Willingness to undergo a repeat liver biopsy among HIV/hepatitis C virus-coinfected and hepatitis C virus-monoinfected patients.

BACKGROUND: Guidelines for chronic hepatitis C virus (HCV) management have recommended that a liver biopsy be repeated at 3-year intervals for HIV/HCV-coinfected patients and 5-year intervals for those with HCV monoinfection to assess fibrosis progression. However, it is unclear if patients are willing to repeat this procedure. OBJECTIVE: To determine the prevalence and factors, particularly HIV coinfection, associated with willingness to repeat a liver biopsy. METHODS: A questionnaire was administered to 235 HCV-infected patients (113 with HIV coinfection) between January 2008 and June 2011 who previously underwent liver biopsy. The main outcome was self-reported willingness to repeat the biopsy. The questionnaire collected data on other hypothesized determinants of willingness to repeat the biopsy. These were evaluated by logistic regression. RESULTS: Among 235 subjects who completed the questionnaire, 32 (14%) reported unwillingness to repeat the biopsy, most commonly because of a perception that it was unimportant for care [13(41%)], concerns regarding pain [12(38%)], and a poor experience with the prior biopsy [7(21%)]. Considering biopsy to be safe [odds ratio (OR), 4.45; 95% CI, 1.50-13.27], important (OR, 4.87; 95% CI, 1.83-12.95), and knowing a person who underwent liver biopsy (OR, 3.45; 95% CI, 1.16-10.23) were associated with willingness to repeat the biopsy. HIV was not associated with willingness to repeat the biopsy (OR, 1.42; 95% CI, 0.67-3.03). CONCLUSIONS: Eighty-six percent of chronic HCV-infected patients were willing to repeat a liver biopsy. HIV was not associated with unwillingness. In patients in whom a repeat liver biopsy is indicated, education on the utility and safety of the biopsy is important to its acceptance.

Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways.

Developmental ocular malformations, including anophthalmia-microphthalmia (AM), are heterogeneous disorders with frequent sporadic or non-Mendelian inheritance. Recurrent interstitial deletions of 14q22-q23 have been associated with AM, sometimes with poly/syndactyly and hypopituitarism. We identify two further cases of AM (one with associated pituitary anomalies) with a 14q22-q23 deletion. Using a positional candidate gene approach, we analyzed the BMP4 (Bone Morphogenetic Protein-4) gene and identified a frameshift mutation (c.226del2, p.S76fs104X) that segregated with AM, retinal dystrophy, myopia, brain anomalies, and polydactyly in a family and a nonconservative missense mutation (c.278A-->G, p.E93G) in a highly conserved base in another family. MR imaging and tractography in the c.226del2 proband revealed a primary brain developmental disorder affecting thalamostriatal and callosal pathways, also present in the affected grandmother. Using in situ hybridization in human embryos, we demonstrate expression of BMP4 in optic vesicle, developing retina and lens, pituitary region, and digits strongly supporting BMP4 as a causative gene for AM, pituitary, and poly/syndactyly. Because BMP4 interacts with HH signaling genes in animals, we evaluated gene expression in human embryos and demonstrate cotemporal and cospatial expression of BMP4 and HH signaling genes. We also identified four cases, some of whom had retinal dystrophy, with "low-penetrant" mutations in both BMP4 and HH signaling genes: SHH (Sonic Hedgehog) or PTCH1 (Patched). We propose that BMP4 is a major gene for AM and/or retinal dystrophy and brain anomalies and may be a candidate gene for myopia and poly/syndactyly. Our finding of low-penetrant variants in BMP4 and HH signaling partners is suggestive of an interaction between the two pathways in humans.

KDOQI clinical practice guidelines and clinical practice recommendations--2006 updates.

In scanning through the KDOQI guidelines for this article, I applaud the Work Group members as there is an emphasis placed on timely education of the patient, their family members, close friends, and/or primary care providers for both HD and PD. We have all seen in our practice setting, how critical education is for our patients. Studies have shown that timely patient education as CKD advances can both improve outcomes and reduce cost. These guidelines certainly emphasize the importance of advocating for education of patients with CKD. We know that we as nephrology nurses are crucial for educating the patient with CKD, the patient with ESRD, family members, and caregivers and for re-enforcing their education.

Continuation of postpartum antiretroviral therapy in a cohort of women infected with human immunodeficiency virus.

A common dilemma for HIV-positive pregnant women is the issue of continuation or cessation of antiretroviral therapy (ART) postpartum. Current guidelines for ART during pregnancy offer no specific recommendations for postpartum ART care. The objective of this study was to ascertain characteristics that would predict cessation or continuation of ART postpartum. In this study, prenatal and medical clinic records were reviewed retrospectively for a cohort of 29 HIV-infected pregnant women who were seen in the Temple University High Risk obstetrics practice from 1997 to 1998. All women took ART during pregnancy, except for one who received i.v. AZT and nevirapine during labor. HIV-specific medical care was provided concurrently during the time of the woman's obstetrics visit by a nurse practitioner and a clinical nurse specialist in consultation with the physician. Factors that were included for review included race, age, use of ART at the time of pregnancy diagnosis, type of ART during pregnancy, CD4 count, HIV-1 ribonucleic acid polymerase chain reaction (RNA PCR) levels, current substance use, disclosure of HIV status to current partner, years of HIV infection, prior HIV infected child, and whether this was a first pregnancy. The two groups of women were divided between those who discontinued ART postpartum and those who continued ART. The data were analyzed with the Kruskal-Wallis test for two groups, or calculations of risk ratios with Fisher's exact test. Study results indicated that 15 out of 29 women (51%) continued ART postpartum. The significant factors for continuation included Latina ethnicity (risk ratio = 0.24, confidence interval = 0.06-0.87), CD4 < 200 mm3 (p = .04), and a greater number of drugs in the antiretroviral regimen 3 versus 2 (p = .05). This study showed that postpartum continuation of ART was associated with identified Latina ethnicity, lower CD4 counts, and a greater number of drugs in the pregnancy regimen. Further study is recommended to understand the clinical impact of intermittent ART, the strategies for postpartum therapy adherence, and clinical follow-up.

Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and learning difficulties.

Duplications of distal 8p with and without significant clinical phenotypes have been reported and are often associated with an unusual degree of structural complexity. Here, we present a duplication of 8p23.1-8p23.2 ascertained in a child with speech delay and a diagnosis of ICD-10 autism. The same duplication was found in his mother who had epilepsy and learning problems. A combination of cytogenetic, FISH, microsatellite, MLPA and oaCGH analysis was used to show that the duplication extended over a minimum of 6.8 Mb between 3 539 893 and 10 323 426 bp. This interval contains 32 novel and 41 known genes, of which only microcephalin (MCPH1) is a plausible candidate gene for autism at present. The distal breakpoint of the duplicated region interrupts the CSMD1 gene in 8p23.2 and the medial breakpoint lies between the MSRA and RP1L1 genes in 8p23.1.An interchromosomal insertion between a normal and polymorphically inverted chromosome 8 is proposed to explain the origin of this duplication. Further mapped imbalances of distal 8p are needed to determine whether the autistic component of the phenotype in this family results from the cumulative imbalance of many genes or dosage imbalance of an individual susceptibility gene.