The UK Soft Drinks Industry Levy (SDIL) (announced in March 2016; implemented in April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order to understand how health policy can become established and resilient to opposition.

Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus.

The United Kingdom Parliament

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Between the announcement (16/03/2016) – royal assent (26/04/2017), two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent – implementation (5/04/2018), one theme was identified 3: The SDIL worked – what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL.

After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal.

Prion disease is a rare, invariably fatal neurodegenerative disease characterized by rapid neuronal degeneration; Mutations to PRNP gene cause genetic prion disease (GPD). In animal models, microglial activation, astrocytosis, and release of neurofilament precede the onset of frank symptoms (Sorce & Nuvolone 2020, Minikel 2020). In humans at risk for GPD, prodromal pathology appears to occur in only a brief window prior to symptom onset (Vallabh et al. 2020, Thompson et al. 2021), but some data suggest that known PRNP mutation carriers may exhibit cognitive abnormalities prior to meeting clinical diagnostic criteria (Mole et al., 2021). We aim to examine pre-symptomatic differences in cognitive processing speed (CPS) and executive function (EF) in PRNP mutation carriers and controls.

Our sample includes two groups from an ongoing observational study on GPD (Vallabh et al., 2020): known PRNP mutation carriers (N = 32, Age M = 45.77, SD = 14.75) and control group of non-carriers with a family history of GPD and healthy controls with no known history (N = 11, Age M = 42.01, SD = 12.43). All participants completed a full cognitive battery at baseline and on an annual basis. We compared first visit cognitive testing measuring CPS and EF using: National Institute of Health (NIH) Toolbox [Pattern Comparison (NIH-PC), Flanker, Dimensional Card Sorting Task (NIH-DCCS)], Trail Making Test (TMT) A and B, and Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test (CWIT).

Independent t-tests and Mann-Whitney U tests compared cognitive test performance between groups. Across all cognitive test measures assessed, none exhibited significant differences between groups after Bonferroni correction for N=10 tests (corrected P > 0.05). Mean scores for mutation carriers were non-significantly lower than controls on TMT-B (Z-score Mdn = .29, SD = 1.33 vs. Z-score Mdn = .96, SD = .97), NIH-PC (Age-corrected Standard Score [ACSS] M = 100.13, SD = 20.76 vs. ACSS score M = 114.82, SD = 14.61) and NIH-Flanker (ACSS score M = 83.58, SD = 9.72 vs. ACSS score M = 90.64, SD = 10.94), and NIH-DCCS (ACSS M = 101.29, SD = 16.37 vs. ACSS score M = 112.00, SD = 16.28) but not for TMT-A or all four conditions of CWIT.

We did not detect any significant cognitive deficits in known PRNP mutation carriers. This is consistent with the lack of prodromal pathological biomarker changes or cognitive changes as reported in Vallabh et al 2020, and with the finding of Mole et al. 2021 that most tests reveal impairment only at a stage where carriers report subjective symptoms. Our results suggest an opportunity for primary prevention to preserve full cognitive health in at-risk individuals. However, small sample size and limited test sensitivity may leave us underpowered to detect subtle deficits. Future research is warranted to further investigate the neuropsychological profile of pre-symptomatic GPD.

Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.

Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.

This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.

This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.

To investigate the potential association between clozapine and antibody deficiency.

Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.

Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31–27.44); IgA, OR = 16.75 (95% CI 2.18–128.60); and IgM, OR = 3.26 (95% CI 1.75–6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).

Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.

S.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.