Cardiometabolic Risk Profiles Associated with Chronic Complications in Overweight and Obese Type 2 Diabetes Patients in South China

Background

Type 2 diabetes is often accompanied by altered cardiometabolic risk profiles, including abdominal obesity, hypertension, and dyslipidaemia. The association of altered cardiometabolic risk profiles with chronic complications of diabetes is not well investigated.

Methods

We recruited 2954 type 2 diabetes patients with a body mass index ≥25 kg/m² who visited the diabetes clinics of 62 hospitals in 21 cities in Guangdong province of China from August 2011 to March 2012. Demographic characteristics, personal and family medical histories, and data on chronic complications of diabetes were collected. Clinical examinations and laboratory assessment were conducted.

Results

Abdominal obesity was found in 91.6% of the study population, elevated blood pressure in 78.3%; elevated serum triacylglycerols in 57.8%, and reduced serum HDL-C in 55.9%. Among the cardiometabolic risk factors, elevated blood pressure was significantly associated with almost all the chronic complications of diabetes. After adjusting for age, gender, duration of diabetes, and HbA1c, elevated blood pressure was significantly associated with diabetic retinopathy (OR 1.63, 95% CI: 1.22–2.19), diabetic nephropathy (OR 3.16, 95% CI: 2.25–4.46), cardiovascular disease (OR 2.71, 95% CI: 1.70–4.32), and stroke (OR 1.90, 95% CI: 1.15–3.12). Abdominal adiposity was significantly associated with diabetic nephropathy (OR 1.39, 95% CI: 1.11–1.74). Elevated triacylglycerols was significantly associated with diabetic retinopathy (OR 1.29, 95% CI: 1.05–1.58) and diabetic nephropathy (OR 1.30, 95% CI: 1.05–1.58). Reduced HDL-C was significantly associated with stroke (OR 1.41, 95% CI: 1.05–1.88).

Conclusions

Altered cardiometabolic risk profiles, and elevated blood pressure in particular, were significantly associated with chronic complications in overweight and obese patients with type 2 diabetes. Future studies on the prevention of chronic complications of diabetes might make lowering blood pressure a primary target.     

Adherence to Guidelines for Avoiding Drug Interactions Associated with Warfarin - A Nationwide Swedish Register Study

Purpose

To investigate the extent to which clinicians avoid well-established drug-drug interactions associated with warfarin. We hypothesised that clinicians would avoid combining non-steroidal anti-inflammatory drugs (NSAIDs), tramadol and sulfamethoxazole with warfarin.

Methods

A cross-sectional analysis of nationwide dispensing data was performed in Swedish individuals 18 years or older (n =  7 563 649). Odds ratios of interacting NSAIDs, tramadol and sulfamethoxazole versus respective prevalence of comparator drugs codeine, and ciprofloxacin in patients co-dispensed interacting warfarin versus patients unexposed was calculated.

Results

The odds of receiving an interacting NSAID versus the comparator codeine was markedly lower in patients with warfarin than in the remaining population (adjusted OR 0.21; 95% CI 0.20 – 0.22). Also, the interacting drugs tramadol and sulfamethoxazole were less common among patients dispensed warfarin as compared to the remaining population, although the decrease was much more modest (adjusted OR 0.83; CI 0.80–0.87 and 0.81; CI 0.73 – 0.90).

Conclusions

In conclusion, Swedish doctors in the vast majority of cases refrain from prescribing NSAIDs to patients already on warfarin. Tramadol and sulfamethoxazole are however rarely avoided.     

Pimecrolimus Cream 1% in the Management of Atopic Dermatitis in Pediatric Patients: A Meta-Analysis

Objective

To evaluate the efficacy and safety of pimecrolimus cream 1% in the treatment of AD in the pediatric population.

Methods

PubMed, EMBASE, Web of Science and Cochrane library databases were searched till July 2013. The randomized and nonrandomized blinded studies of pimecrolimus cream 1% applied twice daily with Jaded score ≥3 in pediatric patients with AD were included. The efficacy outcomes included investigator global assessment (IGA), eczema area and severity index (EASI) scores, pruritus and care giver''s assessments and flares free period. Adverse events were reviewed to assess the safety.

Results

Out of 81 studies, 7 were selected that enrolled 2,170 pediatric patients. The pooled analysis reported that pimecrolimus was no better to vehicle reducing eczema at day-8, day-26 and six weeks (OR 4.95, 95% CI 2.79–8.80), (OR 9.69, 95% CI 4.12–22.83) and (OR 3.83. 95% CI 1.94–7.56), respectively in children. Similarly, pimecrolimus did not show beneficial effects when analyzed for mild or absent pruritus at day 4 (OR 8.29, 95% CI 3.88–17.72 favoring vehicle), day 43 (OR 1.81 95% CI 1.13–2.89 favoring vehicle) and 1 week (OR 2.29, 95%CI 1.45 to 3.60 favoring vehicle) as compared with vehicle. One study comparing pimecrolimus with tacrolimus found no significant difference in achieving mild or absent pruritus (OR 0.94, 95% CI 0.44–1.99). More patients showed an improvement in overall disease in vehicle group at day 8 (OR 3.30, 95% CI 2.03–5.35), day 29 (OR 14.14, 95% CI 6.87–29.13) and day 43 (OR 4.11, 95% CI 2.59–6.52) as compared with pimecrolimus 1% group, as assessed by caregivers. No significant difference was seen between the total AEs in both groups (pimecrolimus vs vehicle/tacrolimus) (OR 1.19, 95% CI 0.85, 1.65)

Conclusion

The results of the present meta-analysis showed that pimecrolimus cream 1% was not significantly better to vehicle for AD in pediatrics population.     

Inappropriate Drugs in Elderly Patients with Severe Cognitive Impairment: Results from the Shelter Study

Background

It has been estimated that Nursing Home (NH) residents with impaired cognitive status receive an average of seven to eight drugs daily. The aim of this study was to determine prevalence and factors associated with use of inappropriate drugs in elderly patients with severe cognitive impairment living in NH in Europe.

Methods

Cross-sectional data from a sample of 1449 NH residents with severe cognitive impairment, participating in the Services and Health for Elderly in Long TERm care (SHELTER) study were analysed. Inappropriate drug use was defined as the use of drugs classified as rarely or never appropriate in patients with severe cognitive impairment based on the Holmes criteria published in 2008.

Results

Mean age of participating residents was 84.2±8.9 years, 1087 (75.0%) were women. Inappropriate drug use was observed in 643 (44.9%) residents. Most commonly used inappropriate drugs were lipid-lowering agents (9.9%), antiplatelet agents (excluding Acetylsalicylic Acid – ASA –) (9.9%), acetylcholinesterase, inhibitors (7.2%) and antispasmodics (6.9%). Inappropriate drug use was directly associated with specific diseases including diabetes (OR 1.64; 95% CI 1.21–2.24), heart failure (OR 1.48; 95% CI 1.04–2.09), stroke (OR 1.43; 95% CI 1.06–1.93), and recent hospitalization (OR 1.69; 95% CI 1.20–2.39). An inverse relation was shown between inappropriate drug use and presence of a geriatrician in the facility (OR 0.55; 95% CI 0.39–0.77).

Conclusion

Use of inappropriate drugs is common among older EU NH residents. Determinants of inappropriate drug use include comorbidities and recent hospitalization. Presence of a geriatrician in the facility staff is associated with a reduced rate of use of these medications.     

Polymorphisms of C242T and A640G in CYBA Gene and the Risk of Coronary Artery Disease: A Meta-Analysis

Background

Coronary artery disease (CAD) is a leading cause of mortality in many countries. Considerable studies have been carried out to investigate the relationship between the C242T and A640G polymorphisms of CYBA gene and CAD, but the results were still inconsistent. Hence we conducted a meta-analysis to clarify the association.

Methods and Results

A total of 21 eligible literatures were included in the meta-analysis. We observed a significant decreased risk of CAD for C242T polymorphism in Asian population under an allelic model (OR 0.75; 95% CI 0.67–0.84) and a dominant model (OR 0.69; 95% CI 0.61–0.79), however, in overall population and other population no significant association was revealed. We also found A640G polymorphism may contribute to reducing CAD risk under an allelic model (OR 0.84; 95% CI 0.75–0.93), dominant model (OR0.77; 95% CI 0.64–0.92) and recessive model (OR0.82; 95% CI 0.69–0.97). No publication bias was found.

Conclusion

Our meta-analysis confirmed a protective effect of C242Tpolymorphism on CAD in Asian population and indicated that A640G polymorphism was significantly associated with decreased risk of CAD.     

Frequency and Risk Factors for Under- and Over-Treatment in Stroke Prevention for Patients with Non-Valvular Atrial Fibrillation in General Practice

Objective

To determine adequacy of antithrombotic treatment in patients with non-valvular atrial fibrillation. To determine risk factors for under- and over-treatment.

Design

Retrospective, cross-sectional study of electronic health records from 36 general practitioners in 2008.

Setting

General practice in the Netherlands.

Subjects

Primary care physicians (n = 36) and patients (n = 981) aged 65 years and over.

Main Outcome Measures

Rates of adequate, under and over-treatment, risk factors for under and over-treatment.

Results

Of the 981 included patients with a mean of age 78, 18% received no antithrombotic treatment (under-treatment), 13% received antiplatelet drugs and 69% received oral anticoagulation (OAC). Further, 43% of the included patients were treated adequately, 26% were under-treated, and 31% were over-treated. Patients with a previous ischaemic stroke were at high risk for under-treatment (OR 2.4, CI 1.6–3.5), whereas those with contraindications for OAC were at high risk for over-treatment (OR 37.0, CI 18.1–79.9). Age over 75 (OR 0.2, CI: 0.1–0.3]), diabetes (OR 0.1, CI: 0.1–0.3), heart failure (OR 0.2, CI: 0.1–0.3), hypertension (OR 0.1, CI: 0.1–0.2) and previous ischaemic stroke (OR 0.04, CI: 0.02–0.11) protected against over-treatment.

Conclusions

In general practice, CHADS₂-criteria are being used, but the antithrombotic treatment of patients with atrial fibrillation frequently deviates from guidelines on this topic. Patients with previous stroke are at high risk of not being prescribed OAC. Contraindications for OAC, however, seem to be frequently overlooked.     

The Impact of Choice of NNRTI on Short-Term Treatment Outcomes among HIV-Infected Patients Prescribed Tenofovir and Lamivudine in Johannesburg,South Africa

Introduction

Recent WHO guidelines for resource-limited settings recommend tenofovir in first-line antiretroviral therapy (ART) yet there are suggestions that patients receiving nevirapine with tenofovir have worse outcomes than those receiving efavirenz. We sought to compare outcomes among those taking nevirapine vs. efavirenz with tenofovir and lamivudine.

Methods

We analyzed data on ART naïve, non-pregnant patients, ≥18 years old without tuberculosis co-infection, initiating tenofovir with lamivudine and either nevirapine or efavirenz between April 1, 2010 and July 31, 2011 (when South Africa’s public-sector use of tenofovir began) at Themba Lethu Clinic in South Africa. We measured virologic suppression (viral load <400 copies/ml), virologic failure (2 consecutive viral loads >1000 copies/ml), and attrition (death/loss to follow-up) all at 12 months after ART initiation. Modified Poisson regression with robust error estimation was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for predictors of each outcome.

Results

2,254 patients were prescribed efavirenz, 131 nevirapine. Patients were followed a median (range) of 12.0 (0.1–12.0) person-months. 62.2% were female and median (IQR) age was 37.7 years (31.5–44.1). Patients prescribed efavirenz had similar initiating CD4 counts (median 132 for both regimens) but were somewhat more likely to be WHO Stage III or IV (39.6% vs. 33.6%) than those prescribed nevirapine. No difference in attrition was found (aRR: 0.83; 95% CI: 0.49–1.41). Among patients with ≥1 viral load within 1 year on ART, those prescribed nevirapine were as likely to reach virologic suppression (aRR: 0.97; 95% CI: 0.88–1.07) but more likely to experience virologic failure (aRR: 1.84; 95% CI: 1.02–3.31) than those prescribed efavirenz.

Conclusions

Our results support the notion that, among patients prescribed tenofovir and lamivudine, virologic failure is more common among those taking nevirapine than among those taking efavirenz. Longer-term follow up and larger studies will be needed to confirm this finding.     

Stevens-Johnson Syndrome Associated with Drugs and Vaccines in Children: A Case-Control Study

Objective

Stevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.

Methods

A multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child’s use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.

Results

Twenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1^st November 1999 and 31^st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0–6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4–86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5–7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8–9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5–6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3–2.8).

Discussion

Our study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.     

Multi-Indication Carbamazepine and the Risk of Severe Cutaneous Adverse Drug Reactions in Korean Elderly Patients: A Korean Health Insurance Data-Based Study

Objective

To evaluate the risk of severe cutaneous adverse drug reactions (SCAR) after exposure to multi-indication antiepileptic drugs for in Korean elderly patients.

Methods

We used a nationwide database from the Korean Health Insurance Review and Assessment Service claims constructed for the monitoring of drug utilization among the entire Korean elderly population from January 2005 to June 2006. We identified cases of SCARs among inpatients aged ≥65 years and those newly diagnosed with erythema multiforme according to the International Classification of Diseases, 10th revision code (L51). Each case was matched to four controls for gender, age, and the first hospitalization date as the index date. The use of carbamazepine, gabapentin, lamotrigine, topiramate, phenobarbital, phenytoin, and valproate during a 60-day period before the index date was compared. A conditional logistic regression analysis was performed to calculate the odds ratios (OR) and 95% confidence intervals (CI) of SCARs for antiepileptic drug.

Results

We identified 286 cases of SCAR and 1,144 matched controls. Among the 25 patients who were prescribed antiepileptic drugs within 60 days of the index date. There were 11 cases (3.8%) of severe ocular manifestations, and most elderly patients were first-time or short-term users of antiepileptic drugs. Among the 10 cases of carbamazepine use, only 2 cases were prescribed carbamazepine for seizure. All antiepileptic drugs were associated with an increased SCAR risk (adjusted OR = 3.42, 95% CI: 1.75–6.63). The SCAR risk was highest in patients treated with carbamazepine (adjusted OR = 10.39, 95% CI: 2.64–40.86, for multi-indication; adjusted OR = 6.84, 95% CI: 1.55–30.10, for neuropathic pain).

Conclusion

Carbamazepine use was associated with a nearly 10-fold increase in severe cutaneous drug reactions in Korean elderly patients. This association was consistently high with SCAR patients who received carbamazepine for neuropathic pain.     

The Burden of Influenza and RSV among Inpatients and Outpatients in Rural Western Kenya, 2009–2012

Background

In Kenya, detailed data on the age-specific burden of influenza and RSV are essential to inform use of limited vaccination and treatment resources.

Methods

We analyzed surveillance data from August 2009 to July 2012 for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) at two health facilities in western Kenya to estimate the burden of influenza and respiratory syncytial virus (RSV). Incidence rates were estimated by dividing the number of cases with laboratory-confirmed virus infections by the mid-year population. Rates were adjusted for healthcare-seeking behavior, and to account for patients who met the SARI/ILI case definitions but were not tested.

Results

The average annual incidence of influenza-associated SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8–3.9) among children <5 years and 0.3 (95% CI 0.2–0.4) among persons ≥5 years; for RSV-associated SARI hospitalization, it was 5.2 (95% CI 4.0–6.8) among children <5 years and 0.1 (95% CI 0.0–0.2) among persons ≥5 years. The incidence of influenza-associated medically-attended ILI per 1,000 was 24.0 (95% CI 16.6–34.7) among children <5 years and 3.8 (95% CI 2.6–5.7) among persons ≥5 years. The incidence of RSV-associated medically-attended ILI was 24.6 (95% CI 17.0–35.4) among children <5 years and 0.8 (95% CI 0.3–1.9) among persons ≥5 years.

Conclusions

Influenza and RSV both exact an important burden in children. This highlights the possible value of influenza vaccines, and future RSV vaccines, for Kenyan children.     

The Association of Cardioprotective Medications with Pneumonia-Related Outcomes

Introduction

Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes.

Materials and Methods

We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events.

Results

Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63–0.77), ACE inhibitors (OR 0.82, 95% CI 0.74–0.91), and ARBs (OR 0.58, 95% CI 0.44–0.77). However, none of the medications were significantly associated with decreased cardiovascular events.

Discussion

While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects.     

Active Case Finding of Tuberculosis (TB) in an Emergency Room in a Region with High Prevalence of TB in Brazil

Setting

Public hospital emergency room (ER) in Porto Alegre, Brazil, a setting with high prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV) infection.

Objective

To determine the prevalence of PTB, using a symptom based active case finding (ACF) strategy in the ER of a public hospital in an area with high prevalence of TB and HIV, as well as variables associated with pulmonary TB diagnosis.

Methods

Cross sectional study. All patients ≥18 years seeking care at the ER were screened for respiratory symptoms and those with cough ≥2 weeks were invited to provide a chest radiograph and two unsupervised samples of sputum for acid-fast bacilli smear and culture.

Results

Among 31,267 admissions, 6,273 (20.1%) reported respiratory symptoms; 197 reported cough ≥2 weeks, of which pulmonary TB was diagnosed in 30. In multivariate analysis, the variables associated with a pulmonary tuberculosis diagnosis were: age (OR 0.94, 95% CI: 0.92–0.97; p<0.0001), sputum production (OR 0.18, 95% CI 0.06–0.56; p = 0.003), and radiographic findings typical of TB (OR 12.11, 95% CI 4.45–32.93; p<0.0001).

Conclusions

This study identified a high prevalence of pulmonary TB among patients who sought care at the emergency department of a tertiary hospital, emphasizing the importance of regular screening of all comers for active TB in this setting.     

Association between MMP1 -1607 1G>2G Polymorphism and Head and Neck Cancer Risk: A Meta-Analysis

Background

MMP1 is an important member of the MMP endopeptidase family that plays a critical role in the development of head and neck cancer (HNC). Several studies have investigated the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC, but their results have been inconsistent. Here, we conducted a meta-analysis to further explore the role of the MMP1 -1607 1G>2G polymorphism in HNC development.

Methods

We identified all eligible studies in the electronic databases of PubMed, ISI Web of Knowledge, MEDLINE, Embase, and Google Scholar (from January 2000 to June 2012). A meta-analysis was performed to evaluate the association between the MMP1 -1607 1G>2G polymorphism and risk of HNC by calculating odds ratios (OR) and 95% confidence interval (CIs).

Results

Twelve studies were included in this meta-analysis. In overall comparison, significant associations were found using the recessive and allelic contrast models (OR, 1.38; 95% CI, 1.07–1.79 and OR, 1.27; 95% CI, 1.05–1.53, respectively), but no association was detected using the dominant model. In the stratified analyses by several variables, significant associations were observed using the recessive, dominant, and allelic contrast models in the Asian population (OR, 1.64; 95% CI, 1.29–2.08; OR, 1.39; 95% CI, 1.06–1.82; and OR, 1.41; 95% CI, 1.21–1.65, respectively), European population (OR, 0.58; 95% CI, 0.40–0.84; OR, 0.64; 95% CI, 0.44–0.92; and OR, 0.68; 95% CI, 0.54–0.85, respectively), and population-based subgroup (OR, 1.24; 95% CI,1.05–1.47; OR,1.48; 95% CI,1.04–2.12; and OR, 1.22; 95% CI, 1.07–1.38, respectively). Furthermore, significant associations were detected in oral cavity cancer and nasopharyngeal cancer under the recessive model.

Conclusion

Our results suggest that the MMP1 -1607 1G>2G polymorphism is associated with risk of HNC and that it plays different roles in Asian and European populations. Further studies with large sample size are needed to validate our findings.     

Cross-Sectional Study of Malnutrition and Associated Factors among School Aged Children in Rural and Urban Settings of Fogera and Libo Kemkem Districts,Ethiopia

Introduction

Little information is available on malnutrition-related factors among school-aged children ≥5 years in Ethiopia. This study describes the prevalence of stunting and thinness and their related factors in Libo Kemkem and Fogera, Amhara Regional State and assesses differences between urban and rural areas.

Methods

In this cross-sectional study, anthropometrics and individual and household characteristics data were collected from 886 children. Height-for-age z-score for stunting and body-mass-index-for-age z-score for thinness were computed. Dietary data were collected through a 24-hour recall. Bivariate and backward stepwise multivariable statistical methods were employed to assess malnutrition-associated factors in rural and urban communities.

Results

The prevalence of stunting among school-aged children was 42.7% in rural areas and 29.2% in urban areas, while the corresponding figures for thinness were 21.6% and 20.8%. Age differences were significant in both strata. In the rural setting, fever in the previous 2 weeks (OR: 1.62; 95% CI: 1.23–2.32), consumption of food from animal sources (OR: 0.51; 95% CI: 0.29–0.91) and consumption of the family''s own cattle products (OR: 0.50; 95% CI: 0.27–0.93), among others factors were significantly associated with stunting, while in the urban setting, only age (OR: 4.62; 95% CI: 2.09–10.21) and years of schooling of the person in charge of food preparation were significant (OR: 0.88; 95% CI: 0.79–0.97). Thinness was statistically associated with number of children living in the house (OR: 1.28; 95% CI: 1.03–1.60) and family rice cultivation (OR: 0.64; 95% CI: 0.41–0.99) in the rural setting, and with consumption of food from animal sources (OR: 0.26; 95% CI: 0.10–0.67) and literacy of head of household (OR: 0.24; 95% CI: 0.09–0.65) in the urban setting.

Conclusion

The prevalence of stunting was significantly higher in rural areas, whereas no significant differences were observed for thinness. Various factors were associated with one or both types of malnutrition, and varied by type of setting. To effectively tackle malnutrition, nutritional programs should be oriented to local needs.     

The Predictive but Not Prognostic Value of MGMT Promoter Methylation Status in Elderly Glioblastoma Patients: A Meta-Analysis

Background

The clinical implication of O6-methylguanine-DNA methyltransferase (MGMT) promoter status is ill-defined in elderly glioblastoma patients. Here we report a meta-analysis to seek valid evidence for its clinical relevance in this subpopulation.

Methods

Literature were searched and reviewed in a systematic manner using the PubMed, EMBASE and Cochrane databases. Studies investigating the association between MGMT promoter status and survival data of elderly patients (≥65 years) were eligible for inclusion.

Results

Totally 16 studies were identified, with 13 studies included in the final analyses. The aggregate proportion of MGMT promoter methylation in elderly patients was 47% (95% confidence interval [CI]: 42–52%), which was similar to the value for younger patients. The analyses showed differential effects of MGMT status on overall survival (OS) of elderly patients according to assigned treatments: methylated vs. unmethylated: (1) temozolomide (TMZ)-containing therapies: hazard ratio [HR] 0.49, 95% CI 0.41–0.58; (2) TMZ-free therapies: HR 0.97, 95% CI 0.77–1.21. More importantly, a useful predictive value was observed by an interaction analysis: TMZ-containing therapies vs. RT alone: (1) methylated tumors: HR 0.48, 95% CI 0.36–0.65; (2) unmethylated tumors: HR 1.14; 95% CI 0.90–1.44.

Conclusion

The meta-analysis reports an age-independent presence of MGMT promoter methylation. More importantly, the study encouraged routine testing of MGMT promoter status especially in elderly glioblastoma patients by indicating a direct linkage between biomarker test and individual treatment decision. Future studies are needed to justify the mandatory testing in younger patients.     

Differential Impact of Two Risk Communications on Antipsychotic Prescribing to People with Dementia in Scotland: Segmented Regression Time Series Analysis 2001–2011

Background

Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact.

Methods

Segmented regression time-series analysis 2001–2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing.

Results

The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI −6.6 to −5.2) and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs.

Conclusions

The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates are falling, antipsychotic prescribing in dementia in Scotland remains unacceptably high.     

Predisposing Risk Factors for Delirium in Living Donor Liver Transplantation Patients in Intensive Care Units

Background

Delirium is one of the main causes of increased length of intensive care unit (ICU) stay among patients who have undergone living donor liver transplantation (LDLT). We aimed to evaluate risk factors for delirium after LDLT as well as to investigate whether delirium impacts the length of ICU and hospital stay.

Methods

Seventy-eight patients who underwent LDLT during the period January 2010 to December 2012 at a single medical center were enrolled. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale was used to diagnose delirium. Preoperative, postoperative, and hematologic factors were included as potential risk factors for developing delirium.

Results

During the study period, delirium was diagnosed in 37 (47.4%) patients after LDLT. The mean onset of symptoms occurred 7.0±5.5 days after surgery and the mean duration of symptoms was 5.0±2.6 days. The length of stay in the ICU for patients with delirium (39.8±28.1 days) was significantly longer than that for patients without delirium (29.3±19.0 days) (p<0.05). Risk factors associated with delirium included history of alcohol abuse [odds ratio (OR) = 6.40, 95% confidence interval (CI): 1.85–22.06], preoperative hepatic encephalopathy (OR = 4.45, 95% CI: 1.36–14.51), APACHE II score ≥16 (OR = 1.73, 95% CI: 1.71–2.56), and duration of endotracheal intubation ≥5 days (OR = 1.81, 95% CI: 1.52–2.23).

Conclusions

History of alcohol abuse, preoperative hepatic encephalopathy, APACHE II scores ≥16 and endotracheal intubation ≥5 days were predictive of developing delirium in the ICU following liver transplantation surgery and were associated with increased length of ICU and hospital stay.     

Cholera Vaccination Campaign Contributes to Improved Knowledge Regarding Cholera and Improved Practice Relevant to Waterborne Disease in Rural Haiti

Background

Haiti''s cholera epidemic has been devastating partly due to underlying weak infrastructure and limited clean water and sanitation. A comprehensive approach to cholera control is crucial, yet some have argued that oral cholera vaccination (OCV) might result in reduced hygiene practice among recipients. We evaluated the impact of an OCV campaign on knowledge and health practice in rural Haiti.

Methodology/Principal Findings

We administered baseline surveys on knowledge and practice relevant to cholera and waterborne disease to every 10th household during a census in rural Haiti in February 2012 (N = 811). An OCV campaign occurred from May–June 2012 after which we administered identical surveys to 518 households randomly chosen from the same region in September 2012. We compared responses pre- and post-OCV campaign.Post-vaccination, there was improved knowledge with significant increase in percentage of respondents with ≥3 correct responses on cholera transmission mechanisms (odds ratio[OR] 1.91; 95% confidence interval[CI] 1.52–2.40), preventive methods (OR 1.83; 95% CI 1.46–2.30), and water treatment modalities (OR 2.75; 95% CI 2.16–3.50). Relative to pre-vaccination, participants were more likely post-OCV to report always treating water (OR 1.62; 95% CI 1.28–2.05). Respondents were also more likely to report hand washing with soap and water >4 times daily post-vaccine (OR 1.30; 95% CI 1.03–1.64). Knowledge of treating water as a cholera prevention measure was associated with practice of always treating water (OR 1.47; 95% CI 1.14–1.89). Post-vaccination, knowledge was associated with frequent hand washing (OR 2.47; 95% CI 1.35–4.51).

Conclusion

An OCV campaign in rural Haiti was associated with significant improvement in cholera knowledge and practices related to waterborne disease. OCV can be part of comprehensive cholera control and reinforce, not detract from, other control efforts in Haiti.