Real-world patient characteristics and treatment patterns in US patients with advanced non-small cell lung cancer.

BACKGROUND: Patients from non-small cell lung cancer (NSCLC) controlled clinical trials do not always reflect real-world heterogeneous patient populations. We designed a study to describe the real-world patient characteristics and treatment patterns of first-line treatment in patients in the US with NSCLC. METHODS: This was an observational, retrospective cohort study based on electronic medical records of US adults with locally advanced or metastatic disease in the ConcertAI Patient360 NSCLC database who initiated first-line treatment with anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy between July 2016 and December 2020. The analysis used patient attributes, clinical characteristics, and treatments from each patient's medical records. RESULTS: A total of 2175 patients were eligible for analysis. The median age was 68 years, and 26.2% of the patients were ≥75 years old. At treatment initiation, 96.4% and 3.6% of the patients had Stage 4 and Stage 3 (B or C) NSCLC, respectively. The most common histology type was nonsquamous adenocarcinoma (66.4%), and 19.8% had Eastern Cooperative Oncology Group performance status ≥2. Immunosuppressive medications were being used by 17.7% of patients, and 11.0% were immunocompromised. Almost all patients had metastases: 64.6% had 1, 23.2% had 2, and 8.0% had ≥3 metastatic sites. Brain metastases were present in 22.9% of patients. Treatment evolution was observed with first-line standard of care shifting from single-agent immunotherapy in 2016 (90.2%) to combination immunotherapy and chemotherapy in 2020 (60.2%). CONCLUSION: Between 2016 and 2020, the first-line treatment paradigm for advanced NSCLC in the US shifted from anti-PD-1/PD-L1 monotherapy to combination chemoimmunotherapy, with increasing biomarker testing. Further research in heterogeneous patient populations to characterize treatment strategies is warranted.

Contextual Factors Related to Conventional and Traditional Tobacco Use Among California Asian Indian Immigrants.

California's tobacco control program contracted for tobacco use surveillance of Asian Indian Americans to address the paucity of information about tobacco use in this community, given their growing proportion of California's population. This study examined correlates of conventional (CTU) and Asian Indian traditional tobacco use (TTU) in a population-based sample of predominantly immigrant Asian Indian adults residing in California (N = 3228). The analytic sample (n = 2140) was limited to self-identified immigrants from India. Descriptive statistics, bivariate analyses, and multivariate logistic regressions were conducted to examine correlates of tobacco use among Asian Indian immigrants related to their acculturation and religious affiliation. While 65% of the sample had ever used traditional tobacco products (paan masala, gutka, bidis), only 25% had ever used conventional tobacco (cigarettes, cigar, pipe, chewing tobacco, snuff). Less than 5% reported tobacco use in the past 30 days. Rates of ever TTU and CTU were higher among men than women. Ethnic enclave residence was not associated with tobacco use. Impaired mental health was associated with CTU, and number of years spent in the U.S. was positively associated with both CTU and TTU. Individuals affiliated with Sikhism were less likely to use tobacco than individuals affiliated with Hinduism. Few population-based studies in the U.S. address both CTU and TTU use among Asian Indian immigrants. Tobacco use in Asian Indian immigrants may be seriously underestimated if surveillance is limited to conventional tobacco products. Interventions to reduce tobacco use should address mental health issues and consider religious affiliation.

Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

OBJECTIVES: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. PATIENTS AND METHODS: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. RESULTS: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. CONCLUSIONS: Results support prostate safety of TRT in newly diagnosed men with HG.

Immune globulins and same-day thrombotic events as recorded in a large health care database during 2008 to 2012.

BACKGROUND: Thrombotic events (TEs) are rare and serious adverse events after administration of immune globulin (IG) products. Our study evaluated the occurrence of same-day TEs for different IG products and ascertained potential risk factors. STUDY DESIGN AND METHODS: This retrospective cohort study utilized HealthCore's Integrated Research Database (HIRD) to assess individuals exposed to IGs during 2008 to 2012. IG products were identified using recorded procedure codes and TEs were ascertained using ICD-9-CM diagnosis codes. The unadjusted same-day TE rates (per 1000 persons exposed) were estimated overall and by IG products, age, and sex. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for same-day TEs by IG products. RESULTS: Of 14,944 individuals exposed to IG products, 233 (15.6 per 1000 persons) had TE diagnosis code(s) recorded on the same-day as the IG exposure. Compared to Gammagard Liquid, Gammaplex (OR, 20.96; 95% CI, 2.45-179.33) and Vivaglobin (OR, 2.74; 95% CI, 1.19-6.32) users had a significantly increased same-day TE risk. Elevated, but nonsignificant TE risks were identified for Octagam, Gamunex, Privigen, and Lyophilized IG(s). An increased TE risk was also found with older age (≥45 years), prior TEs, and other health conditions. CONCLUSION: Our claims-based cohort study suggests a potentially elevated TE risk with different IG products and shows importance of recipient factors such as older age, previous TE, hypercoagulable state(s), and other health conditions. The results of this study suggest the need for continuous evaluation of procoagulant activity and manufacturing processes for IG products to further assure their safety.

Hyperimmune globulins and same-day thrombotic adverse events as recorded in a large healthcare database during 2008-2011.

Thrombotic events (TEs) are rare serious complications following administration of hyperimmune globulin (HIG) products. Our retrospective claims-based study assessed occurrence of same-day TEs following administration of HIGs during 2008-2011 and examined potential risk factors using HealthCore's Integrated Research Database (HIRD(SM) ) and laboratory testing of products' procoagulant Factor XIa activity by U.S. Food and Drug Administration. Multivariable regression was used to estimate same-day TE risk for different products. Of 101,956 individuals exposed to 23 different HIG product groups, 86 (0.84 per 1,000 persons) had a TE diagnosis code (DC) recorded on the same day as HIG administration. Unadjusted same-day TE DC rates (per 1,000 persons) ranged from 0.4 to 148.9 for different products. GamaSTAN S/D IG >10 cc had statistically significantly higher same-day TE DC risk compared to Tetanus IG (OR = 57.57; 95% CI = 19.72-168.10). Increased TE risk was also observed with older age (≥45 years), prior thrombotic events, and hypercoagulable state(s). Laboratory investigation identified elevated Factor XIa activity for GamaSTAN S/D, HepaGam B, HyperHep B S/D, WinRho SDF, HyperRHO S/D full dose, and HyperTET S/D. Our study, for the first time, identified increase in the same-day TE DC risk with GamaSTAN S/D IG >10 cc and suggests potentially elevated TE risk with other HIGs.

Real-world treatment patterns and outcomes of patients with metastatic nonsquamous non-small cell lung cancer after progression on standard-of-care therapy in the United States.

OBJECTIVES: Data to guide treatment selection in metastatic nonsquamous (mNSq) non-small cell lung cancer (NSCLC) after progression on current standard-of-care (SoC) treatment are limited. We investigated patterns of treatment and clinical outcomes following one or more disease progressions on SoC. MATERIALS AND METHODS: Electronic medical records in the ConcertAI Patient360 NSCLC database were analyzed for US adults with mNSq NSCLC who initiated treatment between 2016 and 2021. Analyses were conducted separately for patients who had ≥1 prior lines of therapy and progression(s) without (Cohort 1) or with (Cohort 2) evidence of targetable genetic alterations (EGFR, ALK, or ROS1). Outcomes included real-world progression-free survival (rwPFS) and overall survival (rwOS). RESULTS: Cohorts 1 and 2 included 281 and 109 patients, respectively. In Cohort 1, subsequent treatment was most often with docetaxel monotherapy (18.5%) or docetaxel + ramucirumab (32.4%). Most patients in Cohort 2 received platinum-based doublet chemotherapy with (22.9%) or without (34.9%) immunotherapy. Median rwPFS and rwOS were 2.9 and 7.2 months, respectively, in Cohort 1, and 3.2 and 10.4 months in Cohort 2. Neither the addition of ramucirumab to docetaxel in Cohort 1 nor the addition of immunotherapy to chemotherapy in Cohort 2 was associated with a marked improvement in additional survival. CONCLUSION: Patients with progressive mNSq NSCLC most commonly received later-line docetaxel for cancer without driver mutations, or platinum-based chemotherapy (following one or more lines of tyrosine kinase inhibitor therapy) for cancer with driver mutations, consistent with guideline recommendations. Median survival was poor regardless of subsequent treatment, highlighting the need for more effective options.

Prenatal and postnatal exposure to cell phone use and behavioral problems in children.

BACKGROUND: The World Health Organization has emphasized the need for research into the possible effects of radiofrequency fields in children. We examined the association between prenatal and postnatal exposure to cell phones and behavioral problems in young children. METHODS: Mothers were recruited to the Danish National Birth Cohort early in pregnancy. When the children of those pregnancies reached 7 years of age in 2005 and 2006, mothers were asked to complete a questionnaire regarding the current health and behavioral status of children, as well as past exposure to cell phone use. Mothers evaluated the child's behavior problems using the Strength and Difficulties Questionnaire. RESULTS: Mothers of 13,159 children completed the follow-up questionnaire reporting their use of cell phones during pregnancy as well as current cell phone use by the child. Greater odds ratios for behavioral problems were observed for children who had possible prenatal or postnatal exposure to cell phone use. After adjustment for potential confounders, the odds ratio for a higher overall behavioral problems score was 1.80 (95% confidence interval = 1.45-2.23) in children with both prenatal and postnatal exposure to cell phones. CONCLUSIONS: Exposure to cell phones prenatally-and, to a lesser degree, postnatally-was associated with behavioral difficulties such as emotional and hyperactivity problems around the age of school entry. These associations may be noncausal and may be due to unmeasured confounding. If real, they would be of public health concern given the widespread use of this technology.

Risk of Incident Antidepressant-Treated Depression Associated with Use of 5α-Reductase Inhibitors Compared with Use of α-Blockers in Men with Benign Prostatic Hyperplasia: A Population-Based Study Using the Clinical Practice Research Datalink.

STUDY OBJECTIVE: To estimate the risk of incident antidepressant-treated depression in men with benign prostatic hyperplasia (BPH) who were prescribed 5α-reductase inhibitors (5-ARIs) compared with those prescribed an active comparator, α-blockers (ABs). DESIGN: Retrospective cohort study with a nested case-control analysis. DATA SOURCE: United Kingdom's Clinical Practice Research Datalink. PATIENTS: A total of 77,732 men with a diagnosis of BPH who received a prescription for a 5-ARI only and/or AB between January 1, 1992, and December 31, 2013. Of these men, 2842 had a first-time (incident) diagnosis of depression and received a prescription for an antidepressant within 90 days of the depression diagnosis date (cases); 11,333 controls without a diagnosis of depression were matched to the cases for the case-control analysis. MEASUREMENTS AND MAIN RESULTS: Exposures were classified as 5-ARI only, 5ARI + AB, or AB only. We calculated incidence rates of antidepressant-treated depression and compared rates among users of 5-ARIs only and 5-ARIs + ABs with rates among users of ABs only (i.e., incidence rate ratios [IRRs]). We also calculated odds ratios (ORs) to estimate the risk of incident depression with use of 5-ARIs only and 5-ARIs + ABs compared with ABs only. In this population of men with BPH, the risk of depression was not increased with use of 5-ARIs only (IRR 0.94, 95% confidence interval [CI] 0.85-1.04) or 5-ARIs + ABs (IRR 1.04, 95% CI 0.89-1.21) compared with use of ABs only. In the case-control analysis, exposure to 5-ARIs only (adjusted OR 0.88, 95% CI 0.78-1.01) or 5-ARIs + ABs (adjusted OR 0.90, 95% CI 0.73-1.10) was not associated with the risk of treated depression compared with exposure to ABs only, and results remained null regardless of number of prescriptions or timing of exposure. The risk of incident antidepressant-treated depression increased with longer duration of BPH, independent of study drug exposure. CONCLUSION: In this population of men with treated BPH, use of 5-ARIs, alone or in combination with ABs, did not increase the risk of incident antidepressant-treated depression compared with use of ABs only. Risk of treated depression increased with longer duration of BPH.

Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia.

BACKGROUND: Clinical trial results suggest that 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) may increase the risk of gynecomastia and male breast cancer, but epidemiological studies have been limited. PATIENTS AND METHODS: We conducted a cohort study with nested case-control analyses using the UK Clinical Practice Research Datalink. We identified men diagnosed with BPH who were free from Klinefelter syndrome, prostate, genital or urinary cancer, prostatectomy or orchiectomy, or evidence of gynecomastia or breast cancer. Patients entered the cohort at age ≥40 years and at least 3 years after the start of their electronic medical record. We classified exposure as 5ARIs (alone or in combination with alpha blockers [ABs]), AB only, or unexposed to 5ARIs and ABs. Cases were men who had a first-time diagnosis of gynecomastia or breast cancer. Incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) in the gynecomastia analysis and crude and adjusted odds ratios (ORs) with 95% CIs in both analyses were calculated. RESULTS: Compared to no exposure, gynecomastia risk was elevated for users of 5ARIs (alone or in combination with ABs) in both the cohort (IRR=3.55, 95% CI 3.05-4.14) and case-control analyses (OR=3.31, 95% CI 2.66-4.10), whereas the risk was null for users of AB only. The increased risk of gynecomastia with the use of 5ARIs persisted regardless of the number of prescriptions, exposure timing, and presence or absence of concomitant prescriptions for drugs known to be associated with gynecomastia. The risk was higher for dutasteride than for finasteride. 5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61-3.80). CONCLUSION: In men with BPH, 5ARIs significantly increased the risk of gynecomastia, but not breast cancer, compared to AB use and no exposure.

Risk of erectile dysfunction associated with use of 5-α reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink.

OBJECTIVE:  To estimate the risk of erectile dysfunction in men who used 5-α reductase inhibitors to treat benign prostatic hyperplasia or alopecia. DESIGN:  Cohort studies with nested case-control analyses. SETTING:  UK Clinical Practice Research Datalink. POPULATION:  Two populations of men free of risk factors for erectile dysfunction and other sexual dysfunction or its treatment: men aged 40 or more with benign prostatic hyperplasia who received a prescription for a 5-α reductase inhibitor (finasteride or dutasteride) or α blocker, or both, and men aged 18-59 with alopecia. EXPOSURES:  In the benign prostatic hyperplasia study, exposures were classified as 5-α reductase inhibitors only, 5-α reductase inhibitors+α blockers, or α blockers only. In the alopecia study, exposures were finasteride 1 mg or no treatment. MAIN OUTCOME MEASURES:  Cases were men with a diagnosis of erectile dysfunction or treatment (procedure or prescription for a phosphodiesterase type 5 inhibitor) during follow-up. We calculated incidence rates and adjusted incidence rate ratios with 95% confidence intervals. We also conducted nested case-control analyses to control for major confounders, and calculated adjusted odds ratios with 95% confidence intervals. RESULTS:  In the population with benign prostatic hyperplasia (n=71 849), the risk of erectile dysfunction was not increased with use of 5-α reductase inhibitors only (incidence rate ratio 0.92, 95% confidence interval 0.85 to 0.99; odds ratio 0.94, 95% confidence interval 0.85 to 1.03) or 5-α reductase inhibitors+α blocker (1.09, 0.99 to 1.21, 0.92; 0.80 to 1.06) compared with α blockers only, and remained null regardless of number of prescriptions or timing of use. The risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia, regardless of exposure. For the alopecia population (n=12 346), the risk of erectile dysfunction was not increased for users of finasteride 1 mg compared with unexposed men with alopecia (1.03, 0.73 to 1.44; 0.95, 0.64 to 1.41). CONCLUSION:  5-α reductase inhibitors do not seem to significantly increase the risk of incident erectile dysfunction, regardless of indication for use. Risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia.

Complexities of sibling analysis when exposures and outcomes change with time and birth order.

In this study, we demonstrate the complexities of performing a sibling analysis with a re-examination of associations between cell phone exposures and behavioral problems observed previously in the Danish National Birth Cohort. Children (52,680; including 5441 siblings) followed up to age 7 were included. We examined differences in exposures and behavioral problems between siblings and non-siblings and by birth order and birth year. We estimated associations between cell phone exposures and behavioral problems while accounting for the random family effect among siblings. The association of behavioral problems with both prenatal and postnatal exposure differed between siblings (odds ratio (OR): 1.07; 95% confidence interval (CI): 0.69-1.66) and non-siblings (OR: 1.54; 95% CI: 1.36-1.74) and within siblings by birth order; the association was strongest for first-born siblings (OR: 1.72; 95% CI: 0.86-3.42) and negative for later-born siblings (OR: 0.63; 95% CI: 0.31-1.25), which may be because of increases in cell phone use with later birth year. Sibling analysis can be a powerful tool for (partially) accounting for confounding by invariant unmeasured within-family factors, but it cannot account for uncontrolled confounding by varying family-level factors, such as those that vary with time and birth order.

Cell phone use and behavioural problems in young children.

BACKGROUND: Potential health effects of cell phone use in children have not been adequately examined. As children are using cell phones at earlier ages, research among this group has been identified as the highest priority by both national and international organisations. The authors previously reported results from the Danish National Birth Cohort (DNBC), which looked at prenatal and postnatal exposure to cell phone use and behavioural problems at age 7 years. Exposure to cell phones prenatally, and to a lesser degree postnatally, was associated with more behavioural difficulties. The original analysis included nearly 13 000 children who reached age 7 years by November 2006. METHODS: To see if a larger, separate group of DNBC children would produce similar results after considering additional confounders, children of mothers who might better represent current users of cell phones were analysed. This 'new' dataset consisted of 28 745 children with completed Age-7 Questionnaires to December 2008. RESULTS: The highest OR for behavioural problems were for children who had both prenatal and postnatal exposure to cell phones compared with children not exposed during either time period. The adjusted effect estimate was 1.5 (95% CI 1.4 to 1.7). CONCLUSIONS: The findings of the previous publication were replicated in this separate group of participants demonstrating that cell phone use was associated with behavioural problems at age 7 years in children, and this association was not limited to early users of the technology. Although weaker in the new dataset, even with further control for an extended set of potential confounders, the associations remained.

Prenatal cell phone use and developmental milestone delays among infants.

OBJECTIVE: The aim of this study was to examine if prenatal use of cell phones by pregnant mothers is associated with developmental milestones delays among offspring up to 18 months of age. METHODS: Our work is based upon the Danish National Birth Cohort (DNBC), which recruited pregnant mothers from 1996-2002, and was initiated to collect a variety of detailed information regarding in utero exposures and various health outcomes. At the end of 2008, over 41,000 singleton, live births had been followed with the Age-7 questionnaire, which collected cell phone use exposure for mothers during pregnancy. Outcomes for developmental milestones were obtained from telephone interviews completed by mothers at age 6 and 18 months postpartum. RESULTS: A logistic regression model estimated the odds ratios (OR) for developmental milestone delays, adjusted for potential confounders. Less than 5% of children at age 6 and 18 months had cognitive/language or motor developmental delays. At 6 months, the adjusted OR was 0.8 [95% confidence interval (95% CI) 0.7-1.0] for cognitive/language delay and 0.9 (95% CI 0.8-1.1) for motor development delay. At 18 months, the adjusted OR were 1.1 (95% CI 0.9-1.3) and 0.9 (95% CI 0.8-1.0) for cognitive/language and motor development delay, respectively. CONCLUSIONS: No evidence of an association between prenatal cell phone use and motor or cognitive/language developmental delays among infants at 6 and 18 months of age was observed. Even when considering dose-response associations for cell phone, associations were null.

Prevalence and predictors of smoking behavior among Vietnamese men living in California.

Vietnamese populations in Vietnam and the United States have a high prevalence of smoking. The associations among behavioral risk factors, acculturation, and smoking among the Vietnamese population living in the United States are not well documented. The present study aimed to identify the factors associated with smoking behavior among Vietnamese men living in Santa Clara County, California. A cross-sectional random-digit-dialed telephone survey was conducted. The sampling frame consisted of 27 Vietnamese surnames from the Santa Clara County telephone directory. A total of 660 adult respondents were interviewed to collect information on general health status, alcohol and tobacco use, HIV/AIDS, sexual behavior, injury control, hypertension, cholesterol screening, and acculturation. Of the 660 adults interviewed, 364 (55.2%) were male and 296 (44.8%) were female. Among males, 31.9% were current smokers, and among females, only one woman reported smoking. Univariate analyses revealed that having less than a college education, having poor English language skills, using Vietnamese at home and with friends, being less acculturated, not having a routine physical or blood cholesterol check, and being a binge drinker were significantly associated with an increased likelihood of smoking. Multivariate analysis revealed two independently associated factors: Respondents who were more acculturated were less likely to smoke (OR = 0.38, 95% CI = 0.18-0.83), and those not having cholesterol checked were more likely to smoke (OR = 2.48, 95% CI = 1.30-4.71). Acculturation level was inversely associated with smoking among Vietnamese adult men in Santa Clara County. Other health risk behaviors coexisted with smoking behavior and should be considered in prevention programs.

Cancer incidence and mortality in Asian Indians: a review of literature from the United States, South Asia, and beyond.

OBJECTIVE: The purpose of this paper is to provide a framework for future research and awareness activities in the United States. METHODS: The current literature in the English language on cancer incidence and mortality among Asian Indians was reviewed. RESULTS: Asian Indians comprise 89% of the U.S. South Asian population. There are few studies in the United States or Canada on cancer incidence or mortality. In India, oral and cervical cancers have high incidence and mortality rates, but the rates of cancers common in the West are rising. In Great Britain, cancer rates in the South Asian community are similar to those of their non-Asian counterparts. CONCLUSIONS: Cancer incidence and mortality rates in India and Great Britain provide a foundation for scientific inquiry among this population in the United States, but more data is needed to assess the cancer burden and implement cancer prevention activities in this country.