Novel approach for tracking interdisciplinary research productivity using institutional databases.

This study proposes a new practical approach for tracking institutional changes in research teamwork and productivity using commonly available institutional electronic databases such as eCV and grant management systems. We tested several definitions of interdisciplinary collaborations based on number of collaborations and their fields of discipline. We demonstrated that the extent of interdisciplinary collaboration varies significantly by academic unit, faculty appointment and seniority. Interdisciplinary grants constitute 24% of all grants but the trend has significantly increased over the last five years. Departments with more interdisciplinary grants receive more research funding. More research is needed to improve efficiency of interdisciplinary collaborations.

Quality of MBSAQIP data: bad luck, or lack of QA plan?

BACKGROUND: National clinical registries are commonly used in clinical research, quality improvement, and health policy. However, little is known about methodological challenges associated with these registry analyses that could limit their impact and compromise patient safety. This study examined the quality of Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MSBASQIP) data to assess its usability potential and improve data collection methodologies. METHODS: We developed a single flat file (n = 168,093) using five subsets (Main, BMI, Readmission, Reoperation, and Intervention) of the 2015 MBSAQIP Participant User Data File (PUF). Logic and validity tests included (1) individual profiles of patient's body mass index (BMI) changes over time, (2) individual patient care pathways, and (3) correlation analysis between variable pairs associated with the same clinical encounters. RESULTS: 8888 (5.3%) patients did not have postoperative weight/BMI data; 20% of patients had different units for preoperative and postoperative weights. Postoperative weight measurements ranged between - 71 and 132% of preoperative weight. There were 325 (3.7%) hospital readmissions reported on the day of or day after MBS. The self-reporting of "emergency" vs. "planned" interventions did not correlate with the type of procedure and its indication. Up to 20% of data could potentially be unused for analysis due to data quality issues. CONCLUSIONS: Our analysis revealed various data quality issues in the 2015 MBSAQIP PUF related to completeness, accuracy, and consistency. Since information on where the surgery was performed is lacking, it is not possible to conclude whether these issues represent data errors, patient outliers, or inappropriate care. Including automated data checks and biomedical informatics oversight, standardized coding for complications, additional de-identified facility and provider information, and training/mentorship opportunities in data informatics for all researchers who get access to the data have been shown to be effective in improving data quality and minimizing patient safety concerns.

Disparity in access to bariatric surgery among African-American men.

BACKGROUND: Despite improvements in safety and effectiveness in surgical management of extreme obesity, men and racial minorities are less likely to receive metabolic and bariatric surgery (MBS) compared to other patient groups. This study examines the racial and gender disparities in access to MBS to understand the mechanism that drives these problems and to propose strategies for closing the disparity gap. METHODS: Using 2013-2014 National Health and Nutrition Examination Survey data, we estimated the proportion of individuals, by race and gender, who were eligible for MBS based on Body Mass Index (BMI) and comorbidity profile. We analyzed the 2015 MBS Accreditation and Quality Improvement Program Participant Use Data File to examine differences in patient characteristics, comorbidities, and postsurgical outcomes among African-American (AA) and White men. Predictors of poor outcomes were identified using unconditional logistic regression models. RESULTS: AA men represented 11% of eligible patients but only 2.4% of actual MBS patients. Compared to White men, AA men were younger, had higher BMI, were more likely to have a history of hypertension, renal insufficiency, required dialysis, and had American Society of Anesthesiologists class 4 or 5 (all P values < 0.01). After surgery, AA men were more likely to suffer from postoperative complications (adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.02-1.52) and stayed in the hospital for more than 4 days (aOR 1.51, 95% CI 1.26-1.82) compared to White men. CONCLUSIONS: Despite being eligible for MBS based on both BMI and obesity-related comorbidities, AA men are significantly less likely to undergo MBS. Those AA men who receive surgery are significantly younger than White men but also experience greater comorbidities compared to White men and all women. Further longitudinal studies into patient-, system-, and provider-level barriers are necessary to understand and address these disparities.

Population-based study of outcomes following an initial acute diverticular abscess.

BACKGROUND: Studies examining long-term outcomes following resolution of an acute diverticular abscess have been limited to single-institution chart reviews. This observational cohort study compared outcomes between elective colectomy and non-operative management following admission for an initial acute diverticular abscess. METHODS: The Statewide Planning and Research Cooperative System was queried for unscheduled admissions for an initial acute diverticular abscess in 2002-2010. Bivariable and propensity-matched multivariable analyses compared stoma rates and use of healthcare in patients who had an elective resection and those receiving non-operative management. Diverticulitis recurrence rates were analysed for non-operative management. RESULTS: Among 10 342 patients with an initial acute diverticular abscess, one-third (3270) underwent surgical intervention within 30 days despite initial non-operative management. Of the remaining 7072 patients, 1660 had an elective colectomy within 6 months. Of 5412 patients receiving non-operative management, 1340 (24·8 per cent) had recurrence of diverticulitis within 5 years (median 278 (i.q.r. 93·5-707) days to recurrence). Elective colectomy was associated with higher stoma rates (10·0 per cent, compared with 5·7 per cent for non-operative observation, P < 0·001; odds ratio 1·88, 95 per cent c.i. 1·50 to 2·36), as well as more inpatient hospital days for diverticulitis-related admissions (mean 8·0 versus 4·6 days respectively, P < 0·001; incidence rate ratio (IRR) 2·16, 95 per cent c.i. 1·89 to 2·47) and higher mean diverticulitis-related cost (€70 107 versus €24 490, P < 0·001; IRR 3·11, 2·42 to 4·01). CONCLUSION: Observation without elective colectomy following resolution of an initial diverticular abscess is a reasonable option with lower healthcare costs than operation.

Parents' experiences of managing their child's diabetes using an insulin pump: a qualitative study.

AIMS: Continuous subcutaneous insulin infusion delivered via a pump is increasingly recommended for younger children with Type 1 diabetes. Our aims were: to understand the impact on parents who care for young children using insulin pumps; to help interpret psychological outcomes reported in quantitative research; and to inform provision of support to future parents. METHODS: We conducted in-depth interviews with 19 parents of children (aged ≤ 12 years) with Type 1 diabetes who used an insulin pump. Data were analysed thematically. RESULTS: Parents reported multiple benefits from using insulin pumps, including: no longer having to administer painful injections; fewer restrictions on the frequency, timing and carbohydrate contents of snacks and meals; and improvements in family life and their child's glycaemic control. Parents liked and felt less anxious about using bolus calculators to determine insulin doses; however, parents also described undertaking additional and unanticipated work to manage their child's diabetes using a pump. This included performing more blood glucose tests to calculate insulin doses for snacks and to address their concerns that the pump increased their child's risk of hypoglycaemia. Some parents reported doing additional blood glucose checks because they could adjust pump settings to better manage hypo- and hyperglycaemia. CONCLUSIONS: Parents liked and perceived benefits for their child and themselves from using an insulin pump; however, parents would benefit from being made aware of the additional work involved in using a pump and also from education and support to address concerns about hypoglycaemia. Better measures to evaluate parents' experiences are also recommended.

Challenges of optimizing glycaemic control in children with Type 1 diabetes: a qualitative study of parents' experiences and views.

AIMS: To explore the difficulties parents encounter in trying to achieve clinically recommended blood glucose levels and how they could be better supported to optimize their child's glycaemic control. METHODS: In-depth interviews were conducted with 54 parents of children with Type 1 diabetes (≤ 12 years). Data were analysed thematically. RESULTS: Parents described being reluctant and finding it difficult to keep their child's blood glucose levels consistently within clinically recommended ranges. As well as worrying about their child's ability to detect/report hypoglycaemia, parents highlighted a multitude of factors that had an impact on their child's blood glucose levels and over which they could exercise little control. These included: leaving their child with other caregivers who could not be trusted to detect hypoglycaemia; difficulties remotely monitoring and regulating their child's food consumption and activity; and physical and social changes accompanying childhood development. Most parents used two sets of blood glucose targets, with clinically recommended targets employed when their child was in their immediate care and higher targets when in the care of others. Parents described health professionals as lacking understanding of the difficulties they encountered keeping blood glucose within target ranges and needing more empathetic, tailored and realistic advice. CONCLUSION: It is not parents' fear of hypoglycaemia in isolation that leads to decisions to raise their child's blood glucose but, rather, parental fear in conjunction with other factors and considerations. Hence, to improve diabetes management in children, these factors may need to be addressed; for instance, by training others in diabetes management and using new technologies. Changes to consultations are also recommended.

An exploratory study of positive and incongruent communication in young children with type 1 diabetes and their mothers.

BACKGROUND: The incidence of type 1 diabetes is increasing in young children. However, they are overlooked in treatment adherence and intervention research despite evidence that parents often experience difficulty securing their treatment cooperation, especially with the diet. We investigated positive and incongruent (i.e. the co-occurrence of contradictory verbal and non-verbal messages) communication in the mother-child dyad and their association with child adjustment and dietary adherence outcomes. METHODS: Participants were 23 6- to 8-year-old children with type 1 diabetes and their mothers. We conducted dietary adherence interviews with mothers and performed nutritional analyses to assess children's consumption of extrinsic sugars (e.g. confectionary). Mothers completed a standardized assessment of child psychological adjustment. Mothers and children engaged in a videotaped problem-solving task related to the dietary regimen, with maternal and child utterances and non-verbal behaviours analysed for positive dyadic and incongruent communication. RESULTS: Positive dyadic communication correlated with lower levels of child incongruent communication, fewer behavioural problems and better overall adjustment. Higher levels of maternal and child incongruent communication correlated with more behavioural and emotional problems and poorer overall adjustment. Higher levels of maternal incongruent communication correlated with poorer dietary adherence. CONCLUSIONS: Results converged to form a conceptually and empirically coherent pattern in that behavioural indices of poorer communication in both mother and child consistently correlated with poorer child adjustment outcomes. This study shows that specific features of dyadic, child and maternal communication could be targeted in developmentally sensitive interventions to promote positive communication in the home management of type 1 diabetes care for young children.

Cost-effectiveness of disease-modifying therapy for multiple sclerosis: a population-based study.

OBJECTIVE: To evaluate the cost-effectiveness of disease-modifying therapies (DMTs) in the United States compared to basic supportive therapy without DMT for patients with relapsing multiple sclerosis (MS). METHODS: Using data from a longitudinal MS survey, we generated 10-year disease progression paths for an MS cohort. We used first-order annual Markov models to estimate transitional probabilities. Costs associated with losses of employment were obtained from the Bureau of Labor Statistics. Medical costs were estimated using the Centers for Medicare and Medicaid Services reimbursement rates and other sources. Outcomes were measured as gains in quality-adjusted life-years (QALY) and relapse-free years. Monte Carlo simulations, resampling methods, and sensitivity analyses were conducted to evaluate model uncertainty. RESULTS: Using DMT for 10 years resulted in modest health gains for all DMTs compared to treatment without DMT (0.082 QALY or <1 quality-adjusted month gain for glatiramer acetate, and 0.126-0.192 QALY gain for interferons). The cost-effectiveness of all DMTs far exceeded $800,000/QALY. Reducing the cost of DMTs had by far the greatest impact on the cost-effectiveness of these treatments (e.g., cost reduction by 67% would improve the probability of Avonex being cost-effective at $164,000/QALY to 50%). Compared to treating patients with all levels of disease, starting DMT earlier was associated with a lower (more favorable) incremental cost-effectiveness ratio compared to initiating treatment at any disease state. CONCLUSION: Use of DMT in MS results in health gains that come at a very high cost.

Quantitative risk-benefit analysis of natalizumab.

OBJECTIVE: To model the long-term risks and benefits of natalizumab in individuals with relapsing multiple sclerosis (MS). METHODS: We created a Markov model to evaluate treatment effects on reducing relapses and slowing disease progression using published natural history data and clinical trial results. Health changes, measured in quality-adjusted life-years (QALYs), were based on patient health preferences. Patient cohorts treated with no disease-modifying treatment, natalizumab, subcutaneous interferon beta-1a, and a theoretical "perfect" MS treatment were modeled. Sensitivity analysis was used to explore model uncertainty, including varying risks of developing progressive multifocal leukoencephalopathy (PML). RESULTS: Treatment with natalizumab resulted in 9.50 QALYs over a 20-year time horizon, a gain of 0.80 QALYs over the untreated cohort and 0.38 QALYs over interferon beta-1a. The health loss due to PML was small (-0.06 QALYs). To offset natalizumab's incremental health gain over interferon beta-1a, the risk had to increase from 1 to 7.6 PML per 1,000 patients treated over 17.9 months. The "perfect" MS treatment accumulated 10.59 QALYs over the 20-year time horizon, 1.89 QALYs above the untreated cohort. Interferon beta-1a resulted in greater QALY gains compared with natalizumab if natalizumab's relative relapse reduction was reduced from 68% to 35% or if interferon beta-1a's relative reduction was increased from 32% to 65%. CONCLUSIONS: A more than sevenfold increase in actual risk of progressive multifocal leukoencephalopathy was required to decrease natalizumab's health gain below that of interferon beta-1a, and there remains considerable room for additional gains in health (>50%) beyond those already achieved with current therapies.

Quantifying the risks and benefits of natalizumab in relapsing multiple sclerosis.

Using published data, we quantified the risk and benefits of natalizumab in relapsing multiple sclerosis using quality-adjusted life years (QALYs) as a metric. Over the first 2 years of therapy, the negative health effects from progressive multifocal leukoencephalopathy were small (loss of 0.001 QALYs) relative to the positive effects on relapses and disability resulting in 0.033 QALYs (12 quality-adjusted days) gained. For context, we performed an analogous calculation for interferon beta-1a, which also had a net health benefit of 0.033 QALYs (12 quality-adjusted days).

Contactin associates with Na+ channels and increases their functional expression.

Contactin (also known as F3, F11) is a surface glycoprotein that has significant homology with the beta2 subunit of voltage-gated Na(+) channels. Contactin and Na(+) channels can be reciprocally coimmunoprecipitated from brain homogenates, indicating association within a complex. Cells cotransfected with Na(+) channel Na(v)1.2alpha and beta1 subunits and contactin have threefold to fourfold higher peak Na(+) currents than cells with Na(v)1.2alpha alone, Na(v)1.2/beta1, Na(v)1.2/contactin, or Na(v)1.2/beta1/beta2. These cells also have a correspondingly higher saxitoxin binding, suggesting an increased Na(+) channel surface membrane density. Coimmunoprecipitation of different subunits from cell lines shows that contactin interacts specifically with the beta1 subunit. In the PNS, immunocytochemical studies show a transient colocalization of contactin and Na(+) channels at new nodes of Ranvier forming during remyelination. In the CNS, there is a particularly high level of colocalization of Na(+) channels and contactin at nodes both during development and in the adult. Contactin may thus significantly influence the functional expression and distribution of Na(+) channels in neurons.

Long-range guanine oxidation in DNA restriction fragments by a triplex-directed naphthalene diimide intercalator.

Naphthalene diimide (NDI), a powerful oxidant that binds avidly to DNA by intercalation, is seen to damage the 5' guanine of 5'-GG-3' sites by photoactivated charge transport through DNA. When covalently tethered to the center of a triplex-forming oligonucleotide and delivered by triplex formation within a pyrimidine.purine-pyrimidine motif to a specific site on a restriction fragment, NDI can photooxidize guanine over at least 25-38 bp in each direction from the site of binding. Charge migration occurs in both directions from the NDI intercalator and on both DNA strands of the target, but the oxidation is significantly more efficient to the 3' side of the triplex. NDI and octahedral rhodium intercalators, when tethered directly to the 5' terminus of the triplex-forming strand as opposed to the center, generate significant amounts of oxidative damage only in the immediate vicinity of the intercalation site. Given that long-range charge transport depends on DNA stacking, these results suggest that the base stack is distorted at the 5' end of the triplex region in the duplex-triplex junction. Targeting of photooxidative damage by triplex formation extends our previous studies of long-range charge transport to significantly longer DNA sequences through a strategy that does not require covalent attachment of the photooxidant to the DNA being probed. Moreover, triplex targeting of oxidative damage provides for the first time a typical distance distribution for genomic charge transport of approximately 200 A around the oxidant.

Desflurane reduces the gain of thermoregulatory arteriovenous shunt vasoconstriction in humans.

BACKGROUND: Thermoregulatory responses, such as arteriovenous shunt vasoconstriction, provide substantial protection against core hypothermia. A response can be characterized by its threshold (core temperature triggering response), gain (rate at which response intensity increases, once triggered), and maximum response intensity. Reduced gain decreases the efficacy of a thermoregulatory response at a given threshold because response intensity will increase more slowly than usual. The effects of general anesthesia on the gain of arteriovenous shunt vasoconstriction have not been reported. Accordingly, we tested the hypothesis that desflurane decreases the gain of centrally mediated vasoconstriction. METHODS: We studied seven healthy male volunteers. Each was studied twice: (1) desflurane (end-tidal concentration 0.4 minimum alveolar concentration); and (2) control (no anesthesia). Mean skin and fingertip temperatures were controlled at 35.5 degrees C throughout the study. Core temperature was reduced at a rate of 1.5 degrees C/h by central venous infusion of cold fluid. Fingertip arteriovenous shunt flow was measured using venous occlusion volume plethysmography at 1-min intervals. Flow was also evaluated using the perfusion index and laser Doppler flowmetry. Vasoconstriction thresholds were calculated as the core temperatures triggering fingertip flows of 1.0 ml/min (beginning of vasoconstriction) and 0.25 ml/min (intense vasoconstriction). The gain of vasoconstriction was considered to be the slope of the fingertip flow versus core temperature regression within the linear range from 1.0 ml/min to 0.15 ml/min. The minimum observed flow was considered maximum vasoconstriction intensity. Data are presented as means +/- SD; P < 0.01 was considered statistically significant. RESULTS: The vasoconstriction threshold (when defined using a flow of 1.0 ml/min) was reduced from 36.8 +/- 0.3 degrees C to 35.6 +/- 0.3 degrees C by desflurane anesthesia (P < 0.01). Desflurane reduced the gain of vasoconstriction by a factor of three, from 2.4 to 0.8 ml.min-1.degrees C-1 (P < 0.01). Gains, as determined by the perfusion index and laser Doppler flowmetry, were likewise reduced (P < 0.01). The threshold on the control day was only 0.2 +/- 0.1 degrees C less when significant vasoconstriction was defined as a flow of 0.25 ml/min rather than 1.0 ml/min. Because gain was reduced, however, the threshold during desflurane administration was 0.8 +/- 0.2 degrees C less when significant vasoconstriction was defined by a flow of 0.25 ml/min. Minimum flows were comparable and near zero with and without anesthesia. CONCLUSIONS: The threshold reduction (1.2 degrees C/0.4 minimum alveolar concentration) was similar to that observed previously during isoflurane anesthesia. Similarly, it is established already that maximum vasoconstriction intensity is comparable with and without isoflurane anesthesia. However, the data also indicate that even relatively low desflurane concentrations markedly reduce the gain of vasoconstriction. It is likely that reduced gain (i.e., slow onset of vasoconstriction) contributes to core hypothermia in some surgical patients.

Thermoregulatory thresholds during epidural and spinal anesthesia.

BACKGROUND: There are significant physiologic differences between spinal and epidural anesthesia. Consequently, these two types of regional anesthesia may influence thermoregulatory processing differently. Accordingly, in volunteers and in patients, we tested the null hypothesis that the core-temperature thresholds triggering thermoregulatory sweating, vasoconstriction, and shivering are similar during epidural and spinal anesthesia. METHODS: Six male volunteers participated on three consecutive study days: epidural or spinal anesthesia were randomly assigned on the 1st and 3rd days (approximately T10 level); no anesthesia was given on the 2nd day. On each day, the volunteers were initially warmed until they started to sweat, and subsequently cooled by central venous infusion of cold fluid until they shivered. Mean skin temperature was kept constant near 36 degrees C throughout each study. The tympanic membrane temperatures triggering a sweating rate of 40 g.m-2.h-1, a finger flow less than 0.1 ml/min, and a marked and sustained increase in oxygen consumption (approximately 30%) were considered the thermoregulatory thresholds for sweating, vasoconstriction, and shivering, respectively. Twenty-one patients were randomly assigned to receive epidural (n = 10) or spinal (n = 11) anesthesia for knee and calf surgery (approximately T10 level). As in the volunteers, the shivering threshold was defined as the tympanic membrane temperature triggering a sustained increase in oxygen consumption. RESULTS: The thresholds and ranges were similar during epidural and spinal anesthesia in the volunteers. However, the sweating-to-vasoconstriction (inter-threshold) range, the vasoconstriction-to-shivering range, and the sweating-to-shivering range all were significantly increased by regional anesthesia. The shivering thresholds in patients assigned to epidural and spinal anesthesia were virtually identical. CONCLUSIONS: Comparable sweating, vasoconstriction, and shivering thresholds during epidural and spinal anesthesia suggest that thermoregulatory processing is similar during each type of regional anesthesia. However, thermoregulatory control was impaired during regional anesthesia, as indicated by the significantly enlarged inter-threshold and sweating-to-shivering ranges.