BackgroundIncarcerated populations are disproportionately burdened by hepatitis C virus (HCV) infection. The introduction of highly-effective, direct-acting antiviral (DAA) treatment has potential to substantially reduce the burden of liver disease in this population, but accurate information about access to and utilization of this treatment is currently limited. The goals of this study were to characterize receipt of HCV care and treatment services for a cohort of HCV-infected adults identified in a state prison system, and to describe the complex health needs of this population.MethodsTo estimate the proportion of patients who were treated for HCV while incarcerated, and the proportion linked to HCV care after release from prison, we used a deterministic matching algorithm to link administrative prison data, health care records, and a state public health surveillance database, which captures all positive HCV-related diagnostic test results through automatic laboratory reporting. Individuals not evaluated or treated for HCV while in prison were considered likely to have been linked to care in the community if the HCV surveillance system contained a record of a quantitative HCV RNA or genotype test within 6 months of their release date. Demographic and comorbidity data were manually extracted from the electronic health records for all patients referred for consideration of HCV treatment.ResultsBetween 2011 and 2015, 3126 individuals were known to be living with chronic HCV infection while incarcerated in the state prison system. Of these, 570 (18%) individuals were evaluated for HCV treatment while incarcerated and 328 (10%) initiated treatment with DAAs. Of the 2556 individuals not evaluated for treatment, 1605 (63%) were released from prison during the 5 year study period. Of these, 138 (9%) individuals engaged in HCV care in the community within 6 months. Data describing medical and psychiatric co-morbidities were available for the prison-based treatment cohort, which showed a high prevalence of major depression (39%), anxiety disorder (24%), alcohol misuse (52%), cocaine use (52%) and prior injection drug use (62%).ConclusionDespite HCV treatment advances, linkage to care and treatment rates for criminal-justice involved adults remains low, particularly for those who must seek care in the community after release from prison. Treating criminal-justice involved individuals for HCV during incarceration provides an opportunity to improve linkage to care and treatment rates among this vulnerable population.

Despite Much evidence drawn from studies with Papilio polyxenes (black swallowtail), a specialist that feeds almost exclusively on furanocoumarin-containing species in the Apiaceae and Rutaceae, and Papilio glaucus (tiger swallowtail), a polyphagous insect that rarely encounters plants containing furanocoumarins, indicates that the P450s responsible for furanocoumarin detoxification are evolutionarily related and transcriptionally regulated in response to the presence of furanocoumarins in the larval diet.CYP6B1 cDNAs isolated from P. polyxenes fifth instar larvae (6) encode P450s that metabolize the linear furanocoumarins xanthotoxin (8-methoxypsoralen) and bergapten (5-methoxypsoralen) at high efficiency and the angular furanocoumarins angelicin and sphondin at very low efficiency (7,8). In this species, CYP6BI transcripts are induced primarily in response to xanthotoxin and to a lesser extent by angelicin and bergapten (9, 10). P. polyxenes CYP6B3 transcripts derived from a second, closely related P450 locus (91% nucleotide and 88% amino acid identity to CYP6B1) are induced in response to a wider range of furanocoumarins, including linear and angular forms (11).Even though the generalist P. glaucus rarely encounters furanocoumarins, it has a low constitutive ability to metabolize linear and angular furanocoumarins; this activity can be induced up to 13-fold by xanthotoxin in the larval diet (8). A CYP6B4vJ cDNA isolated from P. glaucus fifth instar larvae is 63% and 61% identical at the amino acid level to CYP6Blvl and CYP6B3vl, respectively, of P. poxenes (8). The CYP6B4v1 cDNA encodes a P450 that metabolizes linear furanocoumarins (isopimpinellin, imperatorin, bergapten) at high efficiencies, other linear furanocoumarins (xanthotoxin, psoralen) at intermediate efficiencies, and angular furanocoumarins (angelicin, sphondin) only at low efficiency (8). Northern blot analysis reveals that CYP6B4 transcripts are highly induced by xanthotoxin (8); the transcriptional responses to other furanocoumarins have not been characterized.The regulatory elements critical for in vivo induction of the P.

Background. Hypomagnesaemia is a common side effect of cyclosporin A (CsA) therapy. Animal studies suggest that magnesium (Mg) supplementation inhibits chronic CsA nephropathy. Methods. To determine if low Mg levels correlate with true CsA-induced nephrotoxicity in humans, we examined kidney transplant biopsy records at our centre for all transplant biopsies performed between 1990 and 2002. We simultaneously reviewed the medical records to determine whether serum Mg levels were checked at the time of biopsy. Those individuals with histologically proven CsA nephrotoxicity were studied. Results. Serum total Mg levels were available for 320 patients, 60 of whom were diagnosed with chronic CsA-mediated nephropathy. Patients were divided in two groups, a low Mg [n ¼ 29, 1.8 (1.67-1.9) mg/dl or 0.74 (0.68-0.78) mmol/l] and a normal Mg group [n ¼ 31, 2.2 (2.0-2.4) mg/dl or 0.9 (0.82-0.98) mmol/l, P<0.05] based on the median Mg level in the entire cohort (2 mg/dl or 0.82 mmol/l). Both groups were analysed for disease progression and graft loss using the slope of creatinine clearance (CCR) and multivariate analyses. Although the CCR at the time of biopsy was greater in the low Mg group [44.3 (36.3-64.3) ml/min vs 37.8 (25.2-47.3) ml/min, P<0.05), the decline in graft function was faster in this group (À8.9±3.5 vs 1±2.7 ml/min/year; P ¼ 0.02) compared with the normal Mg cohort. Using Cox proportional hazards analyses, the adjusted graft survival was significantly reduced in the low Mg group 5 years after biopsy. Conclusions. Our study demonstrates that low serum Mg levels were associated with a faster rate of decline in kidney allograft function and increased rates of graft loss in renal transplant recipients with chronic CsA nephropathy. This suggests that hypomagnesaemia could potentiate CsA-mediated nephropathy.

Objectives. The prevalence of hepatitis C virus (HCV) infection among young adults is rising in Wisconsin. We examined the prevalence of HCV infection among male and female inmates entering two Wisconsin prisons and evaluated existing and alternate risk-based strategies for identifying HCV infection at intake.Methods. We added HCV testing to the intake procedures for all 1,239 adults prison entrants at the Wisconsin Department of Corrections (WDOC) from November 3, 2014, to January 31, 2015. We identified risk factors associated with HCV infection during the routine intake examination and calculated the sensitivity and specificity of risk-based testing strategies for identifying HCV infection.Results. The prevalence of HCV antibody among prison entrants was 12.5% (95% confidence interval [CI] 10.7, 14.4) overall and was almost two times higher at the women's facility (21.3%, 95% CI 15.4, 27.2) than at the men's facility (11.0%, 95% CI 0.0, 12.9) (p,0.001). The sensitivity and specificity of the WDOC risk-based criteria were 88% (95% CI 83, 93) and 80% (95% CI 78, 83), respectively. Adding a new criterion, the 1945-1965 birth cohort, to the risk-based criteria improved the sensitivity to 92% (95% CI 88, 96) and lowered the specificity to 71% (95% CI 68, 74). Compared with entrants without these risk factors, HCV antibody prevalence was significantly higher among prison entrants who had the following risk factors: injection drug use (prevalence ratio [PR] 5 9.9, 95% CI 7.4, 13.2), liver disease (PR59.7, 95% CI 7.8, 12.0), and elevated levels of alanine transaminase (PR53.6, 95% CI 2.7, 4.9).Conclusion. The WDOC risk criteria for HCV testing identified 88% of HCV infections among prison entrants. Including the 1945-1965 birth cohort as a criterion along with the other WDOC risk criteria increased the sensitivity of targeted testing to 92%. These findings may be informative to jurisdictions where universal HCV testing is not feasible because of resource limitations.