Suicide mortality in patients on lithium maintenance therapy

Mood disorders are frequently recurrent and it has been shown that maintenance treatment can reduce long-term morbidity in this condition. It has also been shown that mood disorders carry an increased risk of suicide and that a significant proportion of individuals who commit suicide suffer from a mood disorder. This paper reports the results of a long term follow-up of a cohort of patients attending a specialist mood disorder clinic over a period of 18 years. Sixty-seven suffered from unipolar depression and 36 had bipolar or schizo-affective disorders In order to qualify for entry to the cohort the unipolar patients had to have had at least three episodes of depression and those with bipolar disorders had to have had at least three episodes – with at least one manic episode and one depressive episode. All patients were treated with lithium. The initial treatment refusal rate and drop our rates were low. The mortality from suicide in this group was compared with that reported in five recent studies – all of which involved patients who had not been given maintenance therapy. The standardised mortality ratio (SMR) for all causes for the whole group was 0.93. There were two suicides. In one case the patient had continued treatment with lithium until death and in the other the patient had discontinued treatment 12 months before death. The overall suicide rate was 1.3 per 1000 patient years. Amongst similar groups of patients who had not been given maintenance therapy suicide rates of about 5.5 per 1000 patient years have been reported. It is concluded that maintenance treatment of mood disorders reduces the suicide rate in this vulnerable group of patients.     

Lithium treatment and prophylaxis in unipolar depression

Lithium has a well-recognized role in treating acute mania and serving as a prophylaxis against recurrent bipolar affective illness. Studies in the past few years have shown that the drug may also be used to prevent recurrences of unipolar depression. As a treatment for acute unipolar depression it is less effective than the standard antidepressant drugs or electroconvulsive therapy. However, a therapeutic trial of lithium may be indicated in acutely depressed patients who fail to respond to conventional treatment.     

A Young Woman With Recurrent Gestational Hypercalcemia and Acute Pancreatitis Caused by CYP24A1 Deficiency

The CYP24A1 gene encodes a mitochondrial 24‐hydroxylase that inactivates 1,25(OH)₂D. Loss‐of‐function mutations in CYP24A1 cause hypercalcemia, nephrolithiasis and nephrocalcinosis. We describe a woman with CYP24A1 deficiency and recurrent gestational hypercalcemia. Her first pregnancy, at age 20, resulted with the intrauterine demise of twin fetuses. Postpartum, she developed severe hypercalcemia (14 mg/dL), altered mental status, and acute pancreatitis. Her PTH was suppressed (6 pg/mL) and her 1,25(OH)₂D was elevated (165 and 195 pg/mL on postpartum day 1 and 5, respectively). Between one and three months postpartum, her serum calcium decreased from 11.4 to 10.2 mg/dL while her 1,25(OH)₂D level decreased from 83 to 24 pg/mL. Her 24‐hour urine calcium was 277 mg. Six months postpartum, she became pregnant again. At 14 weeks, her albumin‐corrected calcium level was 10.4 mg/dL and her 1,25(OH)₂D level exceeded 200 pg/mL. To establish the diagnosis of CYP24A1 deficiency, we showed her 24,25(OH)₂D level to be undetectable (<2 ng/mL). Exon sequencing of the CYP24A1 gene revealed a homozygous, 8‐nucleotide deletion in exon 8, causing an S334V substitution and premature termination due to a frame shift (c.999_1006del, p.Ser334Valfs*9). To prevent hypercalcemia, she was advised to discontinue prenatal vitamins, avoid sun exposure and calcium‐rich foods, and start omeprazole and a calcium binder (250 mg K‐Phos‐neutral with meals). Despite these measures, both hypercalcemia (11.5 mg/dL) and acute pancreatitis recurred. Labor was induced and a healthy, normocalcemic boy was delivered. In the absence of lactation, maternal hypercalcemia resolved within 2 months. This report shows that CYP24A1‐deficient subjects may be normocalcemic at baseline. Hypercalcemia may be unmasked by pregnancy through the routine use of calciferol‐containing prenatal vitamins, increased 1‐alpha hydroxylation of VitD by the placenta and maternal kidney, and production of PTHrP by the uteroplacental unit. CYP24A1 deficiency should be considered in patients with unexplained vitamin D‐mediated hypercalcemia. © 2016 American Society for Bone and Mineral Research.     

Return to Work After Shoulder Replacement for Glenohumeral Osteoarthritis Is Similar When Hemiarthroplasty Is Compared to Total Shoulder Arthroplasty

HSS Journal ® - Return to work after shoulder arthroplasty for glenohumeral osteoarthritis (OA) is an important consideration for an aging workforce. The aim of this study was to compare the...     

Estimating 'costs' for cost-effectiveness analysis

Since 1999, the National Institute for Health and Clinical Excellence (NICE) Technology Appraisal Programme has been charged with producing guidance for the NHS in England and Wales on the appropriate use of new and existing healthcare programmes. Guidance is based on an assessment of a number of factors, including cost effectiveness. The identification, measurement and valuation of costs are important components of any cost-effectiveness analysis. However, working through these steps raises a number of important methodological questions. For example, how should 'future' resource use be estimated, and is there a need to consider all 'future' costs? Given that NICE produces national guidance, should national unit cost data be used to value resources or should local variations in negotiated prices be taken into account? This paper was initially prepared as a briefing paper as part of the process of updating NICE's 2004 Guide to the Methods of Technology Appraisal for a workshop on 'costs'. It outlines the issues that were raised in the original briefing paper and the subsequent questions that were discussed at the workshop.     

Social reward-conditioned place preference: a model revealing an interaction between cocaine and social context rewards in rats

A recent thrust in drug abuse research is the influence of social interactions on drug effects. Therefore, the present study examined conditioned place preference (CPP) as a model for assessing interactions between drug and social rewards in adolescent rats. Parameters for establishing social reward-CPP were examined, including the number of conditioning sessions/day (1 or 2), the total number of sessions (2, 8, or 16), and the duration of sessions (10 or 30 min). Subsequently, the effects of cocaine or dextromethorphan on social reward-CPP and play behavior were examined. The results demonstrate that social reward-CPP (i.e., preference shift for an environment paired previously with a rat) was similar using either 1 or 2 conditioning sessions/day and either 10 or 30 min sessions; however, social reward-CPP increased as the number of social pairings increased. Additionally, a low dose of cocaine (2 mg/kg, IP) and a low number of social pairings (2 pairings) failed to produce CPP when examined alone, but together produced a robust CPP, demonstrating an interaction between these rewards. The non-rewarding drug, dextromethorphan (30 mg/kg, IP), failed to enhance social reward-CPP, suggesting that drug-enhanced social reward-CPP is specific to rewarding drugs. Surprisingly, there was no relationship between play behaviors and preference shift in drug-naïve animals. Furthermore, cocaine inhibited play behavior despite enhancing social reward-CPP, suggesting that aspects of social interaction other than play behavior likely contribute to social reward. The findings have important implications for understanding the influence of social context on cocaine reward during adolescence.