DEVELOPMENT AND VALIDATION OF FIRST ORDER DERIVATIVE SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF PARACETAMOL AND TAPENTADOL HYDROCHLORIDE IN TABLET DOSAGE FORM

A simple, precise, accurate and reproducible spectrophotometric method has been developed forSimultaneous estimation of Paracetamol and Tapentadol Hydrochloride by employing first order derivativezero crossing method in 0.1 N Sodium Hydroxide. The first order derivative absorption at 257.1 nm (zerocross point of Paracetamol) was used for quantification of Tapentadol HCl and 289.0 nm (zero cross point ofTapentadol HCl) for quantification of Paracetamol. The linearity was established over the concentrationrange of 15-3

Exploring professionals' understanding, interpretation and implementation of the 'appropriate medical treatment test' in the 2007 amendment of the Mental Health Act 1983.

BACKGROUND: The appropriate medical treatment test (ATT), included in the Mental Health Act (MHA) (1983, as amended 2007), aims to ensure that detention only occurs when treatment with the purpose of alleviating a mental disorder is available. AIMS: As part of the Assessing the Impact of the Mental Health Act (AMEND) project, this qualitative study aimed to assess professionals' understanding of the ATT, and its impact on clinical practice. METHOD: Forty-one professionals from a variety of mental health subspecialties were interviewed. Interviews were coded related to project aims, and themes were generated in an inductive process. RESULTS: We found that clinicians are often wholly relied upon for the ATT. Considered treatment varied depending on the patient's age rather than diagnosis. The ATT has had little impact on clinical practice. CONCLUSIONS: Our findings suggest the need to review training and support for professionals involved in MHA assessments, with better-defined roles. This may enable professionals to implement the ATT as its designers intended. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license

Prevalence of Anxiety and Depression among Outpatients with Type 2 Diabetes in the Mexican Population

Depression and anxiety are common in diabetic patients; however, in recent years the frequency of these symptoms has markedly increased worldwide. Therefore, it is necessary to establish the frequency and factors associated with depression and anxiety, since they can be responsible for premature morbidity, mortality, risk of developing comorbidities, complications, suffering of patients, as well as escalation of costs. We studied the frequency of depression and anxiety in Mexican outpatients with type 2 diabetes and identified the risk factors for depression and anxiety.We performed a study in 820 patients with type 2 diabetes. The prevalence of depression and anxiety was estimated using the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale, respectively. We calculated the proportions for depression and anxiety and, after adjusting for confounding variables, we performed multivariate analysis using multiple logistic regressions to evaluate the combined effect of the various factors associated with anxiety and depression among persons with type 2 diabetes. The rates for depression and anxiety were 48.27% (95% CI: 44.48–52.06) and 55.10% (95% CI: 51.44–58.93), respectively. Occupation and complications in diabetes were the factors associated with anxiety, whereas glucose level and complications in diabetes were associated with depression. Complications in diabetes was a factor common to depression and anxiety (p<0.0001; OR 1.79, 95% CI 1.29–2.4).Our findings demonstrate that a large proportion of diabetic patients present depression and/or anxiety. We also identified a significant association between complications in diabetes with depression and anxiety. Interventions are necessary to hinder the appearance of complications in diabetes and in consequence prevent depression and anxiety

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Exploring professionals’ understanding, interpretation and implementation of the ‘appropriate medical treatment test’ in the 2007 amendment of the Mental Health Act 1983.

Background The appropriate medical treatment test (ATT), included in the Mental Health Act (MHA) (1983, as amended 2007), aims to ensure that detention only occurs when treatment with the purpose of alleviating a mental disorder is available. Aims As part of the Assessing the Impact of the Mental Health Act (AMEND) project, this qualitative study aimed to assess professionals' understanding of the ATT, and its impact on clinical practice. Method Forty-one professionals from a variety of mental health subspecialties were interviewed. Interviews were coded related to project aims, and themes were generated in an inductive process. Results We found that clinicians are often wholly relied upon for the ATT. Considered treatment varied depending on the patient's age rather than diagnosis. The ATT has had little impact on clinical practice. Conclusions Our findings suggest the need to review training and support for professionals involved in MHA assessments, with better-defined roles. This may enable professionals to implement the ATT as its designers intended

Stability and predictors of change in salivary cortisol measures over six years: MESA

A major challenge in characterizing features of the daily cortisol curve is variability in features over time. Few studies have examined the stability of daily features of the cortisol curve over long periods or the predictors of long term changes. Repeated salivary cortisol measures on 580 adults from the MESA Stress study were used to examine the stability of various features of the daily cortisol curve (wakeup value, the cortisol awakening response (CAR), the early and late decline slope and the area under the curve (AUC)), over short periods (several days) and long periods (approximately 6-years) and to investigate the association of demographic factors with the changes. Intraclass correlation coefficients (ICCs) were used to estimate the short and long term stability. Piecewise linear mixed models were used to assess factors associated with changes in features over time. For most features, short term stability (ICCs: 0.17–0.74) was higher than long term stability (ICCs: 0.05–0.42), and long term stability was highest when several days were averaged for each time point. The decline over the day showed the highest long term stability: when several days for each wave were averaged the stability of the daily decline slope across 6 years was similar (or higher) than the stability across short periods. AUC had high stability over short periods (ICCs: 0.65–0.74) but much lower stability across long periods (ICC: 0.05). All features of daily cortisol curve investigated changed significantly over the approximately 6 year follow-up period. The wakeup cortisol became higher; the CAR became smaller; both the early and late decline became flatter; and the AUC became larger. Hispanics experienced significantly larger increases in the wakeup value; and African-Americans and Hispanics showed less flattening over time of the early decline slope than Non-Hispanic Whites. Our findings have implications for characterization of features in studies linking cortisol to health outcomes. The presence of variability over time suggests opportunities for future investigation of the predictors of changes over time as well as the links between these changes and health outcomes

Antecedent longitudinal changes in body mass index are associated with diurnal cortisol curve features: The multi-ethnic study of atherosclerosis

CONTEXT: Prior studies have shown a cross-sectional association between body mass index (BMI) and salivary diurnal cortisol profile features (cortisol features); however, to our knowledge prior population-based studies have not examined the longitudinal association of body-mass index (BMI) with cortisol features. OBJECTIVE: To examine the association of (1) prior annual BMI percent change over 7 years with cortisol features, (2) baseline cortisol features with subsequent change in BMI over 6 years and (3) the association of change in cortisol features with change in BMI over 6 years. DESIGN: Longitudinal study SETTING: Multi-Ethnic Study of Atherosclerosis (MESA) Stress I & II Studies (2004-2006 & 2010-2012) PARTICIPANTS: 1,685 ethnically diverse men and women attended either MESA Stress exam (mean age 65 ± 10 years at MESA Stress I; mean age 69 ± 9 years at MESA Stress II). OUTCOME MEASURES: Log-transformed cortisol features including wake-up cortisol, cortisol awakening response, early decline slope (30 minutes to 2 hours post-awakening), late decline slope (2 hours post-awakening to bedtime), bedtime, and total area under the curve (AUC) cortisol. RESULTS: Over 7 years, following multivariable adjustment, (1) a 1% higher prior annual BMI % increase was associated with a 2.9% (95% CI: −5.0%, −0.8%) and 3.0% (95% CI: −4.7%, −1.4%) lower current wake-up and total AUC cortisol, respectively; (2) there was no significant association between baseline cortisol features and subsequent change in BMI and (3) among participants with BMI ≥ 30 kg/m(2), flattening of the late decline slope was associated with increases in BMI (every 1-unit increase late decline slope were associated with a 12.9% increase (95%CI: −1%, 26.8%) in BMI, respectively). CONCLUSIONS: We found a significant association between prior annual BMI % change and cortisol features, but no significant association between baseline cortisol features and subsequent change in BMI. In participants with obesity increases in BMI were associated with less pronounced declined. Collectively, our results suggest that greater adiposity may lead to a blunted diurnal cortisol profile