Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study.

OBJECTIVES: To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination. DESIGN: Test negative case-control study. SETTING: Kaiser Permanente Southern California (KPSC), an integrated healthcare system. PARTICIPANTS: Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021. INTERVENTIONS: Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination. MAIN OUTCOME MEASURES: Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1-odds ratio)×100%. RESULTS: The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta. CONCLUSIONS: Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.

Personalised relaxation practice to improve sleep and functioning in patients with chronic fatigue syndrome and depression: study protocol for a randomised controlled trial.

BACKGROUND: Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) are both debilitating but heterogeneous conditions sharing core features of fatigue, unrefreshing sleep, and impaired functioning. The aetiology of these conditions is not fully understood, and 'best-practice' treatments are only moderately effective in relieving symptoms. Unrecognised individual differences in the response to such treatments are likely to underlie poor treatment outcomes. METHODS/DESIGN: We are undertaking a two-group, parallel, randomised controlled trial (RCT) comparing the effects of a personalised relaxation intervention on sleep quality, daytime symptoms, and functioning in patients with CFS (n = 64) and MDD (n = 64). Following identification of the method that best enhances autonomic responding (such as heart rate variability), participants randomised to the active intervention will practise their recommended method nightly for 4 weeks. All participants will keep a sleep diary and monitor symptoms during the trial period, and they will complete two face-to-face assessments, one at baseline and one at 4 weeks, and a further online assessment to evaluate lasting effects of the intervention at 2 months. Assessments include self-report measures of sleep, wellbeing, and function and monitoring of autonomic responses at rest, in response to the relaxation method and during nocturnal sleep. Treatment outcomes will be analysed using linear mixed modelling. DISCUSSION: This is the first RCT examining the effects of a personalised relaxation intervention, pre-tested to maximise the autonomic relaxation response, in patients with unrefreshing sleep and fatigue attributed to CFS or MDD. Detailed monitoring of sleep quality and symptoms will enable sensitive detection of improvements in the core symptoms of these debilitating conditions. In addition, repeated monitoring of autonomic functioning can elucidate mechanisms underlying potential benefits. The findings have translational potential, informing novel, personalised symptom management techniques for these conditions, with the potential for better clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR), ACTRN12616001671459 . Registered on 5 December 2016.

Zinc Protoporphyrin-to-Heme Ratio and Ferritin as Measures of Iron Sufficiency in the Neonatal Intensive Care Unit.

OBJECTIVES: To evaluate ferritin and zinc protoporphyrin-to-heme (ZnPP/H) ratios as biomarkers of iron status in neonates, determine how specific clinical events affected these measures, and assess how iron status changed during hospitalization. STUDY DESIGN: We performed a retrospective study of all infants with paired ferritin and ZnPP/H measurements between October 2014 and May 2016. Concordance of these measurements, effects of sepsis, red blood cell transfusion, erythropoietin treatment, and iron supplementation were assessed. Iron status was measured over time. RESULTS: A total of 228 patients (mean birth weight 1.3 kg, median gestational age 29 weeks) were evaluated. Mean log ZnPP/H values in infants with and without sepsis were not significantly different (4.98 µmol/mol vs 4.97 µmol/mol, adjusted P = .103), whereas log-transformed ferritin values increased significantly during infection (5.23 ng/mL vs 4.04 ng/mL, adjusted P < .001). Ferritin also increased more significantly than ZnPP/H following red blood cell transfusion (ferritin: mean 5.03 ng/mL vs 4.0 ng/mL, P < .001; ZnPP/H: mean 4.85 µmol/mol vs 4.98 µmol/mol, P < .001). The mean iron supplementations at 30, 60, and 90 days were 5.4, 6.9, and 7.4 mg/kg/day, respectively. Ferritin values decreased with advancing postnatal age (adjusted P < .001), with 66% of ferritin values less than 76 ng/mL. Treatment with erythropoietin increased ZnPP/H, but not ferritin levels. CONCLUSIONS: Ferritin is more significantly affected by inflammatory events such as sepsis and transfusion than ZnPP/H, thus, ZnPP/H may be a more reliable marker of iron status in this population. Infants showed worsening iron sufficiency over time despite supplementation above American Academy of Pediatrics guidelines.

Hand dermatitis: a review of clinical features, therapeutic options, and long-term outcomes.

Hand dermatitis is a common skin condition that may be chronic, debilitating, and costly for patients, insurers, and employers. The epidemiology, clinical features, occupational issues, and long-term outcomes of hand dermatitis are summarized in this review. Therapeutic options are also discussed in detail, focusing on treatment of recalcitrant hand dermatitis.