Health workers' perceptions on where and how to integrate tobacco use cessation services into tuberculosis treatment; a qualitative exploratory study in Uganda.

BACKGROUND: Tobacco use is associated with exacerbation of tuberculosis (TB) and poor TB treatment outcomes. Integrating tobacco use cessation within TB treatment could improve healing among TB patients. The aim was to explore perceptions of health workers on where and how to integrate tobacco use cessation services into TB treatment programs in Uganda. METHODS: Between March and April 2019, nine focus group discussions (FGDs) and eight key informant interviews were conducted among health workers attending to patients with tuberculosis on a routine basis in nine facilities from the central, eastern, northern and western parts of Uganda. These facilities were high volume health centres, general hospitals and referral hospitals. The FGD sessions and interviews were tape recorded, transcribed verbatim and analysed using content analysis and the Chronic Care Model as a framework. RESULTS: Respondents highlighted that just like TB prevention starts in the community and TB treatment goes beyond health facility stay, integration of tobacco cessation should be started when people are still healthy and extended to those who have been healed as they go back to communities. There was need to coordinate with different organizations like peers, the media and TB treatment supporters. TB patients needed regular follow up and self-management support for both TB and tobacco cessation. Patients needed to be empowered to know their condition and their caretakers needed to be involved. Effective referral between primary health facilities and specialist facilities was needed. Clinical information systems should identify relevant people for proactive care and follow up. In order to achieve effective integration, the health system needed to be strengthened especially health worker training and provision of more space in some of the facilities. CONCLUSIONS: Tobacco cessation activities should be provided in a continuum starting in the community before the TB patients get to hospital, during the patients' interface with hospital treatment and be given in the community after TB patients have been discharged. This requires collaboration between those who carry out health education in communities, the TB treatment supporters and the health workers who treat patients in health facilities.

A cross-sectional study of the association between perfluorinated chemical exposure and cancers related to deregulation of estrogen receptors.

BACKGROUND: Environmental exposures acting through different mechanisms have been linked with a number of cancers. Perfluoroalkyl chemicals (PFCs) are endocrine disrupting chemicals affecting estrogen homeostasis. OBJECTIVES: We examined the association between PFCs and a group of estrogen related cancers and explored if increased non-occupational exposure was associated with increased odds of developing these cancers. We also explored which of these chemical exposures was more correlated with each cancer. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), we selected participants ≥ 20 years of age. Our outcome variable was presence or absence of breast, prostate, ovarian and uterine cancer (yes/no); our exposure variables were serum PFCs. Logistic regression models were used in investigating the association between PFCs and cancer types and between quartiles of PFCs exposure concentrations and presence or absence of cancer while adjusting for covariates. Discriminant analysis was used to assess the correlation between individual PFCs compounds and individual cancer types. RESULTS: PFCs were associated with increased odds of ovarian cancer; PFOA: 1.02(1.01, 1.02), PFOS: 1.01 (1.012, 1.013), PFHS 1.031 (1.030, 1.033), PFDE: 1.29(1.27, 1.30) and increased odds of breast cancer; PFOA: 1.089(1.089, 1.09), PFOS: 1.011(1.011, 1.011), PFNA: 1.031(1.030, 1.033), PFHS: 1.02 (1.02, 1.02), PFDE: 1.19(1.18, 1.19). PFCs were not associated with increased odds of prostate or uterine cancers. Comparing the odds in quartile 4 to quartile 1 for ovarian cancer, PFOA: 1.77(1.75,1.79), PFOS: 2.25(2.22, 2.28), PFHS: 1.86(1.84, 1.88), PFDE: 2.11(2.09, 2.14). For breast cancer, PFOA: 2.30(2.28, 2.31), PFOS: 1.47(1.46, 1.48), PFNA: 1.04(1.03, 1.05), PFHS:7.07(6.97,7.17), PFDE: 1.38(1.37, 1.39). PFOA was more correlated with breast cancer (0.7) and PFHS was more correlated with ovarian cancer (0.9). DISCUSSION: PFCs were associated with increased odds of ovarian and breast cancers with a positive dose-response relationship. PFOA was more correlated with breast cancer and PFHS more with ovarian cancer.

Real-world non-interventional long-term post-authorisation safety study of ruxolitinib in myelofibrosis.

Primary objective of this non-interventional, post-authorisation safety study was to provide real-world safety data [incidence of adverse drug reactions (ADRs)/serious adverse events (SAEs)] on adult patients with myelofibrosis exposed/or not exposed to ruxolitinib. Key secondary objectives included the incidence/outcome of events of special interest (bleeding events, serious/opportunistic infections, second primary malignancies, and deaths). Overall, 462 patients were included [prevalent users = 260, new users = 32, non-exposed = 170 (inclusive of ruxolitinib-switch, n = 57)]. The exposure-adjusted incidence rates (per 100 patient-years) of ADRs (19·3 vs. 19·6) and SAEs (25·2 vs. 25·0) were comparable amongst new-users versus prevalent-users cohorts, respectively; most frequent ADRs across all cohorts included thrombocytopenia, anaemia, epistaxis, urinary tract infection, and herpes zoster. Anaemia, pneumonia, general physical health deterioration, sepsis, and death were the most frequent SAEs across all cohorts. Incidence rates of bleeding events (21·6) and serious/opportunistic infections (34·5) were higher in ruxolitinib-switch cohort versus other cohorts. The incidence rate of second primary malignancies was higher in the prevalent-users cohort (10·1) versus other cohorts. The observed safety profile of ruxolitinib in the present study along with the safety findings from the COMFORT/JUMP/EXPAND studies support the use of ruxolitinib for long-term treatment of patients with myelofibrosis.

Depressive symptoms and health risk among rural adolescents.

OBJECTIVE: To determine the stability of depression and its relationship with health risk factors among rural adolescents. METHODS: A clinic-based longitudinal study was conducted to test for depression and risk factors in 64 participants who attended a rural, primary care, adolescent medicine clinic. The primary measure of risk and depression was the Perkins Adolescent Risk Screen (PARS). Adolescent patients who were aged 12 to 18 years and had PARS assessments during a previous visit to the adolescent clinic were invited to complete a follow-up PARS assessment. RESULTS: The mean age of adolescents at baseline was 12.79 years; 14.59 years at follow-up. With age and gender being controlled, adolescent depression and various adolescent risk indices were significantly related at baseline. Longitudinally, baseline depression score on PARS were related to follow-up: depression, school problems, substance abuse, tobacco use, sexual activity, and violent behavior scores and a history of physical/sexual abuse. On multivariate analysis controlling for other significantly associated variables, the relationship persisted for baseline depression and follow-up: tobacco, substance abuse, depression, and history of physical/sexual abuse. CONCLUSION: This study confirms a strong longitudinal relationship between baseline depressive symptoms and several important risk behaviors/factors measured at follow-up in a clinic population of rural adolescents. Also, longitudinal stability of depression over time is supported.

Detection and characterization of OX40 ligand expression in human airway smooth muscle cells: a possible role in asthma?

BACKGROUND: The airway smooth muscle (ASM) cell, originally thought of as a passive structural cell, is now well recognized as an active participant in the pathologic events that occur during persistent asthma. Cell-surface molecules play an important role in the development of an immune response. A number of cell-surface molecules are expressed on ASM cells, and these might contribute to the inflammatory reaction. OBJECTIVE: The purpose of this study was to determine whether OX40 ligand (OX40L), a molecule known to be involved in T-cell activation, was present on the ASM cell surface. METHODS: We used real-time RT-PCR to detect mRNA expression and flow cytometry, ELISA, and immunoprecipitation to detect the presence of cell-surface protein on ASM cells isolated from asthmatic and nonasthmatic individuals. ELISAs and Western blotting were used to determine the functional outcomes of engagement of OX40L. RESULTS: OX40L was present on both asthmatic and nonasthmatic ASM cells. Engagement of OX40L with recombinant OX40:Fc resulted in a significantly greater increase in release of IL-6 from ASM cells of asthmatic patients than from ASM cells of nonasthmatic patients (P<.01). Ligation of OX40L resulted in a rapid translocation of protein kinase C beta2 to the cell membrane. CONCLUSION: Because the receptor for OX40L, OX40, is expressed on CD4+ T cells within 48 hours of stimulation through the T-cell receptor, elucidation of the cross-talk between OX40 and OX40L could be very important in understanding the interaction of cells present in the inflamed airways of an asthmatic patient.

Differential effects of the antioxidant alpha-lipoic acid on the proliferation of mitogen-stimulated peripheral blood lymphocytes and leukaemic T cells.

The effects of the antioxidant alpha-lipoic acid (LA) on the proliferation of mitogen-stimulated human peripheral blood lymphocytes (HPBL) were investigated in comparison to its effects on the proliferation of two leukaemic T cell lines, Jurkat and CCRF-CEM. At low mM concentrations, LA inhibited in a dose-dependent manner DNA synthesis of HPBL stimulated with either phorbol myristate acetate (PMA) in combination with ionomycin (IoM), or phytohaemagglutinin (PHA). At similar concentrations, LA inhibited the proliferation of Jurkat and CCRF-CEM cells. However, LA was preferentially cytotoxic to the leukaemic cell lines. The selective toxicity of LA to Jurkat cells was shown by electron microscopy (EM) to be due to the induction of apoptosis. Furthermore, LA had different effects on the secretion of interleukin-2 (IL-2) and steady-state levels of IL-2 mRNA in mitogen-stimulated HPBL depending on the mitogens used. LA dramatically increased the induction of IL-2 mRNA and IL-2 protein secretion in PMA/IoM-stimulated HPBL, whereas it inhibited these in HPBL stimulated with PHA. The differential effects of LA on normal and leukaemic T lymphocytes may indicate a new route towards development of therapeutic agents.