Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT.

Neurological and pulmonary adverse effects of subcutaneous methotrexate therapy.

We report the case of a patient receiving subcutaneous methotrexate (MTX) treatment for rheumatoid arthritis (RA) who developed a complex pattern of neurological and pulmonary symptoms. Fluctuant dysarthria, magnetic gait, weakness and dysmetria of the lower limbs, as well as symptoms and signs consistent with a diagnosis of pneumonitis started within 6 weeks of initiating MTX treatment and slowly resolved after its discontinuation. This case highlights the fact that even the relatively low doses of MTX in the therapy of RA can produce neurotoxicity, which can become manifest in a broad range of symptoms.

Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells

The aim of this study was to evaluate adverse effects of multiwalled carbon nanotubes (MWCNT), produced for industrial purposes, on the human epithelial cell line A549. MWCNT were dispersed in dipalmitoyl lecithin (DPL), a component of pulmonary surfactant, and the effects of dispersion in DPL were compared to those in two other media: ethanol (EtOH) and phosphate-buffered saline (PBS). Effects of MWCNT were also compared to those of two asbestos fibers (chrysotile and crocidolite) and carbon black (CB) nanoparticles, not only in A549 cells but also in mesothelial cells (MeT5A human cell line), used as an asbestos-sensitive cell type. MWCNT formed agglomerates on top of both cell lines (surface area 15-35 μm2) that were significantly larger and more numerous in PBS than in EtOH and DPL. Whatever the dispersion media, incubation with 100 μg/ml MWCNT induced a similar decrease in metabolic activity without changing cell membrane permeability or apoptosis. Neither MWCNT cellular internalization nor oxidative stress was observed. In contrast, asbestos fibers penetrated into the cells, decreased metabolic activity but not cell membrane permeability, and increased apoptosis, without decreasing cell number. CB was internalized without any adverse effects. In conclusion, this study demonstrates that MWCNT produced for industrial purposes exert adverse effects without being internalized by human epithelial and mesothelial pulmonary cell lines. [Authors]

Trends in smoking and lung cancer mortality in Switzerland.

Patterns of cigarette smoking in Switzerland were analyzed on the basis of sales data (available since 1924) and national health surveys conducted in the last decade. There was a steady and substantial increase in cigarettes sales up to the early 1970s. Thereafter, the curve tended to level off around an average value of 3,000 cigarettes per adult per year. According to the 1981-1983 National Health Survey, 37% of Swiss men were current smokers, 25% were ex-smokers, and 39% were never smokers. Corresponding porportions in women were 22, 11, and 67%. Among men, smoking prevalence was higher in lower social classes, and some moderate decline was apparent from survey data over the period 1975-1981 mostly in later middle-age. Trends in lung cancer death certification rates over the period 1950-1984 were analyzed using standard cross-sectional methods and a log-linear Poisson model to isolate the effects of age, birth cohort, and year of death. Mortality from lung cancer increased substantially among Swiss men between the early 1950s and the late 1970s, and levelled off (around a value of 70/100,000 men) thereafter. Among women, there has been a steady upward trend which started in the mid-1960s, and continues to climb steadily, although lung cancer mortality is still considerably lower in absolute terms (around 8/100,000 women) than in several North European countries or in North America. Cohort analyses indicate that the peak rates in men were reached by the generation born around 1910 and mortality stabilized for subsequent generations up to the 1930 birth cohort. Among females, marked increases were observed in each subsequent birth cohort. This pattern of trends is consistent with available information on smoking prevalence in successive generations, showing a peak among men for the 1910 cohort, but steady upward trends among females. Over the period 1980-1984, about 90% of lung cancer deaths among Swiss men and about 40% of those among women could be attributed to smoking (overall proportion, 85%).

Adverse effects of intraperitoneal onlay mesh used for incisional hernia repair

Context: In the past 50 years, the use of prosthetic mesh in surgery has dramatically¦changed the management of primary, as well as incisional hernias. Currently, there¦are a large number of different mesh brands and no consensus on the best material,¦nor the best mesh implantation technique to use. The purpose of this study is to¦illustrate the adverse effects of intraperitoneal onlay mesh used for incisional¦hernia repair encountered in patients treated at CHUV for complications after¦incisional hernia repair.¦Materials & Methods: This work is an observational retrospective study. A PubMed¦search and a systematic review of literature were performed. Thereafter, the medical¦records of 22 patients who presented with pain, abdominal discomfort, ileus, fistula,¦abscess, seroma, mesh infection or recurrent incisional hernia after a laparoscopic or¦open repair with intra-abdominal mesh were reviewed.¦Results: Twenty-two persons were reoperated for complications after incisional¦hernia repair with a prosthetic mesh. Ten were male and twelve female, with a¦median age of 58,6 years (range 24-82). Mesh placement was performed by a¦laparoscopic approach in nine patients and by open approach in thirteen others.¦Eight different mesh brands were found (Ultrapro®, Mersilene®, Parietex Composite®,¦Proceed®, DynaMesh®, Gore® DualMesh®, Permacol®, Titanium Metals UK Ltd®).¦Mean time from implantation and reoperation for complication was 34.2 months¦(range 1-147). In our sample of 22 patients, 21 (96%) presented mesh adhesion and¦15 (68%) presented hernia recurrence. Others complications like mesh shrinkage,¦mesh migration, nerve entrapment, seroma, fistula and abscess were also evaluated.¦Conclusion: The majority of articles deal with complications induced by¦intraperitoneal prosthetic mesh, but the effectiveness of mesh has been studied¦mostly on experimental models. Actually and as shown in the present study,¦intraperitoneal mesh placement was associated with severe complications witch may¦potentially be life threatening. In our opinion, intraperitoneal mesh placement should¦only be reserved in exceptional situations, when the modified Rives-Stoppa could not¦be achieved and when tissues covering the mesh are insufficient.

The adverse effects of environmental policy in green markets

We model green markets in which purchasers, either firms orconsumers, have higher willingness-to-pay for lesspolluting goods. The effectiveness of pollution reductionpolicies is examined in a duopoly setting. We show thatduopolists' strategic behaviour may increase pollutionlevels. Maximum emission standards, commonly used in greenmarkets, improve the environmental features of products.Nonetheless, overall pollution levels will rise becausegovernment regulation also affects market shares and bootsfirms' sales. Consequently, social welfare may be reduced.We also explore the effects of technological subsidies andproduct charges, including differentiation of charges.

Lung cancer in the Swiss HIV Cohort Study: role of smoking, immunodeficiency and pulmonary infection.

BACKGROUND: Immunodeficiency and AIDS-related pulmonary infections have been suggested as independent causes of lung cancer among HIV-infected persons, in addition to smoking. METHODS: A total of 68 lung cancers were identified in the Swiss HIV Cohort Study (SHCS) or through linkage with Swiss Cancer Registries (1985-2010), and were individually matched to 337 controls by centre, gender, HIV-transmission category, age and calendar period. Odds ratios (ORs) were estimated by conditional logistic regression. RESULTS: Overall, 96.2% of lung cancers and 72.9% of controls were ever smokers, confirming the high prevalence of smoking and its strong association with lung cancer (OR for current vs never=14.4, 95% confidence interval (95% CI): 3.36-62.1). No significant associations were observed between CD4+ cell count and lung cancer, neither when measured within 1 year (OR for <200 vs ≥500=1.21, 95% CI: 0.49-2.96) nor further back in time, before lung cancer diagnosis. Combined antiretroviral therapy was not significantly associated with lung cancer (OR for ever vs never=0.67, 95% CI: 0.29-1.52), and nor was a history of AIDS with (OR=0.49, 95% CI: 0.19-1.28) or without (OR=0.53, 95% CI: 0.24-1.18) pulmonary involvement. CONCLUSION: Lung cancer in the SHCS does not seem to be clearly associated with immunodeficiency or AIDS-related pulmonary disease, but seems to be attributable to heavy smoking.

Official Positions for FRAX® clinical regarding smoking from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

The worldwide prevalence of smoking has been estimated at about 50% in men, and 10% in women, with larger variations among different populations studied. Smoking has been shown to affect many organ systems resulting in severe morbidity and increased mortality. In addition, smoking has been identified as a predictor of ten-year fracture risk in men and women, largely independent of an individual's bone mineral density. This finding has eventually lead to incorporation of this risk factor into FRAX®, an algorithm that has been developed to calculate an individual's ten-year fracture risk. However, only little, or conflicting data is available on a possible association between smoking dose, duration, length of time after cessation, type of tobacco and fracture risk, limiting this risk factor's applicability in the context of FRAX®.

Adverse effects of high dose carnitine supplementation of total parenteral nutrition on protein and fat oxidation in the critically ill.

The aim of the present study was to investigate the effects of continuous and acute L-carnitine supplementation of total parenteral nutrition (TPN) on protein and fat oxidation in severe catabolism. A critically ill and severely malnourished male patient received TPN (non protein energy = 41 kcal/kg/day, provided equally as fat and glucose) over 38 days, without L-carnitine for 23 days and with carnitine supplements (15 mg/kg/day) for the following 15 days. Subsequently, he was given carnitine-free enteral nutrition for 60 more days. A four-hour infusion of 100 mg L-carnitine was given on day 11 of each TPN period. Indirect calorimetry was carried out after 11 days of either carnitine-free or supplemented TPN and at the initiation of enteral nutrition. Additional measurements were performed 4 hours and 24 hours after the acute infusions of carnitine. The rate of protein oxidation and the respiratory quotient were found to be higher, and the rate of fat oxidation to be lower, with carnitine-supplemented TPN, than with either carnitine-free TPN or enteral nutrition. Acute infusion of carnitine resulted in an increased rate of protein oxidation and a reduced rate of fat oxidation on both TPN-regimens. These unfavourable effects on protein metabolism may be due to an impairment of fat oxidation by excess amounts of carnitine.

Relationship between cigarette smoking and abdominal obesity

BACKGROUND: Although smokers tend to have a lower body-mass index (BMI) than non-smokers, smoking may affect body fat (BF) distribution. Some studies have assessed the association between smoking, BMI and waist circumference (WC), but, to our knowledge, no population-based studies assessed the relation between smoking and BF composition. We assessed the association between amount of cigarette smoking, BMI, WC and BF composition. METHODS: Data was analysed from a cross-sectional population-based study including 6187 Caucasians aged 32-76 and living in Switzerland. Height, weight and WC were measured. BF, expressed in percent of total body weight, was measured by electrical bioimpedance. Obesity was defined as a BMI>=30 kg/m2 and normal weight as a BMI<25 kg/m2. Abdominal obesity was defined as a WC>=102 cm for men and >=88 cm for women and normal WC as <94 cm for men and <80 cm for women. In men, excess BF was defined as %BF >=28.1, 28.7, 30.6 and 32.6 for age groups 32-44, 45-54, 55-64 and 65-76, respectively; the corresponding values for women were 35.9, 36.5, 40.5 and 44.4. Cigarette smoking was assessed using a self-reported questionnaire. RESULTS: 29.3% of men and 25.0% of women were smokers. Prevalence of obesity, abdominal obesity, and excess of BF was 16.9% and 26.6% and 14.2% in men and 15.0%, 33.0% and 27.5% in women, respectively. Smokers had lower age-adjusted mean BMI, WC and percent of BF compared to non-smokers. However, among smokers,mean age-adjusted BMI,WC and BF increased with the number of cigarettes smoked per day: among light (1-10 cig/day), moderate (11-20) and heavy smokers (>20), mean +/-SE %BF was 22.4 +/−0.3, 23.1+/−0.3 and 23.5+/−0.4 for men, and 31.9+/−0.3, 32.6+/−0.3 and 32.9+/−0.4 for women, respectively. Mean WC was 92.9+/−0.6, 94.0+/−0.5 and 96.0+/−0.6 cm for men, and 80.2+/−0.5, 81.3+/−0.5 and 83.3+/−0.7 for women, respectively. Mean BMI was 25.7+/−0.2, 26.0+/−0.2, and 26.1+/−0.2 kg/m2 for men; and 23.6+/−0.2, 24.0+/−0.2 and 24.1+/−0.3 for women, respectively. Compared with light smokers, the age-adjusted odds ratio (95% Confidence Interval) for excess of BF was 1.04 (0.58 to 1.85) formoderatesmokers and 1.06 (0.57 to 1.99) for heavy smokers in men (p-trend = 0.9), and 1.35 (0.92 to 1.99) and 2.26 (1.38 to 3.72), respectively, in women (p-trend = 0.04). Odds ratio for abdominal obesity vs. normal WC was 1.32 (0.81 to 2.15) for moderate smokers and 1.95 (1.16 to 3.27) for heavy smokers in men (p-trend < 0.01), and 1.15 (0.79 to 1.69) and 2.36 (1.41 to 3.93) in women (p-trend = 0.03). Odds ratio for obesity vs. normal weight was 1.35 (0.76 to 2.41) for moderate smokers and 1.33 (0.71 to 2.49) for heavy smokers in men (p-trend = 0.9) and 0.78 (0.45 to 1.35) and 1.44 (0.73 to 2.85), in women (p-trend = 0.08). CONCLUSIONS: WC and BF were positively and dose-dependently associated with the number of cigarettes smoked per day in women, whereas onlyWC was dose dependently and significantly associated with the amount of cigarettes smoked per day in men. This suggests that heavy smokers, especially women, are more likely to have an excess of BF and to accumulate BF in the abdomen compared to lighter smokers.

Outcome of smoking cessation counselling of HIV-positive persons by HIV care physicians.

OBJECTIVES: Smoking is the most prevalent modifiable risk factor for cardiovascular diseases among HIV-positive persons. We assessed the effect on smoking cessation of training HIV care physicians in counselling. METHODS: The Swiss HIV Cohort Study (SHCS) is a multicentre prospective observational database. Our single-centre intervention at the Zurich centre included a half day of standardized training for physicians in counselling and in the pharmacotherapy of smokers, and a physicians' checklist for semi-annual documentation of their counselling. Smoking status was then compared between participants at the Zurich centre and other institutions. We used marginal logistic regression models with exchangeable correlation structure and robust standard errors to estimate the odds of smoking cessation and relapse. RESULTS: Between April 2000 and December 2010, 11 056 SHCS participants had 121 238 semi-annual visits and 64 118 person-years of follow-up. The prevalence of smoking decreased from 60 to 43%. During the intervention at the Zurich centre from November 2007 to December 2009, 1689 participants in this centre had 6068 cohort visits. These participants were more likely to stop smoking [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.07-1.42; P=0.004] and had fewer relapses (OR 0.75; 95% CI 0.61-0.92; P=0.007) than participants at other SHCS institutions. The effect of the intervention was stronger than the calendar time effect (OR 1.19 vs. 1.04 per year, respectively). Middle-aged participants, injecting drug users, and participants with psychiatric problems or with higher alcohol consumption were less likely to stop smoking, whereas persons with a prior cardiovascular event were more likely to stop smoking. CONCLUSIONS: An institution-wide training programme for HIV care physicians in smoking cessation counselling led to increased smoking cessation and fewer relapses.