New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics.

Nearly half of Americans are projected to have obesity by 2030, underscoring the pressing need for effective treatments. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) represent the first agents in a rapidly evolving, highly promising landscape of nascent hormone-based obesity therapeutics. With the understanding of the neurobiology of obesity rapidly expanding, these emerging entero-endocrine and endo-pancreatic agents combined or coformulated with GLP-1 RAs herald a new era of targeted, mechanism-based treatment of obesity. This article reviews GLP-1 RAs in the treatment of obesity and previews the imminent future of nutrient-stimulated hormone-based anti-obesity therapeutics.

MicroRNA-206 as a potential cholesterol-lowering drug is superior to statins in mice.

Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis, and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis, and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol, and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis, and fecal-neutral steroid excretion. MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.

Extensively Drug-Resistant Pseudomonas aeruginosa Outbreak Associated With Artificial Tears.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug-resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak. METHODS: Cases were defined as a US patient's first isolation of P. aeruginosa sequence type 1203 with carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to the Centers for Disease Control and Prevention during 1 January 2022-15 May 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination. RESULTS: We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and 4 (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears versus controls (crude matched OR, 5.0; 95% CI, 1.1-22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. Food and Drug Administration inspection of the manufacturing plant identified likely sources of contamination. CONCLUSIONS: A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the United States. The clinical impacts from this outbreak underscore the need for improved requirements for US OTC product importers.

Incidence and risk factors for invasive fungal infections in patients initiating TNF-alpha inhibitors for inflammatory bowel disease and rheumatoid arthritis.

In a commercial claims database analysis, <0.5% of patients with inflammatory bowel disease or rheumatoid arthritis developed an IFI within one year of initiating TNF-alpha therapy. Histoplasmosis was the most common IFI type. Overall IFI incidence varied based on region, underlying conditions, and use of certain immunosuppressive medications.

Real-world data are not always big data: the case for primary data collection on medication use in pregnancy in the context of birth defects research.

Many examples of the use of real-world data in the area of pharmacoepidemiology include "big data," such as insurance claims, medical records, or hospital discharge databases. However, "big" is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are such an outcome, for which specificity of exposure timing is critical. Studies with primary data collection can be designed to query details about the timing of medication use, as well as type, dose, frequency, duration, and indication, that can better characterize the "real world." Because birth defects are rare, etiologic studies are typically case­control in design, like the National Birth Defects Prevention Study, Birth Defects Study to Evaluate Pregnancy Exposures, and Slone Birth Defects Study. Recall bias can be a concern, but the ability to collect detailed information about both prescription and over-the-counter medication use and other exposures such as diet, family history, and sociodemographic factors is a distinct advantage over claims and medical record data sources. Case­control studies with primary data collection are essential to advancing the pharmacoepidemiology of birth defects. This article is part of a Special Collection on Pharmacoepidemiology.

Mechanisms linking neurological disorders with reproductive endocrine dysfunction: Insights from epilepsy research.

Gonadal hormone actions in the brain can both worsen and alleviate symptoms of neurological disorders. Although neurological conditions and reproductive endocrine function are seemingly disparate, compelling evidence indicates that reciprocal interactions exist between certain disorders and hypothalamic-pituitary-gonadal (HPG) axis irregularities. Epilepsy is a neurological disorder that shows significant reproductive endocrine dysfunction (RED) in clinical populations. Seizures, particularly those arising from temporal lobe structures, can drive HPG axis alterations, and hormones produced in the HPG axis can reciprocally modulate seizure activity. Despite this relationship, mechanistic links between seizures and RED, and vice versa, are still largely unknown. Here, we review clinical evidence alongside recent investigations in preclinical animal models into the contributions of seizures to HPG axis malfunction, describe the effects of HPG axis hormonal feedback on seizure activity, and discuss how epilepsy research can offer insight into mechanisms linking neurological disorders to HPG axis dysfunction, an understudied area of neuroendocrinology.

A Systematic Approach to Evaluating Instrumental Variable Assumptions: Applied Example of Glucose-lowering Medications and Risk for Hospitalized Heart Failure in Older Adults.

One obstacle to adopting instrumental variable (IV) methods in pharmacoepidemiology is their reliance on strong, unverifiable assumptions. We can falsify IV assumptions by leveraging the causal structure, which can strengthen or refute their plausibility and increase the validity of effect estimates. We illustrate a systematic approach to evaluate calendar time IV assumptions in estimating the known effect of thiazolidinediones on hospitalized heart failure. Using cohort entry time before and after 09/2010, when the U.S. Food and Drug Administration issued a safety communication as a proposed IV, we estimated IV and propensity score-weighted 2-year risk differences (RDs) using Medicare data (2008-2014). We (i) performed inequality tests, (ii) identified the negative control IV/outcome using causal assumptions, (iii) estimated RDs after narrowing the calendar time range and excluding patients likely associated with unmeasured confounding, (iv) derived bounds for RDs, and (v) estimated the proportion of compliers and their characteristics. The findings revealed that IV assumptions were violated and RDs were extreme, but the assumptions became more plausible upon narrowing the calendar time range and restricting the cohort by excluding prevalent heart failure (the strongest measured predictor of outcome). Systematically evaluating IV assumptions could help detect bias in IV estimators and increase their validity.

Use of cholesterol-lowering medications in relation to risk of primary liver cancer in the Clinical Practice Research Datalink.

BACKGROUND: Although the relation between statin use and liver cancer risk has been extensively examined, few studies have examined other cholesterol-lowering medications in relation to liver cancer risk. The authors examined five classes of nonstatin medications and liver cancer risk. METHODS: A nested case-control including 3719 cases and 14,876 matched controls was conducted within the Clinical Practice Research Datalink. Additional matches on type 2 diabetes and chronic liver disease were also implemented. The medications examined included cholesterol absorption inhibitors, bile acid sequestrants, fibrates, niacin, and omega-3 fatty acids. Conditional logistic regression estimated odds ratios and 95% confidence intervals. RESULTS: Cholesterol absorption inhibitor use was associated with reduced liver cancer risk in the overall analysis (odds ratio, 0.69; 95% confidence interval, 0.50-0.96) and in analyses based on type 2 diabetes and chronic liver disease status. Although bile acid sequestrant use was associated with increased liver cancer risk in the overall analysis (odds ratio, 5.31; 95% confidence interval, 3.53-7.97), the results of the analyses based on type 2 diabetes and chronic liver disease status were inconsistent. [Correction added on 19 August 2024, after first online publication: In the preceding sentence, the value '3.534' has been changed to '3.54'.]. No associations were observed for the other medications. CONCLUSIONS: Cholesterol absorption inhibitors may be associated with reduced liver cancer risk. Whether bile acid sequestrant use was associated with increased risk was only partially supported in the current study.

No Impact of Concomitant Medications on Efficacy and Safety of Biologics and Small Molecules for Ulcerative Colitis.

BACKGROUND AND AIMS: While participants with inflammatory bowel diseases (IBD) in clinical trials of biologics and small molecule drugs (henceforth, advanced therapies) frequently receive several medications concomitantly, it is unclear how they modify treatment effect. METHODS: Through an individual patient data pooled analysis of ten clinical trials of advanced therapies for moderate-to-severe ulcerative colitis (UC), we assessed whether concomitant exposure to corticosteroids, immunomodulators, 5-aminosalicylates, proton pump inhibitors (PPIs), histamine receptor antagonists (H2RA), opiates, antidepressants, and antibiotics modified the effect of the intervention on treatment efficacy and safety outcomes, using modified Poisson regression model. RESULTS: Of 6044 patients (4280 receiving intervention, 1764 receiving placebo), several received concomitant corticosteroids (47%), immunomodulators (28%), 5-aminosalicylates (68%), PPIs (14%), H2RAs (2%), opiates (7%), antidepressants (6%), and/or antibiotics (5%). After adjusting for confounders and examining treatment efficacy of intervention vs. placebo, we observed no impact of concomitant exposure to corticosteroids (ratio of relative risk of drug vs. placebo with vs. without concomitant exposure: RRR, 0.81 [95% CI,0.63-1.06], 5-aminosalicylates (RRR, 1.04[0.78-1.39]), PPIs (RRR, 0.87 [0.61-1.22]), H2RAs (RRR, 1.72[0.97-14.29]), opiates (RRR, 0.90[0.54-1.49]), antidepressants (RRR, 1.02[0.57-1.83]), and antibiotics (RRR, 0.72[0.44-1.16]) on likelihood of clinical remission. Concomitant exposure to immunomodulators was associated with lower likelihood of achieving clinical remission (RRR, 0.73[0.55-0.97]), particularly with non-TNF antagonists. CONCLUSIONS: In clinical trials of advanced therapies for UC, baseline concomitant exposure to multiple commonly used class of medications does not impact treatment efficacy or safety. These findings directly inform design of regulatory clinical trials with respect to managing concomitant medications at baseline.

Efficacy of antiobesity medications among breast cancer survivors taking aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AI) block estrogen synthesis and are used as long-term adjuvant treatment for breast cancer in postmenopausal women. AI use can be associated with weight gain that can lead to increased cardiometabolic risk. The response to anti-obesity medications (AOM) in patients using AI has yet to be studied. We sought to investigate weight loss outcomes of AOM in patients taking AI for breast cancer treatment. METHODS: This is a matched retrospective cohort study of breast cancer survivors on AI using AOM (AOM/AI group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOM (AOM group). The primary endpoint was total body weight loss percentage (TBWL %) at the last follow-up. We performed mixed linear regression models, including diabetes status at baseline, to assess associations between use of AOM with/without AI with total body weight loss percentage (TBWL%). RESULTS: We included 124 patients: 62 in the AOM/AI group (63.6 ± 10 years, body mass index [BMI] 34.3 ± 7.1 kg/m2) and 62 in the AOM group (62.8 ± 9.9 years, BMI 34.6 ± 6.5 kg/m2). The mean time of follow up was 9.3 ± 3.5 months, with no differences among the two groups. The AOM/AI group had a lower TBWL% compared to the AOM group at the last follow-up -5.3 ± 5.0 vs. -8.2 ± 6.3 (p = 0.005). The results remained significant after adjusting for diabetes status (p = 0.0002). At 12 months, the AOM/AI group had a lower TBWL% compared to the AOM group 6.4 ± 0.8% vs. 9.8 ± 0.9% (p = 0.04). The percentage of patients achieving ≥ 5%, ≥ 10%, and ≥ 15% of weight loss at 12 months was greater in the AOM compared to the AOM/AI group. Although the weight loss response was suboptimal, patients in the AOM/AI group had improvement in fasting glucose, glycated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. CONCLUSIONS: The use of AI in breast cancer survivors is associated with less weight loss response to AOM compared to patients without breast cancer history and who do not take AI. Studies are needed to assess the mechanisms behind the differential weight loss response to AOM in women taking AI.

Warning Labels as a Public Health Intervention: Effects and Challenges for Tobacco, Cannabis, and Opioid Medications.

Warning labels help consumers understand product risks, enabling informed decisions. Since the 1966 introduction of cigarette warning labels in the United States, research has determined the most effective message content (health effects information) and format (brand-free packaging with pictures). However, new challenges have emerged. This article reviews the current state of tobacco warning labels in the United States, where legal battles have stalled pictorial cigarette warnings and new products such as electronic cigarettes and synthetic nicotine products pose unknown health risks. This article describes the emerging research on cannabis warnings; as more places legalize recreational cannabis, they are adopting lessons from tobacco warnings. However, its uncertain legal status and widespread underestimation of harms impede strict warning standards. The article also reviews opioid medication warning labels, suggesting that lessons from tobacco could help in the development of effective and culturally appropriate FDA-compliant opioid warning labels that promote safe medication use and increased co-dispensing of naloxone.

Current perspectives in obesity management: unraveling the impact of different therapy approach in real life obesity care.

BACKGROUND: The challenge of addressing obesity persists in healthcare, necessitating nuanced approaches and personalized strategies. This study aims to evaluate the effects of diverse therapeutic interventions on anthropometric and biochemical parameters in individuals with overweight and obesity within a real-world clinical context. METHODS: A retrospective analysis was conducted on 192 patients (141 females, 51 males) aged 18 to 75, with a BMI ranging from 25 to 30 (14.1%) and BMI ≥ 30 (85.9%), observed over a 12-month period at our Endocrinology Unit. Treatment cohorts comprised individuals following different regimens: Mediterranean Diet (MD), with an approximate daily intake of 1500 kcal for women and 1800 kcal for men (71% patients); Ketogenic Diet (KD), utilizing the VLCKD protocol characterized by a highly hypocaloric dietary regimen < 800 kcal/day (14% patients); metformin, administered using the oral formulation (5% patients); pharmacological intervention with GLP1-RA administered via subcutaneous injection with incremental dosage (10% patients). Supply constraints limited the efficacy of Liraglutide, whereas Semaglutide was excluded from comparisons due to its unavailability for obesity without diabetes. Blood tests were conducted to assess lipid profile, glycemic profile, and anthropometric parameters, including BMI, waist circumference, and waist-to-height ratio. RESULTS: Significant BMI changes were observed from baseline to 6 months across MD, KD, and Liraglutide groups (p < 0.05). KD exhibited notable reductions in waist circumference and waist-to-height ratio within the initial quarter (p < 0.05), with a significant triglyceride decrease after 6 months (p < 0.05), indicating its efficacy over MD. Liraglutide demonstrated a substantial reduction in HbA1c levels in the first quarter (p < 0.05). During the first three months, the ANOVA test on fasting blood glucose showed a statistically significant impact of the time variable (p < 0.05) rather than the specific treatments themselves (Liraglutide and KD), suggesting that adherence during the early stages of therapy may be more critical than treatment choice. CONCLUSIONS: Positive outcomes from targeted interventions, whether pharmacological or dietary should encourage the exploration of innovative, long-term strategies that include personalized treatment alternation. The absence of standardized protocols underscores the importance of careful and tailored planning in managing obesity as a chronic condition.

Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial.

INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.

Association of Coprescribing of Gabapentinoid and Other Psychoactive Medications With Altered Mental Status and Falls in Adults Receiving Dialysis.

RATIONALE & OBJECTIVE: Prescribing psychoactive medications for patients with kidney disease is common, but for patients receiving dialysis, some medications may be inappropriate. We evaluated the association of coprescribing gabapentinoids and other psychoactive potentially inappropriate medications (PPIMs) (e.g., sedatives, opioids) with altered mental status (AMS) and falls, and whether the associations are modified by frailty. STUDY DESIGN: Observational cohort study. SETTING: & Participants: Adults receiving dialysis represented in the United States Renal Data System who had an active gabapentinoid prescription and no other PPIM prescriptions in the prior 6 months. EXPOSURE: PPIM coprescribing, or the presence of overlapping prescriptions of a gabapentinoid and ≥1 additional PPIM. OUTCOMES: Acute care visits for AMS and injurious falls. ANALYTICAL APPROACH: Prentice-Williams-Petersen Gap Time models estimated the association between PPIM coprescribing and each outcome, adjusting for demographics, comorbidities, and frailty (assessed by a validated frailty index (FI)). Each model tested for interaction between PPIM coprescribing and frailty. RESULTS: Overall, PPIM coprescribing was associated with increased hazard of AMS (HR: 1.66 [95% CI 1.44, 1.92]) and falls (HR: 1.55 [95% CI 1.36, 1.77]). Frailty significantly modified the effect of PPIM coprescribing on the hazard of AMS (interaction p=0.01), but not falls. Among individuals with low frailty (FI=0.15), the hazard ratio for AMS with PPIM co-prescribing was 2.14 (95% CI: 1.69, 2.71); while for individuals with severe frailty (FI=0.34), the hazard ratio for AMS with PPIM coprescribing was 1.64 (95% CI: 1.42, 1.89). Individuals with PPIM coprescribing and severe frailty (FI =0.34) had the highest hazard of AMS [HR 4.04 (95% CI: 3.20, 5.10)] and falls [HR 2.77 (95% CI: 2.27, 3.38)] compared to non-frail individuals without PPIM coprescribing. LIMITATIONS: Outcome ascertainment bias; residual confounding. CONCLUSIONS: Compared to gabapentinoid prescriptions alone, PPIM coprescribing was associated with an increased risk of AMS and falls. Clinicians should consider these risks when coprescribing PPIMs to patients receiving dialysis.

Evaluation and Management of Resistant Hypertension: Core Curriculum 2024.

Resistant hypertension is defined as blood pressure above goal despite confirmed adherence to 3 first-line antihypertensive agents or when blood pressure is controlled with 4 or more medications at maximal or maximally tolerated doses. In addition to meeting these criteria, identifying patients with true resistant hypertension requires both accurate in-office blood pressure measurement as well as excluding white coat effects through out-of-office blood pressure measurements. Patients with resistant hypertension are at higher risk for adverse cardiovascular events and are more likely to have a potentially treatable secondary cause contributing to their hypertension. Effective treatment of resistant hypertension includes ongoing lifestyle modifications and collaboration with patients to detect and address barriers to optimal medication adherence. Pharmacologic treatment should prioritize optimizing first-line, once daily, longer acting medications followed by the stepwise addition of second-, third-, and fourth-line agents as tolerated. Physicians should systematically evaluate for and address any underlying secondary causes. A coordinated, multidisciplinary team approach including clinicians with experience in treating resistant hypertension is essential. New treatment options, including both pharmacologic and device-based therapies, have recently been approved, and more are in the pipeline; their optimal role in the management of resistant hypertension is an area of ongoing research.

Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

OBJECTIVES: Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy. METHODS: Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals. RESULTS: Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients. CONCLUSION: Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.

A cost analysis of medications prescribed by vascular surgeons.

OBJECTIVE: Various pharmaceutical cost options have been developed by multiple companies such as GoodRx, Amazon Pharmacy, Mark Cuban Cost Plus Drugs (CPD), Health Warehouse, and local retail pharmacies) to curb the cost of prescription medications prices that patients are having to bear. Vascular surgeons provide long-term continuity of care to patients with vascular disease who often require long-term medical management. This study sought to compare the different pharmaceutical options available for the most prescribed medications by vascular surgeons to their patients and to understand which of them are the most cost-effective. METHODS: The Medicare Part D catalog and vascular surgical literature were evaluated to identify which medications are most prescribed by vascular surgeons. The average price per tablet being paid by patients was identified using the Agency for Healthcare and Research database. The prices per tablet for each of the above pharmaceutical companies were found using online catalogs or coupons. The prices were then compared using analysis of variance and t-tests. RESULTS: All four pharmaceutical cost options provide medication cost savings to patients compared with retail pharmacy costs. Analysis of variance showed that there were statistically significant differences among the different pharmaceutical cost options (F 15.44>2.36; P < .001). Mark Cuban CPD provided the most significant cost advantage over the other pharmaceutical options (P < .01). On a national scale, medications prescribed by vascular surgeons through Mark Cuban CPD could provide a 52% cost reduction to patients with vascular disease with a potential annual savings of over $3 billion dollars for the selected medications. CONCLUSIONS: CPD shows a strong potential for cost savings for patients commonly prescribed medications by vascular surgeons. As a specialty that provides long-term care and establishes long-term relationships with its patients, vascular surgeons have the unique ability to impact their overall health in a meaningful way by limiting the financial burdens associated with vascular-based medication acquisition and utilization.

Endocrine disruption and male reproductive disorders: unanswered questions.

Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health due to impaired foetal androgen production/action. However, the epidemiological evidence supporting this view is equivocal, except for certain phthalates, notably diethyl hexyl phthalate (DEHP). Maternal phthalate exposure levels associated with adverse reproductive changes in epidemiological studies are several thousand-fold lower than those needed to suppress foetal androgen production in rats, and direct studies using human foetal testis tissue show no effect of high phthalate exposure on androgen production. This conundrum is unexplained and raises fundamental questions. Human DEHP exposure is predominantly via food with highest exposure associated with consumption of a Western style (unhealthy) diet. This diet is also associated with increased exposure to the most common EDCs, whether persistent (chlorinated or fluorinated chemicals) or non-persistent (phthalates, bisphenols) compounds, which are found at highest levels in fatty and processed foods. Consequently, epidemiological studies associating EDC exposure and male reproductive health disorders are confounded by potential dietary effects, and vice versa. A Western diet/lifestyle in young adulthood is also associated with low sperm counts. Disentangling EDC and dietary effects in epidemiological studies is challenging. In pregnancy, a Western diet, EDC exposure, and maternal living in proximity to industrial sites are all associated with impaired foetal growth/development due to placental dysfunction, which predisposes to congenital male reproductive disorders (cryptorchidism, hypospadias). While the latter are considered to reflect impaired foetal androgen production, effects resulting from foetal growth impairment (FGI) are likely indirect. As FGI has numerous life-long health consequences, and is affected by maternal lifestyle, research into the origins of male reproductive disorders should take more account of this. Additionally, potential effects on foetal growth/foetal testis from the increasing use of medications in pregnancy deserves more research attention.

Errors and Adherence to Inhaled Medications in Chinese Adults with COPD.

BACKGROUND: Adherence to inhaled medications is key to chronic obstructive pulmonary disease (COPD) control and management. OBJECTIVE: To assess errors and adherence to inhalation therapy in COPD patients, and identify potential factors associated with poor adherence. METHODS: This cross-sectional study was conducted from October 1, 2022, to November 30, 2022, in 24 hospital outpatient departments in different cities of Hunan Province, China. Adherence to inhaled medications was measured using the 10-item Test of Adherence Inventory, and the results were expressed using both descriptive and inferential statistics. RESULTS: A total of 2218 clinically confirmed adult COPD patients completed the questionnaires, and 1423 patients with more than a 3-month history of inhalation therapy were analyzed. This study found that 61.3% of patients made one or more use errors. Not holding the breath after inhalation or holding the breath for less than 3 s had the highest reporting rate (30.7%). A considerable proportion of patients (66.6%) demonstrated suboptimal adherence to inhaled medications. Patients who resided in rural areas (OR 1.45, 95% CI 1.12-1.88), used dual therapy (OR 1.47, 95% CI 1.05-2.05), and exhibited common use errors (OR 3.02, 95% CI 2.39-3.82) were more likely to present suboptimal adherence. Patients with CAT (Chronic Obstructive Pulmonary Disease Assessment Test) score < 10 (OR 0.73, 95% CI 0.56-0.94), a junior high school education and above (OR 0.73, 95% CI 0.57-0.94), and duration of inhaled medication use > 3 years (OR 0.63, 95% CI 0.47-0.83) were associated with better adherence. CONCLUSION: Suboptimal adherence to inhaled medications and many inhalation therapy errors were identified among COPD patients. Common use errors in inhaled medications, CAT score, and education background were predictive of and influenced adherence to inhaled medications. It is necessary to strengthen training in Chinese patients about inhaler use and follow-up intensively with patients throughout treatment, especially for patients with risk factors.

Contribution of Potentially Inappropriate Medications to Polypharmacy-Associated Risk of Mortality in Middle-Aged Patients: A National Cohort Study.

BACKGROUND: The role of potentially inappropriate medications (PIMs) in mortality has been studied among those 65 years or older. While middle-aged individuals are believed to be less susceptible to the harms of polypharmacy, PIMs have not been as carefully studied in this group. OBJECTIVE: To estimate PIM-associated risk of mortality and evaluate the extent PIMs explain associations between polypharmacy and mortality in middle-aged patients, overall and by sex and race/ethnicity. DESIGN: Observational cohort study. SETTING: Department of Veterans Affairs (VA), the largest integrated healthcare system in the US. PARTICIPANTS: Patients aged 41 to 64 who received a chronic medication (continuous use of ≥ 90 days) between October 1, 2008, and September 30, 2017. MEASUREMENT: Patients were followed for 5 years until death or end of study period (September 30, 2019). Time-updated polypharmacy and hyperpolypharmacy were defined as 5-9 and ≥ 10 chronic medications, respectively. PIMs were identified using the Beers criteria (2015) and were time-updated. Cox models were adjusted for demographic, behavioral, and clinical characteristics. RESULTS: Of 733,728 patients, 676,935 (92.3%) were men, 479,377 (65.3%) were White, and 156,092 (21.3%) were Black. By the end of follow-up, 104,361 (14.2%) patients had polypharmacy, 15,485 (2.1%) had hyperpolypharmacy, and 129,992 (17.7%) were dispensed ≥ 1 PIM. PIMs were independently associated with mortality (HR 1.11, 95% CI 1.04-1.18). PIMs also modestly attenuated risk of mortality associated with polypharmacy (HR 1.07, 95% CI 1.03-1.11 before versus HR 1.05, 95% CI 1.01-1.09 after) and hyperpolypharmacy (HR 1.18, 95% CI 1.09-1.28 before versus HR 1.12, 95% CI 1.03-1.22 after). Patterns varied when stratified by sex and race/ethnicity. LIMITATIONS: The predominantly male VA patient population may not represent the general population. CONCLUSION: PIMs were independently associated with increased mortality, and partially explained polypharmacy-associated mortality in middle-aged people. Other mechanisms of injury from polypharmacy should also be studied.