Sumeet Gupta

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology. The Cancer Genome Atlas (TCGA) project reports here its analysis of messenger RNA and microRNA expression, promoter methylation, DNA copy number and exome sequences in 489 high-grade serous ovarian adenocarcinomas. The analyses help establish new tumour subtypes. Among other insights is the finding that while the gene encoding p53 tumour suppressor is mutated in almost all tumours, nine other loci including NF1, BRCA1, BRCA2, RB1 and CDK12 carry recurrent albeit low-prevalence mutations. Homologous recombination is defective in about half of the tumours studied, and Notch and FOXM1 signalling are involved in the pathophysiology.

Lithium is an established treatment for bipolar disorder and an augmenting agent for treatment-resistant depression. Despite awareness of renal adverse effects, including chronic kidney disease, for the past five decades, there has been a lack of research evidence. This has led to debates around the existence and magnitude of the risk. This article discusses the current evidence base regarding the link between lithium and chronic kidney disease, monitoring of renal functions and its clinical implications.

Summary Lithium is one of the most effective psychotropic drugs we have, but it is underused because of its low therapeutic index, the need for regular blood tests and perceptions about its adverse effects, including renal problems. The last include urinary concentration deficits and diabetes insipidus, chronic kidney disease (including renal failure), nephrotic syndrome, hypercalcaemia, hyperparathyroidism and distal tubular acidosis. This article reviews these adverse effects with special emphasis on their management.

SUMMARY Sialorrhoea (hypersalivation) is a common adverse effect of clozapine. If severe, it can affect patients' quality of life and adherence to the treatment. Clinicians therefore need to proactively manage this effect. At present, no drugs are licensed to manage clozapine-induced sialorrhoea, although there are many off-label treatment options, with variable effectiveness. Anticholinergic medications are commonly prescribed for it, but they have limited effect and can worsen constipation. This article gives a brief overview of other practical and pharmacological management options.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: 1. To evaluate the effectiveness of EWS plus TAU or EWS plus psychological therapy versus TAU alone or psychological treatment (without EWS) independently on time to recurrence of any bipolar episode and hospitalisation, and other clinically relevant outcome measures. . 2. To evaluate the effectiveness of intermittent medication used on recognition of EWS without continued mood‐stabilising medication versus TAU involving continued mood‐stabilising medication on time to recurrence of any bipolar episodes.