Prospective, randomized study comparing quinupristin-dalfopristin with linezolid in the treatment of vancomycin-resistant Enterococcus faecium infections

OBJECTIVES: Quinupristin-dalfopristin and linezolid have been shown to be efficacious in the treatment of vancomycin-resistant Enterococcus faecium (VREF) infections. However, the two antibiotics have not been compared in terms of safety and efficacy in a prospective randomized study. The objective of this study was to compare the safety and efficacy of the two drugs in the treatment of VREF infections in cancer patients. PATIENTS AND METHODS: Forty cancer patients with VREF infection were randomized to receive linezolid 600 mg every 12 h or quinupristin-dalfopristin 7.5 mg/kg every 8 h. All patients were followed up for 30 days after discontinuation of study drugs. RESULTS: Linezolid and quinupristin-dalfopristin had comparable clinical responses (58% and 43%, respectively, P = 0.6). Myalgias and/or arthralgias occurred at a frequency of 33% in patients who received quinupristin-dalfopristin, but were not observed in the linezolid group (P = 0.03). In contrast, drug-related thrombocytopenia occurred in 11% of patients who received linezolid, but was not observed in the quinupristin-dalfopristin group (P = 0.2). CONCLUSION: In cancer patients, quinupristin-dalfopristin treatment is associated with a relatively high frequency of myalgias/arthralgias; however, profound thrombocytopenia might limit the choice of linezolid in a subpopulation of cancer patients.     

Assessing the Causal Role of Sleep Traits on Glycated Hemoglobin: A Mendelian Randomization Study

OBJECTIVETo examine the effects of sleep traits on glycated hemoglobin (HbA_1c).RESEARCH DESIGN AND METHODSThis study triangulated evidence across multivariable regression (MVR) and one- (1SMR) and two-sample Mendelian randomization (2SMR) including sensitivity analyses on the effects of five self-reported sleep traits (i.e., insomnia symptoms [difficulty initiating or maintaining sleep], sleep duration, daytime sleepiness, napping, and chronotype) on HbA_1c (in SD units) in adults of European ancestry from the UK Biobank (for MVR and 1SMR analyses) (n = 336,999; mean [SD] age 57 [8] years; 54% female) and in the genome-wide association studies from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) (for 2SMR analysis) (n = 46,368; 53 [11] years; 52% female).RESULTSAcross MVR, 1SMR, 2SMR, and their sensitivity analyses, we found a higher frequency of insomnia symptoms (usually vs. sometimes or rarely/never) was associated with higher HbA_1c (MVR 0.05 SD units [95% CI 0.04–0.06]; 1SMR 0.52 [0.42–0.63]; 2SMR 0.24 [0.11–0.36]). Associations remained, but point estimates were somewhat attenuated after excluding participants with diabetes. For other sleep traits, there was less consistency across methods, with some but not all providing evidence of an effect.CONCLUSIONSOur results suggest that frequent insomnia symptoms cause higher HbA_1c levels and, by implication, that insomnia has a causal role in type 2 diabetes. These findings could have important implications for developing and evaluating strategies that improve sleep habits to reduce hyperglycemia and prevent diabetes.     

Adults with invasive pneumococcal disease: missed opportunities for vaccination

BACKGROUND: The pneumococcal polysaccharide vaccine (PPV) can prevent invasive pneumococcal disease (IPD) in the elderly and those with certain underlying illnesses. However, vaccine uptake remains suboptimal. Identification of missed opportunities for vaccination could guide new strategies for improving uptake. Missed opportunities for vaccination were defined as one or more visits to a hospital, emergency room (ER), or main provider in the 2 years before infection among unvaccinated, adult IPD case-patients with a vaccine indication. METHODS: Adults aged 18 years or older with IPD were identified in six Active Bacterial Core surveillance/Emerging Infections Program Network sites during a 1-year period in 2001 to 2003. Using chart review, patient/proxy interview, a main provider questionnaire, and vaccine questionnaires from additional providers, data were collected on demographics, vaccine indications, vaccine status, and recent healthcare encounters. RESULTS: A total of 1878 cases were enrolled, and 83% had a vaccine indication. Of the 1177 cases with a vaccine indication and sufficient information on recent healthcare encounters, 617 (52%) were unvaccinated. Of these, 566 (92%) had one or more opportunities for vaccination, 54% were hospitalized, 58% had ER visits, and 76% visited their main provider in the 2 years before illness. The number of visits to main providers (median = 6) was higher than hospitalizations (median = 1), and ER visits (median = 1). CONCLUSIONS: One or more missed opportunities for vaccination were documented in nearly all unvaccinated IPD case-patients with a vaccine indication. Most visited their main provider multiple times. Implementation of systematic PPV programs in outpatient settings will likely increase pneumococcal vaccine uptake among high-risk adults.     

Pre-college Matriculation Risk Profiles and Alcohol Consumption Patterns During the First Semesters of College

Excessive alcohol consumption represents a significant concern on U.S. college campuses, and there is a need to identify students who may be at risk for engaging in risky alcohol use. The current study examined how variables measured prior to college matriculation, specifically alcohol-related decision-making variables drawn from the Theory of Reasoned Action (i.e., alcohol expectancies, attitudes, and normative beliefs), were associated with patterns of alcohol use prior to and throughout the first semesters of college. Participants were 392 undergraduate students (56 % female) from a large Northeastern U.S. university. Decision-making variables were assessed prior to college matriculation, and alcohol use was measured with five assessments before and throughout freshman and sophomore semesters. Latent profile analysis was used to identify types of students with distinct patterns of decision-making variables. These decision-making profiles were subsequently linked to distinct patterns of alcohol use using latent transition analysis. Four distinct decision-making profiles were found and were labeled “Anti-Drinking,” “Unfavorable,” “Mixed,” and “Risky.” Five drinking patterns were observed and included participants who reported consistently low, moderate, or high rates of alcohol use. Two patterns described low or non-drinking at the pre-college baseline with drinking escalation during the measurement period. Students’ likelihood of following the various drinking patterns varied according to their decision-making. Findings suggest the early identification of at-risk students may be improved by assessing decision-making variables in addition to alcohol use. The findings also have implications for the design of early identification assessments to identify at-risk college students and for the targeting of alcohol prevention efforts to students based on their alcohol-related attitudes and beliefs.     

A longitudinal study to determine association of various maternal factors with neonatal birth weight at a tertiary care hospital

Background

Neonatal birth weight is a powerful predictor of infant growth and survival and maternal factors like poor knowledge and insufficient dietary intake are significant risk factors. Other preventable determinants like pre pregnant BMI <18.5, low gestational weight gain (GWG) and anemia are also associated with low birth weight. This study was carried out to identify the impact of these maternal factors with risk of low birth weight (LBW).

Methods

A longitudinal study was carried out on 124 booked antenatal cases at a tertiary care center. A validated protocol containing socio demography, food frequency and anthropometry was administered at the 3rd trimester. Birth weight of the newborn was noted after delivery.

Results

26.28% children had low birth weight (<2500 g), 14.6% mothers were thin (BMI < 18.5), 55.3% mothers had a weight gain of less than 9 kgs and 45.5% were anemic. 81.81% mothers with BMI >18.5 and 28.92% women who were educated till high school had a baby with LBW. Most mothers consumed milk and vegetables daily and a few consumed non vegetarian foods but quality and quantity of food were grossly inadequate. GWG levels and Hb levels were significantly different in different birth weight groups and also were significantly associated with low birth weight.

Conclusion

Quality and quantity of maternal dietary intake during pregnancy, even in normal weight mothers (BMI > 18.5), are important determinants of birth weight. Nutritional counseling for mothers during the antenatal period is the cornerstone for healthy mother and healthy child.     

Emotional intelligence and perceived stress in dental undergraduates: a multinational survey

This multinational survey investigated the relationship between emotional intelligence (EI) and perceived stress (PS) in seven countries. First-year dental undergraduates attending a dental school in England, Greece, Romania, South Africa, Australia, and the United States and three schools in Malaysia were invited to complete a set of questionnaires on age, gender, academic background, satisfaction with career choice, EI, and PS. Of 860 questionnaires distributed, 596 were fully completed--a response rate of 69.3 percent. Mean EI score was 123.8 (95 percent CI 122.7-124.9), and mean PS score was 19.1 (95 percent CI 18.6-19.7). Significant differences in EI and PS scores were detected between different countries. Females (p<0.05), younger students (p<0.001), those without a previous higher education qualification (p<0.001), and those not satisfied with their decision to study dentistry (p<0.001) were more likely to report PS when compared to their counterparts. A significant inverse relationship (coefficient=-0.29, p=0.001) between EI and PS was detected. Independent significant predictors of PS identified were gender (beta=0.22, t=5.71, p=0.001), previous higher education qualification (beta=-0.14, t=-2.42, p=0.010), satisfaction with decision to study dentistry (beta=-0.20, t=-5.11, p=0.001), and EI (beta=-0.24, t=-6.09, p=0.001), with the latter being relatively the most important predictor. In conclusion, the inverse relationship between EI and PS has been confirmed in this heterogeneous sample representing diverse sociocultural and academic contexts of dental undergraduates.     

Experience-dependent recovery of vision following chronic deprivation amblyopia

The shift in ocular dominance induced by brief monocular deprivation is greatest during a postnatal critical period and is thought to decline irreversibly thereafter. However, here we demonstrate that complete visual deprivation through dark exposure restores rapid ocular dominance plasticity in adult rats. In addition, the loss of visual acuity resulting from chronic monocular deprivation is reversed if dark exposure precedes removal of the occlusion in adulthood, suggesting a potential use for dark exposure in the treatment of adult amblyopia.     

“Pathologic” fractures: should these be included in epidemiologic studies of osteoporotic fractures?

Summary

Pathologic fractures are often excluded in epidemiologic studies of osteoporosis. Using Medicare administrative data, we identified persons with vertebral and hip fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded as pathologic. Only 25% and 66% of persons with these pathologic fractures had evidence for malignancy.

Introduction

Analyses of osteoporosis-related fractures that use administrative data often exclude pathologic fractures (ICD-9 733.1x) due to concern that these are caused by cancer. We examined “pathologic” fractures of the vertebrae and hip to evaluate their contribution to fracture incidence and assessed the evidence for a malignancy.

Methods

We studied US Medicare beneficiaries age ≥65 with new fractures identified using ICD-9 diagnosis codes 733.13 (pathologic vert), 805.0, 805.2, 805.4, 805.8 (nonpathologic vert); and 733.14 (pathologic hip), 820.0, 820.2, 820.8 (nonpathologic hip). We further examined the proportion of cases with a diagnosis of a malignancy proximate to the fracture.

Results

We identified 44,120 individuals with a vertebral fracture and 60,354 with a hip fracture. Approximately 48% of vertebral fractures and 3% of hip fractures were coded as pathologic. For only approximately 25% of persons with a “pathologic” vertebral fracture ICD-9 code, but 66% of persons with a “pathologic” hip fracture, there was evidence of a possible cancer diagnosis.

Conclusion

Among US Medicare beneficiaries, one fourth of pathologic vertebral fracture and two thirds of pathologic hip fracture cases had evidence for a malignancy. Particularly for vertebral fractures, excluding persons with pathologic fractures in epidemiologic analyses that utilize administrative claims data substantially underestimates the burden of fractures due to osteoporosis.     

Mapping the TYR gene reveals novel and previously reported variants in Eastern Indian patients highlighting preponderance of the same changes in multiple unrelated ethnicities

Oculocutaneous albinism (OCA) is a group of congenital autosomal recessive disorders with seven known subtypes (OCA1–OCA7) characterized by loss or absence of pigmentation in the skin, hair, and eyes. OCA1, caused by pathogenic variations in the tyrosinase (TYR) gene, has been documented to be the most prevalent subtype across the world including India. In the present study, we recruited 53 OCA-affected individuals from 45 unrelated families belonging to 20 different marriage groups/ethnicities of 15 different districts of West Bengal. We took a targeted sequencing-based approach to find the causal variations in the TYR gene. We report here identification of two novel potentially pathogenic variations [NM_000372.4:c.614C>T, NP_000363.1:p.(Pro205Leu), and NM_000372.4:c.1036+1=/G>T], one novel synonymous TYR variant [NM_000372.4:c.204=/A>G, NP_000363.1:p.(Gln68=)], two pathogenic variations documented for the first time in Indian OCA cases [NM_000372.4:c.1147G>A, NP_000363.1:p.(Asp383Asn), and NM_000372.4:c.585G>A, NP_000363.1:p.(Trp195*)], along with nine previously reported pathogenic variants in 36 out of 53 (∼68%) patients recruited. We report common haplotype backgrounds for the two most prevalent variations [NM_000372.4:c.124G>A, NM_000372.4:c.832C>T] in cases belonging to different marriage/ethnic groups, suggesting a possible founder effect. To our knowledge, this is the most comprehensive genetic study on OCA1 from India, firmly establishing OCA1 as the commonest form of albinism in this part of the world.     

Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial

Introduction

Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF.

Methods

We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann’s solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality.

Results

The infusion of half-molar sodium lactate increased (mean ± SD) CO from 4.05 ± 1.37 L/min to 5.49 ± 1.9 L/min (P < 0.01) and TAPSE from 14.7 ± 5.5 mm to 18.3 ± 7 mm (P = 0.02). Plasma sodium and pH increased (136 ± 4 to 146 ± 6 and 7.40 ± 0.06 to 7.53 ± 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality.

Conclusions

Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01981655","term_id":"NCT01981655"}}NCT01981655. Registered 13 August 2013.