The effect of increased fruit and vegetable consumption on blood pressure and lipids: a pooled analysis of six randomised controlled fruit and vegetable intervention trials.

BACKGROUND: Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. OBJECTIVE: To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. DESIGN: Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. RESULTS: The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). CONCLUSION: Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.

Barriers and enablers to medication adherence in glaucoma: A systematic review of modifiable factors using the Theoretical Domains Framework.

PURPOSE: Nonadherence to medication reduces treatment effectiveness, and in chronic conditions it can significantly reduce health outcomes. In glaucoma, suboptimal adherence can lead to sight loss, which places a greater financial burden on society and reduces patients' quality of life. Interventions to improve adherence have so far had limited success and lack robust theoretical underpinnings. A better understanding of the determinants of medication adherence behaviour is needed in order to develop interventions that can target these factors more effectively. This systematic review aims to identify modifiable barriers and enablers to glaucoma medication adherence and identify factors most likely to influence adherence behaviour. RECENT FINDINGS: We searched CINAHL, MEDLINE, PsycINFO, EMBASE, the Cochrane Library and sources of grey literature up to August 2022 for studies reporting determinants of glaucoma medication adherence. Data describing modifiable barriers/enablers to adherence were extracted and analysed using the Theoretical Domains Framework (TDF), a behavioural framework consisting of 14 domains representing theoretical factors that most likely influence behaviour. Data were deductively coded into one of the TDF domains and inductively analysed to generate themes. Key behavioural domains influencing medication adherence were identified by frequency of study coding, level of elaboration and expressed importance. Eighty-three studies were included in the final synthesis. Four key domains influencing glaucoma medication adherence were identified: 'Environmental Context and Resources', 'Knowledge', 'Skills' and 'Memory, Attention and decision processes'. Frequently reported barriers included complex eyedrop regimens, lack of patient understanding of their condition, forgetfulness and difficulties administering eyedrops. Whereas simplified treatments, knowledgeable educated patients and good patient-practitioner relationships were enablers to adherence. SUMMARY: We identified multiple barriers and enablers affecting glaucoma medication adherence. Four theoretical domains were found to be key in influencing adherence behaviour. These findings can be used to underpin the development of behaviour change interventions that aim to improve medication adherence.

The transition zone in Hirschsprung's bowel contains abnormal hybrid ganglia with characteristics of extrinsic nerves.

The aganglionic bowel in short-segment Hirschsprung's disease is characterized both by the absence of enteric ganglia and the presence of extrinsic thickened nerve bundles (TNBs). The relationship between the TNBs and the loss of enteric ganglia is unknown. Previous studies have described decreasing numbers of ganglia with increasing density of TNBs within the transition zone (TZ) between ganglionic and aganglionic gut, and there is some evidence of spatial contact between them in this region. To determine the cellular interactions involved, we have analysed the expression of perineurial markers of TNBs and enteric ganglionic markers for both neural cells and their ensheathing telocytes across four cranio-caudal segments consisting of most proximal ganglionic to most distal aganglionic from pull-through resected colon. We show that in the TZ, enteric ganglia are abnormal, being surrounded by perineurium cells characteristic of TNBs. Furthermore, short processes of ganglionic neurons extend caudally towards the aganglionic region, where telocytes in the TNB are located between the perineurium and nerve fibres into which they project telopodes. Thus, enteric ganglia within the TZ have abnormal structural characteristics, the cellular relationships of which are shared by the TNBs. These findings will help towards elucidation of the cellular mechanisms involved in the aetiology of Hirschsprung's disease.

Operation early-bird: Investigating altered light exposure in military barracks on sleep and performance-a placebo-controlled study.

The manipulation of light exposure in the evening has been shown to modulate sleep, and may be beneficial in a military setting where sleep is reported to be problematic. This study investigated the efficacy of low-temperature lighting on objective sleep measures and physical performance in military trainees. Sixty-four officer-trainees (52 male/12 female, mean ± SD age: 25 ± 5 years) wore wrist-actigraphs for 6 weeks during military training to quantify sleep metrics. Trainee 2.4-km run time and upper-body muscular-endurance were assessed before and after the training course. Participants were randomly assigned to either: low-temperature lighting (LOW, n = 19), standard-temperature lighting with a placebo "sleep-enhancing" device (PLA, n = 17), or standard-temperature lighting (CON, n = 28) groups in their military barracks for the duration of the course. Repeated-measures ANOVAs were run to identify significant differences with post hoc analyses and effect size calculations performed where indicated. No significant interaction effect was observed for the sleep metrics; however, there was a significant effect of time for average sleep duration, and small benefits of LOW when compared with CON (d = 0.41-0.44). A significant interaction was observed for the 2.4-km run, with the improvement in LOW (Δ92.3 s) associated with a large improvement when compared with CON (Δ35.9 s; p = 0.003; d = 0.95 ± 0.60), but not PLA (Δ68.6 s). Similarly, curl-up improvement resulted in a moderate effect in favour of LOW (Δ14 repetitions) compared with CON (Δ6; p = 0.063; d = 0.68 ± 0.72). Chronic exposure to low-temperature lighting was associated with benefits to aerobic fitness across a 6-week training period, with minimal effects on sleep measures.

Worsening vision at age 4-5 in England post-COVID: Evidence from a large database of vision screening data.

PURPOSE: Myopia prevalence has increased in the UK at age 10-16y, but little is known about younger children. We hypothesise that if the 'myopia epidemic' is affecting young children, then there will be increasing rates of bilateral reduced unaided vision (V) at vision screenings of children 4-5 years of age. METHODS: Retrospective anonymised data from computerised vision screening at age 4-5 years were analysed from serial cross-sectional data. Refractive error is not assessed in UK vision screening, so vision was investigated. Data were only included from schools that screened every year from 2015/16 to 2021/22. The criterion used was unaided monocular logMAR (automated letter-by-letter scoring) vision >0.20 in both the right and left eyes, so as to maximise the chances of detecting bilateral, moderate myopia rather than amblyopia. RESULTS: Anonymised raw data were obtained for 359,634 screening episodes from 2075 schools. Once schools were excluded where data were not available for every year and data were cleaned, the final database comprised 110,076 episodes. The proportion (percentage and 95% CI) failing the criterion from 2015/16 to 2021/22 were 7.6 (7.2-8.0), 8.5 (8.1-8.9), 7.5 (7.1-7.9), 7.8 (7.4-8.2), 8.7 (8.1-9.2), 8.5 (7.9-9.0) and 9.3 (8.8-9.7), respectively. The slope of the regression line showed a trend for increasing rates of reduced bilateral unaided vision, consistent with increasing frequency of myopia (p = 0.06). A decreasing linear trendline was noted for children 'Under Professional Care'. CONCLUSIONS: For children 4-5 years of age, there were signs of reduced vision over the last 7 years in England. Consideration of the most likely causes support the hypothesis of increasing myopia. The increase in screening failures highlights the importance of eye care in this young population.

Reproductive performance and progeny sex ratio of female Chukar (Alectoris chukar) breeder partridges reared on restricted feeding regimens.

A hypothesis was tested that quantitative feed restriction affects the reproductive performance and offspring sex ratio of female Chukar breeder partridges. A total of 160 2.5-year-old male and female partridges were randomly allotted to four treatment groups. The birds in the control group were fed ad libitum, whereas those in treatments G95 , G90 , and G85 received 26.1, 24.7, and 23.3 g of feed per bird/day to provide 95%, 90%, and 85% of ad libitum feeding level, respectively. The reproductive performances of female Chukar partridges including egg production, egg quality, fertility rate, duration of fertility, hatchability, chick quality, mortality rate, and offspring sex ratio (using a PCR procedure) were investigated. Feed restriction of all levels decreased the body weight and egg production compared with the ad libitum birds; however, restricted feeding had no significant effect on the egg quality traits. Non-significant effects of treatment on fertility and hatchability rate were found. The restricted feeding reduced the duration of fertility. Furthermore, maternal restricted feeding resulted in decreased chick weights. The results of this study showed that embryonic mortality was not affected by the restricted feeding of Chukar breeder partridges. Interestingly, restricted feeding was associated with a decreased proportion of male offspring. Overall, body weight, egg production, duration of fertility, progeny chick weight, and sex ratio were responsive to restricted feeding where their changes make the restricted feeding regimens to not be practically recommended in breeder partridge production. These results are in contrast to the conventional restricted feeding program implemented in broiler breeder industry.

Referrals from community optometrists in England and their replies: A mixed methods study.

PURPOSE: Community optometrists, through routine eye examinations, identify patients with disease or ocular abnormalities requiring referral to the Hospital Eye Service. In many cases no reply to the referral letter is received, resulting in some patients being re-referred unnecessarily, potentially increasing the number of other patients who lose sight whilst on hospital waiting lists. This study investigated, qualitatively and quantitatively, factors influencing optometric referrals and replies. METHODS: The three-phase, sequential mixed methods study started with a literature review and qualitative phase, interviewing stakeholders to identify issues for exploration in subsequent phases. The second, quantitative phase, undertook documentary analysis of 349 patient referral records from three optometric practice modalities (domiciliary, independently owned, and corporate chain) in England. A final qualitative phase obtained views from stakeholders to explore unexplained findings from the first two phases. RESULTS: Phase 1 identified communication, financial, professional and technological issues for further exploration. In Phase 2, the referral rate was 22.2% for domiciliary provider, 2.1% for independent practice and 2.5% for the corporate chain, with the variation most likely explained by patient age and associated ophthalmic disease, illness and disability. The referral reply rate was 5.7% for domiciliary provider, 25.0% for independent practice and 4.9% for the corporate chain. The community optometrist remained unaware of the outcome of their referral in 72.8% of cases. Qualitative analyses indicate the main factors influencing referral reply rates are technology, the General Medical Practitioner, community optometrists' utility to and utility of the National Health Service and patient mobilisation. CONCLUSIONS: The low referral reply rate creates a break in the feedback loop required to raise the standard of referrals and avoid unnecessary re-referral. Of the factors identified that influence referral reply rates, technology is key in view of the increasing use of online referral platforms. Feedback to the referring optometrist should be embedded in such systems.

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Seasonal Influenza Vaccine: Uptake, Attitude, and Knowledge Among Patients Receiving Immunoglobulin Replacement Therapy.

Influenza is a potential cause of severe disease in the immunocompromised. Patients with hypogammaglobulinemia, in spite of adequate replacement therapy, are at risk of significant morbidity and adverse outcomes. A seasonal vaccine is the primary prophylactic countermeasure to limit disease. The aim of this study was to evaluate the attitude, knowledge, and influenza vaccine uptake among Irish patients receiving immunoglobulin replacement therapy (IgRT), as well as uptake in co-habitants. Fifty-seven percent of patients receiving IgRT at a regional immunology referral center completed a questionnaire evaluation. Seventy-six percent of IgRT patients received the influenza vaccine for the 2019 season. Ninety-eight percent recognized that influenza could be prevented with vaccination, and 81% deemed it a safe treatment. Ninety-three percent correctly identified that having a chronic medical condition, independent of age, was an indication for vaccination. Despite excellent compliance and knowledge, many were not aware that vaccination was recommended for co-habitants, and only 24% had full vaccine coverage at home. Those who received advice regarding vaccination of household members had higher rates of uptake at home. This study demonstrates awareness and adherence to seasonal influenza vaccine recommendations among patients receiving IgRT. Over three quarters felt adequately informed, the majority stating physicians as their information source. We identified an easily modifiable knowledge gap regarding vaccination of household members. This data reveals a need to emphasize the importance of vaccination for close contacts of at-risk patients, to maintain optimal immunity and health outcome.

Sleep duration and physical performance during a 6-week military training course.

Sleep is vital in influencing effective training adaptations in the military. This study aimed to assess the relationship between sleep and changes in physical performance over 6 weeks of military training. A total of 22 officer-trainees (age: 24 ± 5 years) from the New Zealand Defence Force were used for this prospective cohort study. Participants wore wrist-actigraphs to monitor sleep, completed subjective wellbeing questionnaires weekly, and were tested for: 2.4-km run time-trial, maximum press-up and curl-ups before and after 6 weeks of training. Average sleep duration was calculated over 36 nights (6:10 ± 0:28 hr:min), and sleep duration at the mid-point (6:15 hr:min) was used to stratify the trainees into two quantile groups (UNDERS: 5:51 ± 0:29 hr:min, n = 11) and (OVERS: 6:27 ± 0:09 hr:min, n = 11). There were no significant group × time interactions for 2.4-km run, press-ups or curl-ups (p > .05); however, small effects were observed in favour of OVERS for 2.4-km run (59.8 versus 44.9 s; d = 0.26) and press-ups (4.7 versus 3.2 reps; d = 0.45). Subjective wellbeing scores resulted in a significant group × time interaction (p < .05), with large effect sizes in favour of the OVERS group for Fatigue in Week 1 (d = 0.90) and Week 3 (d = 0.87), and Soreness in Week 3 (d = 1.09) and Week 4 (d = 0.95). Sleeping more than 6:15 hr:min per night over 6 weeks was associated with small benefits to aspects of physical performance, and moderate to large benefits on subjective wellbeing measures when compared with sleeping < 6:15 hr:min.

Treating secondary antibody deficiency in patients with haematological malignancy: European expert consensus.

OBJECTIVES: Secondary antibody deficiency (SAD), associated with severe, recurrent or persistent infections, is common in patients with haematological malignancies (HM), but unifying guidance on immunoglobulin replacement therapy (IgRT) in these patients is lacking. We aimed to develop consensus statements for the use of IgRT in patients with HM. METHODS: A Delphi exercise was employed to test the level of agreement on statements developed by a Task Force based on available data and their clinical experience. In Round 1, an Expert Panel, comprising specialist EU physicians caring for patients with HM, helped to refine the statements. In Round 2, experts rated their agreement with the statements. In Round 3, experts who had scored their agreement as ≤4 were invited to review their agreement based on the overall feedback. RESULTS: Three definitions and 20 statements were formulated and tested for consensus, covering measurement of IgG levels, initiation and discontinuation of IgRT, dosing, and the use of subcutaneous IgG. Consensus (agreement ≥70% on Likert-type scale) was reached for all three definitions and 18 statements. CONCLUSIONS: Recommendations have been developed with the aim of providing guidance for the use of IgRT to prevent severe, recurrent or persistent infections in patients with HM and SAD.

Referrals from community optometrists to the hospital eye service in England.

PURPOSE: In the UK, most referrals to the hospital eye service (HES) originate from community optometrists (CO). This audit investigates the quality of referrals, replies, and communication between CO and the HES. METHODS: Optometric referrals and replies were extracted from three practices in England. If no reply letter was found, the records were searched at each local HES unit, and additional replies or records copied. De-identified referrals, replies and records were audited by a panel against established standards to evaluate whether the referrals were necessary, accurate and directed to the appropriate professional. The referral rate (RR) and referral reply rate (RRR) were calculated. RESULTS: A total of 459 de-identified referrals were extracted. The RR ranged from 3.6%-8.7%. The proportion of referred patients who were seen in the HES unit was 63%-76%. From the CO perspective, the proportion of referrals for which they received replies ranged from 26%-49%. Adjusting the number of referrals for cases when it would be reasonable to expect an HES reply, RRR becomes 38%-62%. Patients received a copy of the reply in 3%-21% of cases. Referrals were made to the appropriate service in over 95% of cases, were judged necessary in 93%-97% and were accurate in 81%-98% of cases. The referral reply addressed the reason for the referral in 93%-97% and was meaningful in 94%-99% of cases. The most common conditions referred were glaucoma, cataract, anterior segment lesions, and neurological/ocular motor anomalies. The CO/HES dyad (pairing) in the area with the lowest average household income had the highest RR. CONCLUSIONS: In contrast with the Royal College of Ophthalmologists/College of Optometrists joint statement on sharing patient information, CO referrals often do not elicit a reply to the referring CO. Replies from the HES to COs are important for patient care, benefitting patients and clinicians, and minimising unnecessary HES appointments.

Healthy shopper? Blood pressure testing in a shopping centre Pop-Up in England.

BACKGROUND: Improving detection of elevated blood pressure (BP) remains a public health need. We present results from a Pop-Up health check stationed in shopping centres in England. We hypothesise the rate of case detection is related to measurable 'unhealthiness' of the shopping centres. METHODS: A Pop-Up health check was sited in four and three shopping centres sampled from the top ten unhealthiest and top 15 healthiest shopping regions respectively, following a report ranking towns/cities based on their unhealthy and healthy retail outlets. On one day in each shopping centre, people were approached and consented to BP testing. Outcome measure was people flagged with BP ≥ 140/90 mmHg (cases). RESULTS: We detected 45 (22.6%) and 20 (13.1%) cases from testing 199 and 152 adults in the unhealthy and healthy locations respectively (relative risk 1.72; 95% confidence interval: 1.06 to 2.78). A measure of unhealthy retail outlets (e.g. fast-food outlets) within each shopping centre was associated with detection rate (R2 = 0.61; p = 0.04). CONCLUSION: An association exists between cases of suspect hypertension found in a health check Pop-Up and measured 'unhealthiness' of the shopping centre site. Results hint at strategies for public testing of BP, potentially in the context of reducing health inequalities.

The relationship between unwarranted variation in optometric referrals and time since qualification.

PURPOSE: To investigate variation in optometric referral decision-making and the influence of experience and continuing education and training (CET). METHODS: To gain insight into unwarranted variation in referral activity in the United Kingdom (UK): (1) triage data were audited to investigate source of referral, provisional diagnosis, and outcome; (2) an online system was developed to present two sets of 10 vignettes, designed to avoid prompting answers. Participating optometrists completed 10 pre-CET vignettes, recording their tests and management decisions. The main group of participants chose whatever CET they wished over a 6-month period and then completed another 10 post-CET vignettes. A second group of newly-qualified optometrists completed the vignettes before and after a CET course intervention, followed by a third group of pre-registered optometrists with an intervention of 6-months experience of their pre-registration year. RESULTS: The audit identified 1951 optometric referrals and 158 optometrists (211 referrals were from general medical practitioners), with 122 of the 158 optometrists making fewer than ten referrals. Two newly-qualified optometrists generated 12.5% of the total referrals in the audit (N = 2162). Many suspect glaucoma referrals were based on a single suspect measurement resulting in a high discharge rate after community review, as did referrals for certain fundus-related appearances for which no treatment was indicated. The intervention of gaining CET points appeared to have no significant impact (p = 0.37) on referral decision-making, although this part of the study was underpowered. Self-selection bias was confirmed in the main group. When the main group and newly-qualified practitioners were compared, the number of referrals was negatively associated with time since qualification (p = 0.005). When all 20 referral decisions were compared, all optometrists referring more than 10 vignette patients came from a group of newly-qualified practitioners up to 2 years post-qualification. Pre-registered optometrists generally referred more appropriately than newly-qualified. Upon qualification, there was a significant increase in the number of sight tests undertaken per day (p = <0.0005). CONCLUSIONS: Gaining CET points alone is unlikely to significantly improve referral decision-making. Mentoring and targeted CET for the newly-qualified up to 2 years post-qualification should be considered. Ophthalmology replies to the referring newly-qualified optometrist are vital for moderating future referrals and developing clinical confidence.

Chronic lung disease in common variable immune deficiency (CVID): A pathophysiological role for microbial and non-B cell immune factors.

One of the most common and most severe forms of primary antibody deficiency encountered in the clinical setting is a heterogeneous group of syndromes termed common variable immune deficiency (CVID). This disorder is characterized by reduced immunoglobulin production and increased susceptibility to infection, particularly of the respiratory tract. Infection and subsequent immunological/inflammatory processes may contribute to the development of pulmonary complications such as bronchiectasis and interstitial lung disease. Immunoglobulin replacement and/or antibiotic therapy, to prevent infection, are routinely prescribed treatments. However, chronic lung disease, the major cause of morbidity and mortality in this patient cohort, may still progress. This clinical progression suggests that pathogens recalcitrant to currently prescribed treatments and other immunological defects may be contributing to the development of pulmonary disease. This review describes the potential role of microbiological and non-B cell immunological factors, including T-cells, neutrophils, complement, toll like receptors, and antimicrobial peptides, in the pathogenicity of chronic lung disease in patients with CVID.

X-linked Inhibitor of Apoptosis Complicated by Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) and Granulomatous Hepatitis.

The X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency characterized by Epstein-Barr virus (EBV)-driven hemophagocytic lymphohistiocytosis (HLH), splenomegaly, and colitis. Here, we present, for the first time, granulomatous hepatitis and granulomatous and lymphocytic interstitial lung disease (GLILD) as manifestations of XIAP deficiency. We report successful treatment of GLILD in XIAP deficiency with rituximab and azathioprine and discuss the role of XIAP deficiency in immune dysregulation.

Effectiveness of UK optometric enhanced eye care services: a realist review of the literature.

PURPOSE: UK demographic and legislative changes combined with increasing burdens on National Health Service manpower and budgets have led to extended roles for community optometrists providing locally-commissioned enhanced optometric services (EOS). This realist review's objectives were to develop programme theories that implicitly or explicitly explain quality outcomes for eye care provided by optometrists via EOS and to test these theories by investigating the effectiveness of services for cataract, glaucoma, and primary eye care. METHODS: The review protocol was published on PROSPERO, and RAMESES publication standards were followed. Programme theories were formulated via scoping literature searches and expert consultation. The searching process involved all relevant electronic databases and grey literature, without restrictions on study design. Data synthesis focussed on questioning the integrity of each theory by considering supportive and refuting evidence from the source literature. RESULTS: Good evidence exists for cataract, glaucoma and primary eye care EOS that: with appropriate training, accredited optometrists manage patients commensurate with usual care standards; genuine partnerships can exist between community and hospital providers for cataract and glaucoma EOS; patient satisfaction with all three types of service is high; cost-effectiveness of services is unproven for cataract and primary eye care, while glaucoma EOS cost-effectiveness depends on service type; contextual factors may influence service success. CONCLUSIONS: The EOS reviewed are clinically effective and provide patient satisfaction but limited data is available on cost-effectiveness.