The effect of polypharmacy on healthcare services utilization in older adults with comorbidities: a retrospective cohort study.

BACKGROUND: Older adults are more prone to increasing comorbidities and polypharmacy. Polypharmacy is associated with inappropriate prescribing and an increased risk of adverse effects. This study examined the effect of polypharmacy in older adults on healthcare services utilization (HSU). It also explored the impact of different drug classes of polypharmacy including psychotropic, antihypertensive, and antidiabetic polypharmacy on HSU. METHODS: This is a retrospective cohort study. Community-dwelling older adults aged ≥ 65 years were selected from the primary care patient cohort database of the ambulatory clinics of the Department of Family Medicine at the American University of Beirut Medical Center. Concomitant use of 5 or more prescription medications was considered polypharmacy. Demographics, Charlson Comorbidity index (CCI), and HSU outcomes, including the rate of all-cause emergency department (ED) visits, rate of all-cause hospitalization, rate of ED visits for pneumonia, rate of hospitalization for pneumonia, and mortality were collected. Binomial logistic regression models were used to predict the rates of HSU outcomes. RESULTS: A total of 496 patients were analyzed. Comorbidities were present in all patients, with 22.8% (113) of patients having mild to moderate comorbidity and 77.2% (383) of patients having severe comorbidity. Patients with polypharmacy were more likely to have severe comorbidity compared to patients with no polypharmacy (72.3% vs. 27.7%, p = 0.001). Patients with polypharmacy were more likely to visit the ED for all causes as compared to patients without polypharmacy (40.6% vs. 31.4%, p = 0.05), and had a significantly higher rate of all-cause hospitalization (adjusted odds ratio aOR 1.66, 95 CI = 1.08-2.56, p = 0.022). Patients with psychotropic polypharmacy were more likely to be hospitalized due to pneumonia (crude odds ratio cOR 2.37, 95 CI = 1.03-5.46, p = 0.043), and to visit ED for Pneumonia (cOR 2.31, 95 CI = 1.00-5.31, p = 0.049). The association lost significance after adjustment. CONCLUSIONS: The increasing prevalence of polypharmacy amongst the geriatric population with comorbidity is associated with an increase in HSU outcomes. As such, frequent medication revisions in a holistic, multi-disciplinary approach are needed.

AhRR methylation contributes to disease progression in urothelial bladder cancer.

BACKGROUND: Bladder Cancer (BCa) is the tenth most incident malignancy worldwide. BCa is mostly attributed to environmental exposure and lifestyle, particularly tobacco smoking. The Aryl Hydrocarbon Receptor Repressor (AhRR) participates in the induction of many enzymes involved in metabolizing carcinogens, including tobacco smoke components. Additionally, studies have shown that smoking demethylates the (AhRR) gene in blood, suggesting AhRR demethylation as a specific serum smoking biomarker. OBJECTIVE: This study aimed to validate AhRR demethylation as a smoking biomarker in the target tissue and investigate its contribution to bladder carcinogenesis. METHODS: AhRR percent methylation was tested for its association with patient smoking status and oncogenic outcome indicators, particularly p53, RB1, and FGFR3 activating mutations, muscle-invasiveness, and tumor grade, in 180 BCa tissue-based DNA. RESULTS: Results showed significantly higher AhRR percent methylation in muscle-invasive compared to non-muscle invasive tumors (42.86% vs. 33.98%; p= 0.011), while lower AhRR methylation was significantly associated with FGFR3 Codon 248 mutant genotype compared to wild-type (28.11% ± 9.44 vs. 37.87% ± 22.53; p= 0.036). All other tested associations were non-statistically significant. CONCLUSIONS: Although AhRR methylation did not predict smoking status in BCa tumors, it may be a contributor to carcinogenesis and disease progression. Our findings constitute the basis for further research.

Effect of BPA on CYP450s expression, and nicotine modulation, in fetal rat brain.

Human exposure to bisphenol A (BPA) is mainly due to migration from plastic packaging into food and beverages. Studies reported BPA endocrine disruptions through interactions with different nuclear receptors, including the arylhydrocarbon receptor (AhR). AhR mediates xenobiotic responses and regulates expression of drug-metabolizing enzymes (DMEs), including many CYP450s. This study aimed to assess the effects of BPA maternal exposure on CYP450s expression in fetal brain. Sprague-Dawley dams were exposed to BPA concentrations of 0, 0.5, 5, and 50 mg/L in drinking water, individually, and with nicotine. Fetal brains were isolated at gestational days GD14 and GD19, and protein expression was assessed by Western blotting. Results showed a BPA-induced significant decrease in CYP1B1 expression levels at GD14 (p = 0.001), and CYP19A1 (aromatase) expression at both mid- and late-stage development (p < 0.001). In addition, nicotine individually decreased expression levels of all examined protein targets, significantly for CYP1B1 (p < 0.001), CYP19A1 (p = 0.010), AhRR (p = 0.042), and ARNT (p < 0.001), compared to control. When combined with BPA, nicotine suppressive effects were attenuated at both GD14 and GD19. In conclusion, BPA suppresses CYP1B1 and CYP19A1 expression in fetal brain, and attenuates the suppressive effects of nicotine. Observed effects may be mediated by AhR-ARNT independent mechanisms that need further examination.

Trends & predictors of non-AIDS comorbidities among people living with HIV and receiving antiretroviral therapy in Lebanon.

ABSTRACT: Combined antiretroviral therapy (cART) increased the life expectancy of people living with Human Immunodeficiency Virus (HIV) (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. Consequently, PLHIV are experiencing non-acquired immunodeficiency syndrome (AIDS) associated comorbid conditions including diabetes, hyperlipidemia, hypertension, and cardiovascular disease. The aim of this study is to determine the frequency of non-AIDS associated comorbid conditions among a cohort of PLHIV on cART in Lebanon.Data were collected between November 2018 and December 2019 from 105 voluntary participants. A standardized questionnaire was used to collect demographic and behavioral data including lifestyle, smoking, physical activity, substance use and abuse in addition to co-infections and family history of non-communicable diseases. Moreover, data on occurrence and treatment of cardiovascular disease, hypertension, diabetes, lipid and metabolic disorders as well as mental health were collected. Blood samples were used to assess the levels of fasting blood sugar (FBS), glycosylated hemoglobin (HbA1C), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol, and serum creatinine.Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and cardiovascular disease (9.7%) were mainly reported among study participants. Higher rate of comorbid conditions was observed among participants >40 years of age than those ≤40 years with both hypertension and hyperlipidemia most commonly reported. Older age (odds ratio [OR] 7.6; 95% CI: 1.83-31.98; P = .005) is associated with higher odds of having hyperlipidemia. Moreover, participants on cART for ≥10 years are 5 times more likely to have hyperlipidemia (OR 5; 95% CI: 1.08-22.73; P = .039). Our results also showed that study participants did not experience anxiety, depression or somatic symptoms and that there was no association between these mental disorders and older age or comorbidities.Our results provide important information on HIV trends and associated comorbidities in Lebanon and can be used to improve the management of non-communicable diseases among PLHIV.

Slow N-acetylation as a possible contributor to bladder carcinogenesis.

Bladder cancer (BCa) is an exophytic tumor that presents as either noninvasive confined to the mucosa (NMIBC) or invading the detrusor muscle (MIBC), and was recently further subgrouped into molecular subtypes. Arylamines, major BCa environmental and occupational risk factors, are mainly metabolized by the genetically polymorphic N-acetyltransferases 1, NAT1 and NAT2. In this study, we investigated the association between N-acetyltransferases genetic polymorphism and key MIBC and NMIBC tumor biomarkers and subtypes. A cohort of 250 males with histologically confirmed urothelial BCa was identified. Tumors were genotyped for NAT1 and NAT2 using real-time polymerase chain reaction (PCR), and characterized for mutations in TP53, RB1, and FGFR3 by PCR-restriction fragment length polymorphism. Pathology data and patients' smoking status were obtained from medical records. Pearson χ2 and Fisher exact tests were used to check for associations and interactions. Results show that NAT1 G560 A polymorphism is significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .001), higher tumor grade (high grade vs low grade; P = .011), and higher FGFR3 mutation frequency within the MIBC subgroup (P = .042; .027). NAT2 G857 A polymorphism is also found to be significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .041). Our results indicate that slow N-acetylation is a contributor to bladder carcinogenesis and muscle-invasiveness. These findings highlight NAT1 as a biomarker candidate in BCa and a potential target for drug development.

Trends in Breast Cancer Staging at Diagnosis Associated with Screening Campaigns in Lebanon.

Introduction: Mammography screening has been shown to improve early breast cancer (BC) detection, by shifting the disease at diagnosis to locally confined stages, offering lighter treatments and better prognoses. BC awareness campaigns calling for annual mammography screenings have been ongoing in Lebanon since 2002. Changes in BC staging at diagnosis as a consequence of documented improvements in mammography uptake remain to be described. Materials and Methods: We reviewed 2,822 BC cases identified by pathology reports in the American University of Beirut Medical Center between the years 1990 and 2015. After age stratification, we have trended the extracted stages versus time. Results were compared between the prescreening (1990-2001) and the postscreening period (2002-2015). Results: During the postscreening period, stage I represented 31%, stage II 47%, stage III 14%, and stage IV 8% of the cases. Stage I cases had more than doubled whereas stage III cases showed a mirror decrease compared with the years before the implementation of awareness campaigns. The increase in stage I was significantly more prominent in women aged 40 years and older (from 14% to 32%), compared with the younger group. Shifts in staging happened in parallel with a concurrent rise in reported uptake of mammography screening. Conclusions: Our findings demonstrate significant trends in earlier detection, which are likely associated with an increase in screening uptake and an awareness of BC as a public health issue. Staging data from hospitals all over Lebanon should be available for building national evidence. The Ministry of Public Health should require reporting of BC stage at diagnosis to the National Cancer Registry, as part of the annual cancer incidence reporting in Lebanon.

Bullying Victimization and Use of Substances in High School: Does Religiosity Moderate the Association?

Alcohol, tobacco and other drug use continue to pose serious public health concerns among youth. Bullying victimization has been identified as a risk factor and religiosity a protective factor for adolescent substance use. No previous research has examined the potential moderating role of religiosity. We explore the association between bullying victimization and substance use in adolescents with low and high levels of religiosity. A cross-sectional survey was conducted with a representative sample of high school students in greater Beirut. Binary and multinomial logistic models were used, adjusting for demographics, and stratified by level of religiosity. Of the 986 students responding to the survey, 65% were females; 48% had experienced some form of bullying; and 52% self-rated as low in religiosity. Between 10 and 30% were current users of alcohol or tobacco. Students of lower religiosity levels who had been bullied were more likely to use substances than those who self-rated as high religiosity. Religiosity may be a potential moderator of the association between being bullied and substance use, but the exact mechanisms and underlying reasons need further investigation.

Framingham coronary score in individuals with symptoms or diagnoses of mental disorders: A review and meta-analysis.

Patients with mental disorders have a higher coronary morbidity and mortality as compared to the general population. However, it remains unclear whether their coronary risk scores are higher than those of the general population. We reviewed studies and meta-analyze case-control studies about coronary risk scores in individuals with symptoms or diagnoses of mental disorders. Search was performed in Pubmed and clinical trial registration databases. Four case-control studies were identified, comprising 963 individuals with symptoms or diagnoses of mental disorders and 1681 controls. They focused on the most validated coronary risk score, the Framingham Risk Score 1998 (FRS 1998). The mean FRS 1998 was significantly higher in individuals with symptoms or diagnoses of mental disorders than in the general population 7.9( ±â€¯6.9) vs. 5.0( ±â€¯4.8). FRS 1998 differs between individuals with symptoms or diagnoses of mental disorders and controls (Mean difference:1.84 [95% CI:0.57-3.11], p = 0.005]; high heterogeneity was observed (I2= 78%; p < 0.003). The difference was driven by three FRS 1998 criteria: smoking, diabetes and HDL cholesterolemia. The mean FRS 1998 was significantly higher in men, and to a trend in women. In conclusion, individuals with symptoms or diagnoses of mental disorders have a higher coronary risk score than controls. The FRS 1998 should be used as a simple and objective way of monitoring coronary risk in order to improve prevention of coronary events in psychiatric settings.