SARS-CoV-2 infection and long COVID among California farmworkers.

PURPOSE: The purpose of this cross-sectional study was to determine the prevalence of long COVID and identify its clinical manifestations among farmworkers in California. METHODS: We collected data on sociodemographic characteristics, anthropometrics, clinical chemistries and anti-SARS-CoV-2 immunoglobulin G antibodies, self-reported SARS-CoV-2 infection history, and standardized health tests and scales from 297 farmworkers in California between February and July 2022. RESULTS: Most participants were born in Mexico or Central America, had less than a high school diploma, and were overweight or obese. The prevalence of long COVID (defined as self-reported SARS-CoV-2 infection with symptoms >28 days) among farmworkers with a suspected or test-confirmed infection was 61.8%. Participants with long COVID had higher mean [95% CI] body mass index (32.9 [31.6-34.1]) and high-sensitivity C-reactive protein levels (4.8 [3.7, 6.0]) than those with no COVID-19 history (30.5 [29.3-31.7], and 3.3 [2.2, 4.3], respectively). Farmworkers with long COVID also reported greater fatigue, dyspnea, taste and smell problems, and overall poorer mental and physical health, than those with no COVID-19 history. Farmworkers with long COVID had increased odds of functional limitations compared to those with a self-reported SARS-CoV-2 infection with symptoms ≤28 days (OR [95% CI]: 7.46 [3.26, 17.09]). CONCLUSIONS: A significant proportion of farmworkers experience long COVID with persistent symptoms that limit their ability to perform their work. A comprehensive approach that addresses the unique needs and challenges of farmworkers is warranted given this population's high prevalence of long COVID and the essential nature of their work.

Integration of modeling and simulation to support changes to ondansetron dosing following a randomized, double-blind, placebo-, and active-controlled thorough QT study.

Prolongation of the QT interval has been observed with ondansetron and other members of the 5-HT3 antagonist class. This is the first thorough QTc study of ondansetron conducted in accordance with ICH E14 guidelines, designed to investigate the effect of single intravenous (IV) doses of ondansetron on cardiac conduction compared to placebo and a positive control, moxifloxacin, in healthy subjects. Statistical analysis of dose-response showed the maximum mean difference in QTcF, compared to placebo and corrected for baseline (ddQTcF), was less than 10 milliseconds (ms) after an 8 mg IV dose and approximately 20 ms after the 32 mg dose, each infused over 15 minutes. The concentration-response (Cp-ddQTcF) model resulted in similar predictions for the 8 and 32 mg and was used to predict the maximum mean ddQTcF (upper 90% CI bound) of 9.2 (11.2) ms for 16 mg IV. As a result, single IV doses of ondansetron greater than 16 mg should no longer be used. Adult cancer patients, under 75 years, may receive up to a maximum initial 15-minute IV dose of 16 mg, prior to chemotherapy, followed by 2 additional IV or IM doses of 8 mg for the management of chemotherapy-induced nausea and vomiting (CINV).

Effects of Esomeprazole on the Pharmacokinetics of Lapatinib in Breast Cancer Patients.

The aqueous solubility of lapatinib declines significantly at pH >4, suggesting that its bioavailability might be lowered by acid-reducing drugs. A study was therefore conducted to assess the effects of esomeprazole on lapatinib pharmacokinetics (PK). Women with metastatic human epidermal growth factor receptor 2 positive (HER2(+) ) breast cancer were enrolled. Patients received 1,250 mg lapatinib once daily (QD) in the morning on Days 1-7 (Period 1) and Days 8-14 (Period 2) with 40 mg esomeprazole QD at bedtime 3 hours after dinner on Days 8-14. Lapatinib PK sampling occurred during the 24-hour steady-state dosing intervals on Day 7 (lapatinib alone) and Day 14 (lapatinib with esomeprazole). Esomeprazole treatment resulted in decreased lapatinib bioavailability (mean 26%, range 6-49%) that was inversely associated with patient age as a significant covariate.

Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: a randomized, double-blind, exploratory crossover study.

CONTEXT: Recently, a new oral prolonged-release formulation of morphine sulfate for once-daily dosing has been developed based on an injection-molded matrix (abuse-deterrent, prolonged-release erodible matrix [ADPREM]). OBJECTIVES: The objective of this double-blind, randomized, exploratory crossover study was to assess the efficacy and safety of once-daily ADPREM compared with twice-daily controlled-release morphine (CRM; MST ContinusNapp Pharmaceuticals, Cambridge, UK). METHODS: Thirty-eight adult cancer pain patients participated in the study, which consisted of a run-in period for stabilization and two consecutive fixed-dose treatment periods of two weeks' duration each. Rescue medication, immediate-release morphine sulfate, was available during the entire study for treatment of breakthrough pain (BTP). RESULTS: There was no difference between the treatments in use of rescue medication. The medians of the average number of rescue doses per day were 1.0 and 0.7 during the ADPREM and CRM treatment periods, respectively, with an estimated median difference of 0.07 dose/day (95% confidence interval: -0.21, 0.29). Likewise, no differences between treatments were found for the number of BTP episodes per day or morning and evening ratings of pain intensity (current, average, minimum, and maximum). Median assessment of the drugs was "good" for both treatments, and neither of the treatments was preferred. Steady-state trough concentrations of morphine and its metabolites in plasma before morning dosing were similar after either treatment period. The adverse events were as expected in an opioid-treated cancer population and showed no differences between ADPREM and CRM. CONCLUSION: In this study, dosing with ADPREM at intervals of 24 hours was therapeutically equivalent to CRM dosed at intervals of 12 hours.

Relationship between depression severity entry criteria and antidepressant clinical trial outcomes.

BACKGROUND: We assessed whether increasing the minimum prerandomization Hamilton Depression Rating Scale (HAM-D) score to enrich the severity of the depressed sample affects antidepressant trial outcome. METHODS: Using the Food and Drug Administration Summary Basis of Approval reports, we examined outcome data from 51 clinical trials (11,270 depressed patients) evaluating 10 investigational antidepressants. RESULTS: Using four categories of trials with increasing minimum HAM-D entry trial criteria, we found no statistically significant relationship between prerandomization categories and trial outcome overall. Although there were minor differences in trial outcome among the three categories with the lowest entry criteria (mean 49%, range, 44.4%-50.0%), the antidepressant trials requiring the highest prerandomization HAM-D score (> or = 20 HAM-D 17) had the lowest frequency of positive outcomes (20%), chi(2) = 4.04, df =1, p = .04. Paradoxically, high entry criteria requirements failed to increase reliably actual mean total prerandomization HAM-D scores, although mean total prerandomization HAM-D scores and use of flexible dosing were associated with higher rates of positive outcome. A greater placebo response was seen in trials requiring higher prerandomization depressive symptoms. CONCLUSIONS: In summary, requiring higher prerandomization depressive symptoms was not associated with an increased rate of favorable outcomes among these 51 antidepressant trials.

Court-mediated disputes between physicians and families over the medical care of children.

OBJECTIVE: To describe the judiciary's approach to parent-physician disputes over the care of sick children. DATA SOURCES: Court publications. STUDY SELECTION: Fifty parent-physician disagreements over the care of children led to physician requests for court intervention and resulted in judicial opinions published by the court. The opinions describe 66 children from 20 states. DATA SYNTHESIS: Physicians prevailed at the initial decision in 44 (88%) of the 50 disputes and at the final decision in 40 disputes (80%). Physicians were more likely to prevail in religion-based disputes than in other cases (27 of 30 vs 13 of 20; P<.03), but they were less likely to prevail in disputes concerning life-threatening or potentially disabling conditions (23 of 31 vs 17 of 19; P<.19). Courts acknowledged the pediatric patients' views in only 10 of the disputes (9 of the 19 cases involving adolescents and 1 of the 31 cases involving children younger than 12 years). For most courts, the petitioning physicians provided the only source of scientific information. CONCLUSIONS: Published court opinions create precedents for future decisions and provide insight into the consequences of seeking court intervention for the physician who encounters parental refusal of care.

Analgesics for acute pain: Meeting the United States Food and Drug Administration's requirements for proof of efficacy.

OBJECTIVE: To examine the United States Food and Drug Administration's (FDA) standards for reviews of the scientific basis for efficacy claims for newly approved oral analgesics. METHODS: Comparison of the trial methodologies and results provided by the FDA's medical reviewer in the Summary Bases of Approval (SBA) for the 9 oral acute analgesics approved in the last 10 years: ketorolac, diclofenac potassium, bromfenac, tramadol, hydrocodone/ibuprofen fixed combination, celecoxib, rofecoxib, tramadol/acetaminophen, and valdecoxib. RESULTS: For all 9 new analgesics, studies were conducted in patients with postoperative dental pain and nondental surgical pain. The relief of gynecologic pain was examined for 5 of the new drugs. No studies in other pain models (such as infection, neuropathy, and nonsurgical trauma) supported claims of efficacy for any of the new drugs. The overall designs of the dental and nondental surgical studies, including timing of the single dose of trial drug, timing of evaluations, scales used for evaluations, and the use of both measured and derived outcome variables, were similar across the 8 development programs fully described in SBAs. Other characteristics of the trials, including choice of population for efficacy analyses, methods of carrying forward pain intensity and pain relief scores, and the length of time patients were encouraged to refrain from use of rescue medication differed across the development programs. CONCLUSION: The requirements for approval of new analgesics in the United States encourage the pharmaceutical industry to perform efficacy studies using stylized designs in dental and nondental surgical pain. Studies of the efficacy of new analgesics in other common clinical settings are rarely or never included in development programs.

The first 1000 dendritic cell vaccinees.

Dendritic cells (DCs) are potent antigen-presenting cells that have the ability to stimulate primary T cell antitumor immune responses in animals and humans. Since the first published clinical trial of dendritic cell vaccination in 1995, 98 studies describing more than 1000 vaccinees have been published in peer-reviewed medical journals or presented at the annual meetings of the American Society for Clinical Oncology, the American Association of Cancer Research, or the American Society of Hematology. Trials have been performed in 15 countries. Trials included patients with more than two dozen tumor types; most trials studied patients with malignant melanoma, prostate cancer, colorectal carcinoma, or multiple myeloma, using autologous DCs pulsed with synthetic antigens or idiotype antibodies. The DC vaccines were also prepared by pulsing DCs with tumor lysates or RNA, by transfection with tumor DNA, or by creating tumor cell/DC fusions. Various approaches to vaccine cell numbers, length of vaccine program, site of vaccination, frozen preservation of vaccine, and use of a maturations step for DCs were used. Adverse effects associated with DC vaccination were uncommon; most were mild and self-limited and none were serious. Clinical responses were observed in approximately half the trials. The DC vaccination may provide a safe approach to cancer immunotherapy that can overcome the limited reach and immunogenicity of peptide vaccines.