The use of a bayesian hierarchy to develop and validate a co-morbidity score to predict mortality for linked primary and secondary care data from the NHS in England

Background: We have assessed whether the linkage between routine primary and secondary care records provided an opportunity to develop an improved population based co-morbidity score with the combined information on co-morbidities from both health care settings. Methods: We extracted all people older than 20 years at the start of 2005 within the linkage between the Hospital Episodes Statistics, Clinical Practice Research Datalink, and Office for National Statistics death register in England. A random 50% sample was used to identify relevant diagnostic codes using a Bayesian hierarchy to share information between similar Read and ICD 10 code groupings. Internal validation of the score was performed in the remaining 50% and discrimination was assessed using Harrell’s C statistic. Comparisons were made over time, age, and consultation rate with the Charlson and Elixhauser indexes. Results: 657,264 people were followed up from the 1st January 2005. 98 groupings of codes were derived from the Bayesian hierarchy, and 37 had an adjusted weighting of greater than zero in the Cox proportional hazards model. 11 of these groupings had a different weighting dependent on whether they were coded from hospital or primary care. The C statistic reduced from 0.88 (95% confidence interval 0.88–0.88) in the first year of follow up, to 0.85 (0.85–0.85) including all 5 years. When we stratified the linked score by consultation rate the association with mortality remained consistent, but there was a significant interaction with age, with improved discrimination and fit in those under 50 years old (C=0.85, 0.83–0.87) compared to the Charlson (C=0.79, 0.77–0.82) or Elixhauser index (C=0.81, 0.79–0.83). Conclusions: The use of linked population based primary and secondary care data developed a co-morbidity score that had improved discrimination, particularly in younger age groups, and had a greater effect when adjusting for co-morbidity than existing scores

Hepatotoxicity and effectiveness of a Nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral hepatitis B or C infection in Cameroon

Background: Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) in HIV-infected patients receiving a commonly used nevirapine-based antiretroviral therapy is a major concern for African clinicians owing to its high prevalence, the infrequent testing and treatment of viral hepatitis, and the impact of liver disease on the tolerability and effectiveness of anti-HIV treatment. We compared the hepatotoxicity and the immunological, virological and clinical effectiveness of a nevirapine-based antiretroviral therapy between patients infected with HIV only and patients coinfected with hepatitis B or C virus in Cameroon. Methods: A retrospective cohort study was conducted among HIV-1-infected patients. Plasma HBV DNA and HCV RNA were tested in positive or indeterminate samples for HBsAg or HCV antibodies, respectively. All patients received nevirapine and lamivudine plus stavudine or zidovudine. Results: Of 169 HIV-1-infected patients with a median baseline CD4 count of 135 cells/mm(3) (interquartile range [IQR] 67 218), 21% were coinfected with HBV or HCV. In coinfected patients, the median viral load was 2.47 x 107 IU/mL for HBV (IQR 3680-1.59 x 10(8)) and 928 000 IU/mL for HCV (IQR 178 400-2.06 x 10(6)). Multivariate analyses showed that the risk of hepatotoxicity was 2-fold higher in coinfected patients (p < 0.01). The response to antiretroviral therapy was however comparable between monoinfected and coinfected patients in terms of CD4 cell count increase (p = 0.8), HIV-1 viral load below 400 copies/mL (p = 0.9), death (p = 0.3) and death or new AIDS-defining event (p = 0.1). Nevirapine was replaced by a protease inhibitor in 4 patients owing to hepatotoxicity. Conclusion: This study suggests that the nevirapine-based antiretroviral therapy could be used safely as first-line treatment in patients with low CD4 cell count in Africa despite frequent coinfections with HBV or HCV and infrequent testing of these infections. Although testing for HBV and HCV should be systematically performed before initiating antiretroviral therapy, transaminases elevations at baseline or during treatment should be a decisive argument for testing when hepatitis status is unknown

Aberrant methylation of Polo-like kinase CpG islands in Plk4 heterozygous mice

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC), one of the most common cancers world-wide occurs twice as often in men compared to women. Predisposing conditions such as alcoholism, chronic viral hepatitis, aflatoxin B1 ingestion, and cirrhosis all contribute to the development of HCC.</p> <p>Methods</p> <p>We used a combination of methylation specific PCR and bisulfite sequencing, qReal-Time PCR (qPCR), and Western blot analysis to examine epigenetic changes for the <it>Polo-like kinases </it>(<it>Plks</it>) during the development of hepatocellular carcinoma (HCC) in <it>Plk4 </it>heterozygous mice and murine embryonic fibroblasts (MEFs).</p> <p>Results</p> <p>Here we report that the promoter methylation of <it>Plk4 </it>CpG islands increases with age, was more prevalent in males and that <it>Plk4 </it>epigenetic modification and subsequent downregulation of expression was associated with the development of HCC in <it>Plk4 </it>mutant mice. Interestingly, the opposite occurs with another Plk family member, <it>Plk1 </it>which was typically hypermethylated in normal liver tissue but became hypomethylated and upregulated in liver tumours. Furthermore, upon alcohol exposure murine embryonic fibroblasts exhibited increased <it>Plk4 </it>hypermethylation and downregulation along with increased centrosome numbers and multinucleation.</p> <p>Conclusions</p> <p>These results suggest that aberrant <it>Plk </it>methylation is correlated with the development of HCC in mice.</p

Identifying and characterizing COPD patients in US managed care. A retrospective, cross-sectional analysis of administrative claims data

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020. In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.</p> <p>Methods</p> <p>This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients. We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period. A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million). We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions. Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.</p> <p>Results</p> <p>A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD. Important differences were observed in comorbidities between the younger commercial versus the older Medicare population. Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively. A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%). Utilization of healthcare services also increased with an increase in complexity.</p> <p>Conclusion</p> <p>In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services. Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment.</p

Molecular and Electrophysiological Characterization of GFP-Expressing CA1 Interneurons in GAD65-GFP Mice

The use of transgenic mice in which subtypes of neurons are labeled with a fluorescent protein has greatly facilitated modern neuroscience research. GAD65-GFP mice, which have GABAergic interneurons labeled with GFP, are widely used in many research laboratories, although the properties of the labeled cells have not been studied in detail. Here we investigate these cells in the hippocampal area CA1 and show that they constitute ∼20% of interneurons in this area. The majority of them expresses either reelin (70±2%) or vasoactive intestinal peptide (VIP; 15±2%), while expression of parvalbumin and somatostatin is virtually absent. This strongly suggests they originate from the caudal, and not the medial, ganglionic eminence. GFP-labeled interneurons can be subdivided according to the (partially overlapping) expression of neuropeptide Y (42±3%), cholecystokinin (25±3%), calbindin (20±2%) or calretinin (20±2%). Most of these subtypes (with the exception of calretinin-expressing interneurons) target the dendrites of CA1 pyramidal cells. GFP-labeled interneurons mostly show delayed onset of firing around threshold, and regular firing with moderate frequency adaptation at more depolarized potentials

Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1β

Background There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression. Methodology/Principal Findings Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1β is associated with a selective reduction in Mitofusin 2 (Mfn2) expression, a mitochondrial fusion protein. This decrease in Mfn2 is specific since expression of the remaining components of mitochondrial fusion and fission machinery were not affected. Furthermore, PGC-1β increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1β-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1β increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor α (ERRα). Conclusions/Significance Taken together, our data reveal a novel mechanism by which mammalian cells control mitochondrial fusion. In addition, we describe a novel role of PGC-1β in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Are ICD-10 codes appropriate for performance assessment in asthma and COPD in general practice? Results of a cross sectional observational study

BACKGROUND: The increasing prevalence and impact of obstructive lung diseases and new insights, reflected in clinical guidelines, have led to concerns about the diagnosis and therapy of asthma and COPD in primary care. In Germany diagnoses written in medical records are used for reimbursement, which may influence physicians' documentation behaviour. For that reason it is unclear to what respect ICD-10 codes reflect the real problems of the patients in general practice. The aim of this study was to assess the appropriateness of the recorded diagnoses and to determine what diagnostic information is used to guide medical treatment. METHODS: All patients with lower airway symptoms (n = 857) who had attended six general practices between January and June 2003 were included into this cross sectional observational study. Patients were selected from the computerised medical record systems, focusing on ICD-10-codes concerning lower airway diseases (J20-J22, J40-J47, J98 and R05). The performed diagnostic procedures and actual medication for each identified patient were extracted manually. Then we examined the associations between recorded diagnoses, diagnostic procedures and prescribed treatment for asthma and COPD in general practice. RESULTS: Spirometry was used in 30% of the patients with a recorded diagnosis of asthma and in 58% of the patients with a recorded diagnosis of COPD. Logistic regression analysis showed an improved use of spirometry when inhaled corticosteroids were prescribed for asthma (OR = 5.2; CI 2.9–9.2) or COPD (OR = 4.7; CI 2.0–10.6). Spirometry was also used more often when sympathomimetics were prescribed (asthma: OR = 2.3; CI 1.2–4.2; COPD: OR = 4.1; CI 1.8–9.4). CONCLUSIONS: This study revealed that spirometry was used more often when corticosteroids or sympathomimetics were prescribed. The findings suggest that treatment was based on diagnostic test results rather than on recorded diagnoses. The documented ICD-10 codes may not always reflect the real status of the patients. Thus medical care for asthma and COPD in general practice may be better than initially found on the basis of recorded diagnoses, although further improvement of practice patterns in asthma and COPD is still necessary