adult patients identified in primary care with diagnosed MDD, including a TRD subgroup (≥2 treatment failures as determined by treatment dynamics) was conducted using the Clinical Practice Research Datalink GOLD primary care database linked to Hospital Episode Statistics and Mental Health Services Data Set data (Protocol 19&#95;019R)., Results: 41,375 patients with MDD (mean age 44yrs, 62% female, median follow-up 29mths); and 1,051 (3%) patients with TRD were identified. Mean time-to-TRD was 18 months. Most patients (>99%) received first-line antidepressant monotherapy. Following TRD criteria being met, antidepressant monotherapy use remained most frequent from TRD first-line (70%) to fifth-line (48%). Dual/triple antidepressant use remained constant (range:24%-26%), while augmented antidepressant use increased from TRD first-line (7%) to third-line (17%). Minimal non-pharmacological therapies were observed., Conclusions: Despite current clinical guidelines recommending a stepwise approach, many patients frequently cycle through numerous antidepressants with similar mechanisms of action and efficacy. These findings indicate a high unmet need for new treatments that improve outcomes in these patient populations., (Copyright © 2021. Published by Elsevier Ltd.)

A primary purpose of many prevention-oriented interventions is to improve the general well-being and quality of life for individuals and their communities. Unfortunately, well-being is often poorly defined, with definitions embracing related issues of quality of life, happiness, and physical health. Mental well-being as a concept is also poorly defined, particularly for different population groups. As part of a larger study to assess community-level prevention efforts aimed at men and boys, a participatory approach was used to operationalize mental well-being from a male-centered, community-based perspective using concept mapping. A set of 96 statements perceived as important aspects of mental well-being for men and boys were developed and sorted by 90 participants from the study communities. The 8-cluster solution was selected as the most parsimonious and the best conceptual fit in relation to the mental well-being concept, namely, positive self-worth, supportive community, community connections, positive masculinity, responsive institutions, strong social connection, dignity and respect, and safety. These eight clusters of mental well-being, which were classified into two overarching domains of socio-environmental and emotional well-being, can provide a basis by which to assess community-based programs aimed at this population., (© 2020 Society for Community Research and Action.)

Objective: Ulcerative colitis (UC) is a lifelong, relapsing-remitting disease. Patients non-responsive to pharmacological treatment may require a colectomy. We estimated pre-colectomy and post-colectomy healthcare resource utilisation (HCRU) and costs in England., Design/method: A retrospective, longitudinal cohort study indexing adult patients with UC undergoing colectomy (2009-2015), using linked Clinical Practice Research Datalink/Hospital Episode Statistics data, was conducted. HCRU, healthcare costs and pharmacological treatments were evaluated during 12 months prior to and including colectomy (baseline) and 24 months post-colectomy (follow-up; F-U), comparing baseline/F-U, emergency/elective colectomy and subtotal/full colectomy using descriptive statistics and paired/unpaired tests., Results: 249 patients from 26 165 identified were analysed including 145 (58%) elective and 184 (74%) full colectomies. Number/cost of general practitioner consultations increased post-colectomy (p<0.001), and then decreased at 13-24 months (p<0.05). From baseline to F-U, the number of outpatient visits, number/cost of hospitalisations and total direct healthcare costs decreased (all p<0.01). Postoperative HCRU was similar between elective and emergency colectomies, except for the costs of colectomy-related hospitalisations and medication, which were lower in the elective group (p<0.05). Postoperative costs were higher for subtotal versus full colectomies (p<0.001). At 1-12 month F-U, 30%, 19% and 5% of patients received aminosalicylates, steroids and immunosuppressants, respectively., Conclusion: HCRU/costs increased for primary care in the first year post-colectomy but decreased for secondary care, and varied according to the colectomy type. Ongoing and potentially unnecessary pharmacological therapy was seen in up to 30% of patients. These findings can inform patients and decision-makers of potential benefits and burdens of colectomy in UC., Competing Interests: Competing interests: The research department of MJB has received grant support from Tillotts Pharma and Vifor Pharma (Switzerland). MJB has received honoraria and travel support for consulting or lecturing from Vifor Pharma, Tillotts Pharma and AbbVie. DB, JCC, IM, MDD and RM are employees and stockholders of Pfizer Inc (which funded this study). NB is an employee Pfizer Inc and stockholder of Pfizer Inc (which funded this study). JW, OM and RW are employed by Adelphi Real World, which received funding from Pfizer Inc in connection with the development of this manuscript., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Discordance (misalignment) regarding treatment satisfaction may exist in real-life clinical practice between patients and their physicians. We aimed to assess physician and patient treatment satisfaction levels and associated degree of misalignment in rheumatoid arthritis (RA)., Method: A point-in-time, multinational survey of patients and physicians was conducted in Latin America from December 2014 to October 2015. Physician- and patient-reported satisfaction levels with current RA treatment, alignment levels in satisfaction perception, and factors associated with satisfaction misalignment were assessed through bivariate and logistic regression analyses., Results: Participating physicians (N = 114) completed 555 patient record forms (PRFs); 372 patients completed self-complete questionnaires (PSC). A total of 346 physician-patient pairs were analyzed. Physicians reported satisfaction with current disease control in 270/346 (78.0%) PRFs; patients reported such satisfaction in 286/346 (82.7%) PSCs. Physician-patient alignment was observed in 78.6% of pairs. Compared with aligned patients, misaligned patients were younger, more likely to have moderate or severe disease (physician subjectively defined), deteriorating or unstable disease (physician subjectively defined), been exposed to a greater number of advanced therapy lines (biologic or Janus kinase inhibitor), greater current pain, a current acute episode, poorer health, and greater disability and impairment. Misaligned patients were less likely to be in remission. Logistic regression analysis revealed that misaligned patients were more likely to experience greater activity impairment., Conclusions: High treatment satisfaction and alignment were observed among RA patients and their physicians in Latin America. Misaligned patients were more likely to report more severe disease and were less likely to be in remission. Addressing misalignment may lead to improved RA disease control.Key Points• High treatment satisfaction was observed among RA patients and their treating physicians in Latin America.• One-fifth of physician-patient pairs were misaligned in treatment satisfaction.• Patients misaligned with their physicians reported higher disease activity, lower quality of life, and greater disability than those who were aligned with their physicians.• Understanding and addressing misalignment in treatment satisfaction may improve outcomes in this patient population.

Beatrix, Carthage, Daegal, Dulcie, Fancypants, Fenn, Inca, Naira, and Robyn are newly isolated bacteriophages capable of infecting Mycolicibacterium smegmatis mc 2 155. We discovered, sequenced, and annotated these New Zealand bacteriophages. These phages illustrate that New Zealand harbors a selection of the highly diverse and distributed mycobacteriophage clusters found globally., (Copyright © 2019 Davies et al.)

"Weighing" available evidence in the process of decision-making is unavoidable, yet it is one step that routinely raises suspicions: what evidence should be used, how much does it weigh, and whose thumb may be tipping the scales? This commentary aims to evaluate the current state and future roles of various types of evidence for hazard assessment as it applies to environmental health. In its recent evaluation of the US Environmental Protection Agency's Integrated Risk Information System assessment process, the National Research Council committee singled out the term "weight of evidence" (WoE) for critique, deeming the process too vague and detractive to the practice of evaluating human health risks of chemicals. Moving the methodology away from qualitative, vague and controversial methods towards generalizable, quantitative and transparent methods for appropriately managing diverse lines of evidence is paramount for both regulatory and public acceptance of the hazard assessments. The choice of terminology notwithstanding, a number of recent Bayesian WoE-based methods, the emergence of multi criteria decision analysis for WoE applications, as well as the general principles behind the foundational concepts of WoE, show promise in how to move forward and regain trust in the data integration step of the assessments. We offer our thoughts on the current state of WoE as a whole and while we acknowledge that many WoE applications have been largely qualitative and subjective in nature, we see this as an opportunity to turn WoE towards a quantitative direction that includes Bayesian and multi criteria decision analysis.

An assessment of client functioning was utilized to characterize differences among community residential placement facilities, with the aim of understanding the relationships among settings. Clients recommended for placement in one of nine settings differed significantly on seven scales measuring community living skills, self-care skills, sociability, nuisance behaviors, violence, irritability and nursing needs. Results indicate that community residential settings, although characterized as forming a continuum, may be better conceptualized as an array of settings, where clients may differ in some but not all functional abilities. Facilities may also serve different functions for clients of different ages, either because of expectations concerning older clients or due to different patterns of functioning. Illustrations of the implications that can be drawn for purposes of policy-making and service planning are provided.

A level-of-care instrument developed in Missouri uses discriminant analysis and a criterion measure based on the state's continuum of community residential facilities to assess psychiatric patients' abilities and deficits and to match individual patients with a suitable community setting. The instrument assigned 57 percent of the patients in the sample used in development of the instrument and 43 percent in a validation sample to the same type of residential facility recommended by case managers. The instrument more accurately predicted placement than two instruments that were used earlier in the state and were not based on its specific array of facilities.

A factor analysis of data from 1,295 administrations of a level of care instrument produced a seven-factor solution. The scales developed from these factors through a simple unit weighting procedure were internally reliable and replicable on an additional sample of clients. The seven factors are discussed in terms of level of functioning measures. Results suggest that community living skills and self-care skills are two among several robust dimensions of level of functioning in psychiatric clients. Implications are discussed.