Birth Weight and Risk Factors for Cardiovascular Disease and Type 2 Diabetes in US Children and Adolescents: 10 Year Results from NHANES

Previous studies have shown that birth weight and other birth characteristics may be associated with risk for type 2 diabetes and cardiovascular disease (CVD) later in life; however, results using large US national survey data are limited. Our goal was to determine the aforementioned associations using nationally representative data. We studied children and adolescents 6–15 years using data from the National Health and Nutrition Examination Survey cycles 2001–2010. Survey and examination data included demographic and early childhood characteristics, current health status, physical activity information, anthropometric measurements, dietary data (total energy, saturated fat, sodium, and sugar intakes), biomarkers related to selected risk factors of CVD [systolic blood pressure (SBP), plasma C-reactive protein (CRP) and lipid profiles], and type 2 diabetes [fasting glucose, insulin, and homeostasis model assessment (HOMA)]. Birth weight (proxy-reported) was inversely associated with SBP among girls; SBP levels increased 1.4 mmHg for each 1,000 g decrease in birth weight (p = 0.003) after controlling for potential confounders. Birth weight was not associated with levels of CRP or lipid profiles across the three racial groups. In addition, birth weight was inversely related to levels of fasting insulin and HOMA among non-Hispanic Whites; for each 1,000 g decrease in birth weight, fasting insulin levels increased 9.1 % (p = 0.007) and HOMA scores increased 9.8 % (p = 0.007). Birth weight was inversely associated with the levels of SBP, fasting insulin, and HOMA. These results support a role for birth weight, independent of the strong effects of current body weight status, in increasing risk for CVD and type 2 diabetes.     

A systematic review classifies sources of bias and variation in diagnostic test accuracy studies

ObjectiveTo classify the sources of bias and variation and to provide an updated summary of the evidence of the effects of each source of bias and variation.Study Design and SettingWe conducted a systematic review of studies of any design with the main objective of addressing bias or variation in the results of diagnostic accuracy studies. We searched MEDLINE, EMBASE, BIOSIS, the Cochrane Methodology Register, and Database of Abstracts of Reviews of Effects (DARE) from 2001 to October 2011. Citation searches based on three key papers were conducted, and studies from our previous review (search to 2001) were eligible. One reviewer extracted data on the study design, objective, sources of bias and/or variation, and results. A second reviewer checked the extraction.ResultsWe summarized the number of studies providing evidence of an effect arising from each source of bias and variation on the estimates of sensitivity, specificity, and overall accuracy.ConclusionsWe found consistent evidence for the effects of case–control design, observer variability, availability of clinical information, reference standard, partial and differential verification bias, demographic features, and disease prevalence and severity. Effects were generally stronger for sensitivity than for specificity. Evidence for other sources of bias and variation was limited.     

Obliterative bronchiolitis in rheumatoid arthritis

Two patients with rheumatoid arthritis who developed obliterative bronchiolitis are described. Both patients had received penicillamine. The first patient died in respiratory failure 4 months after the onset of her breathlessness and the diagnosis was confirmed at post-mortem. The second patient was diagnosed with appropriate lung function tests and has been started on azathioprine. Although she is still disabled by breathlessness 12 months after presentation, her condition has stabilised.     

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study

Background/Aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination.Methods: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3′TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction.Results: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance).Conclusions: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotheraphy appears disappointing, and other treatment strategies should be investigated.     

Age-related cataract

Cataract, opacification of the lens, is one of the commonest causes of loss of useful vision, with an estimated 16 million people worldwide affected. Several risk factors have been identified in addition to increasing age--genetic composition, exposure to ultraviolet light, and diabetes. However, no method to halt the formation of a cataractous lens has been shown to be effective. Nevertheless, advances in surgical removal of cataracts, including small-incision surgery, use of viscoelastics, and the development of intraocular lenses, have made treatment very effective and visual recovery rapid in most cases. Despite these advances, cataract continues to be a leading public-health issue that will grow in importance as the population increases and life expectancy is extended worldwide.     

Managing abnormal blood lipids: a collaborative approach

Current data and guidelines recommend treating abnormal blood lipids (ABL) to goal. This is a complex process and requires involvement from various healthcare professionals with a wide range of expertise. The model of a multidisciplinary case management approach for patients with ABL is well documented and described. This collaborative approach encompasses primary and secondary prevention across the lifespan, incorporates nutritional and exercise management as a significant component, defines the importance and indications for pharmacological therapy, and emphasizes the importance of adherence. Use of this collaborative approach for the treatment of ABL ultimately will improve cardiovascular and cerebrovascular morbidity and mortality.     

In vitro generation of HIV type 1 subtype C isolates resistant to enfuvirtide

Enfuvirtide (ENF) is the first in a new class of antiretroviral agents targeting the fusion process of the viral life cycle. ENF is a synthetic 36-amino acid peptide that binds to the HR-1 region of gp41 preventing fusion of viral and cellular membranes. With the introduction of ENF there are now four classes of antiretrovirals each with distinct and different resistance pathways. Resistance to ENF among subtype B HIV-1 isolates is associated with amino acid changes mainly in the HR-1 region, although other regions of envelope have also been implicated. To determine whether subtype C viruses developed resistance mutations similar to subtype B viruses, 11 subtype C and 4 subtype B viruses were passaged in the presence of increasing concentrations of ENF. The subtype C isolates showed varying levels of replication at 1 microg/ml ENF by day 18, but by day 29 all replicated efficiently at 10 microg/ml ENF. All subtype C isolates showed evidence of genotypic changes in gp41 HR-1 following exposure to ENF that included G36S/E/D, I37T, V38M/A/L/E, N/S42D, N43K, L45R/M, and A50T/V. Three subtype C viruses had compensatory changes in the HR-2 region, which corresponds to the ENF sequence, and two isolates had changes in the V3 region. Mutational patterns among the four subtype B viruses were similar to those for subtype C and those previously published in the literature. These data indicate that in vitro resistance to ENF develops rapidly among HIV-1 subtype C isolates. In general, mutational patterns for subtype C were similar to those described for subtype B, suggesting that the mechanism of action for ENF is similar for HIV-1 subtype B and C isolates.     

Factors influencing secondary care pharmacist and nurse independent prescribers’ clinical reasoning: An interprofessional analysis

In the United Kingdom, pharmacist and nurse independent prescribers are responsible for both the clinical assessment of and prescribing for patients. Prescribing is a complex skill that entails the application of knowledge, skills, and clinical reasoning to arrive at a clinically appropriate decision. Decision-making is influenced and informed by many factors. This study, the first of its kind, explores what factors influence pharmacist and nurse independent prescribers during the process of clinical reasoning. A think-aloud methodology immediately followed by a semi-structured interview was conducted with 11 active nurse and 10 pharmacist independent prescribers working in secondary care. Each participant was presented with validated clinical vignettes for the think-aloud stage. Participants chose the clinical therapeutic areas for the vignettes, based on their self-perceived competencies. Data were audio-recorded, transcribed verbatim, and a constant-comparative approach was used for analysis. Influences on clinical reasoning were broadly categorised into themes: social interaction, intrinsic, and contextual factors. These themes showed that intrinsic, sociocultural, and contextual aspects heavily influenced the clinical reasoning processes of prescribers. For example, prescribers were aware of treatment pathways, but chose to refer patient cases to avoid making the final prescribing decision. Exploration of this behaviour in the interviews revealed that previous experience and attitudes such as confidence and cautiousness associated with responsibility were strong influencers within the decision-making process. In addition, strengthening the professional identity of prescribers could be achieved through collaborative work with interprofessional healthcare teams to orient their professional practice from within the profession. Findings from this study can be used to inform the education, training, and practice of independent prescribers to improve healthcare services by improving their professional and interprofessional development.     

Endogenous Pain Modulation Induced by Extrinsic and Intrinsic Psychological Threat in Healthy Individuals

Many factors interact to influence threat perception and the subsequent experience of pain. This study investigated the effect of observing pain (extrinsic threat) and intrinsic threat of pain to oneself on pressure pain threshold (PPT). Forty socially connected pairs of healthy volunteers were threat-primed and randomly allocated to experimental or control roles. An experimental pain modulation paradigm was applied, with non-nociceptive threat cues used as conditioning stimuli. In substudy 1, the extrinsic threat to the experimental participant was observation of the control partner in pain. The control participant underwent hand immersion in noxious and non-noxious water baths in randomized order. Change in the observing participant's PPT from baseline to mid- and postimmersion was calculated. A significant interaction was found for PPT between conditions and test time (F_2,78?=?24.9, P?<?.005). PPT increased by 23.6%?±?19.3% between baseline and during hand immersion (F_1,39?=?43.7, P?<?.005). Substudy 2 investigated threat of imminent pain to self. After a 15-minute break, the experimental participant's PPT was retested (“baseline 2”). Threat was primed by suggestion of whole arm immersion in an icier, larger water bath. PPT was tested immediately before anticipated arm immersion, after which the experiment ended. A significant increase in PPT between “baseline 2” and “pre-immersion” was seen (t?=??7.6, P?=?.005), a pain modulatory effect of 25.8?±?20.7%. Extrinsic and intrinsic threat of pain, in the absence of any afferent input therefore influences pain modulation. This may need to be considered in studies that use noxious afferent input with populations who show dysfunctional pain modulation.