Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC) and patients with HPV-associated HNSCC have a favorable prognosis. Currently there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serological HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among HNSCC patients, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients, immunohistochemical detection of p16 expression in tumors was performed in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases’ tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease (HRE6/E7+ =0.1, 95%CI=0.02–0.3). Neither the presence of HPV16 DNA or p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease ( HRDNA=0.9, 95% CI-0.3–2.9; HRp16=0.3, 95%CI=0.1–1.1). However, the combination of HPV positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HRDNA +/E6/E7+=0.1, 95%CI=0.02–1.0), while E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HRDNA+/E6−/E7−=3.4, 95%CI = 0.6–18.1). Further, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HRp16+/E6/E7+=0.1, 95%CI=0.02–0.4), while patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HRp16+/E6−/E7−=3.1, 95%CI=1.2–7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.

Purpose The study aims to develop and validate algorithms to identify and classify opioid overdoses using claims and other coded data, and clinical text extracted from electronic health records using natural language processing (NLP). Methods Primary data were derived from Kaiser Permanente Northwest (2008–2014), an integrated health care system (~n > 475 000 unique individuals per year). Data included International Classification of Diseases, Ninth Revision (ICD‐9) codes for nonfatal diagnoses, International Classification of Diseases, Tenth Revision (ICD‐10) codes for fatal events, clinical notes, and prescription medication records. We assessed sensitivity, specificity, positive predictive value, and negative predictive value for algorithms relative to medical chart review and conducted assessments of algorithm portability in Kaiser Permanente Washington, Tennessee State Medicaid, and Optum. Results Code‐based algorithm performance was excellent for opioid‐related overdoses (sensitivity = 97.2%, specificity = 84.6%) and classification of heroin‐involved overdoses (sensitivity = 91.8%, specificity = 99.0%). Performance was acceptable for code‐based suicide/suicide attempt classifications (sensitivity = 70.7%, specificity = 90.5%); sensitivity improved with NLP (sensitivity = 78.7%, specificity = 91.0%). Performance was acceptable for the code‐based substance abuse‐involved classification (sensitivity = 75.3%, specificity = 79.5%); sensitivity improved with the NLP‐enhanced algorithm (sensitivity = 80.5%, specificity = 76.3%). The opioid‐related overdose algorithm performed well across portability assessment sites, with sensitivity greater than 96% and specificity greater than 84%. Cross‐site sensitivity for heroin‐involved overdose was greater than 87%, specificity greater than or equal to 99%. Conclusions Code‐based algorithms developed to detect opioid‐related overdoses and classify them according to heroin involvement perform well. Algorithms for classifying suicides/attempts and abuse‐related opioid overdoses perform adequately for use for research, particularly given the complexity of classifying such overdoses. The NLP‐enhanced algorithms for suicides/suicide attempts and abuse‐related overdoses perform significantly better than code‐based algorithms and are appropriate for use in settings that have data and capacity to use NLP.

A retrospective cohort study, supplemented with a nested case-control study, was performed using two administrative databases from commercial health plans in the United States to compare the incidence of pancreatic and thyroid cancer among users of exenatide versus other antidiabetic drugs (OADs). Patients with type 2 diabetes who initiated exenatide or OADs between 1 June 2005 and 30 June 2015 were included. Pancreatic and thyroid cancers were identified using chart-validated algorithms in the cohort study. Cases in the nested case-control study were chart-confirmed pancreatic or thyroid cancers, and controls were sampled using risk-set sampling. The time-fixed analyses comparing 33 629 exenatide initiators with 49 317 propensity-score-matched OAD initiators yielded hazard ratios of 0.76 (95% confidence interval [CI] 0.47-1.21) for pancreatic cancer and 1.46 (95% CI 0.98-2.19) for thyroid cancer. Results in the time-dependent analyses by cumulative duration or dose were similar. Nested case-control analyses yielded rate ratios of 0.48 (95% CI 0.25-0.91) for pancreatic cancer and 0.87 (95% CI 0.59-1.29) for thyroid cancer. This observational study suggested exenatide use was not associated with an increased risk of pancreatic or thyroid cancer. K E Y W O R D S exenatide, GLP-1 receptor agonist, pancreatic cancer, thyroid cancer

Cannabinoids, constituents of marijuana smoke, have been recognized to have potential antitumor properties. However, the epidemiologic evidence addressing the relationship between marijuana use and the induction of head and neck squamous cell carcinoma (HNSCC) is inconsistent and conflicting.Cases (n = 434) were patients with incident HNSCC disease from nine medical facilities in the Greater Boston, MA area between December 1999 and December 2003. Controls (n = 547) were frequency matched to cases on age (±3 years), gender, and town of residence, randomly selected from Massachusetts town books. A questionnaire was adopted to collect information on lifetime marijuana use (decade-specific exposures) and associations evaluated using unconditional logistic regression.After adjusting for potential confounders (including smoking and alcohol drinking), 10 to 20 years of marijuana use was associated with a significantly reduced risk of HNSCC [odds ratio (OR) 10-<20 years versus never users , 0.38; 95% confidence interval (CI), 0.22-0.67]. Among marijuana users moderate weekly use was associated with reduced risk (OR 0.5-<1.5 times versus <0.5 time , 0.52; 95% CI, 0.32-0.85). The magnitude of reduced risk was more pronounced for those who started use at an older age (OR 15-<20 years versus never users , 0.53; 95% CI, 0.30-0.95; OR ≥20 years versus never users , 0.39; 95% CI, 0.17-0.90; P trend < 0.001). These inverse associations did not depend on human papillomavirus 16 antibody status. However, for the subjects who have the same level of smoking or alcohol drinking, we observed attenuated risk of HNSCC among those who use marijuana compared with those who do not.Our study suggests that moderate marijuana use is associated with reduced risk of HNSCC.Marijuana (Cannabis sativa) contains >60 unique compounds known as cannabinoids. The major active cannabinoid in marijuana is Δ 9 -tetrahydrocannabinol (1). Δ 9 -Tetrahydrocannabinol exerts a wide spectrum of biological effects by mimicking endogenous substances (the endocannabinoids anandamide and 2-arachidonoyl glycerol) that activate specific cell surface G-protein-coupled cannabinoid receptors (CB1 and CB2; ref. 2). CB2 receptors are highly expressed on immune cells and are believed to play an important role in immunomodulation by regulating cell migration and cytokine release (3), whereas CB1 receptors are mainly expressed in the central nervous system and involved in inhibition of the release of neurotransmitters (4). Both cannabinoid receptors are involved in transmission of signals via inhibiton of adenylyl cyclase and mitogen-activated protein kinases (5). Both of these signaling pathways are active in chronic inflammatory conditions as well as in malignant diseases, and therefore, cannabinoid receptors and the endocannabiniod system have been recently recognized as potential therapeutic targets in many conditions (2, 4).The association between marijuana use (and its constituent cannabinoids) and cancer has received considerable attention in the recent scien...

Objectives: The aim of this analysis was to describe nirmatrelvir/ritonavir real-world effectiveness in preventing hospitalization among high-risk US COVID-19 patients during SARS-CoV-2 Omicron predominance. Design: An ongoing population-based cohort study with retrospective and prospective collection of electronic healthcare data in the United States. Methods: Data for this analysis were collected from the US Optum de-identified COVID-19 Electronic Health Record (EHR) dataset during December 22, 2021 to June 8, 2022. Key eligibility criteria for inclusion in the database analysis were at least 12-years-old; positive SARS-CoV-2 test, COVID-19 diagnosis, or nirmatrelvir/ritonavir prescription; and high risk of severe COVID-19 based on demographic/clinical characteristics. Potential confounders between groups were balanced using propensity score matching (PSM). Immortal time bias was addressed. Outcome measures: Hospitalization rates within 30 (primary analysis) or 15 (sensitivity analysis) days from COVID-19 diagnosis overall and within subgroups were evaluated. Results: Before PSM, the nirmatrelvir/ritonavir group (n=2811) was less racially diverse, older, and had higher COVID-19 vaccination rates and a greater number of comorbidities than the non-nirmatrelvir/ritonavir group (n=194,542). Baseline characteristics were well balanced across groups (n=2808 and n=10,849, respectively) after PSM. Incidence of hospitalization (95% CI) within 30 days was 1.21% (0.84%, 1.69%) for the nirmatrelvir/ritonavir group and 6.94% (6.03%, 7.94%) for the non-nirmatrelvir/ritonavir group, with a hazard ratio (95% CI) of 0.16 (0.11, 0.22; 84% relative risk reduction). Incidence within 15 days was 0.78% (0.49%, 1.18%) for the nirmatrelvir/ritonavir group and 6.54% (5.65%, 7.52%) for the non-nirmatrelvir/ritonavir group; hazard ratio 0.11 (0.07, 0.17; 89% relative risk reduction). Nirmatrelvir/ritonavir was effective in African American patients (hazard ratio, 0.35 [0.15, 0.83]; 65% relative risk reduction). Relative risk reductions were comparable with overall results across ages and among vaccinated patients. Conclusions: Real-world nirmatrelvir/ritonavir effectiveness against hospitalization during the Omicron era supports EPIC-HR efficacy among high-risk patients. Future research should confirm these early real-world results and address limitations.

Measuring problem prescription opioid use among patients receiving long-term opioid analgesic treatment: development and evaluation of an algorithm for use in EHR and claims data,

Background:Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases.Methods:This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000–2/28/2013 and ≥6 months of previous continuous enrollment (baseline) within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD) patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated.Results:ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk.Conclusions:These results suggest that distribution of patients by age at transition to next stage may be useful for identification of ADPKD patients at risk of rapid progression. The results also suggest that medical claims with diagnosis codes for “unspecified PKD”, in absence of a diagnosis code for autosomal recessive polycystic kidney disease, may be a good proxy for ADPKD.

Background A genome-wide association study for upper aerodigestive tract cancers identified 19 candidate single-nucleotide polymorphisms (SNPs). We used these SNPs to investigate the potential gene-gene and gene-environment interactions in head and neck squamous cell carcinoma (HNSCC) risk. Methods The 19 variants were genotyped using Taqman (Applied Biosystems) assays among 575 cases and 676 controls in our population-based case-control study. Results A restricted cubic spline model suggested both ADH1B and HEL308 modified the association between smoking pack-years and HNSCC. Classification and regression tree analysis demonstrated a higher order interaction between smoking status, ADH1B, FLJ13089 and FLJ35784 in HNSCC risk. Compared with ever smokers carrying ADH1B T/C+T/T genotypes, smokers carrying ADH1B C/C genotype and FLJ13089 A/G+A/A genotypes had a highest risk of HNSCC (OR=1.84). Conclusions Our results suggest that the risk associated with these variants may be specifically important amongst specific exposure groups.