Suicide in current psychiatric in-patients: a case-control study The National Confidential Inquiry into Suicide and Homicide

BACKGROUND: Few controlled studies have investigated factors associated with suicide in current in-patients. We aimed to identify psychosocial, behavioural and clinical risk factors, including variations in care, for in-patient suicide. METHOD: We conducted a national population-based case-control study of people who died by suicide between 1 April 1999 and 31 December 2000 while in psychiatric in-patient care in England. Cases were 222 adult mental health in-patients who died by suicide matched on date of death with 222 living controls. RESULTS: Nearly a quarter of suicides took place within the first week of admission; most of these died on the ward or after absconding. After the first week, however, most suicides occurred away from the ward, the majority of patients having left the ward with staff agreement. Previous deliberate self-harm, recent adverse life events, symptoms of mental illness at last contact with staff and a co-morbid psychiatric disorder were associated with increased risk for suicide. Being off the ward without staff agreement was a particularly strong predictor. Those patients who were detained for compulsory treatment were less likely to die by suicide. Independent predictors of in-patient suicide were male sex, a primary diagnosis of affective disorder and a history of self-harm. Being unemployed or on long-term sick leave appeared to be independently protective. CONCLUSION: Prevention of in-patient suicide should emphasize adequate treatment of affective disorder, vigilance in the first week of admission and regular risk assessments during recovery and prior to granting leave. Use of compulsory treatment may reduce risk.     

Design of a Randomized Placebo-Controlled Trial to Assess Dabigatran and Omeprazole in Patients with Myocardial Injury after Noncardiac Surgery (MANAGE)

Background

Worldwide approximately 200 million adults undergo major surgery annually, of whom 8 million are estimated to suffer a myocardial injury after noncardiac surgery (MINS). There is currently no trial data informing the management of MINS. Antithrombotic agents such as direct oral anticoagulants might prevent major vascular complications in patients with MINS.

Duodenal ulcer

Although the etiology of duodenal ulcer is not known, its treatment with drugs that reduce acid secretion is well accepted. The central role of calcium in stimulus-secretion coupling resulting in acid secretion by gastric parietal cells is documented. However, the status of intracellular calcium in gastric parietal cells in the basal state in patients with duodenal ulcer is not known. Multiple endoscopic gastric mucosal biopsies from the corpus of the stomach of 52 patients were processed and isolated parietal cells were studied. Intracellular calcium was estimated using fura-2-acetoxymethyl ester. Influx and efflux were determined by using radioactive calcium. Acridine orange retention was used to assess acid production. Only calcium influx at 20 min was significantly (P<0.01) more in patients with duodenal ulcer as compared to the control group. There was no difference between the groups in calcium influx at 0 and 60 min; calcium efflux at 0, 20, and 60 min; intracellular free calcium and acid secretion. We conclude that in the unstimulated state calcium homeostasis in isolated parietal cells of patients with duodenal ulcer shows only a minimal difference as compared to controls.     

Total Plasma Homocysteine Level Assessment and Timing of Folate/B12 Supplementation Prior to Initiation of Pemetrexed-Based Chemotherapy for Nonsquamous Non-Small Cell Lung Cancer Patients: An Irrelevant Investigation,an Unnecessary Delay,or Both?

Usefulness of total plasma homocysteine for predicting toxicity from and optimal duration of folate and vitamin B₁₂ supplementation prior to initiation of pemetrexed-based chemotherapy both remain debatable issues following publication of recent data that challenge conventional protocols followed for the same. Randomized trials are needed in an attempt to simplify supportive care schedule during administration of pemetrexed-based chemotherapy for non-squamous NSCLC.This letter is in reference to the study by Takagi et al. in a recent issue of the journal [1]. The authors assessed total plasma homocysteine (tpHcy) concentrations at baseline in a small cohort of advanced nonsquamous non-small cell lung cancer (NSCLC) patients prior to initiation of chemotherapy (pemetrexed and cisplatin), and then correlation of toxicity profiles with baseline tpHcy levels was assessed [1]. In this context, we wish to point out that we performed a similar assessment in a much larger cohort of patients recently [2]. Our population included 111 patients, and we assessed the association of both baseline tpHcy and graded folic acid supplementation (FAS) with clinical outcomes (hematological and nonhematological toxicity, response rates [RR], and overall survival [OS]) after first-line chemotherapy with pemetrexed-platinum doublet.There are several important differences between the study by Takagi et al. [1] and our study [2]. First, the number of patients in our study, although it was a retrospective analysis, was more than three times the number of patients in the study by Takagi et al. Second, our assessment of tpHcy was not just at baseline but also at end of treatment; however, we categorized tpHcy only as being less than the upper limit of normal (ULN), one to two times ULN, or more than two times ULN rather than assessing tpHcy as a continuous variable. Third, patients in our study received FAS in relation to the grouping of tpHcy, namely, 400 μg for tpHcy less than ULN, 700 μg for tpHcy one to two times ULN and 1,000 μg for tpHcy more than two times ULN compared with 350–500 μg in the study by Takagi et al. Fourth, the dose of cisplatin used in our study was 65 mg/m², which is the standard dose for this drug at our center [3]. Fifth, the patient population in our study was predominantly those with unknown EGFR gene mutation/ALK gene rearrangement status compared with the study by Takagi et al., in which almost 30% of patients had one of the two actionable molecular targets. Sixth, patients in our study were initiated on oral ferrous sulfate and FAS as well as injectable vitamin B₁₂ from day 1 of the first cycle of chemotherapy compared with the 24- to 48-hour time period between administration of FAS and B₁₂ in the study by Takagi et al. Seventh, intramuscular injection of 1,000 μg vitamin B₁₂ was given with every dose (every 3 weeks) in our study.The above differences notwithstanding, the results of our study [2] and the study by Takagi et al. [1] are similar in the sense that no association was observed between tpHcy with either hematological or nonhematological toxicity. In addition, in our study, no association was observed with any of the other clinically relevant outcomes assessed, namely, RR and OS. Two other recent studies have also shown that patients receiving FAS and vitamin B₁₂ for less than the recommended pretreatment duration of 5–7 days (including their initiation on the same day as of chemotherapy) have similar outcomes compared with those who did [4, 5].In light of the above evidence and given the fact that FAS in the recommended range of 350–1,000 μg is routine in the current era, there are a few questions that need to be addressed. First, is it really necessary to delay initiation of chemotherapy merely to give FAS and vitamin B₁₂ supplementation for a week? Second, is it really necessary to restrict vitamin B₁₂ to every 3 cycles (9 weeks) or would it be simpler to allow 1,000 μg with every dose (as is being done at our center)? Excess vitamin B₁₂, as opposed to excess FAS, has not been shown to reduce the efficacy of pemetrexed [6]. Third, is assessment of baseline tpHcy actually relevant, and if so, is there a better way of correlating it with any of the clinically relevant outcomes? Perhaps we need a large randomized trial to answer these questions with the ultimate aim of simplifying pemetrexed-based chemotherapy and its associated supportive care schedule.     

Bone-specific alkaline phosphatase – a potential biomarker for skeletal growth assessment

Objective: The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages.

Design: Cross-sectional study.

Setting: Maulana Azad Institute of Dental Sciences, New Delhi, India.

Participants: 150 subjects (75 males and 75 females) in the age group of 8–20 years.

Methods: Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann–Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages.

Results: Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p?Conclusions: BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.     

Extract from Ceratonia siliqua Exhibits Depigmentation Properties

Skin hyper‐pigmentation is a condition initiated by the overproduction of melanin existing in the melanocytes. Melanin pigment is responsible for the colour of skin in humans. It is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of the key enzyme tyrosinase. In continuation with our efforts to identify tyrosinase inhibitors from plants sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were screened for tyrosinase inhibition and diphenolase activity. The bark extract exhibited significant inhibition on mushroom tyrosinase using L‐tyrosine as a substrate and showed diphenolase activity. The extract further significantly lowered tyrosinase mRNA levels in B16‐F10 mouse melanocytes. Bioassay‐guided fractionation led to the isolation of six compounds. Compounds (?)‐epicatechin‐3‐O‐gallate, 1,2,3,6‐tetra‐O‐galloyl‐ß‐D‐glucose and gallocatechin‐3‐O‐gallate showed tyrosinase inhibitions with the IC₅₀ values of 27.52, 83.30 and 28.30 µg/mL, respectively. These compounds also exhibited L‐DOPA activities with IC₅₀ values of >200, 150 and 200 µg/mL, respectively. A clinical study was conducted using 20 volunteers in a patch testing trial for irritancy potential and skin depigmentation. The clinical results showed the sample to be non‐irritant with irritancy potential of ?34.21 and depigmentation trial showed an improvement in the even skin tone of UV induced pigmentation at 3% after 28 days of application. Copyright © 2015 John Wiley & Sons, Ltd.     

Peptide vaccination is superior to genetic vaccination using a recombineered bacteriophage λ subunit vaccine

Genetic immunization holds promise as a vaccination method, but has so far proven ineffective in large primate and human trials. Herein, we examined the relative merits of genetic immunization and peptide immunization using bacteriophage λ. Bacteriophage λ has proven effective in immune challenge models using both immunization methods, but there has never been a direct comparison of efficacy and of the quality of immune response. In the current study, this vector was produced using a combination of cis and trans phage display. When antibody titers were measured from immunized animals together with IL-2, IL-4 and IFNγ production from splenocytes in vitro, we found that proteins displayed on λ were superior at eliciting an immune response in comparison to genetic immunization with λ. We also found that the antibodies produced in response to immunization with λ displayed proteins bound more epitopes than those produced in response to genetic immunization. Finally, the general immune response to λ inoculation, whether peptide or genetic, was dominated by a Th1 response, as determined by IFNγ and IL-4 concentration, or by a higher concentration of IgG2a antibodies.     

Hematopoietic stem cell transplantation in the treatment of peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCL) are a rare group of heterogeneous lymphoproliferative disorders with their origin in the post-thymic T cells. Most PTCL have a relatively poor outcome, with a 5-year overall survival of less than 30%. Anaplastic large cell lymphoma (ALCL) has a better prognosis compared with other subtypes of PTCL. As with aggressive B-cell non-Hodgkin's lymphoma, high-dose chemotherapy followed by autologous stem cell transplantation should be offered to patients with PTCL in their first relapse. Patients with poor-risk features (alk-negative ALCL, histologic subtypes other than ALCL, and high International Prognostic Index score at presentation) may be candidates for autologous stem cell transplantation as first-line therapy. Initial results of allogeneic stem cell transplantation, both with standard and nonmyeloablative conditioning, look promising. Randomized, multi-institutional clinical trials are needed to optimally define the role of stem cell transplantation in PTCL.