ThedaCare

Background: Opioids are utilized for acute pain in hospitalized patients and carry the risk of unintentional toxicity. The relationship between unintentional toxicity within a hospital setting and genetic polymorphisms has not been fully evaluated within the literature to date. Assessment and utilization of pharmacogenetic data may be a way to prevent unintentional toxicity in hospitalized patients and reduce the need for naloxone administration. Objective: This study aimed to provide proof of concept for the comparison of allele frequencies of hospitalized patients who received naloxone for opioid reversal with lab control data allele frequencies to identify variations between groups. Methods: This single-center, exploratory, pilot study enrolled 15 patients. Genotype samples were collected via buccal swab and analyzed using a custom 13 gene panel of genes which impact opioid metabolism. Genes assessed include CYP1A2, CYP3A4/A5, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, UGT2B7, UGT1A3, ABCB1, COMT, OPRM1. The 15 patients were compared to an internal lab control group of 100 patients and separated into preventable and not preventable events for further analysis. Results: CYP3A5 genotype was found to be statistically significantly different between the experimental and control groups (P = .004). This statistically significant difference was also seen in CYP3A5 phenotypes (P = .038). When comparing preventable and not preventable events, a statistically significant difference was found in both the genotype (P = .030) and phenotype (P = .029) of CYP2C19. Other assessed risk factors included mean MME in the 24 hours preceding naloxone being higher among preventable events and hospital or emergency department admission percent risk being higher among not preventable events. Conclusion: Factors other than pharmacogenetics, including opioid route of administration, medication formulation, and overall hospital admission risk, may play an additive role in unintentional toxicity risk. Future research of genotype-guided opioid dosing in pain management services further adds to calculating the risk of unintentional opioid-related adverse effects with standard dosing of this drug class.

BackgroundDirect-acting oral anticoagulants (DOACs) are recommended to reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). However, DOAC dosing inconsistent with FDA-approved product labels is common and associated with poor clinical outcomes.ObjectivesIdentify DOAC dosing inconsistent with FDA-approved product labels in ambulatory care patients with NVAF; identify variables associated with dosing lower and higher than label.DesignRetrospective analysis using electronic health records from nine US healthcare systems.PatientsAdults with NVAF receiving DOAC therapy in 2022.Main MeasuresRates of label-inconsistent dosing; multivariable regression analysis to identify demographic and clinical variables associated with dosing lower and higher than label.Key ResultsAmong 51,128 NVAF patients (56.1% male, 94.3% White, mean [SD] age 73.5 [10.5] years), 5008 (9.8%) were prescribed label-inconsistent doses of DOACs (6.8% lower and 3.0% higher than label). Age ≥ 75 years, renal impairment, and hypertension were significantly associated with inconsistent dosing both higher and lower than label. Female sex and higher weight were significantly associated with dosing lower than label, as were heart failure, vascular or liver disease, and bleeding history. Dosing higher than label was significantly associated with male sex, race (African American/Black), weight < 60 kg, and use of drugs with potential drug-drug interactions. When prescribed by primary care physicians, DOAC doses were 37% (95% CI, 27–49%) more likely to be lower than label and 30% (95% CI, 16–46%) more likely to be higher than label than when prescribed by cardiologists or electrophysiologists. Label-inconsistent dosing varied (6.7 to 15.8%) across participating systems.ConclusionsDOAC dosing inconsistent with label varied by demographics, clinical characteristics, prescriber specialty, and healthcare system, suggesting a need to monitor and assess dosing decisions in NVAF. Identification of variables associated with dosing inconsistencies may enable targeted interventions to ensure label-consistent dosing in vulnerable populations.

Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. To assess the long-term efficacy of acupuncture for CP/CPPS. Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938). Ten tertiary hospitals in China. Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P< 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P<0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported. Sham acupuncture might have had certain physiologic effects. Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment. China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.

Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.