Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.

Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).

These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.

A precision medicine approach to clozapine dosing aims to personalise it in two ways: i) during titration, and ii) for succeeding dose adjustments. This requires valid models of dose/concentration relationships, but cross-sectional models suffer from population-level artefacts and individual problems due to poor adherence or stopping smoking. Longitudinal data sets from two mental health trusts allowed poor adherence and smoking cessation to be identified. We then modelled dose/concentration relationships to construct personalised targets for i) and ii).

Demographics and co-prescribed medication were recorded for 137 patients from Greater Manchester Mental Health (GMMH) Trust who had two or more successive plasma levels and doses from 2016–2018. 412 patients from Pennine Care Foundation Trust (PCFT) who had successive plasma levels and doses from 2009–2023 were also recorded. In each sample, adherent patients (88 from GMMH and 371 from PCFT) were identified after excluding: > two-fold variation between blood samples in clozapine/norclozapine ratios, > two-fold variation in dose/concentration ratios, a clozapine/norclozapine ratio > 3, or a dose/concentration ratio > two standard deviations from the sample mean. Those whose smoking status (smoker vs non-smoker) changed between samples were excluded.

To identify i) titration targets, we used raw data in first samples (checked with logistic regression) to identify dose thresholds which produced most levels above 0.35 μg/ml (therapeutic) and no levels greater than 1 μg/ml (toxic). To model ii) effective dose adjustment, we used the equation Dt = Dc(Ct/Cc) to identify the most effective dose for the second samples. Dt was target dose, Dc current dose, Ct target level (0.45 μg/ml), and Cc current level.

First sample dose/concentration ratio in adherent patients correlated r > 0.75 with second samples’ dose/concentration. >84% of plasma levels were within 20% of the mean across both samples.

1. i. The GMMH dataset titration targets were 325 mg, 300 mg, 225 mg, and 175 mg daily for male smokers, female smokers, male non-smokers, and female non-smokers, respectively. In PCFT, data suggested corresponding targets of 375 mg, 325 mg, 225 mg and 175 mg. Targets avoided toxicity and gave therapeutic levels in > 50% of cases.

2. ii. Target dose, ascertained using the equation, and actual second dose were compared: in adherent cases, toxicity only occurred when actual doses were 1.5-fold greater than target dose, and above target all plasma levels exceeded 0.35 μg/ml in GMMH. PCFT data appeared similar.

Relatively safe and effective titration targets for smokers and non-smokers from both sexes were identified. A simple equation would improve precision and effectiveness of dose adjustment thereafter.

Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.

This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.

Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).

Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.

To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.

Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.

Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).

The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

Diets with a low proportion of energy from protein have shown to cause overconsumption of non-protein energy, known as Protein Leverage. Older adults are susceptible to nutritional inadequacy. The aim was to investigate associations between protein to non-protein ratio (P:NP) and intakes of dietary components and assess the nutritional adequacy of individuals aged 65–75 years from the Nutrition for Healthy Living (NHL) Study.

Cross-sectional. Nutritional intakes from seven-day weighed food records were compared with the Nutrient Reference Values for Australia and New Zealand, Australian Guide to Healthy Eating, Australian Dietary Guidelines and World Health Organisation Free Sugar Guidelines. Associations between P:NP and intakes of dietary components were assessed through linear regression analyses.

NHL Study.

113 participants.

Eighty-eight (59 female and 29 male) with plausible dietary data had a median (interquartile range) age of 69 years (67–71), high education level (86 %) and sources of income apart from the age pension (81 %). Substantial proportions had intakes below recommendations for dairy and alternatives (89 %), wholegrain (89 %) and simultaneously exceeded recommendations for discretionary foods (100 %) and saturated fat (92 %). In adjusted analyses, P:NP (per 1 % increment) was associated with lower intakes of energy, saturated fat, free sugar and discretionary foods and higher intakes of vitamin B12, Zn, meat and alternatives, red meat, poultry and wholegrain % (all P < 0·05).

Higher P:NP was associated with lower intakes of energy, saturated fat, free sugar and discretionary. Our study revealed substantial nutritional inadequacy in this group of higher socio-economic individuals aged 65–75 years.

To describe the incidence of systemic overlap and typical coronavirus disease 2019 (COVID-19) symptoms in healthcare personnel (HCP) following COVID-19 vaccination and association of reported symptoms with diagnosis of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in the context of public health recommendations regarding work exclusion.

This prospective cohort study was conducted between December 16, 2020, and March 14, 2021, with HCP who had received at least 1 dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine.

Large healthcare system in New England.

HCP were prompted to complete a symptom survey for 3 days after each vaccination. Reported symptoms generated automated guidance regarding symptom management, SARS-CoV-2 testing requirements, and work restrictions. Overlap symptoms (ie, fever, fatigue, myalgias, arthralgias, or headache) were categorized as either lower or higher severity. Typical COVID-19 symptoms included sore throat, cough, nasal congestion or rhinorrhea, shortness of breath, ageusia and anosmia.

Among 64,187 HCP, a postvaccination electronic survey had response rates of 83% after dose 1 and 77% after dose 2. Report of ≥3 lower-severity overlap symptoms, ≥1 higher-severity overlap symptoms, or at least 1 typical COVID-19 symptom after dose 1 was associated with increased likelihood of testing positive. HCP with prior COVID-19 infection were significantly more likely to report severe overlap symptoms after dose 1.

Reported overlap symptoms were common; however, only report of ≥3 low-severity overlap symptoms, at least 1 higher-severity overlap symptom, or any typical COVID-19 symptom were associated with infection. Work-related restrictions for overlap symptoms should be reconsidered.

This study aimed to identify a well-fitting and theoretically justified item-level latent factor structure for the Wechsler Memory Scales (WMS)-IV verbal paired associates (VerbalPA) subtest to facilitate the ease and accuracy of score interpretations for patients with lateralized temporal lobe epilepsy (TLE).

Archival data were used from 250 heterogeneous neurosciences patients who were administered the WMS-IV as part of a standard neuropsychological assessment. Three theoretically motivated models for the latent structure of VerbalPA were tested using confirmatory factor analysis. The first model, based on cognitive principles of semantic processing from hub-and-spoke theory, tested whether performance is related to specific semantic features of target words. The second, motivated by the Cattell–Horn–Carroll (CHC) model of cognitive abilities, investigated whether the associative properties of items influence performance. A third, Hybrid model tested whether performance is related to both semantic and associative properties of items. The best-fitting model was tested for diagnostic group effects contrasting the heterogeneous neuroscience patients with subsets of left and right TLE (n = 51, n = 26, respectively) patients.

The Hybrid model was found to have the best fit. Patients with left TLE scored significantly less well than the heterogeneous neurosciences sample on selected semantic factor scores, although the effect size was small.

Future editions of the WMS may consider implementing a semantic scoring structure for the VerbalPA to facilitate test score interpretation. Additionally, these results suggest that principles of hub-and-spoke theory may be integrated into CHC cognitive ability taxonomy.

To assess the contribution of different food groups to total salt purchases and to evaluate the estimated reduction in salt purchases if mandatory maximum salt limits in South African legislation were being complied with.

This study conducted a cross-sectional analysis of purchasing data from Discovery Vitality members. Data were linked to the South African FoodSwitch database to determine the salt content of each food product purchased. Food category and total annual salt purchases were determined by summing salt content (kg) per each unit purchased across a whole year. Reductions in annual salt purchases were estimated by applying legislated maximum limits to product salt content.

South Africa.

The study utilised purchasing data from 344 161 households, members of Discovery Vitality, collected for a whole year between January and December 2018.

Vitality members purchased R12·8 billion worth of food products in 2018, representing 9562 products from which 264 583 kg of salt was purchased. The main contributors to salt purchases were bread and bakery products (23·3 %); meat and meat products (19 %); dairy (12·2 %); sauces, dressings, spreads and dips (11·8 %); and convenience foods (8·7 %). The projected total quantity of salt that would be purchased after implementation of the salt legislation was 250 346 kg, a reduction of 5·4 % from 2018 levels.

A projected reduction in salt purchases of 5·4 % from 2018 levels suggests that meeting the mandatory maximum salt limits in South Africa will make a meaningful contribution to reducing salt purchases.