The Impact of SARS-COV-2 on two Colorectal Cancer screening centres.

BowelScreen paused activity in March 2020 to prioritise the response to the COVID-19 pandemic. The aim of this study was to examine the impact of this delay. Cases affected by the pause and subsequently completed were compared to the same period in 2019. Endoscopy and histology data were obtained from the BowelScreen database and patient records. One-hundred and seven colonoscopies were performed during the study period. This compared with 224 colonoscopies during the same period in 2019. Median lead time to colonoscopy in 2020 was 74 days compared to 34 days in 2019. Adenoma detection rate was 59% for both periods. Advanced adenoma and cancer detection rates were similar in both periods. While there was a marked reduction in activity and significant delays for BowelScreen patients during the first wave of the COVID-19 pandemic, this does not appear to have impacted on clinical outcomes for patients who attended for screening colonoscopy.

Paediatric hospital admissions for psychiatric and psychosocial reasons during the first year of the COVID-19 pandemic.

Increases in youth psychiatric presentations to out-patient and emergency department settings during COVID-19 have been reported. This study, using data from five hospitals in Ireland, examines changes in the number and type of paediatric admissions during COVID-19 (March 2020 - February 2021) compared to the previous two years. ICD-10 classification was used to establish admissions with mental, behavioural, neuro-developmental disorders and psychosocial reasons (MBN-PS). Overall hospital admissions fell by 25.3%, while MBN-PS fell by only 2.6%, mostly during an initial lockdown. Admissions for MBN-PS increased in July-August (9.2%), increased further in September-December (28.3%), returning to pre-COVID-19 levels in January-February 2021. Significant increases were observed among youths with anorexia nervosa (47.8%), other eating disorders (42.9%), and admissions for anxiety (29.6%), with these effects relating to females only. Although admissions for self-harm increased (3%) and rates of ASD admissions reduced (17%), these were not statistically significant. The disproportionate increase in admissions for MBN-PS compared to medical admissions suggests an adverse effect of COVID-19 on youth mental health, for females in particular, and supports previous reports of a pandemic specific increase in eating psychopathology. Combined community and acute service delivery and capacity planning are urgently needed given the prior underfunding of services pre-pandemic.

Measurement of Typhi Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency.

Vaccine-specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi® , a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi-centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) calibrated to an affinity-purified Typhi Vi IgG preparation. Intra- and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99-1·00; R2  > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations  > 7·4 U/ml, the concentration range was 7·7-167 U/ml. In antibody-deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post-vaccination was 107 U/ml (range 31-542 U/ml). Eight of eight patients (100%) had post-vaccination concentration increases of at least threefold and six of eight (75%) of at least 10-fold. In an antibody-deficient population (n = 23), only 30% had post-vaccination concentration increases of at least threefold and 10% of at least 10-fold. The antibody responses to Pneumovax II and Typhim Vi® correlated. We conclude that IgG responses to Typhim Vi® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies.

Predictors of vitamin D status in New Zealand preschool children.

Vitamin D deficiency has adverse health effects in young children. Our aims were to determine predictors of vitamin D status and then to use these factors to develop a practical tool to predict low 25(OH)D concentrations in preschool New Zealand children. A cross-sectional sample of 1329 children aged 2 to <5 years were enrolled from throughout New Zealand in late-winter to spring 2012. 25-Hydroxyvitamin D (25(OH)D) was measured on dried blood spot (DBS) samples collected using finger-prick sampling. Caregivers completed a questionnaire. Mean (SD) DBS 25(OH)D concentration was 52(19)nmol/L. 25(OH)D < 25 nmol/L was present in 86(7%), 25(OH)D < 50 nmol/L in 642(48%), 25(OH)D 50- < 75 nmol/L in 541(41%) and 25(OH)D > 75 nmol/L in 146(11%) of children. Factors independently associated with the risk of 25(OH)D < 25 nmol/L were female gender (OR 1.92,95%CI 1.17-3.14), other non-European ethnicities (not including Maori or Pacific) (3.51,1.89-6.50), had olive-dark skin colour (4.52,2.22-9.16), did not take vitamin D supplements (2.56,1.06-6.18), had mothers with less than secondary-school qualifications (5.00,2.44-10.21) and lived in more deprived households (1.27,1.06-1.53). Children who drank toddler milk (vitamin D fortified cow's milk formula marketed to young children) had a zero risk of 25(OH)D < 25 nmol/L. The predictive tool identified children at risk of 25(OH)D < 25 nmol/L with sensitivity 42%, specificity 97% and ROC area-under-curve 0.76(95%CI 0.67-0.86, p < 0.001). Predictors of low vitamin D status were consistent with those identified in previous studies of New Zealand children. The tool had insufficient predictive ability for use in clinical situations, and suggests a need to promote safe, inexpensive testing to determine vitamin D status in preschool children.

Inflammatory status modulates plasma lipid and inflammatory marker responses to kiwifruit consumption in hypercholesterolaemic men.

BACKGROUND AND AIMS: Kiwifruit has the potential to improve markers of metabolic dysfunction, but the response may be influenced by inflammatory state. We aimed to investigate whether inflammatory state would modulate the effect of consuming two green kiwifruit daily on plasma lipids and markers of inflammation. METHODS AND RESULTS: Eighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in, before randomisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet (intervention) or healthy diet alone (control). Anthropometric measures and fasting blood samples (plasma lipids, serum apolipoproteins A1 and B, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α) and IL-10) were taken at baseline, 4 and 8 weeks. Subjects were divided into low and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs-CRP <1 and 1-3 mg/L, respectively). In the medium inflammatory group the kiwifruit intervention resulted in significant improvements in plasma high-density lipoprotein cholesterol (HDL-C) (mean difference 0.08 [95% CI: 0.03, 0.12] mmol/L [P < 0.001]), total cholesterol (TC)/HDL-C ratio (-0.29 [-0.45, -0.14] mmol/L [P = 0.001]), plasma hs-CRP (-22.1 [-33.6, -4.97]% [P = 0.01]) and IL-6 (-43.7 [-63.0, -14.1]% [P = 0.01]) compared to control treatment. No effects were seen in the low inflammatory group. There were significant between inflammation group differences for TC/HDL-C (P = 0.02), triglyceride (TG)/HDL-C (P = 0.05), and plasma IL-6 (P = 0.04). CONCLUSIONS: Inflammatory state modulated responses to the kiwifruit intervention by improving inflammatory markers and lipid profiles in subjects with modestly elevated CRP, suggesting this group may particularly benefit from the regular consumption of green kiwifruit. Registered 16th March 2010, Australian New Zealand Clinical Trials Registry (no. ACTRN12610000213044), www.ANZCTR.org.au.

The association between family dysfunction and admission to an acute mental health inpatient unit: a prospective study.

OBJECTIVES: With the shift from deinstitutionalization to community care in mental health services, relatives of persons with severe and enduring mental illnesses have had to take over the role as primary caregivers. Disturbed family dynamics have been observed within families with an 'ill' member. Although schizophrenia and related mental illnesses are biologically based disorders, environmental stress (including stress within family relationships) plays a major role in the onset and maintenance of symptoms. With this study, we assume that family dynamics play a central role in the course of severe psychiatric illness and hypothesized that dysfunction within family systems is a prognostic indicator of hospitalization in the course of schizophrenia/bipolar and schizoaffective disorders. METHODS: Prospective, observational cohort study evaluating family functioning of 121 patients (schizophrenia/bipolar and schizoaffective disorder) from community at baseline and followed-up over 12-month period after recruitment. Measurements included demographics, diagnosis, Family Assessment Device - General Functioning, Perceived Criticism Scale, Brief Psychiatric Rating Scale, Global Assessment of Functioning and Social Support Questionnaire-6. RESULTS: Significant differences found between patients admitted and not admitted during the 12-month time period for age (p = 0.003), Brief Psychiatric Rating Scale (BPRS; p = 0.026), Family Assessment Device - General Functioning (FAD-GF; p = 0.007) and Social Support Questionnaire total satisfaction level (p = 0.042) at baseline. Bivariate analysis showed that those admitted into hospital were younger with a higher BPRS score, less social satisfaction and disturbed family dynamics. FAD-GF (p = 0.006) and age (p = 0.022) were significant independent predictors for admission. CONCLUSION: This provides further evidence supporting importance of promoting better family functioning through modified family dynamics, integrating and involving family into the care of such patients.

A 2-4 keV multilayer mirrored channel for the NIF Dante system.

During inertial confinement fusion experiments at the National Ignition Facility (NIF), a capsule filled with deuterium and tritium (DT) gas, surrounded by a DT ice layer and a high-density carbon ablator, is driven to the temperature and densities required to initiate fusion. In the indirect method, 2 MJ of NIF laser light heats the inside of a gold hohlraum to a radiation temperature of 300 eV; thermal x rays from the hohlraum interior couple to the capsule and create a central hotspot at tens of millions degrees Kelvin and a density of 100-200 g/cm3. During the laser interaction with the gold wall, m-band x rays are produced at ∼2.5 keV; these can penetrate into the capsule and preheat the ablator and DT fuel. Preheat can impact instability growth rates in the ablation front and at the fuel-ablator interface. Monitoring the hohlraum x-ray spectrum throughout the implosion is, therefore, critical; for this purpose, a Multilayer Mirror (MLM) with flat response in the 2-4 keV range has been installed in the NIF 37° Dante calorimeter. Precision engineering and x-ray calibration of components mean the channel will report 2-4 keV spectral power with an uncertainty of ±8.7%.

Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses.

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263-272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation in four patients carrying HLA-B27. In three of these patients the mutation occurred late, coinciding with disease progression. In another it occurred within 1 yr of infection and was associated with a virus of syncytium-inducing phenotype. In each case, R264K was tightly associated with a leucine to methionine change at residue 268. After the loss of the cytotoxic T lymphocyte (CTL) response to this epitope and in the presence of high viral load, reversion to wild-type sequence was observed. In a fifth patient, a R264G mutation was detected when HIV-1 disease progressed. Its occurrence was associated with a glutamic acid to aspartic acid mutation at residue 260. Phylogenetic analyses indicated that these substitutions emerged under natural selection rather than by genetic drift or linkage. Outgrowth of CTL escape viruses required high viral loads and additional, possibly compensatory, mutations in the gag protein.

HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function.

The use of peptide-human histocompatibility leukocyte antigen (HLA) class I tetrameric complexes to identify antigen-specific CD8(+) T cells has provided a major development in our understanding of their role in controlling viral infections. However, questions remain about the exact function of these cells, particularly in HIV infection. Virus-specific cytotoxic T lymphocytes exert much of their activity by secreting soluble factors such as cytokines and chemokines. We describe here a method that combines the use of tetramers and intracellular staining to examine the functional heterogeneity of antigen-specific CD8(+) T cells ex vivo. After stimulation by specific peptide antigen, secretion of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1beta, and perforin is analyzed by FACS((R)) within the tetramer-positive population in peripheral blood. Using this method, we have assessed the functional phenotype of HIV-specific CD8(+) T cells compared with cytomegalovirus (CMV)-specific CD8(+) T cells in HIV chronic infection. We show that the majority of circulating CD8(+) T cells specific for CMV and HIV antigens are functionally active with regards to the secretion of antiviral cytokines in response to antigen, although a subset of tetramer-staining cells was identified that secretes IFN-gamma and MIP-1beta but not TNF-alpha. However, a striking finding is that HIV-specific CD8(+) T cells express significantly lower levels of perforin than CMV-specific CD8(+) T cells. This lack of perforin is linked with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation, and specific lysis ex vivo is lower for HIV-specific compared with CMV-specific cells from the same donor. Thus, HIV-specific CD8(+) T cells are impaired in cytolytic activity.

Body composition of New Zealand-born term babies differs by ethnicity, gestational age and sex.

BACKGROUND: Body composition provides important information on nutrition and future metabolic risk. New Zealand has a diverse ethnic population for which there are no newborn body composition data. AIM: To determine body composition in a cohort of New Zealand-born term babies. STUDY DESIGN: Observational study. SUBJECTS: Healthy, term infants between 37+0 and 41+6 weeks' gestation in two hospitals in Auckland, New Zealand. OUTCOME MEASURES: Body composition by air displacement plethysmography and anthropometry measured within 5 days of birth. Parent-identified ethnicity was prioritised according to Ministry of Health criteria. Data were analysed using t-test, ANOVA with Tukey post-hoc tests, quantile regression and are mean(SD). RESULTS: 440 babies (54% male) were included. Pacific Island/Maori (PI/M) were heavier at birth than Asian/Middle Eastern/Latin American/African (Asian+) babies (3403(506) vs 3181(485) g, p < .05). PI/M and European (E) babies were longer with larger head and waist circumferences than Asian+ babies (all p < .05). Absolute fat mass (FM) was not different amongst ethnicities (E, 365(156), PI/M, 347(183), Asian+, 357(188) g) but PI/M babies had significantly lower FM% than Asian+ (9.8(4.3) vs 10.9(4.5) %, p < .05). Fat-free mass (FFM) was greater in PI/M (3056(400) g) than E (2952(345) g (p < .05) and both PI/M and E had greater FFM than Asian+ (2824(363) g, p < .05). Early term babies had less FFM than term and late-term babies (2732(370), 3012(352), 3173(302)g, p < .001) respectively. CONCLUSIONS: Asian+ babies were the smallest babies with the least FFM yet had similar FM and the highest FM%, indicative of a thin, fat phenotype from birth.

A randomised controlled trial evaluating an alternative mouse and forearm support on upper body discomfort and musculoskeletal disorders among engineers.

OBJECTIVES: The aim of this intervention study was to determine the effects of an alternative mouse and/or a forearm support board on the change in upper body discomfort scores and the development of incident musculoskeletal disorders. METHODS: This randomised controlled intervention trial followed 206 engineers for one year. Participants were randomised to receive (1) a conventional mouse only, (2) an alternative mouse only, (3) a forearm support board, or (4) an alternative mouse plus forearm support board. Outcome measures included weekly upper body discomfort scores and incident musculoskeletal disorders. RESULTS: During the study, 42 participants were diagnosed with an incident musculoskeletal disorder. The group that received the forearm support board experienced a reduction in their right upper extremity discomfort (beta-coefficient -0.35, 95% CI -0.67 to -0.03) in comparison to those who did not receive a forearm board. The group that received the alternative mouse had a protective, but non-significant (p = 0.20), effect on incident cases of right upper extremity musculoskeletal disorders (HR 0.57, 95% CI 0.24 to 1.34) and a non-significant reduction in neck/shoulder discomfort (beta-coefficient -0.23, 95% CI -0.056 to 0.10) in comparison to those who received a conventional mouse. CONCLUSIONS: In engineers who use a computer for more than 20 h per week, a forearm support board may reduce right upper extremity discomfort attributed to computer use.

Differential effects of high fat diet and diet-induced obesity on skeletal acquisition in female C57BL/6J vs. FVB/NJ Mice.

The effects of obesity on bone metabolism are complex, and may be mediated by consumption of a high fat diet and/or by obesity-induced metabolic dysregulation. To test the hypothesis that both high fat (HF) diet and diet-induced metabolic disease independently decrease skeletal acquisition, we compared effects of HF diet on bone mass and microarchitecture in two mouse strains: diet-induced obesity (DIO)-susceptible C57BL/6J (B6) and DIO-resistant FVB/NJ (FVB). At 3 wks of age we weaned 120 female FVB and B6 mice onto normal (N, 10% Kcal/fat) or HF diet (45% Kcal/fat) and euthanized them at 6, 12 and 20 weeks of age (N = 10/grp). Outcomes included body mass; percent fat and whole-body bone mineral density (WBBMD, g/cm2) via DXA; cortical and trabecular bone architecture at the midshaft and distal femur via µCT; and marrow adiposity via histomorphometry. In FVB HF, body mass, percent body fat, WBBMD and marrow adiposity did not differ vs. N, but trabecular bone mass was lower at 6 wks of age only (p < 0.05), cortical bone geometric properties were lower at 12 wks only, and bone strength was lower at 20 wks of age only in HF vs. N (p < 0.05). In contrast, B6 HF had higher body mass, percent body fat, and leptin vs. N. B6 HF also had higher WBBMD (p < 0.05) at 9 and 12 wks of age but lower distal femur trabecular bone mass at 12 wks of age, and lower body mass-adjusted cortical bone properties at 20 wks of age compared to N (p < 0.05). Marrow adiposity was also markedly higher in B6 HF vs. N. Overall, HF diet negatively affected bone mass in both strains, but was more deleterious to trabecular bone microarchitecture and marrow adiposity in B6 than in FVB mice. These data suggest that in addition to fat consumption itself, the metabolic response to high fat diet independently alters skeletal acquisition in obesity.

A case of empyema necessitatis.

We present a case of empyema necessitatis presenting with an inflammatory cellulitis of the chest wall. Most of the cases previously reported were due to tuberculosis, pneumococcus or actinomycosis, with only a few cases being due to Staphylococcus aureus, as in this case. Early treatment with antibiotics and surgical drainage can prevent further complications.

Elevated BNP with normal systolic function in asymptomatic individuals at-risk for heart failure: a marker of diastolic dysfunction and clinical risk.

BACKGROUND: B-type natriuretic peptide (BNP) is widely accepted in the evaluation of left ventricular systolic dysfunction and heart failure. However, little is known of the implications of elevated BNP levels in individuals with preserved systolic function (PSF). AIMS: To investigate the drivers and clinical implications of elevated BNP levels in asymptomatic individuals with established PSF. METHODS: We enrolled 154 individuals who all underwent physical examination, BNP evaluation and Doppler-echocardiographic studies. They were divided into those above and below the median BNP level (50 pg/ml). RESULTS: Independent predictors of higher BNP were older age, more severe left ventricular hypertrophy (LVH), reduced E/A ratio and ischaemic heart disease. Survival and multivariable analysis demonstrated more death and/or admission in those above the median BNP (HR: 4.79, p=0.007). CONCLUSIONS: Elevated BNP is the strongest, independent predictor of serious adverse cardiovascular outcomes in this population and requires closer clinical follow-up.

Daily leptin blunts marrow fat but does not impact bone mass in calorie-restricted mice.

Starvation induces low bone mass and high bone marrow adiposity in humans, but the underlying mechanisms are poorly understood. The adipokine leptin falls in starvation, suggesting that hypoleptinemia may be a link between negative energy balance, bone marrow fat accumulation, and impaired skeletal acquisition. In that case, treating mice with leptin during caloric restriction (CR) should reduce marrow adipose tissue (MAT) and improve bone mass. To test this hypothesis, female C57Bl/6J mice were fed a 30% CR or normal (N) diet from 5 to 10 weeks of age, with daily injections of vehicle (VEH), 1mg/kg leptin (LEP1), or 2mg/kg leptin (LEP2) (N=6-8/group). Outcomes included body mass, body fat percentage, and whole-body bone mineral density (BMD) via peripheral dual-energy X-ray absorptiometry, cortical and trabecular microarchitecture via microcomputed tomography (µCT), and MAT volume via µCT of osmium tetroxide-stained bones. Overall, CR mice had lower body mass, body fat percentage, BMD, and cortical bone area fraction, but more connected trabeculae, vs N mice (P<0.05 for all). Most significantly, although MAT was elevated in CR vs N overall, leptin treatment blunted MAT formation in CR mice by 50% vs VEH (P<0.05 for both leptin doses). CR LEP2 mice weighed less vs CR VEH mice at 9-10 weeks of age (P<0.05), but leptin treatment did not affect body fat percentage, BMD, or bone microarchitecture within either diet. These data demonstrate that once daily leptin bolus during CR inhibits bone marrow adipose expansion without affecting bone mass acquisition, suggesting that leptin has distinct effects on starvation-induced bone marrow fat formation and skeletal acquisition.

Time to surgical review: an assessment of the traditional model of emergency surgical care.

BACKGROUND: The traditional model for emergency surgical care consists of an on-call team providing service to the emergency department, while simultaneously balancing the demands of elective work. Various newer models, such as the "surgeon of the week" aim to reduce the conflict between elective and emergency duties. Despite the recent focus on newer models, there remains no data on the effectiveness of the traditional model. We aim to assess the efficacy of the traditional model in a large regional hospital. METHODS: A retrospective study between July 2009 and March 2010 was performed. Primarily, we assessed the initial time to surgical consultation after emergency department referral. Secondarily, we evaluated the impact of time periods, days of week, and case-mix etiology on this consultation time. RESULTS: The overall median time to surgical consultation after emergency department referral was 30 min (N = 860, P = 0.709). However, the median time to consultation was 60, 30, and 20 min for daytime, evening and night time, respectively (*P < 0.001). Trauma cases had a median time of 15 min, vascular had 45 min, neoplasm had 120 min, while other categories (upper and lower gastroenterology, and skin related) were 30 min (*P = 0.025). DISCUSSION: Newer models of acute surgical care have desirable outcomes in consultation times. However, regional and economical implications have a substantial impact on which model is feasible at local levels. We demonstrated that the traditional model still remains effective in a large sized tertiary referral unit.

Faecal mycobacteria and their relationship to HIV-related enteritis in Lusaka, Zambia.

The prevalence of infection with mycobacteria, both typical and atypical, is increasing along with prevalence of infection with HIV. Patients with pulmonary tuberculosis (PTB) and patients with chronic diarrhoea are forming a growing proportion of the patient population in hospitals in central Africa. To investigate the possibility that mycobacteria may be responsible for some of the HIV-related enteropathy seen in Lusaka, we studied 89 patients in four different diagnostic groups, clinically, by Mantoux test and by microscopy and culture of stool specimens for mycobacteria. In the HIV-positive group with chronic diarrhoea (n = 31), two patients were found to have mycobacteria on faecal smear and three were culture positive while of the 15 HIV-negative controls, three were smear positive and three were culture positive. Of the 15 patients with proven PTB, three had positive faecal smears but none were culture positive. In the fourth group of 24 patients with suspected PTB, seven were smear positive and five, culture positive. Only in this last group was there some correlation between smear results and culture results. Although this last finding is difficult to explain, it appears that there is no correlation between the symptom of chronic diarrhoea and the presence of mycobacteria in the stool. We conclude that mycobacteria do not play a significant role in the pathogenesis of HIV-related enteropathy in Lusaka.

Cutaneous tuberculosis of the penis and sexual transmission of tuberculosis confirmed by molecular typing.

A case of culture-positive primary cutaneous Mycobacterium tuberculosis infection of the penis was diagnosed in a male patient; 1 year later, endometrial tuberculosis was diagnosed in the patient's wife. These organisms were confirmed to be indistinguishable by use of molecular techniques.