Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure.

INTRODUCTION: Smoking and smoke exposure among pregnant women remain persistent public health issues. Recent estimates suggest that approximately one out of four nonsmokers have measurable levels of cotinine, a marker indicating regular exposure to secondhand smoke. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy. However, most of these studies have relied upon self-reported measures of smoking. AIMS AND METHODS: To more accurately assess smoke exposure resulting from both smoking and secondhand exposure in mothers during pregnancy, we used Bayesian regression models to estimate the association of cotinine levels with tobacco retail outlet (TRO) exposure and a neighborhood deprivation index (NDI) in six counties in North Carolina centered on Durham County. RESULTS: Results showed a significant positive association between TRO exposure (ß = 0.008, 95% credible interval (CI) = [0.003, 0.013]) and log cotinine after adjusting for individual covariates (eg, age, race/ethnicity, education, marital status). TRO exposure was not significant after including the NDI, which was significantly associated with log cotinine (ß = 0.143, 95% CI = [0.030, 0.267]). However, in a low cotinine stratum (indicating secondhand smoke exposure), TRO exposure was significantly associated with log cotinine (ß = 0.005, 95% CI = [0.001, 0.009]), while in a high cotinine stratum (indicating active smoking), the NDI was significantly associated with log cotinine (ß = 0.176, 95% CI = [0.005, 0.372]). CONCLUSIONS: In summary, our findings add to the evidence that contextual factors are important for active smoking during pregnancy. IMPLICATIONS: In this study, we found several significant associations that suggest a more nuanced understanding of the potential influence of environmental- and individual-level factors for levels of prenatal smoke exposure. Results suggested a significant positive association between TRO exposure and cotinine levels, after adjusting for the individual factors such as race, education, and marital status. Individually, NDI was similarly positively associated with cotinine levels as well. However, when combining TRO exposure alongside NDI in the same model, TROs were no longer significantly associated with overall cotinine levels.

Quality of life among women diagnosed with breast Cancer: A randomized waitlist controlled trial of commercially available mobile app-delivered mindfulness training.

OBJECTIVE: The primary objective was to evaluate the efficacy of commercially available mobile app-delivered mindfulness training (AMT), compared with waitlist control (WC), on quality of life (QOL) among women diagnosed with breast cancer. The secondary outcome was dispositional mindfulness. Enrollment, app utilization, and study completion are reported as feasibility objectives. METHODS: Women diagnosed with breast cancer ≤5 years (n = 112) were randomized to AMT (n = 57) or WC (n = 55), over 8 weeks, with 4 weeks of follow-up. We conducted linear mixed effects models to examine group by observation interactions on QOL and dispositional mindfulness at baseline, during intervention (5-weeks), post-intervention (9-weeks), and follow-up (12-weeks post-baseline). RESULTS: Participants assigned to AMT reported higher QOL, compared with those assigned to WC, from baseline through follow-up t(258.40) = 3.09, P < 0.01, 95% CI [2.71, 11.90]. Participants assigned to AMT also reported higher dispositional mindfulness, compared with those assigned to WC, from baseline through follow-up t(268.44) = 2.04, P = 0.04, 95% CI [0.01, 0.57]. App utilization data was obtained from 34 participants. Fewer participants assigned to AMT completed all study assessments, compared with participants assigned to WC, (χ21  = 7.07, P = 0.008). CONCLUSIONS: Findings suggest commercially available AMT may proffer some benefit to women seeking to enhance their QOL following breast cancer diagnosis.

Chronic Health Conditions, Disability, and Physical and Cognitive Limitations Among LGBTQ+ Cancer Survivors.

BACKGROUND: Cancer survivors are at high risk for chronic health conditions and physical and cognitive limitations. However, few studies have explored these outcomes among LGBTQ+ survivors. METHODS: We used pooled, weighted Behavioral Risk Factor Surveillance System data from 23 states that completed two specific modules from 2020-2022. We calculated age-adjusted prevalence for heart disease, asthma, COPD, depressive disorders, myocardial infarction, kidney disease, stroke, diabetes, hearing disability, vision disability, cognitive limitations, and difficulty walking, dressing, and running errands in LGBTQ+, lesbian, gay, or bisexual (LGB), transgender or gender non-conforming (TGNC), and non-LGBTQ+ cancer survivors. Four multivariable logistic regression models controlling for different factors were run for each outcome. RESULTS: Of 40,990 cancer survivors, 1,715 were LGBTQ+. LGBTQ+ survivors had significantly higher age-adjusted prevalence of all outcomes. The prevalence of all outcomes was highest among TGNC survivors except for depressive disorders and cognitive limitations. LGBTQ+ survivors had higher odds of reporting asthma (aOR: 1.5, 95%CI:1.2-1.9), depressive disorders (aOR: 1.9, 95%CI:1.6-2.4), kidney disease (aOR: 1.5, 95%CI:1.1-2.1), stroke (aOR: 1.7, 95%CI:1.3-2.3), diabetes (aOR: 1.3, 95%CI:1.0-1.6), vision disability (aOR: 1.6, 95%CI:1.2-2.2), cognitive limitations (aOR: 2.3, 95%CI:1.8-2.9), difficulty walking (aOR: 1.7, 95%CI:1.3-2.0), dressing (aOR: 2.0, 95%CI:1.5-2.7), and running errands (aOR: 1.6, 95%CI:1.3-2.1). In TGNC models, TGNC cancer survivors had increased odds of most outcomes. CONCLUSIONS: LGBTQ+ cancer survivors have an elevated burden of all chronic health conditions, disabilities, and limitations assessed. TGNC cancer survivors experience even higher burden of the same outcomes. IMPACT: Findings highlight substantial disparities regarding the health of LGBTQ+ cancer survivors.

Pegvaliase for the treatment of phenylketonuria: Final results of a long-term phase 3 clinical trial program.

Phenylketonuria (PKU) is a genetic disorder caused by deficiency of the enzyme phenylalanine hydroxylase (PAH), which results in phenylalanine (Phe) accumulation in the blood and brain, and requires lifelong treatment to keep blood Phe in a safe range. Pegvaliase is an enzyme-substitution therapy approved for individuals with PKU and uncontrolled blood Phe concentrations (>600 µmol/L) despite prior management. Aggregated results from the PRISM clinical trials demonstrated substantial and sustained reductions in blood Phe with a manageable safety profile, but also noted individual variation in time to and dose needed for a first response. This analysis reports longer-term aggregate findings and characterizes individual participant responses to pegvaliase using final data from the randomized trials PRISM-1 (NCT01819727) and PRISM-2 (NCT01889862), and the open-label extension study 165-304 (NCT03694353). In 261 adult participants with a mean of 36.6 months of pegvaliase treatment, 71.3%, 65.1%, and 59.4% achieved clinically significant blood Phe levels of ≤600, ≤360, and ≤ 120 µmol/L, respectively. Some participants achieved blood Phe reductions with <20 mg/day pegvaliase, although most required higher doses. Based on Kaplan-Meier analysis, median (minimum, maximum) time to first achievement of a blood Phe threshold of ≤600, ≤360, or ≤ 120 µmol/L was 4.4 (0.0, 54.0), 8.0 (0.0, 57.0), and 11.6 (0.0, 66.0) months, respectively. Once achieved, blood Phe levels remained below clinical threshold in most participants. Sustained Phe response (SPR), a new method described within for measuring durability of blood Phe response, was achieved by 85.5%, 84.7%, and 78.1% of blood Phe responders at blood Phe thresholds of ≤600, ≤360, or ≤ 120 µmol/L, respectively. Longer-term safety data were consistent with previous reports, with the most common adverse events (AEs) being arthralgia, injection site reactions, headache, and injection site erythema. The incidence of most AEs, including hypersensitivity AEs, was higher during the early treatment phase (≤6 months) than later during treatment. In conclusion, using data from three key pegvaliase clinical trials, participants treated with pegvaliase were able to reach clinically significant blood Phe reductions to clinical thresholds of ≤600, ≤360, or ≤ 120 µmol/L during early treatment, with safety profiles improving from early to sustained treatment. This study also supports the use of participant-level data and new ways of looking at durable blood Phe responses to better characterize patients' individual PKU treatment journeys.

Availability of buprenorphine/naloxone films and naloxone nasal spray in community pharmacies in Texas, USA.

BACKGROUND AND AIMS: Patients with opioid use disorder (OUD) must be able to obtain prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) from a pharmacy promptly to reduce risk for a recurrence of use and subsequent morbidity and mortality. Telephone audits have identified concerning gaps in availability of NNS within US pharmacies, but the availability of BUP/NX has not been rigorously evaluated. This study estimated the availability of BUP/NX and NNS in the US state of Texas and compared availability by pharmacy type and metropolitan status. DESIGN: A cross-sectional telephone audit with a secret shopper approach conducted from 18 May 2020 to 7 June 2020. Setting and Participants A random sample of 800 of 5078 (16%) community pharmacies licensed with the Texas State Board of Pharmacy. MEASUREMENTS: Primary outcomes included availability of a 1-week supply of generic BUP/NX 8/2 mg films and a single unit of NNS 4 mg, overall and by pharmacy type. Secondary outcomes included willingness and estimated time-frame to order BUP/NX if unavailable. FINDINGS: Data from 704 pharmacies (471 chain, 233 independent) were included for analyses. Of these, 34.1% of pharmacies (45.0% of chains versus 12.0% of independents, P < 0.0001) were willing and able to dispense a 1-week supply of generic BUP/NX and a single unit of NNS. BUP/NX alone was available in 42.2% of pharmacies (52.4% of chains versus 21.5% of independents, P < 0.0001). NNS alone was available in 60.1% of pharmacies (77.9% of chains versus 24.0% of independents, P < 0.0001). Of the 397 pharmacies with generic BUP/NX unavailable, 62.2% of pharmacies (73.9% of chains versus 48.0% of independents, P < 0.0001) indicated willingness to order. CONCLUSIONS: Most pharmacies in Texas do not appear to be willing and able to dispense prescribed buprenorphine/naloxone films and naloxone nasal spray to patients with opioid use disorder in a timely manner. Deficiencies in availability are markedly more pronounced in independent pharmacies compared with chain pharmacies.

Therapy with 2'-O-Me Phosphorothioate Antisense Oligonucleotides Causes Reversible Proteinuria by Inhibiting Renal Protein Reabsorption.

Antisense oligonucleotide therapy has been reported to be associated with renal injury. Here, the mechanism of reversible proteinuria was investigated by combining clinical, pre-clinical, and in vitro data. Urine samples were obtained from Duchenne muscular dystrophy (DMD) patients treated with drisapersen, a modified 2'O-methyl phosphorothioate antisense oligonucleotide (6 mg/kg). Urine and kidney tissue samples were collected from cynomolgus monkeys (Macaca fascicularis) dosed with drisapersen (39 weeks). Cell viability and protein uptake were evaluated in vitro using human conditionally immortalized proximal tubule epithelial cells (ciPTECs). Oligonucleotide treatment in DMD patients was associated with an increase in urinary alpha-1-microglobulin (A1M), which returned to baseline following treatment interruptions. In monkeys, increased urinary A1M correlated with dose-dependent accumulation of oligonucleotide in kidney tissue without evidence of tubular damage. Furthermore, oligonucleotides accumulated in the lysosomes of ciPTECs and reduced the absorption of A1M, albumin, and receptor-associated protein, but did not affect cell viability when incubated for up to 7 days. In conclusion, phosphorothioate oligonucleotides appear to directly compete for receptor-mediated endocytosis in proximal tubules. We postulate that oligonucleotide-induced low molecular weight proteinuria in patients is therefore a transient functional change and not indicative of tubular damage.