COVID-19 ethnic inequalities in mental health and multimorbidities: protocol for the COVEIMM study.

PURPOSE: The COVID-19 pandemic may have exacerbated ethnic health inequalities, particularly in people with multiple long-term health conditions, the interplay with mental health is unclear. This study investigates the impact of the pandemic on the association of ethnicity and multimorbidity with mortality/service use among adults, in people living with severe mental illnesses (SMI). METHODS: This study will utilise secondary mental healthcare records via the Clinical Record Interactive Search (CRIS) and nationally representative primary care records through the Clinical Practice Interactive Research Database (CPRD). Quasi-experimental designs will be employed to quantify the impact of COVID-19 on mental health service use and excess mortality by ethnicity, in people living with severe mental health conditions. Up to 50 qualitative interviews will also be conducted, co-produced with peer researchers; findings will be synthesised with quantitative insights to provide in-depth understanding of observed associations. RESULTS: 81,483 people in CRIS with schizophrenia spectrum, bipolar or affective disorder diagnoses, were alive from 1st January 2019. Psychiatric multimorbidities in the CRIS sample were comorbid somatoform disorders (30%), substance use disorders (14%) and personality disorders (12%). In CPRD, of 678,842 individuals with a prior probable diagnosis of COVID-19, 1.1% (N = 7493) had an SMI diagnosis. People in the SMI group were more likely to die (9% versus 2% in the non-SMI sample) and were more likely to have mental and physical multimorbidities. CONCLUSION: The effect of COVID-19 on people from minority ethnic backgrounds with SMI and multimorbidities remains under-studied. The present mixed methods study aims to address this gap.

Trends in the delivery of elective general paediatric surgery.

INTRODUCTION: There has been regular dialogue regarding the importance of developing clinical networks to compensate for the steady decline in general paediatric surgery performed by adult surgeons. Despite this dialogue, there are no contemporary published data to quantify the issue. This report documents patterns in delivery of general paediatric surgery in England and shows what is being performed where and by whom. MATERIALS AND METHODS: Using the Surgical Workload Outcome Database, we compared hospital-level data between 2009 and 2017. Inclusion criteria were children under 18 years admitted to NHS hospitals in England for elective general paediatric surgery. Data were analysed with an online statistical package performing paired t-tests. RESULTS: There was no real change in the overall number of elective general paediatric surgical marker cases, but the type mix has changed. The number of marker cases performed by adult surgeons fell by 34% (4699 vs 3090 p < 0.05). The number of marker cases performed by specialist paediatric surgeons increased by 21% (8184 vs 9862 p < 0.05). This increase in workload occurred in both tertiary (21% increase) and peripheral (18% increase) centres. When analysing data by operation type it was apparent that 78% of the increased workload was attributable to an increase in orchidopexy rate. CONCLUSION: Best practice is to treat children close to home by staff with the right skills. This study shows significant shifts in the general paediatric surgical workload. It is important to monitor these trends for successful succession planning as well as configuration of services.

Do animal exhibitors support and follow recommendations to prevent transmission of variant influenza at agricultural fairs? A survey of animal exhibitor households after a variant influenza virus outbreak in Michigan.

Influenza A viruses circulate in swine and can spread rapidly among swine when housed in close proximity, such as at agricultural fairs. Youth who have close and prolonged contact with influenza-infected swine at agricultural fairs may be at increased risk of acquiring influenza virus infection from swine. Animal and human health officials have issued written measures to minimize influenza transmission at agricultural exhibitions; however, there is little information on the knowledge, attitudes, and practice (KAP) of these measures among animal exhibitors. After an August 2016 outbreak of influenza A(H3N2) variant ("H3N2v") virus infections (i.e., humans infected with swine influenza viruses) in Michigan, we surveyed households of animal exhibitors at eight fairs (including one with known H3N2v infections) to assess their KAP related to variant virus infections and their support for prevention measures. Among 170 households interviewed, most (90%, 151/167) perceived their risk of acquiring influenza from swine to be low or very low. Animal exhibitor households reported high levels of behaviours that put them at increased risk of variant influenza virus infections, including eating or drinking in swine barns (43%, 66/154) and hugging, kissing or snuggling with swine at agricultural fairs (31%, 48/157). Among several recommendations, including limiting the duration of swine exhibits and restricting eating and drinking in the animal barns, the only recommendation supported by a majority of households was the presence of prominent hand-washing stations with a person to monitor hand-washing behaviour (76%, 129/170). This is a unique study of KAP among animal exhibitors and highlights that animal exhibitor households engage in behaviours that could increase their risk of variant virus infections and have low support for currently recommended measures to minimize infection transmission. Further efforts are needed to understand the lack of support for recommended measures and to encourage healthy behaviours at fairs.

Cryopreserved human umbilical cord patch for in-utero spina bifida repair.

OBJECTIVE: To identify a patch system to repair surgically created spina bifida in a sheep model for its efficacy in healing the skin defect, protecting the underlying spinal cord and reducing the Chiari II malformation. METHODS: Spina bifida was created surgically in 16 fetuses from eight timed-pregnant sheep at gestational age of 75 days. Two fetuses did not survive the procedure. Repeat hysterotomy was performed at 95 days' gestation to cover the defect with either biocellulose film with underwater adhesive (BCF-adhesive) (n = 7) or human umbilical cord with suture (HUC-suture) (n = 7). Three fetuses without formation of the defect served as reference controls. The skin healing was examined by direct visualization after a planned Cesarean section at term, followed by histological analysis using hematoxylin and eosin and Masson's trichrome stains. Mid-sagittal sections of the fetal cranium and upper cervical spine were analyzed by a pediatric neuroradiologist who was blinded to the type of patch received. RESULTS: Three fetuses that received the BCF-adhesive and six fetuses that received the HUC-suture survived to term for final analysis. As a result of dislodgment of the BCF-adhesive, all spina bifida defects repaired using BCF-adhesive were not healed and showed exposed spinal cord with leakage of cerebrospinal fluid. In contrast, all spinal defects repaired by HUC-suture were healed with complete regrowth of epidermal, dermal and subdermal tissue components, with no exposed spinal cord. The maximal skin wound width was 21 ± 3.6 mm in the BCF-adhesive group but 3 ± 0.8 mm in the HUC-suture group (P < 0.001). The spinal cord area (P = 0.001) and the number of anterior horn cells (P = 0.03) was preserved to a greater degree in the HUC-suture group than in the BCF-adhesive group, whilst psammoma bodies, signifying neuronal degeneration, were only observed in the BCF-adhesive group. Anatomic changes, indicative of Chiari II malformation, were seen in all three fetuses of the BCF-adhesive group but in none of the HUC-suture group (P < 0.01). CONCLUSION: Cryopreserved umbilical cord graft is a promising regenerative patch for intrauterine repair of spina bifida.

Cryopreserved human amniotic membrane and a bioinspired underwater adhesive to seal and promote healing of iatrogenic fetal membrane defect sites.

INTRODUCTION: We investigated the ability of cryopreserved human amniotic membrane (hAM) scaffold sealed with an underwater adhesive, bio-inspired by marine sandcastle worms to promote healing of iatrogenic fetal membrane defects in a pregnant swine model. METHODS: Twelve Yucatan miniature pigs underwent laparotomy under general anesthesia at 70 days gestation (term = 114 days). The gestational sacs were assigned to uninstrumented (n = 24) and instrumented with 12 Fr trocar, which was further randomized into four different arms-no hAM patch, (n = 22), hAM patch secured with suture (n = 16), hAM patch with no suture (n = 14), and hAM patch secured with adhesive (n = 9). The animals were euthanized 20 days after the procedure. Gross and histological examination of the entry site was performed for fetal membrane healing. RESULTS: There were no differences in fetal survival, amniotic fluid levels, or dye-leakage from the amniotic cavity between the groups. The fetal membranes spontaneously healed in instrumented sacs without hAM patches. In sacs with hAM patches secured with sutures, the patch was incorporated into the swine fetal membranes. In sacs with hAM patches without sutures, 100% of the patches were displaced from the defect site, whereas in sacs with hAM patches secured with adhesive 55% of the patches remained in place and showed complete healing (p = 0.04). DISCUSSION: In contrast to humans, swine fetal membranes heal spontaneously after an iatrogenic injury and thus not an adequate model. hAM patches became incorporated into the defect site by cellular ingrowth from the fetal membranes. The bioinspired adhesive adhered the hAM patches within the defect site.

Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Study cohort.

OBJECTIVE: To ascertain whether objectively measured obstructive sleep apnea (OSA) independently increases the risk of all cause death, cardiovascular disease (CVD), coronary heart disease (CHD), stroke or cancer. DESIGN: Community-based cohort. SETTING AND PARTICIPANTS: 400 residents of the Western Australian town of Busselton. MEASURES: OSA severity was quantified via the respiratory disturbance index (RDI) as measured by a single night recording in November-December 1990 using the MESAM IV device, along with a range of other risk factors. Follow-up for deaths and hospitalizations was ascertained via record linkage to the end of 2010. RESULTS: We had follow-up data in 397 people and then removed those with a previous stroke (n = 4) from the mortality/ CVD/CHD/stroke analyses and those with cancer history from the cancer analyses (n = 7). There were 77 deaths, 103 cardiovascular events (31 strokes, 59 CHD) and 125 incident cases of cancer (39 cancer fatalities) during 20 years follow-up. In fully adjusted models, moderate-severe OSA was significantly associated with all-cause mortality (HR = 4.2; 95% CI 1.9, 9.2), cancer mortality (3.4; 1.1, 10.2), incident cancer (2.5; 1.2, 5.0), and stroke (3.7; 1.2, 11.8), but not significantly with CVD (1.9; 0.75, 4.6) or CHD incidence (1.1; 0.24, 4.6). Mild sleep apnea was associated with a halving in mortality (0.5; 0.27, 0.99), but no other outcome, after control for leading risk factors. CONCLUSIONS: Moderate-to-severe sleep apnea is independently associated with a large increased risk of all-cause mortality, incident stroke, and cancer incidence and mortality in this community-based sample.

Evaluating the effectiveness of a smoking warning label on raising patient awareness of smoking and bladder cancer.

PURPOSE: We assessed the knowledge of patients with regard to the association between smoking and bladder cancer, and examined the impact of a novel smoking warning label on raising awareness of this issue. MATERIALS AND METHODS: We conducted a prospective cross-sectional study involving patients who presented to urology and family practice clinics. A questionnaire was used to assess knowledge regarding the association between smoking and various diseases. Participants were also asked to evaluate a novel smoking warning label for bladder cancer. RESULTS: A total of 291 (97%) patients responded to the questionnaire including 143 (95.3%) at urology clinics and 148 (98.7%) at family practice clinics. Overall only 45.2% of respondents were aware of the association between smoking and bladder cancer compared to 97.4% who knew that there was an association between smoking and lung cancer. There were no significant differences in knowledge between those at urology and family practice clinics. After viewing the warning label, 58.1% of respondents stated that it had changed their opinion on smoking and bladder cancer, and 74.8% felt that this label would be an effective tool to raise awareness of the issue. Patients who changed their opinion had statistically significantly less initial knowledge about the association between smoking and bladder cancer (36.7% vs 57.5% for those who did not change their opinion, p <0.001). CONCLUSIONS: Awareness of the link between smoking and bladder cancer remains low. The use of a smoking warning label may help raise awareness of this important public health issue.

Snoring is not associated with all-cause mortality, incident cardiovascular disease, or stroke in the Busselton Health Study.

STUDY OBJECTIVES: To ascertain whether objectively measured snoring increases mortality, cardiovascular disease, or stroke risk over the effects of obstructive sleep apnea and other established risk factors. DESIGN: Community-based cohort. PARTICIPANTS: 400 residents of the Western Australian town of Busselton. INTERVENTIONS: N/A. MEASUREMENTS: Snoring and obstructive sleep apnea were quantified via the percentage of the night spent snoring and the respiratory disturbance index as measured by a single night recording in November-December 1990 by a home sleep apnea monitoring device (MESAM IV), along with a range of cardiovascular disease risk factors. Follow-up for deaths and cardiovascular hospitalizations was ascertained via record linkage until the end of 2007. RESULTS: Our analytical sample of 380 people was made up of the 397 people for whom the authors had follow-up data, minus 17 people who reported a previous stroke or heart attack at baseline (n = 380/400 = 95% of cohort). Snoring was observed for a mean/median of 32.0/27.4% of the night (standard deviation = 23.9%; range = 0-97.2%). There were 46 deaths, 68 cardiovascular events, and 24 strokes during 17 yr of follow-up. Snoring as either a categoric or continuous variable was not significantly associated with death, incident cardiovascular disease, or stroke in both unadjusted Cox regression models and in models that adjusted for obstructive sleep apnea and other risk factors. CONCLUSIONS: No measure of snoring was associated with all-cause mortality, or incident cardiovascular disease or stroke over 17 yr in this community-based sample.

Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study.

BACKGROUND: Previously published cohort studies in clinical populations have suggested that obstructive sleep apnea (OSA) is a risk factor for mortality associated with cardiovascular disease. However, it is unknown whether sleep apnea is an independent risk factor for all-cause mortality in a community-based sample free from clinical referral bias. METHODS: Residents of the Western Australian town of Busselton underwent investigation with a home sleep apnea monitoring device (MESAM IV). OSA was quantified via the respiratory disturbance index (RDI). Mortality status was determined in 397/400 participants (99.3%) after up to 14 years (mean follow-up 13.4 years) by data matching with the Australian National Death Index and the Western Australian Death Register. Univariate analyses and multivariate Cox proportional hazards modelling were used to ascertain the association between sleep apnea and mortality after adjustment for age, gender, body mass index, mean arterial pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes, and medically diagnosed angina in those free from heart attack or stroke at baseline (n = 380). RESULTS: Among the 380 participants, 18 had moderate-severe OSA (RDI > or = 15/hr, 6 deaths) and 77 had mild OSA(RDI 5 to < 15/hr, 5 deaths). Moderate-to-severe OSA was independently associated with greater risk of all-cause mortality (fully adjusted hazard ratio [HR] = 6.24, 95% CL 2.01, 19.39) than non-OSA (n = 285, 22 deaths). Mild OSA (RDI 5 to < 15/hr) was not an independent risk factor for higher mortality (HR = 0.47, 95% CL 0.17, 1.29). CONCLUSIONS: Moderate-to-severe sleep apnea is independently associated with a large increased risk of all-cause mortality in this community-based sample.

The relative kinetics of clotting and lysis provide a biochemical rationale for the correlation between elevated fibrinogen and cardiovascular disease.

BACKGROUND: Elevated plasma fibrinogen is a well known risk factor for cardiovascular disease. The mechanistic rationale for this is not known. OBJECTIVES: These studies were carried out to determine the fibrinogen concentration dependencies of clotting and lysis times and thereby determine whether these times rationalize the correlation between an increased risk of cardiovascular disease and elevated plasma fibrinogen. METHODS: The time courses of clot formation and lysis were measured by turbidity in systems comprising a) fibrinogen, thrombin and plasmin, or b) fibrinogen, thrombin, plasminogen and t-PA, or c) plasma, thrombin and t-PA. From the lysis times, k(cat) and K(m) values for plasmin action on fibrin were determined. RESULTS: The time to clot increased linearly from 2.9 to 5.6 minutes as the fibrinogen concentration increased from 1 to 9 microM and did not increase further as the fibrinogen concentration was raised to 20 microM. In contrast, the clot lysis time increased linearly over the input fibrinogen concentration range of 2 to 20 microM. A similar linear trend was found in the two systems with t-PA and plasminogen. Apparent K(m) and k(cat) values for plasmin were 1.1 +/- 0.6 microM and 28 +/- 2 min(-1), respectively. K(m) values for plasmin in experiments initiated with t-PA and plasminogen were 1.6 +/- 0.2 microM in the purified system and 2.1 +/- 0.9 microM in plasma. CONCLUSION: As the concentration of fibrinogen increases, especially above physiologic level, the balance between fibrinolysis and clotting shifts toward the latter, providing a rationale for the increased risk of cardiovascular disease associated with elevated fibrinogen.

Treatment of ocular squamous cell carcinomas in cattle with interleukin-2.

In total, 174 bovine ocular squamous cell carcinomas of varying sizes (20 to 2800 mm(2) in area) were treated daily with peritumoural injections of solvent, or solvent containing 5000 U, 20,000 U, 200,000 U, 500,000 U, 1 million U or 2 million U interleukin-2 (IL-2) for 10 days. The tumours were measured and clinically staged before treatment and at one, three, four, nine and 20 months after treatment. After 20 months, 14 per cent of the tumours treated with the solvent had regressed completely, a significantly smaller proportion than the 55 per cent treated with 5000 U IL-2, 52 per cent treated with 20,000 U IL-2, 58 per cent treated with 200,000 U IL-2, 50 per cent treated with 500,000 U IL-2, 69 per cent of tumours treated with 1 million U IL-2, 52 per cent treated with 2 million U IL-2. The tumours on the third eyelid and limbus were the most responsive.

Thoracoscopic repair of diaphragmatic eventration.

We report a 6-month-old child who presented with recurrent chest infections associated with a right diaphragmatic eventration. Failure in conservative management lead to thoracoscopic plication at 17 months of age and discharge on the third postoperative day. At one year followup he is completely free from all symptoms, and his chest x-ray demonstrates a marked improvement in the position of the diaphragm. We recommend thoracoscopy as a viable approach in treating this condition in children.

Laparoscopic versus open donor nephrectomy.

BACKGROUND: As compared with open donor nephrectomy (OpenDN), laparoscopic donor nephrectomy (LapDN) offers donors more rapid recovery and recipients equivalent graft function, but LapDN costs remain greater. This study compared LapDN and OpenDN with cost-utility analysis. METHODS: Utilities were assessed with time trade-off, probabilities derived from systematic review of the literature and the costs derived from 27 OpenDN and 34 LapDN patients treated contemporaneously. A societal perspective was taken. Lost employment costs were included. An incremental cost-effectiveness ratio (ICER) was calculated with best- and worst-case scenarios for confidence intervals. Sensitivity analyses assessed robustness. RESULTS: LapDN costs are lower (11,170.71 dollars vs 12,631.91 dollars), whereas quality of life (QOL) is superior (0.7247 vs 0.6585 quality-adjusted life years [QALY], rendering LapDN a dominant strategy. The model was robust to all variables, and LapDN remained dominant from a payer perspective. In a worst-case scenario, the ICER for LapDN was at most 2,231.61 dollars per QALY. CONCLUSIONS: LapDN offers improved QOL at lower costs, despite the fact that this analysis included patients treated during the learning curve of LapDN at our institution. By potentially increasing organ donor rates, LapDN may be further cost saving by decreasing the number of patients receiving dialysis.

Health-related quality of life after laparoscopic and open nephrectomy.

BACKGROUND: Postoperative recovery often is assessed with parameters (pain and return to work) susceptible to bias. This study sought objectively to compare postoperative health-related quality of life (HRQL) after laparoscopic and open nephrectomy with the Postoperative Recovery (PRS) (a validated questionnaire designed to assess pain), activities of daily living (ADL), and HRQL in postoperative patients. METHODS: Patients undergoing contemporaneous laparoscopic and open nephrectomy received the PRS pre- and postoperatively. The results were analyzed with analysis of covariance (ANCOV) and survival analysis. RESULTS: The 33 open nephrectomy and 38 laparoscopic patients in this study were comparable in age, gender, body mass index (BMI) and employment. Laparoscopic operative time was longer (p = 0.015), and the hospital stay was shorter (p<0.001). Laparoscopic patients had higher HRQL scores from postoperative days 3 to 365 (p<0.001), and they returned to preoperative HRQL faster (p<0.001). CONCLUSIONS: An objective HRQL instrument confirms that laparoscopic nephrectomy patients recover faster and with a higher HRQL than open surgery patients. The PRS can be modified for use after other abdominal procedures, and may prove useful for comparisons of other minimally invasive surgical techniques.

Antioxidant status of young children: response to an antioxidant supplement.

OBJECTIVE: To study oxidative stress indicators in healthy young children and their response to a commercially available fruit- and vegetable-based antioxidant supplement. DESIGN: Healthy children were randomly assigned to a placebo and a supplement (commercial antioxidant supplement produced from dried fruit and vegetable extracts and fortified with antioxidants, resembling a gummy-type candy). The placebo and the supplement were taken in 2 doses per day for 21 days. SUBJECTS: Participants were 39 children (26 boys and 13 girls) aged 5 to 10 years. Research was conducted at Primary Children's Medical Center and the University of Utah, Salt Lake City. MAIN OUTCOME MEASURES: Breath and urine samples were collected on days 1 and 21 and assayed for breath pentane and urine 8-hydroxydeoxyguanosine, malondialdehyde, nitrites, and 8-isoprostane as noninvasive indicators of oxidative stress. Urine oxygen radical absorbance capacity was measured at days 1 and 21 as an indirect indicator of the antioxidant capacity of the body. Three-day food records were collected at the beginning and end of the study to measure intake of dietary fruit; vegetable; and antioxidant vitamins A, C, and E. STATISTICAL ANALYSIS: Descriptive statistics, repeated measures analysis of variance, paired t tests, and Pearson r correlations. RESULTS: Markers of oxidative stress were not significantly different between the placebo and supplement groups at day 1 or day 21. The oxidative stress indicators of the healthy children in this study appear to be similar to those of healthy adults and were not changed by antioxidant supplementation. The diet record analyses indicated that mean fruit and vegetable intakes (2.75 servings/day) were similar to the national average intake for children in the United States. APPLICATIONS/CONCLUSIONS: This research presents original information on the subject of oxidative stress in healthy children. The results of this study may be useful as reference baseline markers to use in conjunction with clinical dietary evaluations and for future research with healthy children and with children in disease states who are subject to elevated levels of oxidative stress.

Hybrid hydrogels cross-linked by genetically engineered coiled-coil block proteins.

Hybrid hydrogels of hydrophilic synthetic polymers cross-linked by protein modules undergo externally triggered volume transitions as a result of protein conformational changes. To investigate the influence of coiled-coil protein structure and stability on hydrogel volume transition, a series of block proteins containing interspersed naturally derived recombinant coiled-coils was synthesized. Proteins were characterized using circular dichroism, size exclusion chromatography, gel electrophoresis, and analytical ultracentrifugation. The block proteins formed self-associating oligomers and displayed thermal unfolding profiles indicative of a hierarchic higher-order structure. Hybrid hydrogels were assembled from an N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer and His-tagged block proteins through metal complexation. A temperature-induced decrease in hydrogel swelling was observed, and the onset temperature of the volume transition corresponded to the onset temperature of protein unfolding. We conclude that stimuli-responsive properties of hybrid hydrogels can be tailored by engineering the structure and properties of protein cross-links.

Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium.

There is an established relationship between the monoaminergic neurotransmitter system and mood disorders. In an attempt to define further the pathophysiology of mood disorders, research is focussing on intracellular second messenger systems, including cyclic adenosine 3',5'-monophosphate (cAMP) and the polyphosphoinositol generated second messengers. The availability of tissue from the Stanley Foundation Neuropathology Consortium has offered us the opportunity to make a number of observations with respect to these second messenger systems in tissue from patients with major depressive disorder and bipolar affective disorder. There is evidence that antidepressants stimulate components of the cAMP pathway in patients with depression while mood stabilizers blunt the same pathway in patients with bipolar disorder. Furthermore, downstream targets of this pathway appear to be altered in patients with mood disorders. The relations between changes in second messenger systems, gene transcription, and clinical effects of current therapeutic regimens has implications for development of novel treatments of mood disorders.