Key associations for hepatitis C virus genotypes in the Middle East and North Africa

This study aimed to investigate the epidemiology of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA) through an analytical and quantitative meta-regression methodology. For the most common genotypes 1, 3, and 4, country/subregion explained more than 77% of the variation in the distribution of each genotype. Genotype 1 was common across MENA, and was more present in high-risk clinical populations than in the general population. Genotype 3 was much more present in Afghanistan, Iran, and Pakistan than the rest of countries, and was associated with transmission through injecting drug use. Genotype 4 was broadly disseminated in Egypt in all populations, with overall limited presence elsewhere. While genotype 2 was more present in high-risk clinical populations and people who inject drugs, most of the variation in its distribution remained unexplained. Genotypes 5, 6, and 7 had low or no presence in MENA, limiting the epidemiological inferences that could be drawn. To sum up, geography is the principal determinant of HCV genotype distribution. Genotype 1 is associated with transmission through high-risk clinical procedures, while genotype 3 is associated with injecting drug use. These findings demonstrate the power of such analytical approach, which if extended to other regions and globally, can yield relevant epidemiological inferences.     

Evidence for asymmetric distribution of sciatic nerve endometriosis

OBJECTIVE: To investigate if a lateral asymmetry exists in the distribution of endometriotic lesions of the sciatic nerve. DATA SOURCES: All articles on sciatic nerve endometriosis identified by MEDLINE and EMBASE database searches were retrieved, and additional reports were collected by systematically reviewing all references. Monographs on endometriosis published in the last 15 years were consulted. METHODS OF STUDY SELECTION: We considered articles in which the presence of an endometriotic lesion of the sciatic nerve and the affected side were assessed. We also included reports lacking histological examination of sciatic nerve specimens but with a surgical diagnosis of pelvic endometriosis. Two authors abstracted data independently on standardized forms. The number of women and the side of the lesion were obtained from individual studies, and the combined frequency of left- and right-side sciatic nerve endometriosis in published reports was computed. TABULATION, INTEGRATION, AND RESULTS: Thirty-two reports including 63 subjects were selected. Endometriosis of the sciatic nerve was on the right side in 41 patients, on the left in 20, and bilateral in two. Considering only patients with unilateral sciatic nerve endometriosis, the observed proportion of right-side lesions (41 of 61 [67.2%]; 95% confidence interval 54.0%, 78.7%) significantly differed from the expected proportion of 50% (chi(2)(1) 7.23, P =.007). Among the 16 cases of histological demonstration of endometriosis infiltrating sciatic nerve roots or fibers, ten had it on the right side (62.5%) and six on the left. Twenty-six of the 38 subjects (68.4%) with surgical demonstration of pelvic endometriosis but without histopathologic evidence of direct sciatic nerve involvement were affected by right cyclic sciatica. CONCLUSION: The finding that two thirds of patients with sciatic nerve endometriosis had right-side lesions constitutes further evidence against the coelomic metaplasia theory. The interposition of the sigmoid colon between the regurgitated endometrial cells implanted on the left posterolateral pelvic peritoneum seems to protect the left lumbosacral plexus and sciatic nerve.     

Visual outcomes of open globe injury patients with traumatic cataracts

International Ophthalmology - Open globe injury (OGI) is a serious form of ocular trauma that can significantly lower quality of life post-injury due to comorbidities. This study was designed to...     

Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting

The potent growth-promoting activity of insulin-like growth factor-II (IGF-II) is highly regulated during development but frequently up-regulated in tumors. Increased expression of the normally monoallelic (paternally expressed) mouse (Igf2) and human (IGF2) genes modify progression of intestinal adenoma in the Apc(Min/+) mouse and correlate with a high relative risk of human colorectal cancer susceptibility, respectively. We examined the functional consequence of Igf2 allelic dosage (null, monoallelic, and biallelic) on intestinal adenoma development in the Apc(Min/+) by breeding with mice with either disruption of Igf2 paternal allele or H19 maternal allele and used these models to evaluate an IGF-II-specific therapeutic intervention. Increased allelic Igf2 expression led to elongation of intestinal crypts, increased adenoma growth independent of systemic growth, and increased adenoma nuclear beta-catenin staining. By introducing a transgene expressing a soluble form of the full-length IGF-II/mannose 6-phosphate receptor (sIGF2R) in the intestine, which acts as a specific inhibitor of IGF-II ligand bioavailability (ligand trap), we show rescue of the Igf2-dependent intestinal and adenoma phenotype. This evidence shows the functional potency of allelic dosage of an epigenetically regulated gene in cancer and supports the application of an IGF-II ligand-specific therapeutic intervention in colorectal cancer.     

Random error in cardiovascular meta-analyses: How common are false positive and false negative results?

Background

Cochrane reviews are viewed as the gold standard in meta-analyses given their efforts to identify and limit systematic error which could cause spurious conclusions. The potential for random error to cause spurious conclusions in meta-analyses is less well appreciated.

Methods

We examined all reviews approved and published by the Cochrane Heart Group in the 2012 Cochrane Library that included at least one meta-analysis with 5 or more randomized trials. We used trial sequential analysis to classify statistically significant meta-analyses as true positives if their pooled sample size and/or their cumulative Z-curve crossed the O'Brien-Fleming monitoring boundaries for detecting a RRR of at least 25%. We classified meta-analyses that did not achieve statistical significance as true negatives if their pooled sample size was sufficient to reject a RRR of 25%.

Results

Twenty three (41%) of the 56 meta-analyses reported statistically significant results, and 19 (83%) were true positives. Of the 33 non-statistically significant meta-analyses, 12 (36%) were true negatives. Overall, 25 (45%) of the 56 published Cochrane reviews were too small to detect/rule out an effect size of at least 25% — 12 were acknowledged as such by their authors. Of the 22 meta-analyses which were reported to be conclusive by their authors, 12 (55%) contained insufficient data to detect/rule out a 25% relative treatment effect.

Conclusion

False positive and false negative meta-analyses are common but infrequently recognized, even among methodologically robust reviews published by the Cochrane Heart Group. Meta-analysts and readers should incorporate trial sequential analysis when interpreting results.     

Guselkumab: A Review in Moderate to Severe Plaque Psoriasis

Guselkumab (Tremfya^®) is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that blocks the interleukin-23 (IL-23)-mediated signalling pathway and is the first in its class to be approved in adults with moderate to severe plaque psoriasis in several countries, including the USA and EU. In the VOYAGE trials, guselkumab was superior to placebo and to adalimumab at week 16 in terms of the proportion of patients achieving an Investigator Global Assessment (IGA) score of 0/1 and ≥ 90% improvement from baseline in Psoriasis Area and Severity index score (PASI 90 response), with benefits of guselkumab over adalimumab maintained at week 24. To date, the beneficial effects of guselkumab treatment in these trials were maintained for up to 2 years. Inadequate responders to ustekinumab who were then randomized to guselkumab in NAVIGATE showed better responses than those randomized to ustekinumab between weeks 28–40, with a significantly greater mean number of visits at which patients had IGA 0/1 and ≥ 2-grade improvement in IGA score, as well as higher proportions of patients achieving PASI 90 and PASI 100 at week 52. Treatment with guselkumab improved health-related quality of life (HR-QOL) and patient-reported outcomes in all trials and was generally well tolerated. Guselkumab, administered by subcutaneous injection, is a useful new option for patients with moderate to severe plaque psoriasis.