BackgroundUsher syndrome (USH) is an autosomal recessive disorder comprising retinitis pigmentosa, hearing loss and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous with three distinctive clinical types (I–III) and nine Usher genes identified. This study is a comprehensive clinical and genetic analysis of 172 Usher patients and evaluates the contribution of digenic inheritance.MethodsThe genes MYO7A, USH1C, CDH23, PCDH15, USH1G, USH2A, GPR98, WHRN, CLRN1 and the candidate gene SLC4A7 were sequenced in 172 UK Usher patients, regardless of clinical type.ResultsNo subject had definite mutations (nonsense, frameshift or consensus splice site mutations) in two different USH genes. Novel missense variants were classified UV1-4 (unclassified variant): UV4 is ‘probably pathogenic’, based on control frequency <0.23%, identification in trans to a pathogenic/probably pathogenic mutation and segregation with USH in only one family; and UV3 (‘likely pathogenic’) as above, but no information on phase. Overall 79% of identified pathogenic/UV4/UV3 variants were truncating and 21% were missense changes. MYO7A accounted for 53.2%, and USH1C for 14.9% of USH1 families (USH1C:c.496+1G>A being the most common USH1 mutation in the cohort). USH2A was responsible for 79.3% of USH2 families and GPR98 for only 6.6%. No mutations were found in USH1G, WHRN or SLC4A7.ConclusionsOne or two pathogenic/likely pathogenic variants were identified in 86% of cases. No convincing cases of digenic inheritance were found. It is concluded that digenic inheritance does not make a significant contribution to Usher syndrome; the observation of multiple variants in different genes is likely to reflect polymorphic variation, rather than digenic effects.

BackgroundLymphogranuloma venereum (LGV) is caused by Chlamydia trachomatis serovars L1-L3. This study determined the positivity for LGV testing before and after introduction of universal LGV testing of positive rectal Chlamydia trachomatis samples in men who have sex with men (MSM).MethodsFrom March 2015 to February 2018, MSM with rectal C. trachomatis were not routinely tested for LGV at the Melbourne Sexual Health Centre unless they had HIV or symptoms of proctitis. From February 2018, universal testing for LGV of all positive rectal C. trachomatis specimens in men over the age of 25 years, regardless of symptoms was undertaken. LGV positivity was defined as the detection of LGV-associated C. trachomatis serovars.ResultsThere were 3429 and 4020 MSM who tested positive for rectal chlamydia in the selective and universal LGV-testing periods, respectively. Of the total 3027 assessable specimens in both periods, 97 (3.2%; 95% CI 2.6% to 3.9%) specimens tested positive for LGV. LGV positivity in the selective testing period was higher than in the universal testing period (6.6% (33/502) vs 2.5% (64/2525), p<0.001). The proportion of LGV cases that were asymptomatic increased from 15.2% (5/33) in the selective testing period to 34.4% (22/64) in the universal testing period (p=0.045). Of the 70 symptomatic LGV cases symptoms included rectal discharge (71.4%, n=45) and rectal pain (60.0%, n=42).ConclusionUniversal LGV testing of all positive rectal chlamydia samples in MSM compared with selective testing led to the detection of asymptomatic rectal LGV, which constituted 34% of rectal LGV cases.

SUMMARY Current first-line antiretroviral therapy comprises a combination of drugs that are generally well tolerated. Adverse effects include hypersensitivity reactions, renal and liver toxicity, rhabdomyolysis, hyperlipidaemia, weight gain and neuropsychiatric disorders Most drug–drug interactions related to antiretroviral therapy involve drug absorption, metabolism or elimination. Some interactions may increase toxicity or reduce the effectiveness of antiretroviral therapy potentially resulting in treatment failure Routinely checking for adverse drug effects and potential drug–drug interactions is an important part of the care of people taking antiretroviral therapy. This includes asking about the patient’s use of over-the-counter and complementary medicines

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