PROTOCOL: The support needs of families living with parental mental illness: A qualitative systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows: To review existing qualitative research on the experiences of families living with parental mental illness from the perspective of (i) children, (ii) parents who have a mental illness) and (ii) the well parent. To synthesise qualitative evidence on the experience of living with parental mental illness and the experience of and attitude towards services from the perspective of (i) children, (ii) parents who have a mental illness and (ii) the well parent in order to develop the understanding of the needs of families and the implications for service provision.

New psychoactives within polydrug use trajectories-evidence from a mixed-method longitudinal study.

AIMS: To provide public health-related research evidence on types and usage patterns of new psychoactive substances (NPS), developmental pathways into NPS and decision-making factors for, and associated harms of, NPS use. DESIGN: Three-phase mixed-methods design, including a latent class analysis (LCA) of the longitudinal Belfast Youth Development Study (BYDS), a narrative analysis of interviews with NPS users and a three-step approach manual method modelling using regressions to reveal classes of substance use and their associated predictors and outcomes. SETTING: Northern Ireland. PARTICIPANTS: A total of 2039 people who responded to the questions on 'ever use' of the drug variables included at wave 7 (aged 21 years) of the BYDS. Eighty-four narrative interviews with NPS users. MEASUREMENTS: Categories of drug use identified by LCA. Predictors and outcomes included measures of family, partners, peers, substance use, school, delinquency and mental health. FINDINGS: A four-class solution provided the best fit for the data: alcohol; alcohol and tobacco; alcohol, tobacco and cannabis; and polydrug (the latter including NPS). The qualitative analysis yielded a taxonomy that distinguished how NPS operate within a wider range of drug repertoires from experimental to problematic. CONCLUSIONS: In Northern Ireland, new psychoactive substances appear to be a feature of broader polydrug use rather than a standalone class of drug use.

Is a chest radiograph after thoracostomy tube removal necessary? A cost-effective analysis.

BACKGROUND: Following placement of tube thoracostomy (TT) for evacuation of traumatic hemopneumothorax (HPTX), controversy persists over the need for routine post-TT removal chest radiograph (CXR). Current research demonstrates routine CXR may offer no advantage over clinical observation alone while simultaneously increasing hospital resource utilization. As such, we hypothesized that in resolved traumatic HPTXs routine post-TT removal CXR to assess recurrent PTX compared to clinical observation is not cost-effective. METHODS: We performed a decision-analytic model to evaluate the cost-effectiveness of routine CXR compared to clinical observation following TT removal. Our base case was a patient that sustained thoracic trauma with radiographic and clinical resolution of HPTX following TT evacuation. Cost, utility and probability estimates were generated from published literature, with costs represented in 2019 US dollars and utilities in Quality-Adjusted Life Years (QALYs). Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Decision-analytic model identified that clinical observation after TT removal was the dominant strategy with increased benefit at less cost, when compared to routine CXR, with a net cost of $194.92, QALYs of 0.44. In comparison, routine CXR demonstrated an increase of $821.42 in cost with 0.43 QALYs. On probabilistic sensitivity analysis the clinical observation strategy was found cost-effective in 99.5% of 10,000 iterations. CONCLUSION: In trauma patients with clinical and radiographic evidence of a resolved HPTX, the adoption of clinical observation in lieu of post-TT removal CXR is cost-effective. Routine CXR following TT removal accrues more cost without additional benefit. The practice of routinely obtaining a CXR following TT removal should be scrutinized.

School bonding and ethos in trajectories of offending: Results from the Belfast Youth Development Study.

BACKGROUND: Aspects of the school environment, such as school attachment levels, are linked to adolescent offending. Previous research has not clarified whether a school- or individual-level intervention approach to improving pupil school attachment and commitment is most likely to reduce adolescent offending. AIM: The present study assessed the impact of individual- and school-level variables on offending behaviour from ages 14-16 years. SAMPLE: The participants were 4,049 young people from 42 mainstream schools who took part in the Belfast Youth Development Study. METHOD: Multilevel modelling was used to examine the relative influence of individual- and school-level variables on offending behaviour in adolescence. RESULTS: Pupils who had high levels of school commitment and attachment and were involved in fewer fights at age 13 reported lower levels of offending at age 14 years. Differences between schools accounted for 7% of the variation in offending. Lower individual-level commitment was associated with higher initial levels of offending at age 14 if the school-level ethos was of higher commitment. Lack of safety at the school level appeared to be detrimental for young people not exposed to socio-economic deprivation. CONCLUSIONS: Individual-level targeted interventions are likely to be a more cost-effective approach of reducing offending behaviour in adolescence. Additional, albeit smaller, reductions in offending levels could be achieved through school-level interventions in some school types (e.g., deprived areas).

Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation.

Neutrophilic inflammation with prolonged neutrophil survival is common to many inflammatory conditions, including chronic obstructive pulmonary disease (COPD). There are few specific therapies that reverse neutrophilic inflammation, but uncovering mechanisms regulating neutrophil survival is likely to identify novel therapeutic targets. Screening of 367 kinase inhibitors in human neutrophils and a zebrafish tail fin injury model identified ErbBs as common targets of compounds that accelerated inflammation resolution. The ErbB inhibitors gefitinib, CP-724714, erbstatin and tyrphostin AG825 significantly accelerated apoptosis of human neutrophils, including neutrophils from people with COPD. Neutrophil apoptosis was also increased in Tyrphostin AG825 treated-zebrafish in vivo. Tyrphostin AG825 decreased peritoneal inflammation in zymosan-treated mice, and increased lung neutrophil apoptosis and macrophage efferocytosis in a murine acute lung injury model. Tyrphostin AG825 and knockdown of egfra and erbb2 by CRISPR/Cas9 reduced inflammation in zebrafish. Our work shows that inhibitors of ErbB kinases have therapeutic potential in neutrophilic inflammatory disease.

Longitudinal Social Network Analysis of Peer, Family, and School Contextual Influences on Adolescent Drinking Frequency.

PURPOSE: The aim of the study was to identify the mechanisms relating to parental control, adolescent secrecy, and school context that shape patterns of adolescent drinking frequency and appraise the implications for systems-level intervention. METHODS: The Belfast Youth Development Study collected information on friendship networks in schools, alcohol use, and Stattin and Kerr's parental monitoring subscales across 5 years of postprimary school education in annual waves from age 11-15 years. Stochastic Actor-Oriented Models were fitted to 22 schools (N = 3,220) to assess friendship formation and peer influence processes related to drinking frequency and their variation by parental control or child secrecy. Meta-regressions and summary statistic ego-alter selection tables assessed how network and behavior co-evolution varied according to school gender and the proportion of weekly or more frequent drinkers in each school. RESULTS: Adolescents tended to mimic their peers' drinking levels, and frequent drinkers befriended those who drank similarly to them. Those with high parental control were less likely to befriend low-control peers, whereas low-control pupils were more likely to befriend each other. Adolescents with low-control parents nominated fewer friends in schools with higher proportions of drinking frequently. There was a tendency toward befriending highly secretive peers in boys schools only. CONCLUSIONS: Our results suggest that the optimal strategy for selecting seed nodes in a diffusion of innovations network intervention may vary according to school context, and that targeting family interventions around parent characteristics may modify the wider school network, potentially augmenting network intervention processes.

Postoperative Pain and Opioid Use After Thyroid and Parathyroid Surgery-A Pilot, Prospective SMS-Based Survey.

BACKGROUND: New persistent opioid use has been identified following minor surgical procedures and may contribute to the national opioid epidemic. Prescription patterns vary and we have limited data on patient pain experiences in the outpatient setting. We devised a novel short messaging service survey to record pain scores and opioid use following outpatient thyroid or parathyroid surgery. MATERIALS AND METHODS: Automated short messaging service was sent daily starting the evening of the operation until postoperative day (POD) 10. Pain was assessed on a 0-10 numeric pain rating scale and opioid use over the prior 24 h was queried. RESULTS: A total of 1264 survey questions were sent with overall response rate of 84.3%. Fifty-three of 58 patients had a response rate >50% and were included in the final analysis. Average pain score was highest on POD1 at 3.2. Overall, 42.5% of patients utilized opioids on POD0, 55.6% on POD1, and steadily decreased to 7% by POD10. Overall, 34% of patients did not utilize any opioids postoperatively. Scaled total pain scores were higher in patients with thyroid surgery (23.5 versus 12.1, P = 0.02) and lower in those who reported alcohol use (14.9 versus 31.6, P < 0.02). Scaled total opioid days were lower in those aged >60 (1.5 versus 3.6, P < 0.01) and higher in those with active tobacco use (4.5 versus 2.3, P = 0.04). Pain scores correlated weakly with total opioid days (r = 0.32). CONCLUSIONS: We demonstrate a novel approach of obtaining patient reported daily, prospective pain scores. This may help us understand patient pain and opioid use in the acute postoperative period especially following outpatient surgery.

The longitudinal relationship of alcohol problems and depressive symptoms and the impact of externalising symptoms: findings from the Belfast Youth Developmental Study.

PURPOSE: The aim of the present study was to contribute to the inconsistent literature on the comorbid relationship of alcohol problems and depressive symptoms from late adolescent to emerging adulthood by accounting for their trajectories and their conjoint relationship while controlling for the influence of externalising symptoms. METHODS: We utilised data, from a longitudinal school cohort from Northern Ireland (Belfast Youth Developmental Study), over three time points where the participants were 16, 17 and 21 years of age. A total of 3118 participants were included, 1713 females and 1405 males. Second-order latent growth models were applied to examine growth trajectories. Parallel process growth models were used to assess whether growth trajectories of the symptoms were associated. Externalising symptoms were subsequently added as a covariate. RESULTS: Alcohol problems among males significantly increased over time but decreased in females. Depressive symptoms initially increased then decreased in both genders. Results indicated associations of the alcohol problems and depression, both initially and with time. Accounting for externalising symptoms only somewhat diminished this effect in males but not in females. An increase of initial levels of depression was associated with a decrease in alcohol problems over time. This association was only true among females. After controlling for externalising symptoms, the relationship was no longer observed. CONCLUSIONS: The present study provides further evidence of a significant relationship of alcohol problems and depression in adolescents and further supports a small literature indicating that depression may have protective effects of alcohol problems. Finally, the study shows the importance of accounting for externalising symptoms.

Trends in Adrenal Surgery-The Changing Nature of Tumors and Patients.

BACKGROUND: The volume of adrenal surgery is increasing. There has been a concern that the widespread use of axial imaging and minimally invasive approaches has led to changing indications for adrenalectomy. We reviewed trends in adrenal surgery at a single academic institution. MATERIALS AND METHODS: This was a retrospective analysis of all patients who underwent adrenal surgery between 1993 and 2018 by the endocrine surgery service. Patient demographics, diagnosis, operative details, and perioperative complications were evaluated. Trend analysis was performed across ordered year groups (<2000, 2000-2004, 2005-2009, 2010-2014, and 2015-2018). RESULTS: We identified 732 patients who underwent 751 adrenal operations. Fifty-seven percent of the patients were women, and the median age was 51 y (range: 5-88). There was an increase in the number of procedures performed (P < 0.01, trend analysis). Over time, there was a higher proportion of patients with hypertension (54.7% [<2000] versus 73.6% [>2015], P < 0.01), diabetes (4.7% versus 22.1%, P = 0.01), and classified as American Society of Anesthesiology class 3/4 (15.7% versus 45.7%, P < 0.01). More patients had their adrenal lesion found incidentally (19.4% versus 39.3%, P < 0.01), and there was a larger proportion of pheochromocytomas (25% versus 36.4%, P < 0.01) and fewer nonfunctioning adenomas (7.4% versus 4.3%, P = 0.03). Median tumor size decreased from 3.5 cm to 2.9 cm (P = 0.03). Complication rates increased over time (8.3% versus 15%, P < 0.01), but the overall 30-d mortality remained low (0.3%). CONCLUSIONS: Adrenal surgery is being performed more commonly with an increasing number of incidentalomas and pheochromocytomas. Our patients have higher comorbidities with increase in complication rates over time, although perioperative mortality remains low. This highlights the importance of a thorough preoperative evaluation to identify suitable patients who may benefit from adrenalectomy.

Treatment of Primary Aldosteronism Reduces the Probability of Obstructive Sleep Apnea.

BACKGROUND: Aldosterone excess is hypothesized to worsen obstructive sleep apnea (OSA) symptoms by promoting peripharyngeal edema. However, the extent to which primary aldosteronism (PA), hypertension, and body mass index (BMI) influence OSA pathogenesis remains unclear. METHODS: We conducted a cross-sectional study of PA patients from our endocrine database to retrospectively evaluate OSA probability before and after adrenalectomy or medical management of PA. A control group of patients undergoing adrenalectomy for nonfunctioning benign adrenal masses was also evaluated. We categorized patients as high or low OSA probability after evaluation with the Berlin Questionnaire, a validated 10-question survey that explores sleep, fatigue, hypertension, and BMI. RESULTS: We interviewed 91 patients (83 PA patients and eight control patients). Median follow-up time was 2.6 y. The proportion of high OSA probability in all PA patients decreased from 64% to 35% after treatment for PA (mean Berlin score 1.64 versus 1.35, P < 0.001). This decline correlated with improvements in hypertension (P < 0.001) and fatigue symptoms (P = 0.03). Both surgical (n = 48; 1.69 versus 1.33, P < 0.001) and medical (n = 35; 1.57 versus 1.37, P = 0.03) treatment groups demonstrated reduced OSA probability. BMI remained unchanged after PA treatment (29.1 versus 28.6, P = nonsignificant), and the impact of treatment on OSA probability was independent of BMI. The control surgical group showed no change in OSA probability after adrenalectomy (1.25 versus 1.25, P = nonsignificant). CONCLUSIONS: Both surgical and medical treatments of PA reduce sleep apnea probability independent of BMI and are associated with improvements in hypertension and fatigue. Improved screening for PA could reduce OSA burden.

Interventions and Innovation to Prevent Surgical Site Infection in Colorectal Surgery: A Cost-Effectiveness Analysis.

BACKGROUND: Surgical site infection (SSI), particularly in colorectal surgery, continues to cause substantial morbidity and cost. Both process- and product-based interventions have been proposed and implemented. No cost-effectiveness analysis of such interventions has been published. MATERIALS AND METHODS: This study used a decision-analytic model to evaluate the cost-effectiveness of strategies for the prevention of SSI. Costs, utilities, and transition probabilities were obtained from literature review. We used a lifetime time horizon, captured with explicit event modeling for a year plus quantification of enduring health outcomes. We represented costs in 2017 US dollars and health effects in Quality-Adjusted Life Years (QALYs). Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Both process- and device-based strategies were dominant-clinically superior and also less expensive-compared with no intervention. Two types of double-ring wound protection barrier devices with greater anticontamination functionality were found to be both clinically superior and cost-saving compared with bundled process measures and simpler single-ring devices. Gains in QALYs were 230 per 1000 patients, and cost savings were 2.2 million dollars per 1000 patients, driven primarily by the high cost of SSI. CONCLUSIONS: We found process-based interventions and wound protection devices to be superior to no intervention in the prevention of SSI. Double ring devices offered a distinct advantage over simpler devices, with small reductions in SSI risk leading to substantial cost savings. Further innovation in device-based wound protection devices may offer increased prevention of SSI at acceptable cost-effectiveness levels.

Risk Factors Associated With Perioperative Complications and Prolonged Length of Stay After Laparoscopic Adrenalectomy.

Importance: Laparoscopic adrenalectomy is the gold standard for most adrenal disorders and its frequency in the United States is increasing. While national and administrative databases can adjust for patient factors, comorbidities, and institutional variations, granular disease-specific data that may significantly influence the incidence of perioperative complications and length of stay (LOS) are lacking. Objective: To investigate factors associated with perioperative complications and LOS after laparoscopic adrenalectomy. Design, Setting, and Participants: This cohort study was carried out at a single academic medical center, with all patients who underwent laparoscopic adrenalectomy between 1993 and 2017 by the endocrine surgery department. Multivariable linear and logistic regression were used to obtain adjusted odds ratios (ORs). Main Outcomes and Measures: The primary outcome was perioperative complications with a Dindo-Clavien grade of 2 or more. The secondary outcome was prolonged length of stay, defined as a stay longer than the 75th percentile of the overall cohort. Results: We identified 640 patients who underwent 653 laparoscopic adrenalectomies, of whom 370 (56.7%) were female. The median age was 51 (range, 5-88) years. A total of 76 complications with a Dindo-Clavien grade of 2 or more occurred in 55 patients (8.4%), with postoperative mortality in 2 patients (0.3%). The median hospital length of stay was 1 day (range, 0-32 days). Factors independently associated with increased complications were American Society of Anesthesiologists class 3 or 4 (OR, 2.78 [95% CI, 1.39-5.55]; P < .01), diabetes (OR, 2.39 [95% CI, 1.14-5.01]; P = .02), conversion to hand-assisted or open surgery (OR, 5.32 [95% CI, 1.84-15.41]; P < .01), a diagnosis of pheochromocytoma (OR, 4.31 [95% CI, 1.43-13.05]; P = .01), and a tumor size of 6 cm or greater (OR, 2.47 [95% CI, 1.05-5.78]; P = .04). Prolonged length of stay was associated with age 65 years or older (OR, 2.44 [95% CI, 1.31-4.57]; P = .01), an American Society of Anesthesiologists class 3 or 4 (OR, 3.48 [95% CI, 1.88-6.41]; P < .01), any procedural conversion (OR, 63.28 [95% CI, 12.53-319.59]; P < .01), and a tumor size of 4 cm or larger (4-6 cm: OR, 2.38 [95% CI, 1.21-4.67]; P = .01; ≥6 cm: OR, 2.46 [95% CI, 1.12-5.40]; P = .03). Conclusions and Relevance: Laparoscopic adrenalectomy remains safe for most adrenal disorders. Patient comorbidities, adrenal pathology, and tumor size are associated with the risk of complications and length of stay and should all be considered in selecting and preparing patients for surgery.

The Belfast Youth Development Study (BYDS): A prospective cohort study of the initiation, persistence and desistance of substance use from adolescence to adulthood in Northern Ireland.

BACKGROUND: Substance misuse persists as a major public health issue worldwide with significant costs for society. The development of interventions requires methodologically sound studies to explore substance misuse causes and consequences. This Cohort description paper outlines the design of the Belfast Youth Development (BYDS), one of the largest cohort studies of its kind in the UK. The study was established to address the need for a long-term prospective cohort study to investigate the initiation, persistence and desistance of substance use, alongside life course processes in adolescence and adulthood. The paper provides an overview of BYDS as a longitudinal data source for investigating substance misuse and outlines the study measures, sample retention and characteristics. We also outline how the BYDS data have been used to date and highlight areas ripe for future work by interested researchers. METHODS: The study began in 2000/1 when participants (n = 3,834) were pupils in their first year of post-primary education (age 10/11 years, school year 8) from over 40 schools in Northern Ireland. Children were followed during the school years: Year 9 (in 2002; aged 12; n = 4,343), Year 10 (in 2003; aged 13; n = 4,522), Year 11 (in 2004; aged 14; n = 3,965) and Year 12 (in 2005; aged 15; n = 3,830) and on two more occasions: 2006/07 (aged 16/17; n = 2,335) and 2010/11 (aged 20/21; n = 2,087). Data were collected on substance use, family, schools, neighbourhoods, offending behaviour and mental health. The most novel aspect of the study was the collection of detailed social network data via friendship nominations allowing the investigation of the spread of substance use via friendship networks. In 2004 (school year 11; respondents aged 14), a sub-sample of participants' parents (n = 1,097) and siblings (n = 211) also completed measures on substance use and family dynamics. RESULTS: The most recent wave (in 2010/2011; respondents aged 20/21 years) indicated lifetime use of alcohol, tobacco and cannabis among the cohort was 94, 70 and 45 per cent, respectively. The paper charts the development of drug use behaviour and some of the key results to date are presented. We have also identified a number of key areas ripe for analysis by interested researchers including sexual health and education. CONCLUSIONS: We have established a cohort with detailed data from adolescence to young adulthood, supplemented with parent and sibling reports and peer network data. The dataset, allowing for investigation of trajectories of adolescent substance use, associated factors and subsequent long-term outcomes, constitutes an important resource for longitudinal substance misuse research. A planned further wave as the cohort enter their late twenties and potential to link to administrative data sources, will further enrich the datasets.

Hidden in Plain Sight: Transoral and Submental Thyroidectomy as a Compelling Alternative to "Scarless" Thyroidectomy.

BACKGROUND: Minimally invasive and remote access thyroid surgery has been evolving with the transoral endoscopic thyroidectomy vestibular approach (TOETVA) emerging as a true "scarless" thyroidectomy. In this study, we describe a hybrid transoral and submental thyroidectomy (TOaST) technique for thyroid lobectomy. MATERIALS AND METHODS: A TOaST right thyroid lobectomy was performed for a 4 cm cytologically benign right thyroid nodule. Initial incision was made in the submental region with two additional 5 mm lateral ports inserted transorally. Right thyroid lobectomy proceeded via standard TOETVA with intact specimen extraction via the submental incision. RESULTS: The patient was discharged home on postoperative day 1. Final pathology showed a 4.2 cm follicular adenoma. Cosmetic results and patient satisfaction were excellent. DISCUSSION: This is the first reported case of a hybrid TOaST technique. It aims to maintain the principles and advantages of TOETVA while addressing its limitations related to large tumor extraction, mental nerve injury, and chin sensory changes. The shorter distance of dissection required may reduce postoperative pain. This approach may expand the indications for transoral thyroidectomy while maintaining excellent cosmetic outcomes.

Patient Frailty Should Be Used to Individualize Treatment Decisions in Primary Hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder that predominantly affects patients >60 and is increasing in prevalence. Identifying risk factors for poor outcomes after parathyroidectomy in older adults will help tailor operative decision making. The impact of frailty on surgical outcomes in parathyroidectomy has not been established. METHODS: We performed a retrospective review of patients ≥40 years who underwent parathyroidectomy in the 2005-2010 ACS NSQIP. Frailty was assessed using the modified frailty index (mFI). Multivariable regression was used to determine the association of frailty with 30-day complications, length of stay (LOS), and reoperation. RESULTS: We identified 13,123 patients ≥40 who underwent parathyroidectomy for PHPT. The majority of patients were not frail, with 80% with a low NSQIP mFI score (0-1 frailty traits), 19% with an intermediate mFI score (2-3), and 0.9% with a high mFI score (≥4). Overall 30-day complications were rare, occurring in 141 (1.1%) patients. Increasing frailty was associated with an increased risk of complications with adjusted odds ratios (ORs) of 1.76 (95% CI 1.20-2.59; p = 0.004) for intermediate and 8.43 (95% CI 4.33-16.41; p < 0.001) for high mFI score. Patient age was independently associated with an increased risk of complications only when ≥75, as was African-American race. Anesthesia with local, monitored anesthesia care, or regional block was the only factor associated with decreased odds of complications. A high NSQIP mFI was also associated with a significant 4.77-day adjusted increase in LOS (95% CI 4.28-5.25; p < 0.001) and increased odds of reoperation (OR 4.20, 95% CI 1.64-10.74; p = 0.003). CONCLUSION: Patient frailty is associated with increased complications, reoperation and prolonged LOS in patients undergoing parathyroidectomy for PHPT. The risks of surgical management should be weighed against potential benefits in frail patients with PHPT to individualize treatment decisions in this vulnerable population.

Validity and Reliability of Baseline Testing in a Standardized Environment.

OBJECTIVE: The Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) is a computerized neuropsychological test battery commonly used to determine cognitive recovery from concussion based on comparing post-injury scores to baseline scores. This model is based on the premise that ImPACT baseline test scores are a valid and reliable measure of optimal cognitive function at baseline. Growing evidence suggests that this premise may not be accurate and a large contributor to invalid and unreliable baseline test scores may be the protocol and environment in which baseline tests are administered. This study examined the effects of a standardized environment and administration protocol on the reliability and performance validity of athletes' baseline test scores on ImPACT by comparing scores obtained in two different group-testing settings. METHOD: Three hundred-sixty one Division 1 cohort-matched collegiate athletes' baseline data were assessed using a variety of indicators of potential performance invalidity; internal reliability was also examined. RESULTS: Thirty-one to thirty-nine percent of the baseline cases had at least one indicator of low performance validity, but there were no significant differences in validity indicators based on environment in which the testing was conducted. Internal consistency reliability scores were in the acceptable to good range, with no significant differences between administration conditions. CONCLUSIONS: These results suggest that athletes may be reliably performing at levels lower than their best effort would produce.

Recombinant Parathyroid Hormone Versus Usual Care: Do the Outcomes Justify the Cost?

BACKGROUND: Hypoparathyroidism is a potential outcome of anterior neck surgery. Commonly it is managed by calcium and vitamin D supplementation in large doses, with attendant side effects. A recombinant human parathyroid hormone (rhPTH) is now available in the USA, offering a potentially more effective treatment. No cost-effectiveness model investigating this new medication versus standard care has yet been published. METHODS: We constructed a decision analytic model comparing usual care versus rhPTH treatment for postsurgical hypoparathyroidism. Threshold and sensitivity analyses on key parameters were conducted to assess robustness of the model. Costs and health outcomes were represented in US dollars and quality-adjusted life-years (QALYs). RESULTS: The rhPTH strategy was both more costly and more effective than the usual care (UC) strategy. In the base case, UC cost $37,196 and provided 7.54 QALYs. The rhPTH strategy cost $777,224 and provided 8.46 QALYs for an incremental cost-effectiveness ratio of $804,378/QALY. As this was above our willingness-to-pay of $100,000, treatment with rhPTH was not considered cost-effective. The model was robust to all other parameters. CONCLUSIONS: To our knowledge, this is the first formal cost-effectiveness analysis of rhPTH in comparison with UC. Our model suggests that although the new treatment is slightly more effective than UC, the modest gain in quality of life for patients who are reasonably well-managed by UC does not justify the cost. However, consideration must be given to rhPTH for patients who have failed UC, as the expenditure may be justified in that context.

Less is more: cost-effectiveness analysis of surveillance strategies for small, nonfunctional, radiographically benign adrenal incidentalomas.

BACKGROUND: Guidelines for management of small adrenal incidentalomas are mutually inconsistent. No cost-effectiveness analysis has been performed to evaluate rigorously the relative merits of these strategies. METHODS: We constructed a decision-analytic model to evaluate surveillance strategies for <4cm, nonfunctional, benign-appearing adrenal incidentalomas. We evaluated 4 surveillance strategies: none, one-time, annual for 2 years, and annual for 5 years. Threshold and sensitivity analyses assessed robustness of the model. Costs were represented in 2016 US dollars and health outcomes in quality-adjusted life-years. RESULTS: No surveillance has an expected net cost of $262 and 26.22 quality-adjusted life-years. One-time surveillance costs $158 more and adds 0.2 quality-adjusted life-years for an incremental cost-effectiveness ratio of $778/quality-adjusted life-years. The strategies involving more surveillance were dominated by the no surveillance and one-time surveillance strategies less effective and more expensive. Above a 0.7% prevalence of adrenocortical carcinoma, one-time surveillance was the most effective strategy. The results were robust to all sensitivity analyses of disease prevalence, sensitivity, and specificity of diagnostic assays and imaging as well as health state utility. CONCLUSION: For patients with a < 4cm, nonfunctional, benign-appearing mass, one-time follow-up evaluation involving a noncontrast computed tomography and biochemical evaluation is cost-effective. Strategies requiring more surveillance accrue more cost without incremental benefit.

Association of Patient Frailty With Increased Morbidity After Common Ambulatory General Surgery Operations.

Importance: Frailty is a measure of decreased physiological reserve that is associated with morbidity and mortality in major elective and emergency general surgery operations, independent of chronological age. To date, the association of frailty with outcomes in ambulatory general surgery has not been established. Objective: To determine the association between frailty and perioperative morbidity in patients undergoing ambulatory general surgery operations. Design, Setting, and Participants: A retrospective cohort study was conducted of 140 828 patients older than 40 years of age from the 2007-2010 American College of Surgeons National Surgical Quality Improvement Program Participant Use File who underwent ambulatory and 23-hour-stay hernia, breast, thyroid, or parathyroid surgery. Data analysis was performed from August 18, 2016, to June 21, 2017. Main Outcomes and Measures: The association between the National Surgical Quality Improvement Program modified frailty index and perioperative morbidity was determined via multivariable logistic regression with random-effects modeling to control for clustering within Current Procedural Terminology codes. Results: A total of 140 828 patients (80 147 women and 60 681 men; mean [SD] age, 59.3 [12.0] years) underwent ambulatory hernia (n = 71 455), breast (n = 51 267), thyroid, or parathyroid surgery (n = 18 106). Of these patients, 2457 (1.7%) experienced any type of perioperative complication and 971 (0.7%) experienced serious perioperative complications. An increasing modified frailty index was associated with a stepwise increase in the incidence of complications. In multivariable analysis adjusting for age, sex, race/ethnicity, anesthesia type, tobacco use, renal failure, corticosteroid use, and clustering by Current Procedural Terminology codes, an intermediate modified frailty index score (0.18-0.35, corresponding to 2-3 frailty traits) was associated with statistically significant odds ratios of 1.70 (95% CI, 1.54-1.88; P < .001) for any complication and 2.00 (95% CI, 1.72-2.34; P < .001) for serious complications. A high modified frailty index score (≥0.36, corresponding to ≥4 frailty traits) was associated with statistically significant odds ratios of 3.35 (95% CI, 2.52-4.46; P < .001) for any complication and 3.95 (95% CI, 2.65-5.87; P < .001) for serious complications. Anesthesia with local and monitored anesthesia care was the only modifiable covariate associated with decreased odds of serious 30-day complications, with an adjusted odds ratio of 0.66 (95% CI, 0.53-0.81; P < .001). Conclusions and Relevance: Frailty is associated with increased perioperative morbidity in common ambulatory general surgery operations, independent of age, type of anesthesia, and other comorbidities. Surgeons should consider frailty rather than chronological age when counseling and selecting patients for elective ambulatory surgery.

NR4A orphan nuclear receptor family members, NR4A2 and NR4A3, regulate neutrophil number and survival.

The lifespan of neutrophils is plastic and highly responsive to factors that regulate cellular survival. Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signaling, which positively regulates neutrophil survival. The aim of this study was to define transcriptional responses to PKA activation and to delineate the roles of these factors in neutrophil function and survival. In human neutrophil gene array studies, we show that PKA activation upregulates a significant number of apoptosis-related genes, the most highly regulated of these being NR4A2 and NR4A3 Direct PKA activation by the site-selective PKA agonist pair N6/8-AHA (8-AHA-cAMP and N6-MB-cAMP) and treatment with endogenous activators of PKA, including adenosine and prostaglandin E2, results in a profound delay of neutrophil apoptosis and concomitant upregulation of NR4A2/3 in a PKA-dependent manner. NR4A3 expression is also increased at sites of neutrophilic inflammation in a human model of intradermal inflammation. PKA activation also promotes survival of murine neutrophil progenitor cells, and small interfering RNA to NR4A2 decreases neutrophil production in this model. Antisense knockdown of NR4A2 and NR4A3 homologs in zebrafish larvae significantly reduces the absolute neutrophil number without affecting cellular migration. In summary, we show that NR4A2 and NR4A3 are components of a downstream transcriptional response to PKA activation in the neutrophil, and that they positively regulate neutrophil survival and homeostasis.