Clinical and echocardiographic predictors of outcomes in patients with peripartum cardiomyopathy: A single centre, six month follow-up study.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) is an important cause of maternal mortality and morbidity. But, there is a paucity of prospective data on outcomes and prognostic markers in patients receiving contemporary evidence-based therapy, particularly in developing countries. METHODS: This was a single centre, prospective, cohort study on 43 PPCM patients who were followed for 6 months. The primary endpoint was a composite incidence of decompensation related re-hospitalization, all-cause death, and poor recovery (defined as left ventricular ejection fraction, LVEF: <45% at 6 months). Multivariate logistic regression analysis was performed to identify the independent predictors and Kaplan-Meier plots for event (re-hospitalization or death) free survival were computed at their optimal cut-offs. RESULTS: Mean LVEF at presentation was 34.7%. Two patients died during index hospitalization but there were no deaths during follow-up and 63.4% of patients had full LV recovery after discharge. 32.5% of the study population experienced the composite endpoint with high left atrial volume index (LAVi), and low right ventricular fractional area change (RVFAC) at presentation as independent predictors. Use of Inotropic therapy during index hospitalization (with dobutamine or levosimendan) and bromocriptine therapy were not associated with better outcome. CONCLUSIONS: At the end of 6 months after PPCM diagnosis, about 61% of patients had full LV functional recovery with a mortality rate of 4.7%. RVFAC (<31.4% with 86% accuracy) and LAVi (>29.6 ml/m2 with 72% accuracy) at presentation but not LVEF, predicts poor outcomes. Presence of both these risk factors at index hospitalization was associated with a significantly lower event free survival compared to patients without these predictors.

Do probiotics prevent antibiotic-associated diarrhoea? Results of a multicentre randomized placebo-controlled trial.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) is a side-effect of antibiotic consumption and probiotics have been shown to reduce AAD. METHODS: A multicentre, double-blind, placebo-controlled, randomized trial was conducted to evaluate the role of Lactobacillus casei DN114001 (combined as a drink with two regular yoghurt bacterial strains) in reducing AAD and Clostridioides difficile infection in patients aged over 55 years. The primary outcome was the incidence of AAD during 2 weeks of follow-up. RESULTS: A total of 1127 patients (mean age ± standard deviation: 73.6 ± 10.5) were randomized to the active group (N = 549) or placebo group (N = 577). Both groups were followed up as per protocol. The proportion of patients experiencing AAD during follow-up was 19.3% (106/549) in the probiotic group vs 17.9% (103/577) in the placebo group (unadjusted odds ratio 1.10, 95% confidence interval 0.82-1.49, P = 0.53). CONCLUSIONS: No significant evidence was found of a beneficial effect of the specific probiotic formulation in preventing AAD in this elderly population drawn from a number of different UK hospitals. However, in the UK and in many other healthcare systems there have, in recent years, been many changes in antibiotic stewardship policies, an overall decrease in incidence in C. difficile infection, as well as an increased awareness of infection prevention, and modifications in nursing practice. In light of these factors, it is impossible to conclude definitively from the current trial that the study-specific probiotic formulation has no role in preventing AAD, and it is our view that further trials may be indicated, controlling for these variables.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Arterial compliance may be reduced by ingestion of red wine.

The aim of this study was to assess the effect of alcohol on blood pressure and arterial compliance over 24 h in a group of volunteers, comparing the same group of subjects on two consecutive but separate days, one with alcohol intake (alcohol day) and one free of alcohol (control day). We studied 18 healthy subjects (mean age 34.2 years, range 25-53). The subjects received the two days in random order. On the alcohol day, the subjects were asked to drink two glasses of red wine (12% ethanol) between 1830 hours and 0430 hours. Measurements of heart rate, blood pressure and QKD interval (Q wave to Korotkoff (K) sound, diastolic phase (D) using Diasys Integra (Novacor, France)) were recorded (usually 1500 hours to 1500 hours). Three 'ingestion' periods were defined, from 1500 hours to 1830 hours ('before'), 1900 hours to 0430 hours ('during') and from 0430 hours to the following afternoon ('after') on both the alcohol day and on the control day. Red wine increased heart rate during alcohol ingestion and reduced arterial compliance after ingestion. The significant effect of interaction between day and ingestion period on heart rate, diastolic blood pressure and QKD were found, suggesting that the differences in response among the ingestion periods depended on whether alcohol has been consumed that day. For the first time our study indicates the effect of alcohol on 24 h arterial stiffness in a healthy group of volunteers.

Rapid diagnosis and simultaneous identification of tuberculous and bacterial meningitis by a newly developed duplex polymerase chain reaction.

The present study describes the development and evaluation of a duplex polymerase chain reaction (D-PCR) for diagnosis and simultaneous identification of tuberculous meningitis (TBM) and bacterial meningitis (BM) in a single reaction. A D-PCR with primers amplifying portions of the Mycobacterium tuberculosis IS6110 and the eubacteria 16SrDNA sequence in a same reaction mix was developed and tested on DNA extracted from 150 clinical CSF samples from different categories (TBM = 39, BM = 26, control infectious and non-infectious category = 85). The results indicate a clear differentiation between bands for eubacteria and M. tuberculosis with an analytical sensitivity of 10(3) cfu/ml for eubacteria and 10(2) cfu/ml for M. tuberculosis. When evaluated in clinical samples, D-PCR overall diagnosed 100 % confirmed TBM and 100 % confirmed BM cases with overall specificity of 96.5 %. D-PCR can be an effective tool for diagnosis and simultaneous identification of TBM or BM in a single PCR reaction. It saves time, cost, labour and sample amount and help in administration of appropriate antimicrobial therapy. The proposed diagnostic assay would be helpful in correct and rapid management of TBM and BM patients.

Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A1 chieve study.

AIM: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. MATERIALS AND METHODS: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH) insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. RESULTS: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216) switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6%) to week 24 (1.0%) in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001), while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. CONCLUSION: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort.

The role of the humoral immune response to Clostridium difficile toxins A and B in susceptibility to C. difficile infection: a case-control study.

Antibody levels to Clostridium difficile toxin A (TcdA), but not toxin B (TcdB), have been found to determine risk of C. difficile infection (CDI). Historically, TcdA was thought to be the key virulence factor; however the importance of TcdB in disease is now established. We re-evaluated the role of antibodies to TcdA and TcdB in determining patient susceptibility to CDI in two separate patient cohorts. In contrast to earlier studies, we find that CDI patients have lower pre-existing IgA titres to TcdB, but not TcdA, when compared to control patients. Our findings suggest that mucosal immunity to TcdB may be important in the early stages of infection and identifies a possible target for preventing CDI progression.

Inter-rater reliability of the assessment of adverse drug reactions in the hospitalised elderly.

BACKGROUND: The identification and assessment of adverse drug reactions (ADRs) is very challenging especially among the older person. Inter observer reliability of an ADR classification system by different healthcare providers is vital to establish the validity of the reaction. OBJECTIVE: To assess the inter-rater reliability of an ADR classification system in hospitalised elderly patients and to investigate the differences in reliability by different professions. METHODS: From a cohort of 330 elderly patients, patients who experienced a suspected medication related incident (n=87) were selected. The data were analysed by four healthcare professionals (2 pharmacists and 2 physicians) who independently classified the events into event type, types of adverse drug reactions, severity and preventability after a standardised induction based on previously published criteria. Fleiss' kappa was used to assess the level of agreement between the four raters. The difference in level of agreement between the professions was assessed using the weighted least-squares approach for comparing correlated kappa of Barnhart et al. RESULTS: Pharmacists and physicians showed high agreement in the identification and on the type and causality of ADRs. However there was lower (moderate) agreement for the severity (kappa = 0.61) and preventability of ADR (kappa = 0.48). Statistically significant differences were also noted between the professions; pharmacists have higher agreement in the classification of preventability (p=0.03) whereas the physicians pairs showed stronger agreement for classifying severity (p<0.001). CONCLUSION: Despite the high agreement in the identification, type and causality of ADRs, physicians and pharmacists have difficulties in classifying preventability and severity in a reliable way. A multi-disciplinary approach would enable each profession to share their expert knowledge in order to facilitate better or safer patient care.

Influence of cohorting patients with Clostridium difficile infection on risk of symptomatic recurrence.

BACKGROUND: Cohorting of patients with Clostridium difficile infection (CDI) is recommended when single side-rooms are unavailable. Although patients may remain infectious after cessation of diarrhoea, continued cohorting may place them at increased risk of reinfection. AIM: To identify risk factors for CDI recurrence and to determine whether cohorting of patients is associated with increased risk of recurrence. METHODS: Data describing patient demographics, comorbidity, CDI severity and treatment were collected for 248 CDI patients at our hospital between October 2008 and June 2011. The primary outcome was symptomatic recurrence within 30 days of diagnosis. FINDINGS: One hundred and thirty-eight (55.6%) CDI patients were admitted to the cohort ward. These patients were more likely to have severe CDI (odds ratio: 1.95; 95% confidence interval: 1.10-3.46; P = 0.022) and receive vancomycin (1.59; 0.94-2.68; P = 0.083) than patients who were not cohorted. Twenty-six patients (10.5%) suffered recurrence (21 cohorted and five not cohorted). Urinary infection on admission (5.16; 2.10-12.64; P < 0.001), cohorting (3.77; 1.37-10.35; P = 0.01) and concomitant antibiotics (2.07; 0.91-4.72; P = 0.083) were associated with increased risk of recurrence. On multivariate analysis, cohorting (3.94; 1.23-12.65; P = 0.021) and urinary infection (4.27; 1.62-11.24; P = 0.003) were significant predictors of recurrence. CONCLUSION: Patients admitted to a C. difficile cohort ward may be at increased risk of recurrence because they are at increased risk of reinfection. Hospitals using cohort wards to control C. difficile should manage patient flow through the cohort to minimize this risk.

Loop-mediated isothermal amplification for rapid and reliable diagnosis of tuberculous meningitis.

Diagnosis of tuberculous meningitis (TBM) is often difficult. A reliable, simple, and rapid diagnostic test that can be performed in any standard laboratory could be helpful in TBM diagnosis. In this study, a loop-mediated isothermal amplification assay (LAMP) was evaluated to rapidly detect and diagnose TBM infection and was compared to the performance of nested PCR. Six specific primers were used to recognize the IS6110 genomic sequence from Mycobacterium tuberculosis, which included one forward outer primer, one reverse outer primer, two respective inner primers, and two loop primers. The optimum reaction temperature and time were 63°C and 60 min, respectively. Nested PCR was performed targeting the IS6110 region from M. tuberculosis using a commercial kit. The LAMP method yielded a sensitivity of 88.23% and a specificity of 80%, compared to the nested-PCR assay, which yielded a sensitivity of 52.9% and a specificity of 90% for TBM diagnosis. Comparative experiments showed that the LAMP assay is a rapid, sensitive, and specific method to detect TBM infection and that it is superior to the nested-PCR assay. LAMP is very simple, and it can be performed in any laboratory and in rural settings.

Efficacy of Shanvac-B recombinant DNA hepatitis B vaccine in health care workers of Northern India.

BACKGROUND: Health care workers (HCWs) constitute a high-risk population of HBV infection. There are limited data on the efficacy of vaccination in HCWs in India. This study was to evaluate the efficacy of indigenous recombinant hepatitis B vaccine, Shanvac-B, in HCWs. METHODS: In 597 HCWs screened before the vaccination, 216 (36.2%) showed the presence of at least one of the markers of HBV/HCV infection. Of the remaining 381 (63.8%) HCWs who were considered for vaccination, only 153 (age 18-45 years; 48 males and 105 females) were available for final assessment. These HCWs received 20 microg of vaccine at 0, 1 and 6 months. They were asked for the reactogenicity and monitored for the seroprotective efficacy of the vaccination. Anti-HBs titres were measured after vaccination at 1, 2 and 7 months. The presence of anti-HBs titers equal to 1 MIU/ml was considered as seroconversion and that of titres greater than 10 MIU/ml as seroprotection. RESULTS: After vaccination, 32 males (67%) and 76 females (72%) showed seroconvertion; finally 12 (25%) of the males and 47 (45%) of the females were seroprotected. Seroprotection at 2 and 7 months was more dominant in the females than in the males (96% vs. 56%, P=0.001, 100% vs. 85%, P=0.0001), respectively. Geometric mean titres of anti-HBs after vaccination were also higher in the females than in the males (257+/-19.7 vs. 29+/-1.88 MIU/ml, P=0.01, 1802+/-35.2 vs. 306+/-13.6 MIU/ml, P< or =0.05, 6465+/-72 vs. 2142+/-73.6 MIU/ml, P<0.05). Seven male HCWs showed unsatisfactory response, non-response (n=3, 6%) and hypo-response (< or =10 MIU/ml, n=4, 8%) at the end of vaccination. Smoking and alcoholism were significantly correlated with unsatisfactory response. No significant adverse effects of vaccination were observed in any HCW. CONCLUSIONS: The presence of HBsAg in HCWs indicates that a high proportion of HCWs are infected with HBV and HCV in India. Recombinant indigenous vaccine Shanvac-B is highly efficacious in HCWs, and its immunogenicity is significantly higher in females than in males. However, pre-vaccination screening of HCWs is strongly recommended in India.

Ageing and vascular ageing.

There is an age related decline in various physiological processes. Vascular ageing is associated with changes in the mechanical and the structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance. Arterial compliance can be measured by different parameters like pulse wave velocity, augmentation index, and systemic arterial compliance. There is evidence that arterial compliance is reduced in disease states such as hypertension, diabetes, and end stage renal failure. Changes in arterial compliance can be present before the clinical manifestation of cardiovascular disease. Pharmacological and non-pharmacological measures have been shown to improve arterial compliance. Arterial compliance may constitute an early cardiovascular risk marker and may be useful in assessing the effects of drugs on the cardiovascular system. Pharmacogenetics and genetics of arterial compliance in the future will improve our knowledge and understanding about vascular ageing.

Takayasu's arteritis: a cause of prolonged arterial stiffness.

OBJECTIVES: Cardiovascular disease is a major cause of mortality and morbidity in patients with Takayasu's arteritis (TA). Increased arterial stiffness is an independent risk factor and predictor of cardiovascular mortality in a variety of diseases. Pulse wave velocity (PWV) and the augmentation index (AI) are used as clinical measurements of arterial stiffness. METHODS: Data are presented from 10 patients with TA and 11 normal controls obtained between 2000 and 2004. Arterial compliance was assessed non-invasively by measurement of PWV, using the Complior system, and calculation of the aortic AI. RESULTS: TA patients (mean age 40.8+/-13.2 yr) were compared with a control group of healthy women from a parallel study (mean age 32.3+/-5.5 yr). The mean carotid-femoral PWV (PWV-CF) was higher in TA patients (P = 0.03). In addition, both aortic AI derived from the radial artery (P = 0.002) and carotid AI (P = 0.03) were higher in TA patients compared with controls. PWV-CF did not correlate with CRP (r = - 0.23, P = 0.23) or ESR (r = - 0.19, P = 0.27). Similar results were obtained for the correlation of carotid-radial PWV with CRP (r = 0.15, P = 0.32) and ESR (r = 0.33, P = 0.14). CONCLUSIONS: Our data show that TA is associated with elevated arterial stiffness in the central aorta, which may persist when the disease is quiescent. These data suggest that PWV represents a means by which cardiovascular risk can be detected and monitored in TA, and highlights the importance of effective management of cardiovascular risk factors in these patients.