An Online Survey of Family Members' Beliefs and Attitudes About Smoking and Mental Illness.

OBJECTIVE: Family beliefs about smoking and cessation may influence whether individuals with mental illness who smoke use effective cessation treatment. We surveyed family members online regarding beliefs about smoking and cessation among people with mental illness. Method: Two hundred fifty-six family members of individuals with mental illness completed an online survey. Responses were summarized and t tests were used to compare responses based on the family member's smoking status. RESULTS: One-quarter of respondents agreed that people with mental illness must smoke to manage mental health symptoms, nearly half (48%) expressed uncertainty about the whether nicotine replacement therapy is harmful for this population, and 69% believed that family members do not have the skills to help an individual with mental illness quit smoking. CONCLUSIONS: Misconceptions about smoking and mental illness and uncertainty about the safety of cessation treatment may interfere with family support for quitting smoking among people with mental illness.

Intralesional administration of VAX014 facilitates in situ immunization and potentiates immune checkpoint blockade in immunologically cold tumors.

BACKGROUND: Immunologically cold tumors with an 'immune desert' phenotype lack tumor-infiltrating lymphocytes (TILs) and are typically impervious to systemic immune checkpoint blockade (ICB). Intratumoral treatment of tumors with immunomodulatory agents can promote local tumor inflammation leading to improved T cell responses in injected tumors. Addition of systemic ICB increases response frequency and immune-mediated clearance of injected and distal non-injected lesions, and this promising approach is being widely investigated clinically. In this work, we evaluate and characterize the local and systemic antitumor immunotherapeutic activity of VAX014, a novel non-viral targeted oncolytic agent based on recombinant bacterial minicells, following intratumoral administration and in combination with systemic ICB. METHODS: The immunotherapeutic activity of VAX014 following weekly intratumoral administration was investigated in multiple preclinical tumor models with B16F10 murine melanoma serving as the primary model for evaluation of immune desert tumors. Mice bearing a single intradermal tumor were used to evaluate tumor response and overall survival (OS), assess changes in immune cell populations, and explore global changes to immunotranscriptomes of injected tumors. Mice bearing bilateral intradermal tumors were then used to evaluate non-injected tumors for changes in TIL populations and phenotypes, compare immunotranscriptomes across treatment groups, and assess distal non-injected tumor response in the context of monotherapy or in combination with ICB. RESULTS: VAX014 demonstrated strong immune-mediated tumor clearance of injected tumors coinciding with significantly elevated CD8+ TILs and upregulation of multiple immune pathways essential for antitumor immune responses. Modest activity against distal non-injected immune desert tumors was observed despite elevated levels of systemic antitumor lymphocytes. Combination with systemic CTLA-4 blockade improved survival and elevated TILs but did not improve clearance rates of non-injected tumors. Immunotranscriptomes of non-injected tumors from this treatment combination group exhibited upregulation of multiple immune pathways but also identified upregulation of PD-1. Further addition of systemic PD-1 blockade led to rapid clearance of non-injected tumors, enhanced OS, and provided durable protective immunological memory. CONCLUSIONS: Intratumoral administration of VAX014 stimulates local immune activation and robust systemic antitumor lymphocytic responses. Combination with systemic ICB deepens systemic antitumor responses to mediate clearance of injected and distal non-injected tumors.

Body mass index and nutritional intake following Elexacaftor/Tezacaftor/Ivacaftor modulator therapy in adults with cystic fibrosis.

BACKGROUND: Elexacaftor/Tezacaftor/Ivacaftor (ETI) modulator therapy is often associated with increased body mass index (BMI) in people with cystic fibrosis (CF). This is thought to reflect improved clinical stability and increased appetite and nutritional intake. We explored the change in BMI and nutritional intake following ETI modulator therapy in adults with CF. METHODS: Dietary intake, measured with myfood24®, and BMI were collected from adults with CF at baseline and follow-up as part of an observational study. Changes in BMI and nutritional intake in participants who commenced ETI therapy between time points were assessed. To contextualize findings, we also assessed changes in BMI and nutritional intake between study points in a group on no modulators. RESULTS: In the pre and post ETI threapy group (n = 40), BMI significantly increased from 23.0 kg/m2 (IQR 21.4, 25.3) at baseline to 24.6 kg/m2 (IQR 23.0, 26.7) at follow-up (p<0.001), with a median of 68 weeks between time points (range 20-94 weeks) and median duration of ETI therapy was 23 weeks (range 7-72 weeks). There was a significant decrease in energy intake from 2551 kcal/day (IQR 2107, 3115) to 2153 kcal/day (IQR 1648, 2606), p<0.001. In the no modulator group (n = 10), BMI and energy intake did not significantly change between time points (p>0.05), a median of 28 weeks apart (range 20-76 weeks). CONCLUSIONS: These findings tentatively suggest that the increase in BMI with ETI therapy may not simply be attributable to an increase in oral intake. Further exploration into the underlying aetiology of weight gain with ETI therapy is needed.

Pathogenesis, investigation and dietary and medical management of gastroparesis.

Delayed gastric emptying (gastroparesis) is associated with significant morbidity and, occasionally, mortality; clinicians therefore need a high index of suspicion to avoid missing the diagnosis. This review discusses the aetiology, diagnostic criteria and investigations pertinent to gastroparesis, and also critically reviews the evidence for nutritional and medical management strategies. Dietary manipulation plays a key role in management, and simple adjustment to meal routines and diets can lead to an improvement in symptoms, whereas alternative feeding routes play an important role in more severe cases. The role of pharmaceutical intervention is less clear; prokinetics and antiemetics are often prescribed; however, evidence for their efficacy is lacking, whereas gastric electric stimulation has an evolving role in the management of patients with symptoms refractory to medical therapies. The optimal treatment of gastroparesis would be to resolve symptoms and normalise gastric emptying times, and this may be achieved with future treatments that target the underlying pathology. For most patients with mild to moderate disease, dietary intervention plays a central role in the management of gastroparesis.

A dietary survey to determine if patients with coeliac disease are meeting current healthy eating guidelines and how their diet compares to that of the British general population.

OBJECTIVES: To assess the dietary intake of people with coeliac disease (CD) and to determine if they are meeting the current dietary reference values (DRVs). To compare dietary intakes of people with CD to the dietary intake of the general population. The nutritional contribution of gluten-free products (GFPs) and current purchasing trends was also evaluated. SUBJECTS/METHODS: 106 patients were invited to participate via post. Three-day food diary to assess intake and a short simple questionnaire that looked at purchasing trends of GFP. RESULTS: Forty-nine patients returned the food diary and 48 returned the questionnaire. Patients were found to have a low intake of energy, non-starch polysaccharides (NSPs), vitamin D and calcium. They were obtaining a significantly lower proportion of energy from fat and a significantly higher proportion of energy from protein than the DRVs (P<0.05). Intake was comparable to the general population for most nutrients, except they had a significantly greater intake of protein, a lower intake of fat and a significantly lower intake of vitamin D (P<0.05). Specialist GFP, especially those obtained on prescription, were an important source of energy, carbohydrate, NSP, calcium and iron. CONCLUSIONS: Patients with CD are at risk of having an inadequate intake of calcium, NSP and vitamin D. Specialist GFP, which were obtained on prescription, helped patients get a balanced diet and without these patients would be at an increased risk of many deficiencies.

A survey of people with inflammatory bowel disease to investigate their views of food and nutritional issues.

Survey aims were to investigate the dietary concerns, beliefs and opinions of people with inflammatory bowel disease (IBD), and differences between those with Crohn's disease (CD) or ulcerative colitis (UC). A cross-sectional postal questionnaire was sent to people with IBD who were booked into an adult IBD or Gastroenterology clinic over a 6-week period. There were 416 eligible people and 168 (40%) responded. Sixty-four (42%) people indicated that food affects their symptoms a lot or severely. Eighty (51%) respondents indicated that diet was important or extremely important in controlling symptoms. Significantly more people with CD reported meat, fatty foods, chocolate and salad as a trigger than people with UC. Significantly more people with UC reported wheat as a trigger. More people with CD avoided meat and chocolate than UC. This survey highlights the importance of nutrition and diet to people with IBD. Frequent food avoidance was reported. This may impact on nutrition-related health problems.