Abstract
As advanced non-small cell lung cancer (aNSCLC) is being increasingly divided into rare oncogene-driven subsets, conducting randomised trials becomes challenging. Using real-world data (RWD) ...to construct control arms for single-arm trials provides an option for comparative data. However, non-randomised treatment comparisons have the potential to be biased and cause concern for decision-makers. Using the example of pralsetinib from a RET fusion-positive aNSCLC single-arm trial (NCT03037385), we demonstrate a relative survival benefit when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts. Quantitative bias analyses show that results for the RWD-trial comparisons are robust to data missingness, potential poorer outcomes in RWD and residual confounding. Overall, the study provides evidence in favour of pralsetinib as a first-line treatment for RET fusion-positive aNSCLC. The quantification of potential bias performed in this study can be used as a template for future studies of this nature.
Background
Despite known differences in breast cancer by both race and sexual orientation, data on the intersectional experiences of Black sexual minority women (BSMW) along the care continuum are ...scant. This study sought to understand delays in breast cancer care by examining the intersection of race and sexual orientation.
Methods
This online, cross‐sectional survey enrolled racially and sexually diverse women aged ≥ 35 years who had been diagnosed with breast cancer within the prior 10 years or had an abnormal screening in the prior 24 months. The authors calculated summary statistics by race/sexual orientation categories, and they conducted univariate and multivariable modeling by using multiple imputation for missing data.
Results
BSMW (n = 101) had the highest prevalence of care delays with 5.17‐fold increased odds of a care delay in comparison with White heterosexual women (n = 298) in multivariable models. BSMW reported higher intersectional stigma and lower social support than all other groups. In models adjusted for race, sexual orientation, and income, intersectional stigma was associated with a 2.43‐fold increase in care delays, and social support was associated with a 32% decrease in the odds of a care delay.
Conclusions
Intersectional stigma may be an important driver of breast cancer inequities for BSMW. Reducing stigma and ensuring access to appropriate social support that addresses known barriers can be an important approach to reducing inequities in the breast cancer care continuum.
Black sexual minority women are 5 times more likely to have delays in breast cancer care than White heterosexual women. Experiences of intersectional stigma increase the odds of a care delay, whereas social support decreases the odds of a care delay.
Purpose We present surgical modifications that improved the outcome of cutaneous ureterostomies. Materials and Methods A total of 310 patients with a median age of 71 years (range 38 to 88) underwent ...cutaneous ureterostomy as urinary diversion. Median followup was 25 months (range 1 to 172). The technique included 1) transposition of the left ureter above the inferior mesenteric artery, 2) mobilization of the ileocecal segment with repositioning above each terminal ureter, 3) abdominal wall hiatus fixation with 4 angle sutures and 4) YV plasty of the ureters with edge-to-edge anastomosis for stomal creation. In the 161 group 1 patients (59.1%) the Double-J® stents were removed in less than 3 months. Stents remained longer than 3 months in the 111 group 2 patients (40.8%). Results Of the 272 patients ureteral obstruction developed in 36 (13.2%). Ureteral obstruction was on the right side in 6 patients (2.2%), on the left side in 27 (9.9%) and bilateral in 3 (1.1%). Ureteral obstruction was treated with restenting in 20 cases (55.4%), stomal revision in 12 (33.3%) and conversion to a conduit in 4 (11%). Ureteral obstruction developed on the right side, on the left side and bilaterally in 3.7%, 13.7% and 1.82% of the patients in group 1, and in 0%, 4.5% and 0%, respectively, of those in group 2. Stenting time impacted only the left ureter with less obstruction in the group with longer stent placement (greater than 3 months) (p = 0.01). Conclusions As with other types of urinary diversion, left ureteral obstruction is a common complication of bilateral cutaneous ureterostomies. Long-term stenting for greater than 3 months and the applied surgical modifications improved the clinical outcome of this type of urinary diversion.
Atopic dermatitis (AD) is an inflammatory skin condition strongly associated with
colonization and infection.
strains shift in populations in ~10-year intervals depending on virulence factors. Shifts ...in
virulence factors may in part explain the racial differences observed in the levels of prevalence and severity of AD. AD
isolates collected from 2011 to 2014 (103 isolates) and in 2008 (100 isolates) were examined for the prevalence of genes encoding superantigens (SAgs). The strains from 2011 to 2014 were obtained from AD patients as a part of the National Institute of Allergy and Infectious Diseases (NIAID) Atopic Dermatitis Research Network (ADRN). The prevalence of SAg genes was investigated temporally and racially. The enterotoxin gene cluster (EGC) was more prevalent in the 2011-2014 AD isolates than in the 2008 AD isolates. The prevalences of virulence factor genes were similar in European American (EA) and Mexican American (MA) patients but differed in 6 of 22 SAg genes between EA and African American (AA) or MA and AA isolates; notably, AA isolates lacked
, the gene encoding toxic shock syndrome toxin 1 (TSST-1). The presence of
and
(enterotoxin-like P) was associated with decreased clinical severity and increased blood eosinophils, respectively. The EGC is becoming more prevalent, consistent with the previously observed 10 years of cycling of
strains. Race-specific
selection may account for differences in virulence factor profiles. The lack of TSST-1-positive (TSST-1
) AD
in AA is consistent with the lack of AAs acquiring TSST-1-associated menstrual toxic shock syndrome (TSS).
Monitoring pathogen emergence provides insight into how pathogens adapt in the human population. Secreted virulence factors, important contributors to infections, may differ in a manner dependent on the strain and host. Temporal changes of
toxigenic potential, for example, in encoding toxic shock syndrome toxin 1 (TSST-1), contributed to an epidemic of TSS with significant health impact. This study monitored changes in atopic dermatitis (AD)
isolates and demonstrated both temporal and host infection differences according to host race based on secreted superantigen potential. The current temporal increase in enterotoxin gene cluster superantigen prevalence and lack of the gene encoding TSST-1 in AAs predict differences in infection types and presentations.
Pharmacies have been endorsed as alternative vaccine delivery sites to improve vaccination rates through increased access to services. Our objective was to identify challenges and facilitators to ...adolescent and adult vaccination provision in pharmacy settings in the United States. We recruited 40 licensed pharmacists in states with different pharmacy vaccination laws. Eligible pharmacists previously administered or were currently administering human papillomavirus (HPV); tetanus, diphtheria, and pertussis (TDAP); or meningitis (meningococcal conjugate vaccine MCV4) vaccines to adolescents aged 9 to 17 years. Pharmacists participated in a semistructured survey on in-pharmacy vaccine provision. Pharmacists commonly administered vaccinations to age-eligible adolescents and adults: influenza (100%, 100%), pneumococcal (35%, 98%), TDAP (80%, 98%), MCV4 (60%, 78%), and HPV (45%, 53%). Common challenges included reimbursement/insurance coverage (28%, 78%), education of patients/parents (30%, 40%), and pharmacists’ time constraints (28%, 35%). Three-quarters of pharmacists reported that vaccination rates could be increased. National efforts should expand insurance coverage for vaccine administration reimbursement and improve data information systems to optimize provision within pharmacies.
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense ...by killing
, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against
was performed on isolates of coagulase-negative
(CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by
The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including
and
These AMPs were strain-specific, highly potent, selectively killed
, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by
These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra‐epithelial ...neoplasia (CIN). A total of 45 studies presented data on post‐treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon‐alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow‐up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow‐up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post‐treatment HPV persistence estimates varied widely and were influenced by patient age, HPV‐type, detection method, treatment method, and minimum HPV post‐treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post‐treatment HPV DNA testing practices and persistence estimates.
Trichomonas vaginalis (TV) is the most common curable sexually transmitted infection (STI) worldwide. Trichomonas vaginalis infection is associated with an increased risk of pelvic inflammatory ...disease, human immunodeficiency virus transmission, and preterm birth in women. Data on the prevalence and risk factors for TV infection in sub-Saharan African countries remain scarce.
A total of 350 Kenyan female sex workers, aged 18 to 50 years, participated in a 2-year longitudinal study of the acquisition of STIs, including TV infection. Every 3 months, cervical and vaginal brush samples were collected for STI testing. At baseline, a sociodemographic and behavior questionnaire was administered. Testing for TV, Chlamydia trachomatis (CT), Neisseria gonorrhoeae, Mycoplasma genitalium, and high-risk human papillomavirus was performed using APTIMA assays.
The TV baseline prevalence was 9.2% (95% confidence interval 95% CI, 6.3-12.7%) and 2-year cumulative TV incidence was 8.1 per 1000 person months (6.9-9.3). Risk factors for higher TV prevalence at baseline were CT infection (adjusted prevalence ratio PR, 8.53; 95% CI, 3.35-21.71), human immunodeficiency virus seropositivity (PR, 3.01; 95% CI, 1.45, 6.24) and greater than 4 years of sex work (PR, 2.66; 95% CI, 1.07-6.60). Risk factors for elevated 2-year TV incidence were CT (hazard ratio HR, 4.28; 95% CI, 1.36-13.50), high-risk human papillomavirus infection (HR, 1.91; 95% CI, 1.06-3.45) and history of smoking (HR, 2.66; 95% CI, 1.24-5.73).
CT infection was positively associated with both prevalent and 2-year incident TV infections.
Prenatal and early-life exposure to maternal stress and depression is linked to development of recurrent wheezing in young children.
We sought to determine whether maternal stress and depression in ...early life are associated with nonatopic wheezing phenotype in urban children.
The Urban Environment and Childhood Asthma Study examined a birth cohort of children at high risk for asthma in low-income neighborhoods. Prenatal and postnatal (through age 3 years) maternal stress and depression scores were compared with respiratory phenotypes through age 10 years (multinomial regression), self-reported colds (linear regression), and detection of respiratory viruses (Poisson regression).
Scores for maternal depression, and, to a lesser extent, maternal perceived stress, were positively related to multiple wheezing phenotypes. In particular, cumulative measures of maternal depression in the first 3 years were related to the moderate-wheeze-low-atopy phenotype (odds ratio, 1.13; 1.05, 1.21; P < .01). Considering indicators of respiratory health that were used to identify the phenotypes, there were multiple positive associations between early-life scores for maternal stress and depression and increased wheezing illnesses, but no consistent relationships with lung function and some inverse relationships with allergic sensitization. Cumulative maternal stress and depression scores were associated with cumulative number of respiratory illnesses through age 3 years.
Among high-risk, urban children, maternal stress and depression in early life were positively associated with respiratory illnesses and a moderate-wheeze-low-atopy phenotype. These results suggest that treating stress and depression in expectant and new mothers could reduce viral respiratory illnesses and recurrent wheeze during the preschool years and some forms of childhood asthma.
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BACKGROUNDThis study aimed to examine the agreement between sexually transmitted infection (STI) screening using self-collected specimens and physician-collected specimens, and to investigate the ...acceptability of self-collection for screening in an 18-month study of female sex workers in a high-risk, low-resource setting.
METHODSA total of 350 female sex workers in Nairobi, Kenya, participated in a prospective study from 2009 to 2011. Women self-collected a cervicovaginal specimen. Next, a physician conducted a pelvic examination to obtain a cervical specimen. Physician- and self-collected specimens were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium (MG) using Aptima nucleic acid amplification assays (Hologic). Specimens were collected at 3-month intervals over 18-month follow-up. κ Statistics measured agreement of positivity between self-collection and physician collection.
RESULTSBaseline STI prevalence was 2.9% for N. gonorrhoeae, 5.2% for C. trachomatis, 9.2% for T. vaginalis, and 20.1% for MG in self-collected samples, and 2.3%, 3.7%, 7.2%, and 12.9%, respectively, in physician-collected samples. κ Agreement was consistently strong (range, 0.66–1.00) for all STIs over the 18-month study period, except for MG, which had moderate agreement (range, 0.50–0.75). Most participants found self-collection easy (94%) and comfortable (89%) at baseline, with responses becoming modestly more favorable over time.
CONCLUSIONSSelf-collected specimen screening results showed strong agreement to clinical-collected specimens, except for MG, which was consistently detected more commonly in self-collected than in physician-collected specimens. Acceptability of the self-collection procedure was high at baseline and increased modestly over time. In high-risk, low-resource settings, STI screening with self-collected specimens provides a reliable and acceptable alternative to screening with physician-collected specimens.
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