Analysis of Decreasing Adverse Events with Endoscopic Ultrasound in a New Advanced Endoscopy Program Over Time

Digestive Diseases and Sciences - New innovations and increasing utility of endoscopic ultrasound (EUS) are associated with rare but serious risks. We investigate the rates and risk factors for...     

Resident recognition of open-angle glaucoma

To test an educational intervention’s effect on improving detection of glaucoma by direct ophthalmoscopy, 14 medicine residents examined five patients, two with ophthalmoscopic changes of glaucoma and three with normal fundi. The residents observed a standardized slide/narrative educational intervention reviewing glaucomatous ophthalmoscopic changes and then re-examined the same patients eight to 12 weeks later. The intervention’s odds of improving residents’ diagnostic impression were significant (OR=2.2; 95% CI=1.3–36), with significant improvement in sensitivity (p=0.02) and a trend toward improved specificity. These findings confirm that the diagnosis of glaucomatous ocular changes on eye examinations by medicine residents can be improved with a brief educational intervention. Presented in abstract form at the annual meeting of the Society of General Internal Medicine, Medical Education Section, April 29–May 1, 1992, Washington, DC, and at the Southern regional meeting of the Society of General Internal Medicine, Medical Education Section, January 29–31, 1992, New Orleans, Louisiana.     

Abnormal function of the bone marrow microenvironment in chronic myelogenous leukemia: role of malignant stromal macrophages

The bone marrow microenvironment supports and regulates the proliferation and differentiation of hematopoietic cells. Dysregulated hematopoiesis in chronic myelogenous leukemia (CML) is caused, at least in part, by abnormalities in CML hematopoietic progenitors leading to altered interactions with the marrow microenvironment. The role of the microenvironment itself in CML has not been well characterized. We examined the capacity of CML stroma to support the growth of long-term culture-initiating cells (LTC-IC) obtained from normal and CML marrow. The growth of normal LTC-IC on CML stroma was significantly reduced compared with normal stroma. This did not appear to be related to abnormal production of soluble factors by CML stroma because normal LTC- IC grew equally well in Transwells above CML stroma as in Transwells above normal stroma. In addition, CML and normal stromal supernatants contained similar quantities of both growth-stimulatory (granulocyte colony-stimulating factor (CSF), interleukin-6, stem cell factor, granulocyte-macrophage CSF, and interleukin-1 beta) and growth- inhibitory cytokines (transforming growth factor-beta, macrophage inflammatory protein-1 alpha, and tumor necrosis factor-alpha). The relative proportion of different cell types in CML and normal stroma was similar. However, polymerase chain reaction and fluorescence in situ hybridization studies showed the presence of bcr-abl-positivo cells in CML stroma, which were CD14+ stromal macrophages. To assess the effect of these malignant macrophages on stromal function, CML and normal stromal cells were separated by fluorescence-activated cell sorting into stromal mesenchymal cell (CD14-) and macrophage (CD14+) populations. CML and normal CD14- cells supported the growth of normal LTC-IC equally well. However, the addition of CML macrophages to normal or CML CD14- mesenchymal cells resulted in impaired progenitor support. This finding indicates that the abnormal function of CML bone marrow stroma is related to the presence of malignant macrophages. In contrast to normal LTC-IC, the growth of CML LTC-IC on allogeneic CML stromal layers was not impaired and was significantly better than that of normal LTC-IC cocultured with the same CML stromal layers. These studies demonstrate that, in addition to abnormalities in CML progenitors themselves, abnormalities in the CML marrow microenvironment related to the presence of malignant stromal macrophages may contribute to the selective expansion of leukemic progenitors and suppression of normal hematopoiesis in CML.     

Survey of US Correctional Institutions for Routine HCV Testing

To ascertain HCV testing practices among US prisons and jails, we conducted a survey study in 2012, consisting of medical directors of all US state prisons and 40 of the largest US jails, that demonstrated a minority of US prisons and jails conduct routine HCV testing. Routine voluntary HCV testing in correctional facilities is urgently needed to increase diagnosis, enable risk-reduction counseling and preventive health care, and facilitate evaluation for antiviral treatment.There are an estimated 4 to 7 million persons in the United States infected with HCV.1,2 Morbidity and mortality from HCV are increasing and in 2007, death from HCV exceeded that from HIV infection for the first time.3,4 Persons who inject drugs are at increased risk for HCV infection and for being incarcerated. Multiple studies have demonstrated high HCV prevalence rates among persons behind bars.5–7 In 2010, the Institute of Medicine (IOM) called for the development of comprehensive viral hepatitis services for incarcerated populations including offering testing, hepatitis B virus vaccination, education, and medical management in partnership with community providers.8Despite the Centers for Disease Control and Prevention (CDC) releasing HCV testing recommendations in 1998 and subsequent recommendations for prevention and control of viral hepatitis within correctional facilities in 2003,9-10 recent studies estimate that 50% of persons infected with HCV are unaware of their infection,11–14 thus reducing opportunities for risk-reduction counseling and treatment. In response to this, the CDC updated HCV testing recommendations for the US general population in 2012, which added at least 1-time testing among persons born between 1945 and 1965, now commonly referred to as the “birth cohort” screening recommendations.15 However, the 2012 recommendations did not provide a specific testing recommendation for incarcerated individuals. Given the increased prevalence of HCV among criminal justice populations, we conducted a survey among US prisons and jails to gain a better understanding of current HCV testing practices within correctional facilities.     

The Lived Experience of Managing HIV and Chronic Pain: Qualitative Interviews with Patients and Healthcare Providers

AIDS and Behavior - People living with HIV (PLWH) experience higher rates of comorbid chronic pain conditions compared to the general population. Managing HIV and chronic pain, two stigmatized...     

Insulin resistance-associated genetic variants in type 1 diabetes

AimsTo examine candidate insulin resistance single nucleotide polymorphisms (SNPs) for associations with glycemic control, insulin resistance, BMI, and complications in an observational type 1 diabetes (T1D) cohort: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study.MethodsIn 422 European-ancestry participants, we assessed associations using additive models between 15 candidate SNPs and 25-year mortality, cardiovascular disease, microalbuminuria, overt nephropathy and proliferative retinopathy, and 25-year mean HbA1c, estimated glucose disposal rate (eGDR, inverse measure of insulin resistance), and BMI.ResultsThe A allele of rs12970134 was associated with higher mean HbA1c (β = +0.34 ± 0.09, p = 0.00009) and nominally associated with worse eGDR (p = 0.02). Further analyses suggest the HbA1c association may be modified by diabetes therapy regimen: rs12970134 AA genotype was associated with higher HbA1c under non-intensive therapy conditions (<3 insulin injections/day or monitoring blood glucose<3 times/day [p = 0.004]), but not under intensive therapy (≥3 injections/day or insulin pump and monitoring glucose≥3 times/day [p = 0.71]). There were no significant associations between any SNPs and BMI or complications.Conclusionsrs12970134, near MC4R, is strongly associated with HbA1c in this cohort. Further exploration of this genomic region is warranted, as it may hold promise for discovering new therapeutic targets to improve glycemic control in T1D.     

A USA-based registry for pulmonary arterial hypertension: 1982-2006.

The aim of this study was to define the epidemiology of World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH) in a large referral centre in the USA. The Pulmonary Hypertension Connection registry, initiated in 2004, evaluated all patients in a single USA practice from 1982-2006. For comparison, the authors divided the group by incident versus prevalent cohorts, aetiology and by treatment era. In total, 578 patients (77% female) aged 48+/-14 yrs were entered. Of these, 80% had class III or IV symptoms. Over time, connective tissue disease-associated PAH increased, while referrals for HIV remained low. One-third of patients were referred on calcium channel blocker therapy even though only 4.6% had an acute response to vasodilator challenge. When compared by treatment era, there were no differences in the severity of PAH. However, survival had improved over time, with a 1-yr survival of 85% in the incident cohort. In the USA, pulmonary arterial hypertension patients are still referred to tertiary centres too late. Referral of connective tissue disease is increasing, while referral of HIV remains low. Inappropriate calcium channel blocker treatment is common. Survival rates have increased but remain low suggesting that prognosis is improving but PAH is still a progressive, fatal disease.     

The prognostic importance of different definitions of worsening renal function in congestive heart failure

BACKGROUND: Worsening renal function in patients hospitalized for heart failure portends a poor prognosis. However, criteria used to define worsening renal function are arbitrary, and the implications of different definitions remain unclear. We therefore compared the prognostic importance of various definitions of worsening renal function in 1,002 patients hospitalized for congestive heart failure (CHF). METHODS AND RESULTS: The patient population was 49% female, aged 67 +/- 15 years. Twenty-three percent had a prior history of renal failure, 73% had known depressed ejection fraction, and 63% had known CHF. On admission to the hospital, 47% were receiving ACE inhibitors, 22% beta-blockers, 70% diuretics and 6% NAID's. 72% developed increased serum creatinine during the hospitalization, with 20% developing an increase of > or = 0.5 mg/dL. Worsening renal function predicted both in-hospital mortality and length of stay > 10 days. Even an increased creatinine of 0.1 mg/dL was associated with worse outcome. Sensitivity for death decreased from 92% to 65% as the threshold for increased creatinine was raised from 0.1 to 0.5 mg/dL, with specificity increasing from 28% to 81%. At a threshold of a 0.3 mg/dL increase, sensitivity was 81% and specificity was 62% for death and 64% and 65% for length of stay >10 days. Adding a requirement of final creatinine of > or = 1.5 mg/dL improved specificity. CONCLUSIONS: This analysis demonstrates that any detectable decrease in renal function is associated with increased mortality and prolonged hospital stay. This suggests that therapeutic interventions which improve renal function might be beneficial.