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Background: Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification.Aim: To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification.Design: Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England.Method: Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded.Results: Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95% confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point.Conclusion: There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison. [ABSTRACT FROM AUTHOR]

Abstract Background In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are currently buprenorphine and methadone, both are recommended by national clinical guidelines. However, these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons. Methods/Design This study uses randomised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification, given in the context of routine care, within three UK prisons. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome will be abstinence status eight days after detoxification, as determined by a urine test. Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification. Trial registration Current Controlled Trials ISRCTN58823759

In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene RAD51C are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. RAD51C promoter methylation (me RAD51C ) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the RAD51C promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with RAD51C gene silencing and homologous recombination deficiency (HRD). PDX models lost me RAD51C following treatment with PARPi rucaparib or niraparib, where a single unmethylated copy of RAD51C was sufficient to drive PARPi resistance. Genomic copy number profiling of one of the PDX models using SNP arrays revealed that this resistance was acquired independently in two genetically distinct lineages.In a cohort of 12 patients with RAD51C -methylated HGSC, various patterns of me RAD51C were associated with genomic "scarring," indicative of HRD history, but exhibited no clear correlations with clinical outcome. Differences in methylation stability under treatment pressure were also observed between patients, where one HGSC was found to maintain me RAD51C after six lines of therapy (four platinum-based), whereas another HGSC sample was found to have heterozygous me RAD51C and elevated RAD51C gene expression (relative to homozygous me RAD51C controls) after only neoadjuvant chemotherapy.As me RAD51C loss in a single gene copy was sufficient to cause PARPi resistance in PDX, methylation zygosity should be carefully assessed in previously treated patients when considering PARPi therapy. SIGNIFICANCE: Homozygous RAD51C methylation is a positive predictive biomarker for sensitivity to PARP inhibitors, whereas a single unmethylated gene copy is sufficient to confer resistance., (©2021 American Association for Cancer Research.)

The medical records of 155 dogs with patellar luxation (PL) from three different centres were analysed. Each case was classified according to the nature of its luxation and any concurrent orthopaedic conditions plus the age at diagnosis were also noted. Measurements relating to angle of inclination (AOI) of the femoral neck and medio-lateral bowing of the femur and tibia at the stifle were also recorded. The femoral and tibial data were compared to dogs with another orthopaedic condition in a case-control assessment. Labradors were most commonly affected (21%). Most luxations were medial (92%) and 54% of affected dogs were female. The mean AOI of the hip was 148.95 degrees . There was a statistically significant difference between the stifles of dogs with PL compared to a control population. This study concluded that PL in large breeds is increasing. Lateral luxation was uncommon and was not associated exclusively with large breeds. Females were more likely to have PL than males and being female was a risk factor associated with coxa valga. There are significant differences in medio-lateral stifle conformation between dogs with PL and control dogs.