Adherence to National Comprehensive Cancer Network ALK Testing Guidelines for Patients with Advanced Non-Small Cell Lung Cancer in U.S. Community Medical Centers

BackgroundNational Comprehensive Cancer Network (NCCN) guidelines recommend biomarker testing as the first step in the management of patients with advanced non‐small cell lung cancer (aNSCLC). We assessed anaplastic lymphoma kinase (ALK) testing rates and factors related to underuse in community medical systems between 2012 and 2019 to understand guideline adoption.MethodsA retrospective observational study using a nationwide electronic health record (EHR)‐derived deidentified database was conducted. Patients with aNSCLC diagnosed in community medical centers from January 2012 to May 2019 were included to describe the ALK testing trend. This cohort was further restricted to patients diagnosed after 2015 to understand factors associated with testing underuse using mixed‐effects multivariable logistic regression models.ResultsTrends for increased ALK testing rates by year were observed in both NCCN guideline‐eligible patients (59.5% in 2012 to 84.1% in 2019) and ‐ineligible patients (15.6% to 50.8%) in a cohort of 41,728 patients. Histology type and smoking status had the greatest impact on test use. Compared with patients with nonsquamous histology and no smoking history, patients with squamous histology and no smoking history (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 5.6–10.4), NSCLC histology not otherwise specified (NOS) with smoking history (aOR, 3.4; 95% CI, 2.8–4.2); NSCLC NOS/nonsmoker (aOR, 1.8; 95% CI, 1.1–3.2), and nonsquamous/smoker (aOR, 1.5; 95% CI, 1.3–1.7) were less likely to be tested. Factors related to underuse also included Eastern Cooperative Oncology Group performance status, stage at initial diagnosis, and demographics.ConclusionThis analysis of real‐world data shows increasing test use by year; however, one fifth of patients eligible for ALK testing still remain untested and potentially missing therapeutic options.Implications for PracticeAdvancement in treatment of lung cancer is accompanied by an increasing number of tests that should be run to determine potential therapy options for each patient. This study assessed adoption of testing recommendations for anaplastic lymphoma kinase rearrangements in a national database. Although test use increased over the time period studied (2012–2019), there is still room for improvement. Efforts are needed to increase test use in undertested groups, thus enabling eligible patients to benefit from novel lung cancer therapies.     

Quality of life in schizophrenia: a review of the literature from 1995 to 2000

The measurement of the quality of life of patients diagnosed with psychiatric disorders has become central to evaluating the effectiveness of treatments offered by Australian mental health services. The importance of quality of life as an indicator of the outcomes of interventions has been reflected by a large body of research seeking to measure the impact of variables such as gender, ethnicity and duration of illness on the measurable quality of life of an individual diagnosed with schizophrenia. This study aims to review and synthesize the recent literature in which quality of life has been measured by the use of at least one quality of life instrument. It is concludes that while the measurement of quality of life is valuable as a measure of outcomes, it should be treated as only one means of doing so .     

Inhibition of ileal bile acid transport lowers plasma cholesterol levels by inactivating hepatic farnesoid X receptor and stimulating cholesterol 7 alpha-hydroxylase

We investigated the effect of SC-435, a competitive inhibitor of ileal apical sodium-dependent bile acid cotransporter (ASBT) on ileal bile acid absorption and the hepatic nuclear receptor FXR (farnesoid X receptor), which regulates cholesterol 7 alpha-hydroxylase (CYP7A1) activity and mRNA levels. Eighteen New Zealand White (NZW) rabbits were divided into 2 groups: controls (n = 10) and fed SC-435 125 mg/kg/d for 1 week (n = 8). In rabbits treated with SC-435, fecal bile acid outputs increased by more than 8 times, reflecting substantial bile acid malabsorption. Plasma cholesterol levels decreased 26%, while bile acid pool sizes and biliary bile acid outputs did not change after treatment. CYP7A1 activity increased 64% and mRNA rose by 4 times after treatment. The expression of FXR target genes in the liver, short heterodimer partner (SHP) and bile salt export pump (BSEP), decreased 11.6 and 2.6 times, respectively, after treatment, which indicates inactivation of hepatic FXR. However, the mRNA levels of ileal bile acid binding protein (IBABP) did not change significantly, while ileal ASBT mRNA expression increased by 2.4 times after treatment. Rabbits treated with SC-435 developed ileal bile acid malabsorption, which decreased the return of bile acids (FXR ligands) to the liver to inactivate hepatic FXR, which upregulated CYP7A1 and lowered plasma cholesterol levels. Although fecal bile acid malabsorption was substantial, increased bile acid production from hepatic cholesterol kept biliary bile acid outputs intact. Thus, a new balance was reached in the liver, where increased bile acid synthesis compensated for diminished ileal bile acid absorption to maintain the circulating enterohepatic bile acid pool.     

Dysgerminoma in a female with turner syndrome and Y chromosome material: A case-based review of literature

We report a 17-year-old girl evaluated for primary amenorrhea. Cytogenetic analysis of the peripheral blood lymphocytes revealed normal autosomes with 46X inv (Y) confirming the diagnosis of Turner's syndrome with Y cell line. Treatment was initiated with conjugated estrogen while recommending bilateral prophylactic oophorectomy to the patient. One year later the patient presented with abdominal mass, biopsy of the specimen following resection confirmed dysgerminoma originating from right ovary with no invasion or metastasis. The literature is reviewed with regard to the various pathogenetic mechanisms proposed for the development of germ cell tumors in ovary, the cytogenetic findings and recommendations to handle such scenario.     

Noninsulin-dependent diabetes mellitus: effects on sperm morphological and functional characteristics, nuclear DNA integrity and outcome of assisted reproductive technique

The aim of the study was to compare the semen characteristics and nuclear DNA fragmentation in spermatozoa of diabetic and nondiabetic men undergoing assisted reproduction and correlate them with pregnancy outcome. Semen characteristics and nuclear DNA fragmentation were analysed using computer-aided semen analysis system and sperm chromatin dispersion assay (SCD), respectively. Spermatozoa from diabetic patients showed significantly lower progressive (Type A) motility (14.64 ± 9.60 versus 17.99 ± 11.51, P < 0.02) and increased nuclear DNA fragmentation (37.05 ± 12.68 versus 21.03 ± 10.13, P < 0.001). Furthermore, a positive correlation was observed in diabetic patients in terms of blastocyst formation rate (38.13% versus 55.46%, P < 0.001), pregnancy rate (28.57% versus 46.34%, P < 0.001) and miscarriage rate (50.0% versus 24.56%, P < 0.001). The higher percentage of sperm DNA damage because of oxidative stress seen in diabetic patients may be responsible for the poor embryonic development and pregnancy outcome in these individuals.     

Visceral leishmaniasis elimination targets in India,strategies for preventing resurgence

ABSTRACT

Introduction: Visceral leishmaniasis (VL) is a fatal parasitic disease caused by a parasite belonging to the Leishmania donovani complex and transmitted by infected female Phlebotomous argentipes sand flies. The VL elimination strategy in the Indian subcontinent (ISC), which has a current goal of reducing the incidence of VL to below 1/10,000 of population by the year 2020, consists of rapid detection and treatment of VL to reduce the number of human reservoirs as well as vector control using indoor residual spraying (IRS). However, as the incidence of VL declines toward the elimination goal, greater targeting of control methods will be required to ensure appropriate early action to prevent the resurgence of VL.

Area covered: We discuss the current progress and challenges in the VL elimination program and strategies to be employed to ensure sustained elimination of VL.

Expert commentary: The VL elimination initiative has saved many human lives; however, for VL elimination to become a reality in a sustained way, an intense effort is needed, as substantial numbers of endemic subdistricts (primary health centers (PHCs) blocks level) are yet to reach the elimination target. In addition to effective epidemiological surveillance, appropriate diagnostic and treatment services for VL at PHCs will be needed to ensure long-term sustainability and prevent reemergence of VL.