Risk of intracranial meningioma in patients with acromegaly: a systematic review.

Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of insulin-like growth factor 1 (IGF-1) which leads to the insidious onset of clinical manifestations. The most common primary central nervous system (CNS) tumors, meningiomas originate from the arachnoid layer of the meninges and are typically benign and slow-growing. Meningiomas are over twice as common in women as in men, with age-adjusted incidence (per 100,000 individuals) of 10.66 and 4.75, respectively. Several reports describe co-occurrence of meningiomas and acromegaly. We aimed to determine whether patients with acromegaly are at elevated risk for meningioma. Investigation of the literature showed that co-occurrence of a pituitary adenoma and a meningioma is a rare phenomenon, and the majority of cases involve GH-secreting adenomas. To the best of our knowledge, a systematic review examining the association between meningiomas and elevated GH levels (due to GH-secreting adenomas in acromegaly or exposure to exogenous GH) has never been conducted. The nature of the observed coexistence between acromegaly and meningioma -whether it reflects causation or mere co-association -is unclear, as is the pathophysiologic etiology. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022376998.

Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection.

INTRODUCTION: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3. METHODS: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea within 8 weeks post-treatment) was analyzed adjusting for baseline patient characteristics. HRQL was measured using the Clostridioides difficile Quality of Life Survey (Cdiff32); absolute scores and change from baseline in total and domain (physical, mental, and social) scores were summarized and compared between arms. Analyses were conducted for the trial's blinded phase only. RESULTS: Among 86 eligible patients (32.8% of the overall trial population, RBL 53 [61.6%], placebo 33 [38.4%]), RBL-treated patients had significantly lower odds of recurrence (i.e., greater probability of treatment success) at week 8 vs. placebo (odds ratio 0.35 [95% confidence interval 0.13, 0.98]). Probability of treatment success at week 8 was 81% for RBL and 60% for placebo, representing 21% absolute and 35% relative increases for RBL (crude proportions 79.2% vs. 60.6%; relative risk 0.53, p = 0.06). Additionally, RBL was associated with significantly higher Cdiff32 total (change score difference 13.5 [standard deviation 5.7], p < 0.05) and mental domain (16.2 [6.0], p < 0.01) scores vs. placebo from baseline to week 8. CONCLUSION: Compared to placebo, RBL demonstrated a significantly higher treatment success in preventing further rCDI and enhanced HRQL among patients at first recurrence, establishing RBL as an effective treatment to prevent further recurrences in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03244644.

Health Economic Assessments of Hyaluronic Acid Treatments for Knee Osteoarthritis: A Systematic Review.

INTRODUCTION: Hyaluronic acid (HA) use to treat knee osteoarthritis (OA) has been extensively investigated in the literature. There are also multiple economic assessments comparing intra-articular HAs with oral anti-inflammatory medicines and other conservative measures (NSAIDs), as well as different types and formulations of HA. Owing to the broad landscape of evidence across this area, it is important to further understand the empirical data comparing HA products, as well as the health economic implications that exist between commercially available HAs. This systematic review aims to identify and summarize the available evidence comparing commercially available HA products in the USA, as well as the health economic evidence and socioeconomic outcomes associated with HA use for knee OA. METHODS: A systematic literature review within the OVID Medline, Embase, HealthStar, and Cochrane EBM HTA databases was conducted. Articles were screened for eligibility, and a qualitative summary of the findings was provided based on specific themes: (1) trials comparing the safety and/or efficacy of two or more HA products in knee OA, (2) economic/cost analyses of HA use in knee OA, and (3) studies investigating healthcare resource utilization in patients treated with HA for knee OA. RESULTS: The search strategy identified 398 studies, 27 of which were deemed eligible: 21 health economic analyses with US relevance and six head-to-head trials of HA products available in the USA, cumulatively assessing 5,782,156 patients with knee OA. The evidence demonstrates a clear distinction between high and low molecular weight HAs, as both efficacy and cost analyses provided favorable results for the high molecular weight options. In all but one cost analysis, HA use was a cost-effective option when compared to routine nonoperative care, captured in administrative databases, which typically included NSAID use and/or corticosteroids. HA saw benefits in delaying the need for total knee arthroplasty (TKA), decreasing the use of rescue medication, and limiting the need for additional corticosteroid injection. The included evidence highlights that the treatment's cost-effectiveness is improved when HA is utilized in earlier stages of the disease, as opposed to when HA is reserved for late stages of knee OA. Additionally, among HAs, Bio-HA and Hylan G-F 20 evidence made up the majority of available literature with beneficial efficacy and cost outcomes. Head-to-head evidence between them indicated similar pain outcomes; however, Bio-HA required less rescue with acetaminophen and had fewer joint effusions in this comparison. CONCLUSIONS: The available efficacy and safety data as well as health economic analyses on the use of HA for knee OA management suggest that there are economic benefits of this treatment option. From a healthcare system perspective, the body of HA literature summarizes favorable costs profile, decreased opioid and corticosteroid use as rescue medication, and a delay to the need for TKA in patients who have HA included in their treatment regimen.

Temporal and spatial analysis of astrocytes following stroke identifies novel drivers of reactivity.

Astrocytes undergo robust gene expression changes in response to a variety of perturbations, including ischemic injury. How these transitions are affected by time, and how heterogeneous and spatially distinct various reactive astrocyte populations are, remain unclear. To address these questions, we performed spatial transcriptomics as well as single nucleus RNAseq of ~138,000 mouse forebrain astrocytes at 1, 3, and 14 days after ischemic injury. We observed a widespread and temporally diverse response across many astrocyte subtypes. We identified astrocyte clusters unique in injury, including a transiently proliferative substate that may be BRCA1-dependent. We also found an interferon-responsive population that rapidly expands to the perilesion cortex at 1 day and persists up to 14 days post stroke. These lowly abundant, spatially restricted populations are likely functionally important in post-injury stabilization and resolution. These datasets offer valuable insights into injury-induced reactive astrocyte heterogeneity and can be used to guide functional interrogation of biologically meaningful reactive astrocyte substates to understand their pro- and anti-reparative functions following acute injuries such as stroke.

Effect of Fecal Microbiota, Live-Jslm (REBYOTA [RBL]) on Health-Related Quality of Life in Patients With Recurrent Clostridioides difficile Infection: Results From the PUNCH CD3 Clinical Trial.

Background: Recurrence of Clostridioides difficile infection (rCDI) is common, prolonging disease morbidity and leading to poor quality of life. We evaluated disease-specific health-related quality of life (HRQL) in patients with rCDI treated with fecal microbiota, live-jslm (REBYOTA [RBL]; Rebiotix) versus placebo. Methods: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3). The disease-specific Clostridioides difficile Quality of Life Survey (Cdiff32) was administered at baseline and at weeks 1, 4, and 8. Changes in Cdiff32 total and domain (physical, mental, social) scores from baseline to week 8 were compared between RBL and placebo and for responders and nonresponders. Results: Findings were analyzed in a total of 185 patients (RBL, n = 128 [69.2%]; placebo, n = 57 [30.8%]) with available Cdiff32 data. Patients from both arms showed significant improvements in Cdiff32 scores relative to baseline across all outcomes and at all time points (all P < .001); RBL-treated patients showed significantly greater improvements in mental domain than those receiving placebo. In adjusted analyses, RBL-treated patients showed greater improvements than placebo in total score and physical and mental domains (all P < .05). Similar improvement in mental domain was observed among responders, while nonresponders showed numerical improvements with RBL but not placebo. Conclusions: In a phase 3 double-blinded clinical trial, RBL-treated patients reported more substantial and sustained disease-specific HRQL improvements than placebo-treated patients. Clinical Trials Registration: ClinicalTrials.gov NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).

Fabricated High-Strength, Low-Elastic Modulus Biomedical Ti-24Nb-4Zr-8Sn Alloy via Powder Metallurgy.

With the huge demands of an aging society, it is urgent to develop a new generation of non-toxic titanium alloy to match the modulus of human bone. Here, we prepared bulk Ti2448 alloys by powder metallurgy technology, and focused on the influence of the sintering process on the porosity, phase composition, and mechanical properties of the initial sintered samples. Furthermore, we performed solution treatment on the samples under different sintering parameters to further adjust the microstructure and phase composition, so as to achieve strength enhancement and reduction of Young's modulus. Solution treatment can effectively inhibit the continuous α phase precipitated along the grain boundaries of the ß matrix, which is beneficial to the fracture resistance. Therefore, the water-quenched sample exhibits good mechanical properties due to the absence of acicular α-phase. Samples sintered at 1400 °C and subsequently water quenched have excellent comprehensive mechanical properties, which benefit from high porosity and the smaller feature size of microstructure. To be specific, the compressive yield stress is 1100 MPa, the strain at fracture is 17.5%, and the Young's modulus is 44 GPa, which are more applicable to orthopedic implants. Finally, the relatively mature sintering and solution treatment process parameters were screened out for reference in actual production.

Economic Impact of Recurrent Clostridioides difficile Infection in the USA: A Systematic Literature Review and Cost Synthesis.

INTRODUCTION: Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America. METHODS: English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer's perspective. RESULTS: A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to $82,268. CONCLUSIONS: While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers.

Cost-Effectiveness Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) Versus Standard of Care for the Prevention of Recurrent Clostridioides difficile Infection in the USA.

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) is common and associated with considerable clinical and economic consequences. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We sought to evaluate cost-effectiveness of FMBL compared to standard of care (SOC) from a US third-party payer perspective among patients with one or more (≥ 1) recurrences. METHODS: A Markov model with a lifetime time horizon was developed. The model population included adult patients who had ≥ 1 recurrence after a primary CDI episode and had completed ≥ 1 round of antibiotics, or had ≥ 2 severe CDI episodes resulting in hospitalization within the last year. The model consisted of six health states with an 8-week model cycle: rCDI, absence of CDI after recurrence, colectomy, ileostomy, ileostomy reversal, and death. Drug costs and rCDI-related medical costs were estimated in 2022 US dollars and discounted at 3% annually. Deterministic sensitivity analyses were performed. RESULTS: Compared to SOC, FMBL at $9000/course resulted in an incremental cost-effectiveness ratio (ICER) of $18,727 per quality-adjusted life year (QALY) gained. The incremental cost was $5336 (FMBL $79,236, SOC $73,900) and the incremental effectiveness was 0.285 QALYs (FMBL 10.346, SOC 10.061). The cumulative drug acquisition and administration costs for the FMBL and SOC arms were $24,245 and $16,876, while rCDI-related medical costs for FMBL and SOC were $54,991 and $57,024, respectively. The ICER in the subgroup of patients at first recurrence was $13,727 per QALY gained. FMBL remained cost-effective across all sensitivity analyses. CONCLUSIONS: FMBL was found to be cost-effective compared to SOC for the prevention of rCDI with more benefits among patients at first recurrence, with an ICER far below the payer ICER threshold of $100,000. Patients treated with FMBL experienced higher total QALYs and reduced healthcare resource utilization, including reduced hospitalizations.

Budget Impact Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) for Preventing Recurrent Clostridioides difficile Infection in the US.

INTRODUCTION: Patients with Clostridioides difficile infection (CDI) often experience recurrences (rCDI), which are associated with high morbidity, mortality, and healthcare expenditures. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We quantified the budget impact of FMBL during the first 3 years following introduction from a third-party US payer perspective. METHODS: A decision-tree model was used to estimate the budget impact of one-course FMBL by comparing costs under the scenario with FMBL to the scenario without FMBL (standard of care) in patients with one or more (≥ 1) recurrences after a primary episode of CDI and had completed ≥ 1 round of antibiotic treatments. Drug costs, rCDI-related medical costs, and budget impact over 1-3 years were estimated in 2022 US dollars. One-way sensitivity analyses were performed. RESULTS: For an insurance plan with a population size of 1,000,000, 468 patients per year were estimated to have ≥ 1 rCDI. The budget impact of one-course FMBL at $9000/course was cost-saving at an¼ average of -$0.0039 on a per-member-per-month (PMPM) basis, an average of -$8.30 on a per-treated-member-per-month (PTMPM) basis, and a total of -$139,865 on a plan level assuming 5%, 15%, and 20% of patients receive FMBL over 1-3 years, respectively. The scenario with FMBL entry was associated with higher drug costs (difference at $0.0474 PMPM; $101.26 PTMPM; $1,706,445 total plan) and lower rCDI-related medical costs (difference at -$0.0513 PMPM; -$109.56 PTMPM; -$1,846,309 total plan). The budget impact of FMBL in patients at first rCDI was cost-saving at -$0.0139 PMPM, -$84.78 PTMPM, corresponding to an annual savings of $500,022. CONCLUSIONS: FMBL has a cost-saving budget impact for a US payer, with higher initial drug costs being offset by savings in rCDI-related medical costs. Greater cost saving was found in patients at first recurrence.

The effect of treatment on work productivity in patients with bladder cancer.

OBJECTIVE: To describe the impact of bladder-preserving treatment vs. cystectomy on work productivity and activity impairment (WPAI) among patients with bladder cancer. METHODS: Using cross-sectional survey data, we constructed 2-part models involving both logistic and linear prediction to describe the relationship between WPAI and treatment modality among patients with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). RESULTS: A total of 848 patients were included in the analysis. Patients with NMIBC who had cystectomy were more likely to experience activity impairment compared with those receiving bladder-preserving treatment (OR: 4.25, 95% CI: 2.28-7.93). Among patients with MIBC, cystectomy was protective against increasing presenteeism (e^ß: 0.41, 95% CI: 0.23-0.71) and productivity loss (e^ß: 0.44, 95% CI: 0.21-0.88); however, the opposite effect was seen for absenteeism treatment (e^ß: 4.82, 95% CI: 1.72-13.49). CONCLUSION: Cystectomy increased the odds of experiencing activity impairment for patients with NMIBC. However, for patients with MIBC, cystectomy appears to be protective for presenteeism and productivity loss. Further work is needed in order to better understand these important relationships and improve both patient counseling and shared decision-making.

Perceived Barriers and Facilitators of Implementing a Multicomponent Intervention to Improve Communication With Older Adults With and Without Dementia (SHARING Choices) in Primary Care: A Qualitative Study.

INTRODUCTION: Implementing patient- and family-centered communication strategies has proven challenging in primary care, particularly for persons with dementia. To address this, we designed SHARING Choices, a multicomponent intervention combining patient and family partnered agenda setting, electronic portal access, and supports for advance care planning (ACP). This qualitative descriptive study describes factors affecting SHARING Choices implementation within primary care. METHODS: Semi-structured interviews or focus groups with patient/family dyads (family, friends, unpaid caregivers) and primary care stakeholders (clinicians, staff, administrators) elicited perceived barriers and facilitators of SHARING Choices implementation. Field notes and interview transcripts were coded using template analysis along the Consolidated Framework for Implementation Research (CFIR) constructs. Content analysis identified themes not readily categorized within CFIR. RESULTS: About 22 dyads, including 14 with cognitive impairment, and 30 stakeholders participated in the study. Participants were receptive to the SHARING Choices components. Enablers of SHARING Choices included adaptability of the intervention, purposive engagement of family (particularly for patients with dementia), consistency with organizational priorities, and the relative advantage of SHARING Choices compared to current practices. Perceived barriers to implementation included intervention complexity, space constraints, workflow, and ACP hesitancy. The ACP facilitator was perceived as supportive in addressing individual and organizational implementation barriers including patient health and technology literacy and clinician time for ACP discussions. CONCLUSIONS: Patients, family, and primary care clinicians endorsed the objectives and individual components of SHARING Choices. Strategies to enhance adoption were to simplify materials, streamline processes, leverage existing workflows, and embed ACP facilitators within the primary care team.

3D Printing Soft Matters and Applications: A Review.

The evolution of nature created delicate structures and organisms. With the advancement of technology, especially the rise of additive manufacturing, bionics has gradually become a popular research field. Recently, researchers have concentrated on soft robotics, which can mimic the complex movements of animals by allowing continuous and often responsive local deformations. These properties give soft robots advantages in terms of integration and control with human tissue. The rise of additive manufacturing technologies and soft matters makes the fabrication of soft robots with complex functions such as bending, twisting, intricate 3D motion, grasping, and stretching possible. In this paper, the advantages and disadvantages of the additive manufacturing process, including fused deposition modeling, direct ink writing, inkjet printing, stereolithography, and selective laser sintering, are discussed. The applications of 3D printed soft matter in bionics, soft robotics, flexible electronics, and biomedical engineering are reviewed.

Design principles of protein switches.

Protein switches perform essential roles in many biological processes and are exciting targets for de novo protein design, which aims to produce proteins of arbitrary shape and functionality. However, the biophysical requirements for switch function - multiple conformational states, fine-tuned energetics, and stimuli-responsiveness - pose a formidable challenge for design by computation (or intuition). A variety of methods have been developed toward tackling this challenge, usually taking inspiration from the wealth of sequence and structural information available for naturally occurring protein switches. More recently, modular switches have been designed computationally, and new methods have emerged for sampling unexplored structure space, providing promising new avenues toward the generation of purpose-built switches and de novo signaling systems for cellular engineering.

Take-Over Intention during Conditionally Automated Driving in China: Current Situation and Influencing Factors.

Drivers' take-over intention is important for the design of the automated driving systems and affects the safety of automated driving. This study explored the influence factors on drivers' take-over intention during conditionally automated driving, examined the correlations among factors through path analysis, and established a take-over intention model. A questionnaire survey was conducted in Hefei, China, and a sample of 277 drivers was obtained. Our study shows that the average take-over intention of those aged under 20 is lower than that of the older age groups. In the positive emotions (PE) scenarios, the take-over intention of aged 31-40 is significantly higher than that of the other age groups. Education and occupation have a significant influence on the take-over intention. The perceived ease of use (PEofU) and perceived usefulness (PU) of automated driving are significantly negatively correlated with drivers' take-over intention in the road conditions (RC) and climate conditions (CC) scenarios. In addition, through path model analysis, our study shows that trust in the safety of autonomous vehicles (AVs) plays an important role in drivers' take-over intention. Technology acceptance, risk perception and self-efficacy has indirectly correlated with take-over intention through trust in the safety of AVs. In general, drivers with lower technology acceptance, lower self-efficacy and higher risk perception are less likely to trust automated driving technology and have shown stronger intention to take-over the control of the vehicles.

Healthcare provider satisfaction with environmental conditions in rural healthcare facilities of 14 low- and middle-income countries.

Healthcare provider (HCP) satisfaction is important for staff retention and effective health service delivery. Inadequate resources, understaffing, and ineffective organizational structure may reduce HCP satisfaction in low- and middle-income countries (LMICs). Some qualitative studies have described links between environmental conditions and job satisfaction in HCPs; however, few studies have explored this link using survey data. This study explores associations between HCP satisfaction and water, sanitation, and hygiene (WaSH) infrastructure, cleanliness, and infection prevention and control (IPC) practices in rural healthcare facilities (HCFs) in LMICs. This study analyzes 2002 HCFs in rural areas of 14 LMICs. Generalized linear mixed-effects logistic regression models were used to analyze the association between HCP satisfaction, WaSH infrastructure, and cleanliness and IPC practices. Most respondents reported that they were unsatisfied with water (65%), sanitation (68%), and hygiene infrastructure (54%) at their HCF. Insufficient supply and poor quality of WaSH resources were the most commonly reported reasons for provider dissatisfaction. Respondents were less likely to report dissatisfaction with cleanliness and IPC practices (36%). Dissatisfaction with cleanliness and IPC were most reported because patients and staff did not wash their hands at the correct times or with proper materials, or because the facility was not clean. Several characteristics of the WaSH environment were significantly associated with provider satisfaction at their HCFs, including acceptable water quality, readily available supply of water (on premises and improved), accessible supply of WaSH infrastructure to people with reduced mobility, accessible supplies of sanitation and hygiene materials, and sufficient training and budgeting for WaSH or IPC needs. Our results suggest that the provision of on premises, improved water service accessible to people with reduced mobility, interventions that prioritize the acceptability of sanitation facilities within the local context, and the provision of hygienic materials are key interventions to improve HCP satisfaction. Dedicated funding and oversight should be established at the HCF level to ensure access to consumable hygiene and IPC products and maintenance of WASH infrastructure. Improvements to WaSH in HCF may improve HCP satisfaction and ultimately patient outcomes.

Occurrence of Lead and Other Toxic Metals Derived from Drinking-Water Systems in Three West African Countries.

BACKGROUND: Exposure to toxic metals (TMs) such as lead can cause lifelong neurodevelopmental impairment and other adverse outcomes. TMs enter drinking water from human activity, geogenic contamination, and corrosion of water system components. Several studies report TM contamination in piped systems and private wells in high-income countries (HICs). However, few robust studies report on TM contamination in low- and middle-income countries (LMICs). OBJECTIVES: We characterized the occurrence and investigated sources of TM contamination in 261 rural water systems in three West African LMICs to inform prevention and management. METHODS: Water samples were collected from 261 community water systems (handpumps and public taps) across rural Ghana, Mali, and Niger. Scrapings were collected from accessible components of a subset of these systems using a drill with acid-washed diamond-tipped bits. Samples were analyzed by inductively coupled plasma (ICP) mass spectrometry or ICP optical emission spectroscopy. RESULTS: Of the TMs studied, lead most frequently occurred at levels of concern in sampled water system components and water samples. Lead mass fractions exceeded International Plumbing Code (IPC) recommended limits (0.25% wt/wt) for components in 82% (107/130) of systems tested; brass components proved most problematic, with 72% (26/36) exceeding IPC limits. Presence of a brass component in a water system increased expected lead concentrations in drinking-water samples by 3.8 times. Overall, lead exceeded World Health Organization (WHO) guideline values in 9% (24/261) of drinking-water samples across countries; these results are broadly comparable to results observed in many HICs. Results did not vary significantly by geography or system type. DISCUSSION: Ensuring use of lead-free (<0.25%) components in new water systems and progressively remediating existing systems could reduce drinking-water lead exposures and improve health outcomes for millions. However, reflexive decommissioning of existing systems may deprive users of sufficient water for health or drive them to riskier sources. Because supply chains for many water system components are global, TM monitoring, prevention, and management may be warranted in other LMICs beyond the study area as well. https://doi.org/10.1289/EHP7804.

The Impact of Progression on Healthcare Resource Utilization and Costs Among Patients with High-Grade Non-Muscle Invasive Bladder Cancer After Bacillus Calmette-Guérin Therapy: A Retrospective SEER-Medicare Analysis.

INTRODUCTION: We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy. METHODS: Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. RESULTS: Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]. CONCLUSIONS: Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.

A randomized intervention involving family to improve communication in breast cancer care.

We examined the effects of a communication intervention to engage family care partners on patient portal (MyChart) use, illness understanding, satisfaction with cancer care, and symptoms of anxiety in a single-blind randomized trial of patients in treatment for breast cancer. Patient-family dyads were recruited and randomly assigned a self-administered checklist to clarify the care partner role, establish a shared visit agenda, and facilitate MyChart access (n = 63) or usual care (n = 55). Interviews administered at baseline, 3, 9 (primary endpoint), and 12 months assessed anxiety (GAD-2), mean FAMCARE satisfaction, and complete illness understanding (4 of 4 items correct). Time-stamped electronic interactions measured MyChart use. By 9 months, more intervention than control care partners registered for MyChart (77.8 % vs 1.8%; p < 0.001) and logged into the patient's account (61.2% vs 0% of those registered; p < 0.001), but few sent messages to clinicians (6.1% vs 0%; p = 0.247). More intervention than control patients viewed clinical notes (60.3% vs 32.7%; p = 0.003). No pre-post group differences in patient or care partner symptoms of anxiety, satisfaction, or complete illness understanding were found. Intervention patients whose care partners logged into MyChart were more likely to have complete illness understanding at 9 months (changed 70.0% to 80.0% vs 69.7% to 54.6%; p = 0.03); symptoms of anxiety were numerically lower (16.7% to 6.7% vs 15.2% to 15.2%; p = 0.24) and satisfaction numerically higher (15.8-16.2 vs 18.0-17.4; p = 0.25). A brief, scalable communication intervention led to greater care partner MyChart use and increased illness understanding among patients with more engaged care partners (NCT03283553).

SHARING Choices: A Pilot Study to Engage Family in Advance Care Planning of Older Adults With and Without Cognitive Impairment in the Primary Care Context.

CONTEXT: Few advance care planning (ACP) interventions proactively engage family or address the needs of older adults with and without cognitive impairment in the primary care context. OBJECTIVES: To pilot a multicomponent intervention involving: an introductory letter describing a new clinic initiative and inviting patients to complete a patient-family pre-visit agenda-setting checklist, share their electronic health information with family, and talk about their wishes for future care with a trained ACP facilitator (SHARING Choices). METHODS: SHARING Choices was delivered to 40 patient-family dyads from 3 primary care clinics. Facilitators completed post-ACP reports. Patient and family participants completed baseline and 6-week surveys. RESULTS: Patients were on average 75 years (range 65-90). Family were spouses (85.0%) or adult children (15.0%). At 6 weeks, nearly half of dyads participated in ACP conversations (n = 19) or used the agenda-setting checklist (n = 17), one-third (n = 13) registered family to access the patient's portal account, and most (n = 28) provided the primary care team with a new or previously completed advance directive. Of 12 patients who screened positive for cognitive impairment, 9 completed ACP conversations and 10 provided the clinic with an advance directive. ACP engagement, measured on a 4-point scale, was comparatively lower at baseline and 6 weeks among family (3.05 and 3.19) than patients (3.56 and 3.54). Patients remarked that SHARING Choices clarified communication and preferences while family reported a better understanding of their role in ACP and communication. CONCLUSION: SHARING Choices was acceptable among older adults with and without cognitive impairment and may increase advance directive completion.