Trends in Condom Use and Risk Behaviours after Sexual Exposure to HIV: A Seven-Year Observational Study

Objective

We aimed to determine the trends in numbers and percentages of sexually exposed persons to HIV (SE) consulting an ED for post-exposure prophylaxis (PEP), as well as predictors of condom use.

Study Design

We conducted a prospective-observational study.

Methods

We included all SE attendances in our Emergency Department (ED) during a seven-year study-period (2006–2012). Trends were analyzed using time-series analysis. Logistic Regression was used to define indicators of condom use.

Results

We enrolled 1851 SE: 45.7% reported intercourse without condom-use and 12.2% with an HIV-infected partner. Significant (p<0.01) rising trends were observed in the overall number of SE visits (+75%), notably among men having sex with men (MSM) (+126%). There were rising trends in the number and percentage of those reporting intercourse without condom-use in the entire population +91% (p<0.001) and +1% (p>0.05), in MSM +228% (p<0.001) and +49% (p<0.001), in Heterosexuals +68% (p<0.001) and +10% (p = 0.08). Among MSM, significant rising trends were found in those reporting high-risk behaviours: anal receptive (+450% and +76%) and anal insertive (+l33% and +70%) intercourses. In a multivariate logistic regression analysis, heterosexuals, vaginal intercourse, visit during the night-shift and short time delay between SE and ED visit, were significantly associated with condom-use.

Conclusion

We report an increasing trend in the number of SE, mainly among MSM, and rising trends in high-risk behaviours and unprotected sexual intercourses among MSM. Our results indicate that SE should be considered as a high-risk population for HIV and sexually transmitted diseases.     

Isoniazid,Pyrazinamide and Rifampicin Content Variation in Split Fixed-Dose Combination Tablets

Setting

In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets.

Objective

To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis.

Design

Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets.

Results

All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings.

Conclusion

In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.     

Passive Smoking Exposure from Partners as a Risk Factor for ER+/PR+ Double Positive Breast Cancer in Never-Smoking Chinese Urban Women: A Hospital-Based Matched Case Control Study

Background

The relationship between passive smoking exposure (PSE) and breast cancer risk is of major interest.

Objective

To evaluate the relationship between PSE from partners and breast cancer risk stratified by hormone-receptor (HR) status in Chinese urban women population.

Design

Hospital-based matched case control study.

Setting

Chinese urban breast cancer patients without current or previous active smoking history in China Medical University 1st Hospital, Liaoning Province, China between Jan 2009 and Nov 2009.

Patients

Each breast cancer patient was matched 1∶1 with healthy controls by gender and age (±2 years) from the same hospital.

Measurements

The authors used unconditional logistic regression analyses to estimate odds ratio for women with PSE from partners and breast cancer risk.

Results

312 pairs were included in the study. Women who endured PSE had significantly increased risk of breast cancer (adjusted OR: 1.46; 95% CI: 1.05–2.03; P = 0.027), comparing with unexposed women. Women who exposed to >5 cigarettes/day also had significant increased risk (adjusted OR: 1.99; 95% CI: 1.28–3.10; P = 0.002), as were women exposed to passive smoke for 16–25 years (adjusted OR: 1.87 95% CI: 1.22–2.86; P = 0.004), and those exposed to > 4 pack-years (adjusted OR: 1.71 95% CI: 1.17–2.50; P = 0.004). Similar trends were significant for estrogen receptor (ER)/progesterone receptor (PR) double positive subgroup(adjusted OR: 1.71; 2.20; 1.99; 1.92, respectively), but not for ER+/PR−, ER−/PR+, or ER−/PR− subgroups.

Limitations

limitations of the hospital-based retrospective study, lack of information on entire lifetime PSE and low statistical power.

Conclusions

Our findings provide further evidence that PSE from partners contributes to increased risk of breast cancer, especially for ER/PR double positive breast cancer, in Chinese urban women.     

Association between Exposure to Environmental Tobacco Smoke and Biomarkers of Oxidative Stress Among Patients Hospitalised with Acute Myocardial Infarction

Objective

To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.

Design

An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.

Setting

Nine acute hospitals in Scotland.

Participants

Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).

Intervention

None.

Main outcome measures

Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.

Results

After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).

Conclusions

Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.     

Formulation and In Vitro,In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

Introduction

Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.

Methodology

Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO₃) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.

Results and Discussion

Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO₃ produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower C_max and higher T_max compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours.

Conclusion

In conclusion, in order to suggest a better drug delivery system with constant favorable release, resulting in optimized absorption and less side effects, formulated CP-HPMC-SA based imatinib mesylate floating sustained-release tablets can be a promising candidate for cancer chemotherapy.     

Skeletal Muscle Insulin Resistance Associated with Cholesterol-Induced Activation of Macrophages Is Prevented by High Density Lipoprotein

Background

Emerging evidence suggests that high density lipoprotein (HDL) may modulate glucose metabolism through multiple mechanisms including pancreatic insulin secretion as well as insulin-independent glucose uptake into muscle. We hypothesized that HDL may also increase skeletal muscle insulin sensitivity via cholesterol removal and anti-inflammatory actions in macrophages associated with excess adiposity and ectopic lipid deposition.

Methods

Human primary and THP-1 macrophages were treated with vehicle (PBS) or acetylated low density lipoprotein (acLDL) with or without HDL for 18 hours. Treatments were then removed, and macrophages were incubated with fresh media for 4 hours. This conditioned media was then applied to primary human skeletal myotubes derived from vastus lateralis biopsies taken from patients with type 2 diabetes to examine insulin-stimulated glucose uptake.

Results

Conditioned media from acLDL-treated primary and THP-1 macrophages reduced insulin-stimulated glucose uptake in primary human skeletal myotubes compared with vehicle (primary macrophages, 168±21% of basal uptake to 104±19%; THP-1 macrophages, 142±8% of basal uptake to 108±6%; P<0.05). This was restored by co-treatment of macrophages with HDL. While acLDL increased total intracellular cholesterol content, phosphorylation of c-jun N-terminal kinase and secretion of pro- and anti-inflammatory cytokines from macrophages, none were altered by co-incubation with HDL. Insulin-stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition.

Conclusion

Inhibition of insulin-stimulated glucose uptake in primary human skeletal myotubes by conditioned media from macrophages pre-incubated with acLDL was restored by co-treatment with HDL. However, these actions were not linked to modulation of common pro- or anti-inflammatory mediators or insulin signaling via Akt.     

The Effect of Aerobic Exercise on Intrahepatocellular and Intramyocellular Lipids in Healthy Subjects

Background

Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass).

Aim

To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy.

Methods

Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO_2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO_2max) using ¹H-MR-spectroscopy.

Results

Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO_2max, 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (−22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity.

Conclusions

IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions.

Trial Registration

ClinicalTrial.gov {"type":"clinical-trial","attrs":{"text":"NCT00491582","term_id":"NCT00491582"}}NCT00491582     

Relationship of C5L2 Receptor to Skeletal Muscle Substrate Utilization

Objective

To investigate the role of Acylation Stimulating Protein (ASP) receptor C5L2 in skeletal muscle fatty acid accumulation and metabolism as well as insulin sensitivity in both mice and human models of diet-induced insulin resistance.

Design and Methods

Male wildtype (WT) and C5L2 knockout (KO) mice were fed a low (LFD) or a high (HFD) fat diet for 10 weeks. Intramyocellular lipid (IMCL) accumulation (by oil red O staining) and beta-oxidation HADH enzyme activity were determined in skeletal muscle. Mitochondria were isolated from hindleg muscles for high-resolution respirometry. Muscle C5L2 protein content was also determined in obese type 2 diabetics and age- and BMI matched men.

Results

IMCL levels were increased by six-fold in C5L2KO-HFD compared to WT-HFD mice (p<0.05) and plasma insulin levels were markedly increased in C5L2KO-HFD mice (twofold, p<0.05). Muscle HADH activity was elevated in C5L2KO-LFD mice (+75%, p<0.001 vs. WT-LFD) and C5L2KO-HFD displayed increased mitochondrial fatty acid oxidative capacity compared to WT-HFD mice (+23%, p<0.05). In human subjects, C5L2 protein content was reduced (−48%, p<0.01) in type 2 diabetic patients when compared to obese controls. Further, exercise training increased C5L2 (+45%, p = 0.0019) and ASP (+80%, p<0.001) in obese insulin-resistant men.

Conclusion

The results suggest that insulin sensitivity may be permissive for coupling of C5L2 levels to lipid storage and utilization.     

Health Behaviours and Potentially Preventable Hospitalisation: A Prospective Study of Older Australian Adults

Objective

Several studies have demonstrated the effects of health behaviours on risk of chronic diseases and mortality, but none have investigated their contribution to potentially preventable hospitalisation (PPH). We aimed to quantify the effects on risk of PPH of six health behaviours: smoking; alcohol consumption; physical activity; fruit and vegetables consumption; sitting time; and sleeping time.

Design/Setting

Prospective observational study in New South Wales, Australia.

Subjects

267,006 men and women aged 45 years and over.

Outcome Measures

PPH admissions and mortality during follow-up according to individual positive health behaviours (non-smoking, <14 alcoholic drinks per week, ≥2.5 hours of physical activity per week, ≥2 servings of fruit and 5 servings of vegetables per day, <8 hours sitting and ≥7 hours sleeping per day) and the total number of these behaviours.

Results

During an average of 3 years follow-up, 20971 (8%) participants had at least one PPH admission. After adjusting for potential confounders, participants who reported all six positive health behaviours at baseline had 46% lower risk of PPH admission (95% CI 0.48–0.61), compared to those who reported having only one of these behaviours. Based on these risk estimates, approximately 29% of PPH admissions in Australians aged 45 years and over were attributable to not adhering to the six health behaviours. Estimates were similar for acute, chronic and vaccine-preventable categories of PPH admissions.

Conclusions

Individual and combined positive health behaviours were associated with lower risk of PPH admission. These findings suggest that there is a significant opportunity to reduce PPH by promoting healthy behaviours.     

Efficacy and Safety of Inhaled Carbon Monoxide during Pulmonary Inflammation in Mice

Background

Pulmonary inflammation is a major contributor to morbidity in a variety of respiratory disorders, but treatment options are limited. Here we investigate the efficacy, safety and mechanism of action of low dose inhaled carbon monoxide (CO) using a mouse model of lipopolysaccharide (LPS)-induced pulmonary inflammation.

Methodology

Mice were exposed to 0–500 ppm inhaled CO for periods of up to 24 hours prior to and following intratracheal instillation of 10 ng LPS. Animals were sacrificed and assessed for intraalveolar neutrophil influx and cytokine levels, flow cytometric determination of neutrophil number and activation in blood, lung and lavage fluid samples, or neutrophil mobilisation from bone marrow.

Principal Findings

When administered for 24 hours both before and after LPS, inhaled CO of 100 ppm or more reduced intraalveolar neutrophil infiltration by 40–50%, although doses above 100 ppm were associated with either high carboxyhemoglobin, weight loss or reduced physical activity. This anti-inflammatory effect of CO did not require pre-exposure before induction of injury. 100 ppm CO exposure attenuated neutrophil sequestration within the pulmonary vasculature as well as LPS-induced neutrophilia at 6 hours after LPS, likely due to abrogation of neutrophil mobilisation from bone marrow. In contrast to such apparently beneficial effects, 100 ppm inhaled CO induced an increase in pulmonary barrier permeability as determined by lavage fluid protein content and translocation of labelled albumin from blood to the alveolar space.

Conclusions

Overall, these data confirm some protective role for inhaled CO during pulmonary inflammation, although this required a dose that produced carboxyhemoglobin values close to potentially toxic levels for humans, and increased lung permeability.     

Do Intravenous N-Acetylcysteine and Sodium Bicarbonate Prevent High Osmolal Contrast-Induced Acute Kidney Injury? A Randomized Controlled Trial

Background

N-acetylcysteine (NAC) or sodium bicarbonate (NaHCO₃), singly or combined, inconsistently prevent patients exposed to radiographic contrast media from developing contrast-induced acute kidney injury (CI-AKI).

Objective

We asked whether intravenous isotonic saline and either NaHCO₃ in 5% dextrose or else a high dose of NAC in 5% dextrose prevent CI-AKI in outpatients exposed to high-osmolal iodinated contrast medium more than does saline alone.

Methods

This completed prospective, parallel, superiority, open-label, controlled, computer-randomized, single-center, Brazilian trial ({"type":"clinical-trial","attrs":{"text":"NCT01612013","term_id":"NCT01612013"}}NCT01612013) hydrated 500 adult outpatients (214 at high risk of developing CI-AKI) exposed to ioxitalamate during elective coronary angiography and ventriculography. From 1 hour before through 6 hours after exposure, 126 patients (group 1) received a high dose of NAC and saline, 125 (group 2) received NaHCO₃ and saline, 124 (group 3) received both treatments, and 125 (group 4) received only saline.

Results

Groups were similar with respect to age, gender, weight, pre-existing renal dysfunction, hypertension, medication, and baseline serum creatinine and serum cystatin C, but diabetes mellitus was significantly less prevalent in group 1. CI-AKI incidence 72 hours after exposure to contrast medium was 51.4% (257/500), measured as serum creatinine > (baseline+0.3 mg/dL) and/or serum cystatin C > (1.1· baseline), and 7.6% (38/500), measured as both serum creatinine and serum cystatin C > (baseline+0.3 mg/dL) or > (1.25 · baseline). CI-AKI incidence measured less sensitively was similar among groups. Measured more sensitively, incidence in group 1 was significantly (p<0.05) lower than in groups 2 and 3 but not group 4; adjustment for confounding by infused volume equalized incidence in groups 1 and 3.

Conclusion:

We found no evidence that intravenous isotonic saline and either NaHCO₃ or else a high dose of NAC prevent CI-AKI in outpatients exposed to high osmolal iodinated contrast medium more than does saline alone.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01612013","term_id":"NCT01612013"}}NCT01612013.     

Age at Adiposity Rebound Is Associated with Fat Mass in Young Adult Males—The GOOD Study

Objective

Age at adiposity rebound (AR) is associated with obesity and Type 2 Diabetes in adults. The aim of the present study was to investigate the role of age at AR in adult fat mass, fat distribution and pubertal timing for a Swedish cohort.

Patients and Methods

This is a retrospective cohort study. Detailed growth charts were retrieved for the men participating in the population-based GOOD (Gothenburg Osteoporosis and Obesity Determinants) study (n = 573). Body composition was analysed using dual X-ray absorptiometry and computed tomography at 18–20 years of age. Age and BMI at AR were calculated using pediatric growth charts and AR was defined as the lowest BMI between 3 and 9 years of age.

Results

Subjects were divided into early (age at AR below 5.4 years of age), middle (age at AR 5.4 to 6.8 years of age) and late (age at AR after 6.8 years of age) age at AR tertiles. Subjects in the early age at AR tertile had higher young adult BMI (+8%), whole body fat mass (+34%) and amount of subcutaneous adipose tissue (+61%) than the subjects in the middle and late tertiles (p<0.01). The early age at AR tertile had an increased risk of obesity (Odds Ratio 4.1 [95% CI 1.2–13.9]) compared with the middle and late tertiles. In addition, the early age at AR tertile had Peak Height Velocity (PHV) 7 months earlier than the late tertile.

Conclusions

Early age at AR was associated with young adult obesity as a consequence of a high amount of subcutaneous adipose tissue in men. In addition we made the novel observation that early age at AR was associated with an early puberty in men.     

Early Life Disease Programming during the Preconception and Prenatal Period: Making the Link between Stressful Life Events and Type-1 Diabetes

Background

To assess the risk of developing Type-1 diabetes among children who were exposed to maternal bereavement during the prenatal or 1-year preconception period.

Methods

We identified N = 1,548,746 singleton births born in Denmark between January 1^st 1979 through December 31^st 2004, and their next of kin. Altogether, 39,857 children were exposed to bereavement during their prenatal life. The main outcome of interest was hospitalization for type-1 diabetes (ICD 8: 249; ICD 10: E10).

Results

We found the strongest association for type-1 diabetes among children exposed to traumatic father or sibling deaths (aIRR: 2.03, 1.22–3.38); the association was mainly seen for girls (aIRR: 2.91, 1.61–5.26).

Conclusions

We found evidence to suggest that female fetuses exposed to severe prenatal stress are at increased risk for developing type-1 diabetes.     

Efficacy of Admission Screening for Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae

Objective

We hypothesized that admission screening for extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) reduces the incidence of hospital-acquired ESBL-E clinical isolates.

Design

Retrospective cohort study.

Setting

12 hospitals (6 screening and 6 non-screening) in Toronto, Canada.

Patients

All adult inpatients with an ESBL-E positive culture collected from 2005–2009.

Methods

Cases were defined as hospital-onset (HO) or community-onset (CO) if cultures were positive after or before 72 hours. Efficacy of screening in reducing HO-ESBL-E incidence was assessed with a negative binomial model adjusting for study year and CO-ESBL-E incidence. The accuracy of the HO-ESBL-E definition was assessed by re-classifying HO-ESBL-E cases as confirmed nosocomial (negative admission screen), probable nosocomial (no admission screen) or not nosocomial (positive admission screen) using data from the screening hospitals.

Results

There were 2,088 ESBL-E positive patients and incidence of ESBL-E rose from 0.11 to 0.42 per 1,000 inpatient days between 2005 and 2009. CO-ESBL-E incidence was similar at screening and non-screening hospitals but screening hospitals had a lower incidence of HO-ESBL-E in all years. In the negative binomial model, screening was associated with a 49.1% reduction in HO-ESBL-E (p<0.001). A similar reduction was seen in the incidence of HO-ESBL-E bacteremia. When HO-ESBL-E cases were re-classified based on their admission screen result, 46.5% were positive on admission, 32.5% were confirmed as nosocomial and 21.0% were probable nosocomial cases.

Conclusions

Admission screening for ESBL-E is associated with a reduced incidence of HO-ESBL-E. Controlled, prospective studies of admission screening for ESBL-E should be a priority.     

Organ Dysfunction among Piglets Treated with Inhaled Nitric Oxide and Intravenous Hydrocortisone during Prolonged Endotoxin Infusion

Objective

It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables.

Design

Randomized controlled trial.

Setting

University animal laboratory.

Subjects

Domestic piglets (n = 30).

Interventions

Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid.

Measurements and Main Results

Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups.

Conclusions

This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion.     

Low intensity,long-term outpatient rehabilitation in COPD: a randomised controlled trial

Background

Most pulmonary rehabilitation programmes currently involve 2–3 sessions per week as recommended by international guidelines. We aimed to investigate whether relevant improvements in physical capabilities and quality of life in patients with chronic obstructive pulmonary disease (COPD) could be achieved by a long-term, low intensity, once weekly rehabilitation programme using limited resources.

Methods

100 patients with moderate to severe COPD were randomised to a continuous outpatient interdisciplinary rehabilitation programme or standard care. Physiotherapy-led supervised outpatient training sessions were performed once weekly in addition to educational elements. Outcome measures at baseline and after 26 weeks were 6-minute-walk-test, cycle ergometry, and health-related quality of life.

Results

37 patients in the training group and 44 patients in the control group completed the study. After 26 weeks there were clinically significant differences between the groups for 6 minute-walk-distance (+59 m, 95% CI 28–89 m), maximum work load (+7.4 Watt, 95% CI 0.5-13.4 Watt) and St. George’s Respiratory Questionnaire score (−5 points, 95% CI −10 to −1 points). Total staff costs of the programme per participant were ≤ €625.

Conclusion

Clinically meaningful improvements in physical capabilities and health-related quality of life may be achieved using long-term pulmonary rehabilitation programmes of lower intensity than currently recommended. Trial registration: clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01195402","term_id":"NCT01195402"}}NCT01195402.     

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program – A Markov Model

Background

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.

Objective

To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.

Design

Markov decision model.

Data Sources

Published data.

Target Population

Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.

Time Horizon

The 5 years after initial evaluation for OSAS.

Perspective

Societal.

Interventions

Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.

Outcomes measures

Quality of life, survival and costs for each screening strategy.

Results of base-case analysis

Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.

Results of sensitivity analysis

Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.

Conclusions

CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.     

Combination Therapy with Antibiotics and Anthrax Immune Globulin Intravenous (AIGIV) Is Potentially More Effective than Antibiotics Alone in Rabbit Model of Inhalational Anthrax

Background

We have evaluated the therapeutic efficacy of AIGIV when given in combination with levofloxacin and the effective window of treatment to assess the added benefit provided by AIGIV over standard antibiotic treatment alone in a New Zealand white rabbit model of inhalational anthrax.

Methods

Rabbits were exposed to lethal dose of aerosolized spores of Bacillus anthracis (Ames strain) and treated intravenously with either placebo, (normal immune globulin intravenous, IGIV) or 15 U/kg of AIGIV, along with oral levofloxacin treatment at various time points (30–96 hours) after anthrax exposure.

Results

The majority of treated animals (>88%) survived in both treatment groups when treatment was initiated within 60 hours of post-exposure. However, reduced survival of 55%, 33% and 25% was observed for placebo + levofloxacin group when the treatment was initiated at 72, 84 and 96 hours post-exposure, respectively. Conversely, a survival rate of 65%, 40% and 71% was observed in the AIGIV + levofloxacin treated groups at these time points.

Conclusions

The combination of AIGIV with antibiotics provided an improvement in survival compared to levofloxacin treatment alone when treatment was delayed up to 96 hours post-anthrax exposure. Additionally, AIGIV treatment when given as an adjunct therapy at any of the time points tested did not interfere with the efficacy of levofloxacin.