Prescribing for patients taking antiretroviral therapy.

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.

Universal lymphogranuloma venereum (LGV) testing of rectal chlamydia in men who have sex with men and detection of asymptomatic LGV.

BACKGROUND: Lymphogranuloma 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). METHODS: From 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. RESULTS: There 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). CONCLUSION: Universal 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.

HSV-associated proctitis presenting without perianal lesions: why testing and empirical treatment may be important.

A man in his late 30s presented with a several-day history of rectal pain, discharge and bleeding associated with systemic upset. Sexual history revealed receptive anal sex with several male partners in the 2 weeks preceding his clinic visit. Examination of the perianal area was unremarkable. Proctoscopy showed evidence of non-ulcerative proctitis. Microscopy for Gram stain showed pus cells plus extracellular Gram-negative diplococci. The patient was treated for presumptive gonorrhoea and chlamydial infection with ceftriaxone, azithromycin and doxycycline. The patient failed to improve with this treatment regimen. Rectal swab results at 48 hours confirmed the causative agent to be herpes simplex virus (HSV) type 2. The patient was recalled and treated successfully with valaciclovir. This case serves as a useful reminder to clinicians to consider HSV in the differential diagnosis of sexually transmitted proctitis, in the absence of perianal or anorectal ulceration.

Does the Flipped Classroom improve exam performance in medical education? A systematic review.

This article was migrated. The article was marked as recommended. Background: The 'flipped classroom' (FC) is a blended learning model in which educational material is delivered on-line prior to class, students then apply this knowledge through discussion and problem solving activities in class. Its effectiveness in medical education is debated. The aim of this systematic review is to assess the outcomes of studies which have compared the exam performance of traditional didactic teaching (DT) to the FC in medical education. Methods: A broad based literature search was performed in accordance with PRISMA protocol. MESH terms were 'flipped classroom', 'flipped teaching', 'blended learning' and 'medical education'. The outcomes of interest were test score results following FC compared to DT methods. Results: Eleven studies with a total of 2052 study participants were included in the review. Four studies demonstrated a significant improvement in test scores using FC compared to DT; four showed no significant difference and three demonstrated mixed results. Discussion and Conclusions: The results of this review are equivocal. Study heterogeneity in design, participants and subject covered may account for some of this disparity. Two studies provide evidence that the FC results in improved performance on higher cognitive tasks however further robust, in depth studies are required to demonstrate this conclusively.

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

BACKGROUND: Usher 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. METHODS: The 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. RESULTS: No 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. CONCLUSIONS: One 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.

Nox1-dependent reactive oxygen generation is regulated by Rac1.

Rac1 has been implicated in the generation of reactive oxygen species (ROS) in several cell types, but the enzymatic origin of the ROS has not been proven. The present studies demonstrate that Nox1, a homolog of the phagocyte NADPH-oxidase component gp91(phox), is activated by Rac1. When Nox1 is co-expressed along with its regulatory subunits NOXO1 and NOXA1, significant ROS generation is seen. Herein, co-expression of constitutively active Rac1(G12V), but not wild-type Rac1, resulted in marked further stimulation of activity. Decreased Rac1 expression using small interfering RNA reduced Nox1-dependent ROS. CDC42(G12V) failed to increase activity, and small interfering RNA directed against CDC42 failed to decrease activity, pointing to specificity for Rac. TPR domain mutants of NOXA1 that interfere with Rac1 binding were ineffective in supporting Nox1-dependent ROS generation. Immunoprecipitation experiments demonstrated a complex containing Rac1(G12V), NOXO1, NOXA1, and Nox1. CDC42(G12V) could not substitute for Rac1(G12V) in such a complex. Nox1 formed a complex with Rac1(G12V) that was independent of NOXA1 and NOXO1, consistent with direct binding of Rac1(G12V) to Nox1. Rac1(G12V) interaction with NOXA1 was enhanced by Nox1 and NOXO1, suggesting cooperative binding. A model is presented comparing activation by regulatory subunits of Nox1 versus gp91(phox) (Nox2) in which Rac1 activation provides a major trigger that acutely activates Nox1-dependent ROS generation.