Dose-related Increase In Risk Research Articles

Postmenopausal Bleeding: An Update

The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose endometrial carcinoma and endometrial intraepithelial neoplasia and to find out the real source. Postmenopausal bleeding is ‘endometrial cancer until proven otherwise’, although only 1-14% of such patients will actually have cancer. Clinical risk factors of endometrial carcinoma such as obesity, unopposed estrogen use, polycystic ovary syndrome, diabetes mellitus and family history of gynaecologic malignancy also should be considered during evaluation. Postmenopausal bleeding usually attributed to an intrauterine source, but it may arise from the cervix, vagina, vulva or fallopian tubes & ovaries. The origin of bleeding can also involve non-gynaecologic sites, such as the urethra, bladder, anus/rectum/bowel, or perineum.
 Meticulous history and thorough physical examination are must. Initial evaluation is by TVS, if endometrial thickness (ET) is <4mm no further evaluation is required but follow up consultation must. If ET is> 4mm, hysteroscopic evaluation and endometrial sampling is recommended
 Blind endometrial sampling is not accurate as only reveals when endometrial cancer exceeds more than 50% of the endometrial surface area so may be done if hysteroscopic evaluation is not possible. Higher dose of progesterone may be required for endometrial protection when higher doses of estradiol as hormone replacement therapy are used, or in women with high BMI. Unopposed estrogen therapy is associated with a duration and dose-related increase in risk of endometrial hyperplasia and cancer. Endometrial protection requires an adequate dose and duration of progestogen. Endometrial hyperplasia with atypia has much malignant potential but endometrial hyperplasia without atypia may be managed medically with 3 monthly endometrial sampling, if no regression or further progression hysterectomy is the choice of treatment. Finally, patient counseling with discussion of risks /benefits of different options of treatment modalities is the cornerstone of success of addressing postmenopausal bleeding.

Association of stressful life events with accelerated bone loss in older men: the osteoporotic fractures in men (MrOS) study.

Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events. Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss. Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change). Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was -0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p < 0.001), but not after multivariable adjustment (p = 0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04-1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p = 0.08). In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.

Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis.

BackgroundThe use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD) has been associated with an increased risk of pneumonia in controlled clinical trials and case-control analyses.ObjectiveUsing claims databases as a research model of real-world diagnosis and treatment, to determine if the use and dose of inhaled corticosteroids (ICS) among patients with newly diagnosed COPD are associated with increased risk of pneumonia.Patients and methodsThis was a retrospective cohort analysis of patients diagnosed with COPD between January 01, 2006 and September 30, 2010, drawn from databases (years 2006–2010). Patients (aged ≥45 years) were followed until first pneumonia diagnosis, end of benefit enrollment, or December 31, 2010, whichever was earliest. A Cox proportional hazard model was used to assess the association of ICS use and risk of pneumonia, controlling for baseline characteristics. Daily ICS use was classified into low, medium, and high doses (1 μg–499 μg, 500 μg–999 μg, and ≥1000 μg fluticasone equivalents daily) and was modeled as a time-dependent variable.ResultsAmong 135,445 qualifying patients with a total of 243,097 person-years, there were 1020 pneumonia incidences out of 5677 person-years on ICS (crude incidence rate, 0.180 per person-year), and 27,730 pneumonia incidences out of 237,420 person-years not on ICS (crude incidence rate, 0.117 per person-year). ICS use was associated with a dose-related increase in risk of pneumonia, with adjusted hazard ratios (versus no use; (95% confidence interval) of 1.38 (1.27–1.49) for low-dose users, 1.69 (1.52–1.88) for medium-dose users, and 2.57 (1.98–3.33) for high-dose users (P < 0.01 versus no use and between doses).ConclusionThe use of ICS in newly diagnosed patients with COPD is potentially associated with a dose-related increase in the risk of pneumonia.

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease‐modifying antirheumatic drugs, and anti–tumor necrosis factor therapy

Pneumonia is a major cause of mortality and morbidity in rheumatoid arthritis (RA). This study was undertaken to determine the rate and predictors of hospitalization for pneumonia and the extent to which specific RA treatments increase pneumonia risk. RA patients (n = 16,788) were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments. After adjustment for covariates, prednisone use increased the risk of pneumonia hospitalization (hazard ratio [HR] 1.7 [95% confidence interval 1.5-2.0]), including a dose-related increase in risk (< or = 5 mg/day HR 1.4 [95% confidence interval 1.1-1.6], > 5-10 mg/day HR 2.1 [95% confidence interval 1.7-2.7], > 10 mg/day HR 2.3 [95% confidence interval 1.6-3.2]). Leflunomide also increased the risk (HR 1.2 [95% confidence interval 1.0-1.5]). HRs for etanercept (0.8 [95% confidence interval 0.6-110]) and sulfasalazine (0.7 [95% confidence interval 0.5-1.0]) did not reflect an increased risk of pneumonia. HRs for infliximab, adalimumab, and methotrexate were not significantly different from zero. There is a dose-related relationship between prednisone use and pneumonia risk in RA. No increase in risk was found for anti-tumor necrosis factor therapy or methotrexate. These data call into question the belief that low-dose prednisone is safe. Because corticosteroid use is common in RA, the results of this study suggest that prednisone exposure may have important public health consequences.

Can Lung Cancer Risk Among Nickel Refinery Workers Be Explained by Occupational Exposures Other Than Nickel?

Exposures in nickel refineries represent complex chemical mixtures, but only the effect of nickel has been evaluated quantitatively in epidemiologic studies of nickel workers. For a Norwegian refinery, time- and department-specific exposure estimates were developed for arsenic, sulfuric acid mists, and cobalt in air on the basis of personal measurements and chemical data on raw materials and process intermediates. Exposure to asbestos, as well as employment in high-risk occupations outside the refinery, were assessed. We conducted a case-control study nested in a cohort of refinery workers, with 213 cases (diagnosed 1952-1995) and 525 age-matched controls. We analyzed lung cancer risk, adjusted for smoking, by cumulative exposure and duration of work. There was a substantial association between cumulative exposure to water-soluble nickel and lung cancer risk. Weaker effects were suggested for exposure to arsenic at the refinery and for occupational exposures outside the refinery for 15 years or more. No detectable excess risk was found for refinery exposure to asbestos or sulfuric acid mists, and no dose-related increase in risk was seen from cobalt. Exposure to water-soluble nickel remained the most likely explanation for the excess lung cancer risk in the cohort. Other occupational exposures did not confound the strong dose-related effect of nickel to any appreciable degree.

Chloramphenicol

Chloramphenicol

Prior exposure to medical and dental x-rays related to tumors of the parotid gland.

Findings from this population-based study in Los Angeles County suggest, for the first time, that tumors of the parotid gland are related to prior exposure to diagnostic medical and dental radiography. Responses to interviews with 408 patients with a parotid tumor (269 benign tumors and 139 malignant tumors) were compared to responses of 408 neighborhood controls. Cumulative exposure of the parotid gland from diagnostic radiography was associated with a dose-related increase in risk of malignant tumors (P for trend less than .05; relative risk for exposure to greater than or equal to 50 rad = 3.4; 95% confidence interval = 1.02-11.46). Benign tumors showed a weaker positive association, and exposure before age 20 to a major diagnostic examination (full-mouth or panoramic dental radiography or medical radiography to the head) increased risk (relative risk = 1.8; confidence interval = 1.13-2.91). This study also confirmed the association of malignant tumors with prior radiation treatment to the head or neck; 28% of these tumors are attributable to exposure of the parotid gland from diagnostic and therapeutic radiation.