30-day Window Research Articles

Charlson Comorbidity Index score predicts adverse post-operative outcomes after far lateral lumbar discectomy

IntroductionThe Charlson Comorbidity Index (CCI) score has been shown to predict 10-year all-cause mortality and post-neurosurgical complications but has never been examined in a far lateral disc herniation (FLDH) population. This study aims to correlate CCI score with adverse outcomes following FLDH repair. Patients and MethodsAll patients (n = 144) undergoing discectomy for FLDH at a single, multihospital academic medical system (2013—2020) were retrospectively analyzed. CCI scores were determined for all patients. Univariate logistic regression was used to determine the ability of CCI score to predict adverse outcomes. ResultsMean age of the population was 61.72 ± 11.55 years, 69 (47.9%) were female, and 126 (87.5%) were non-Hispanic white. Patients underwent either open (n = 92) or endoscopic (n = 52) FLDH repair. Average CCI score among the patient population was 2.87 ± 2.42. Each additional point in CCI score was significantly associated with higher rates of readmission (p = 0.022, p = 0.014) in the 30-day and 30–90-day post-surgery window, respectively, and emergency department visits (p = 0.011) within 30-days. CCI score also predicted risk of reoperation of any kind (p = 0.013) within 30 days of the index operation. In addition, CCI score was predictive of risk of reoperation of any kind (p = 0.008, p < 0.001; respectively) and repeat neurosurgical intervention (p = 0.027, p = 0.027) within 30-days and 90-days of the index admission (either during the same admission or after discharge). ConclusionsThis study suggests that CCI score is a useful metric to predict of numerous adverse postoperative outcomes following discectomy for FLDH.

Predictors of serious, preventable, and costly medical complications in a population of adult spinal deformity patients

Background ContextIn 2008, the Centers for Medicare and Medicaid Services (CMS) established a list of hospital-acquired conditions (HACs) with significant deleterious effects on both patients and providers. Adult spinal deformity (ASD) surgery is complex and highly invasive, and as such may result in significant morbidity including these HACs. PurposeIdentify predictors for developing the most common HACs among adult spinal deformity (ASD) patients undergoing corrective surgery. Study Design/SettingRetrospective analysis. Patient SampleOne thousand one hundred and seventy-one ASD patients. Outcome MeasuresHACs, Health-Related Quality of Life scores(HRQLs), Reoperation, Integrated Health State (IHS) MethodsASD pts undergoing surgery (>18 years, scoliosis ≥20°, SVA ≥5 cm, PT ≥25° and/or TK >60°) with complete data at BL and up to 2 years post-op were included. Patients were stratified by presence of >1 HAC, defined as at least one superficial/deep SSI, UTI, DVT, or PE within a 30-day post-op window. Random forest analysis generated 5,000 Conditional Inference Trees to compute a variable importance table for top predictors of HACs. An area-under-the-curve (AUC) methodology compared normalized HRQL scores between groups to determine an IHS with 2-year follow-up. ResultsTotal of 1,171 pts (59.8 years, 76.2%F, 28.1kg/m2) underwent corrective ASD surgery, with 1,053 pts in the non-HAC group and 118 in the HAC group. Of these pts, 25.4% had UTI, 15.4% DVT, 19.2% superficial SSI, 20.8% deep SSI, and 19.2% PE. HAC pts were on average older (63.5 vs 59.3, p=.004) and more often frail (51.3 vs 39.7%, p=.021) than non-HAC pts. Postop LOS and reoperation were most associated with HAC groups: [1] LOS >7 days [2] reoperation. Patient-related predictors of HACs were [3] age >50 yerr, [4] frailty, and [13] BMI >31. Procedure-related predictors of HACs were [5] operative-time >405 minutes, [6] levels fused >9, EBL >1450 mL, and [11] decompression. BL radiographic predictors were [7] PT >20°, [9] PI-LL>6°, [10] TL Cobb angle >15°, [12] SVA C7-S1 >29 mm. No differences were observed between groups with regards to IHS ODI (0.73 vs 0.74, p=.863), SRS (1.3 vs1.3, p=.374), NRS Back (0.6 vs 0.6, p=.158). HAC had higher rates of reoperation than non-HAC (0.08 vs 0.01, p=.066), and any HAC within 30-days of index was a significant predictor of reoperation (OR: 2.448 [1.94–3.09], p<.001). ConclusionsIn a population of ASD patients, HACs were associated with length of stay, reoperation, age, and frailty. Radiographic parameters such as pelvic tilt >20°, PI-LL >6°, & SVA >29 mm also increased odds of HACs, and should raise postoperative awareness for HAC development.

453 Cost-Effectiveness of Requalifying for Positive Airway Pressure Treatment After Initial Nonadherence

Abstract Introduction Obstructive sleep apnea (OSA) is effectively treated with continuous positive airway pressure (CPAP). However, many people are not able to become adherent in the initial 90-day trial window for this therapy. Medicare requires a polysomnography and repeat trial documenting adherence before continuing payment for these services. Oral appliance therapy (OAT) is also an OSA first-line therapy but is less effective than CPAP. Methods We created a decision tree to model 4 strategies over a 5-year time horizon: (1) current policy, (2) direct referral for CPAP equipment, (3) OAT followed by CPAP under current policy, and (4) OAT followed by direct CPAP referral in a the Medicare population with mild-moderate OSA and nonadherence to a first attempt at CPAP therapy. Medicare fee schedules in 2020 defined costs. Incremental cost-effectiveness (ICER) was used to identify the supreme strategy Results The current policy was the most expensive. Both the current policy and direct DME referral were dominated by starting with OAT. OAT followed by titration was the most cost-effective strategy with an ICER of $42,586.47. The ICER was sensitive to adherence in the direct CPAP strategy and probability of getting CPAP equipment (vs. lost to follow-up). Conclusion Starting with OAT therapy in those that were CPAP nonadherent on first attempt is cost-effective. Despite decreased effectiveness, the increase adherence to OAT make it an attractive option for retrial of OSA therapy. If OAT therapy fails, the current policy is more cost-effective than direct CPAP referral. Support (if any) This study was supported Career Development Award IK2CX001882 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences Research and Development Service. The contents of this work do not represent the views of the Department of Veterans Affairs or the United States government.

Association of prescription opioid use on mortality and hospital length of stay in the intensive care unit.

ObjectiveSeveral studies show that chronic opioid dependence leads to higher in-hospital mortality, increased risk of hospital readmissions, and worse outcomes in trauma cases. However, the association of outpatient prescription opioid use on morbidity and mortality has not been adequately evaluated in a critical care setting. The purpose of this study was to determine if there is an association between chronic opioid use and mortality after an ICU admission.DesignA single-center, longitudinal retrospective cohort study of all Intensive Care Unit (ICU) patients admitted to a tertiary-care academic medical center from 2001 to 2012 using the MIMIC-III database.SettingMedical Information Mart for Intensive Care III database based in the United States.PatientsAdult patients 18 years and older were included. Exclusion criteria comprised of patients who expired during their hospital stay or presented with overdose; patients with cancer, anoxic brain injury, non-prescription opioid use; or if an accurate medication reconciliation was unable to be obtained. Patients prescribed chronic opioids were compared with those who had not been prescribed opioids in the outpatient setting.InterventionsNone.Measurements and main resultsThe final sample included a total of 22,385 patients, with 2,621 (11.7%) in the opioid group and 19,764 (88.3%) in the control group. After proceeding with bivariate analyses, statistically significant and clinically relevant differences were identified between opioid and non-opioid users in sex, length of hospital stay, and comorbidities. Opioid use was associated with increased mortality in both the 30-day and 1-year windows with a respective odds ratios of 1.81 (95% CI, 1.63–2.01; p<0.001) and 1.88 (95% CI, 1.77–1.99; p<0.001), respectively.ConclusionsChronic opioid usage was associated with increased hospital length of stay and increased mortality at both 30 days and 1 year after ICU admission. Knowledge of this will help providers make better choices in patient care and have a more informed risk-benefits discussion when prescribing opioids for chronic usage.

Spatial tale of G-7 and BRICS stock markets during COVID-19: An event study

The unprecedented outbreak of COVID-19 has affected every aspect of the human life, be it health, social, or economic dimensions. The anxiety and uncertainty wobbled the economies of affected countries worldwide. This study attempts to quantify the impact of COVID-19 on the performance of major stock markets of G-7 nations vis-à-vis BRICS nations. An event study methodology is employed to capture the effect of the systematic event in the form of Buy and Hold Abnormal Returns (BHAR) and Average Buy and Hold Abnormal Returns (ABHAR). The study considers a 90-day observation window, consisting of six sub-event windows after the COVID-19 news up-doves the world, and 120 days prior to the selected event date to estimate average expected returns. BHAR values in the four event windows are statistically significant, covering stock markets from panic and nosedive to their correction and recovery. ABHAR values reported are significantly negative in the event window ranging from –0.15% to –38.43% for G-7 and –0.06% to –37.12% for BRICS nations. Despite similar ABHAR trends, the BHAR values and correlation matrix exhibit a diverse reaction in BRICS nations compared to the highly synchronized reaction in the G-7 group of nations in the COVID period.

Association Between Management of Continuous Subcutaneous Basal Insulin Administration and HbA1C.

While we expect that patients who adjust their insulin delivery algorithms between clinic visits to have better glucose control compared to those who do not, this effect has not been quantified. This is a single-center retrospective cohort study including pediatric and adult patients with type 1 diabetes evaluating insulin pump self-management behaviors. Basal insulin dose information was obtained from the Glooko-Diasend database, and used to quantify the frequency and magnitude of basal insulin daily dose adjustments within the 90-day window preceding HbA1c measurement. We use a linear mixed-effects model to analyze associations between frequency/magnitude of daily basal insulin changes and HbA1c. We present data on 114 adult (44 ± 17 years, 60% female) and 212 pediatric (12 ± 4 years, 50% female) patients. Individuals changed their basal insulin dose on 72%-94% (interquartile range [IQR]) of observed days relative to the previous day. These changes varied 0.6%-2.4% IQR from the previous day's value. In pediatric patients, lower HbA1c was associated with more frequent daily profile adjustments, while controlling for rate of hypoglycemia (z = -3.2, P = .001). In adults, there was no relationship between HbA1c and magnitude or frequency of basal profile adjustments. Pediatric patients who frequently modify their basal insulin exhibit somewhat better clinical outcomes, although the magnitude by which their basal amount is changed does not contribute to this effect.

Exploring the inter-subject variability in the relationship between glucose monitoring metrics and glycated hemoglobin for pediatric patients with type 1 diabetes.

Despite the widespread diffusion of continuous glucose monitoring (CGM) systems, which includes both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM), an effective application of CGM technology in clinical practice is still limited. The study aimed to investigate the relationship between isCGM-derived glycemic metrics and glycated hemoglobin (HbA1c), identifying overall CGM targets and exploring the inter-subject variability. A group of 27 children and adolescents with type 1 diabetes under multiple daily injection insulin-therapy was enrolled. All participants used the isCGM Abbott's FreeStyle Libre system on average for eight months, and clinical data were collected from the Advanced Intelligent Distant-Glucose Monitoring platform. Starting from each HbA1c exam date, windows of past 30, 60, and 90days were considered to compute several CGM metrics. The relationships between HbA1c and each metric were explored through linear mixed models, adopting an HbA1c target of 7%. Time in Range and Time in Target Range show a negative relationship with HbA1c (R2>0.88) whereas Time Above Range and Time Severely Above Range show a positive relationship (R2>0.75). Focusing on Time in Range in 30-day windows, random effect represented by the patient's specific intercept reveals a high variability compared to the overall population intercept. This study confirms the relationship between several CGM metrics and HbA1c; it also highlights the importance of an individualized interpretation of the CGM data.

Coincidence of temperature extremes and phenological events of grapevines

A growing number of studies have highlighted the consequences of climate change on agriculture, including the impacts of climate extremes such as drought, heat waves and frost. The aim of this study was to assess the influence of temperature extremes on various phenological events of grapevine varieties in Southwest Switzerland (Leytron, Canton of Valais). We aimed to capture the occurrence of extreme events in specific years in various grapevine varieties and at different phenological phases to rank the varieties based on their sensitivity to temperature extremes and thus quantify their robustness. Phenological observations (1978–2018) of six Vitis vinifera varieties (Arvine, Chardonnay, Chasselas, Gamay, Pinot noir and Syrah) were subjected to event coincidence analysis. Extreme events were defined as values in the uppermost or lowermost percentiles of the timing of the phenophases and daily temperatures within a 30-day window before the phenophase event occurred. Significantly more extreme temperature and phenological events occurred in Leytron between 2003 and 2017 than in the earlier years, with the years 2007, 2011, 2014 and 2017 being remarkable in terms of the number of extreme coincidence events. Moreover, bud development and flowering experienced significantly more extreme coincidence events than other phenophases; however, the occurrence rate of extreme coincidence events was independent of the phenophase. Based on the total number of extreme events, the varieties did not differ in their responses to temperature extremes. Therefore, event coincidence analysis is an appropriate tool to quantify the occurrence of extreme events. The occurrence of extreme temperature events clearly affected the advancement of the timings of phenological events in various grapevines. However, there were no varietal differences in terms of response to extreme temperatures; thus, additional research is warranted to outline the best adaptation measures.

The impact of gender on long-term outcomes following supratentorial brain tumor resection

Purpose Gender is a known social determinant of health which has been linked disparities in medical care. This study intends to assess the impact of gender on 90-day and long-term morbidity and mortality outcomes following supratentorial brain tumor resection in a coarsened-exact matched population. Materials and Methods A total of 1970 consecutive patients at a single, university-wide health system undergoing supratentorial brain tumor resection over a six-year period (09 June 2013 to 26 April 2019) were analyzed retrospectively. Coarsened Exact Matching was employed to match patients on key demographic factors including history of prior surgery, smoking status, median household income, American Society of Anesthesiologists (ASA) grade, and Charlson Comorbidity Index (CCI), amongst others. Primary outcomes assessed included readmission, ED visit, unplanned reoperation, and mortality within 90 days of surgery. Long-term outcomes such as mortality and unplanned return to surgery during the entire follow-up period were also recorded. Results Whole-population regression demonstrated significantly increased mortality throughout the entire follow-up period for the male cohort (p = 0.004, OR = 1.32, 95% CI = 1.09 − 1.59); however, no significant difference was found after coarsened exact matching was performed (p = 0.08). In both the whole-population regression and matched-cohort analysis, no significant difference was observed between gender and readmission, ED visit, unplanned reoperation, or mortality in the 90-day post-operative window, in addition to return to surgery after throughout the entire follow-up period. Conclusion After controlling for confounding variables, female birth gender did not significantly predict any difference in morbidity and mortality outcomes following supratentorial brain tumor resection. Difference between mortality outcomes in the pre-matched population versus the matched cohort suggests the need to better manage the underlying health conditions of male patients in order to prevent future disparities.

A Randomized Controlled Pilot Trial to Test the Efficacy of Intranasal Chlorpheniramine Maleate With Xylitol for the Treatment of Allergic Rhinitis.

The prevalence of allergic rhinitis (AR), including symptoms of sneezing, nasal itching, airflow obstruction, and nasal discharge caused by histamine and immunoglobulin E (IgE)-mediated reactions, is ~30% in the U.S. Recent studies seem to suggest that the allergic inflammatory processes in AR may be induced by the interaction between an allergen (trigger) and the nasal microbiome (substrate). In this study, we have identified two agents with antihistaminic and microbiome-modulating characteristics that can be administered intranasally, namely, chlorpheniramine maleate (CPM) and xylitol (X). This study aimed to test the efficacy of intranasal CPM plus xylitol (CPM+X) nasal for the treatment of AR in an outpatient setting. A multicenter, randomized, double-blind, 30-day pilot study was conducted during the spring of 2019. After starting five days of placebo therapy (run-in period), patients with moderate-to-severe AR nasal symptoms were randomized to treatment with CPM+X (n=16) spray and nasal saline placebo (PLB; n=13). Both treatments were administered in the form of one spray dose (~100 µL of the solution containing 1.25 mg CPM) per nostril twice a day. Outcome variables were the changes in visual analog scale (VAS) and daily symptoms score (DSS) at days 1, 5, 10, 15, 25, and 30 after the initiation of the treatment. ANOVA (analysis of variance) with repeated revealed a significant treatment-by-time interaction such that the CPM+X group had a significant decrease (p < 0.05) in both DSS (∆-3.0 ± 2.7) and VAS (∆-3.8 ± 2.0) scores compared to PLB after 30 days. The difference in DSS and VAS scores between the groups was evident just after five days (day 10) of using CPM+X. The CPM+X scores were significantly lower (p < 0.008) starting from day 10 compared with day 1, whereas there were no statistically significant (p > 0.008) changes in the PLB during the 30-day treatment window. The present data suggest that nasal CPM+X use effectively improves AR symptoms. A large-scale study of the long-term effects of CPM+X for the treatment of other chronic respiratory disorders and the potential microbiome-modulating effects warrants further investigation.

Treatment of Long-term Sudden Sensorineural Hearing Loss as an Otologic Migraine Phenomenon.

To describe a cohort of patients presenting with long-term sudden sensorineural hearing loss (SSNHL) treated with prophylactic migraine and intratympanic steroid therapy. Patients presenting to a neurotology clinic at least 6 weeks from SSNHL onset were included. All patients received migraine prophylactic medication (nortriptyline, topiramate, and/or verapamil) and lifestyle changes for at least 6 weeks, as well as intratympanic steroid injections, if appropriate. Twenty-one patients (43% female) with a mean age of 64 ± 11 years who presented 9 ± 8 months (median = 5) from symptom onset were included. Posttreatment hearing thresholds were significantly improved compared with pretreatment thresholds at 500 Hz (49 ± 19 dB versus 55 ± 20 dB, p = 0.01), 1000 Hz (52 ± 19 dB versus 57 ± 21 dB, p = 0.03), low-frequency pure-tone average (53 ± 15 dB versus 57 ± 17 dB, p = 0.01), and speech-frequency pure-tone average (57 ± 13 dB versus 60 ± 15 dB, p = 0.02). Posttreatment word-recognition-score (WRS) and speech-recognition-threshold (SRT) were also significantly improved (45 ± 28% versus 70 ± 28% and 57 ± 18 dB versus 50 ± 16 dB, respectively, both p < 0.01). Notably, ≥15% improvement in WRS and ≥10 dB improvement in SRT was observed in 13 (68%) and 8 (40%) patients, respectively. Of the 11 patients who presented with initial < 50% WRS, 8 (73%) had improved posttreatment >50% WRS with an average improvement of 39 ± 9%. Migraine medications in addition to intratympanic steroid injections significantly improved SRT and hearing frequencies in 40% and 29% of SSNHL patients, respectively, while significant WRS recovery was observed in most (68%) patients. This suggests SSNHL may be an otologic migraine phenomenon, which may be at least partially reversible even after the traditional 30-day postonset window.

Case Series of Ultrasonic Navigated Osteotomy for the Treatment of Spinal Chordomas

Chordomas present challenges for en bloc surgical resection, which optimally reduces local recurrence and increases patient survival. Navigated ultrasonic osteotomy, also known as piezosurgery, provides a distinct advantage for achieving negative margins after en bloc resection. Eight consecutive patients with chordomas (2 cervical, 3 lumbar, and 3 sacral) treated with navigated ultrasonic osteotomy to achieve en bloc resection were identified from our institutional spine tumor database (2016-2019) and retrospectively reviewed. En bloc resection, with negative margins, was achieved in all cases. Two patients (25%) were women, and mean age at surgery was 44 ± 11 years. Median estimated blood loss was 1000 mL (interquartile range: 263-1500 mL). Median length of hospital stay was 10 days (interquartile range: 3-19.5 days). Two patients required a revision procedure. Two patients had complications requiring readmission within the 30-day postoperative window. Mean duration of follow-up for the cohort was 900 ± 554 days. Navigated ultrasonic osteotomy is an effective surgical technique to achieve en bloc resection of chordomas with negative margins and disease-free survival. To date, this represents the first reported cohort of patients undergoing the procedure as described here. Future studies should include larger sample sizes for more robust clinical outcome data to further elucidate the benefits of piezosurgery for obtaining en bloc chordoma resection.

Changes in utilization of immediate-release, extended-release, and liquid formulation medications relative to bariatric surgery: a segmented regression analysis.

Changes in gut anatomy following bariatric surgery impacts medication absorption, often requiring changes in medication formulations. To assess changes in utilization of extended-release (ER), immediate-release (IR), and liquid formulations 360 days before and after bariatric surgery. Large U.S. administrative claims database of privately insured beneficiaries, January 2005 through December2018. We included patients aged ≥18 years with 360 days of continuous enrollment before and after date of bariatric surgery (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]). The proportion of each formulation (ER, IR, or liquid) of oral prescription medications filled during the study period were assessed in twelve 30-day windows before and after bariatric surgery and stratified by bariatric surgery type. Segmented regression analysis was used to assess filled medication categorized by formulation before and after bariatric surgery overall and RYGB relative to SG. Among 122,866 included patients, there were increases in the proportion of patients on each formulation before and after surgery attributed to proton pump inhibitors, opioids, antiemetics, and ursodiol. After removing these acutely used medications, we found a 40% immediate reduction in patients on ER medications (P < .0001), 15% immediate reduction in patients on IR medications (P < .0001), and a nonsignificant increase in patients on liquid formulations (P = .1340). Despite reductions in ER formulations, many patients continued on this formulation which may potentially contribute to poor outcomes.

Colectomy Incidence Rates in Five-Year Data From the Observational Postmarketing Ulcerative Colitis Study of Originator Infliximab.

This analysis of the Observational Postmarketing Ulcerative Colitis Study examined incidence rates of colectomy in patients with ulcerative colitis who received originator infliximab (IFX) or conventional therapies (ConvRx) as per their treating physician. Cox proportional hazards models compared time to colectomy for both treatment groups. A secondary analysis examined colectomy incidence rates based on IFX exposure timing (defined by a 90-day window after the last IFX dose date). Of 2239 patients with data, 1059 enrolled in IFX and 1180 enrolled in ConvRx (including 296 patients who switched to IFX). Patients in the IFX group had more severe disease at baseline vs the ConvRx group (percentage with baseline partial Mayo score 7-9: 46.0% vs 30.5%, respectively). During 5 years of follow-up, 271 patients (12.1% of enrolled patients) had colectomy. Enrollment in the IFX group was associated with a higher risk of colectomy (hazard ratio = 3.12; 95% confidence interval, 2.25-4.34; P < 0.001) compared with enrollment in the ConvRx group. A total of 174 colectomies occurred in the IFX group, but 97 of these colectomies occurred ≥90 days after the last IFX dose date. Colectomy was reported at a higher rate in the IFX group than in the ConvRx group, although patients in the IFX group had more severe disease at baseline and most of the colectomies occurred after patients had been off of IFX for ≥90 days.

Intrapancreatic MSC transplantation facilitates pancreatic islet regeneration

BackgroundType 1 diabetes mellitus (T1D) is characterized by the autoimmune destruction of the pancreatic β cells. The transplantation of mesenchymal stromal/stem cells (MSC) was reported to rescue the damaged pancreatic niche. However, there is an ongoing discussion on whether direct physical contact between MSC and pancreatic islets results in a superior outcome as opposed to indirect effects of soluble factors released from the MSC entrapped in the lung microvasculature after systemic administration. Hence, MSC were studied in direct contact (DC) and indirect contact (IDC) with murine pancreatic β cell line MIN6-cells damaged by nitrosourea derivative streptozotocin (STZ) in vitro. Further, the protective and antidiabetic outcome of MSC transplantation was evaluated through the intrapancreatic route (IPR) and intravenous route (IVR) in STZ-induced diabetic NMRI nude mice.MethodsMSC were investigated in culture with STZ-damaged MIN6-cells, either under direct contact (DC) or separated through a semi-permeable membrane (IDC). Moreover, multiple low doses of STZ were administered to NMRI nude mice for the induction of hyperglycemia. 0.5 × 106 adipose-derived mesenchymal stem cells (ADMSC) were transferred through direct injection into the pancreas (IPR) or the tail vein (IVR), respectively. Bromodeoxyuridine (BrdU) was injected for the detection of proliferating islet cells in vivo, and real-time polymerase chain reaction (RT-PCR) was employed for the measurement of the expression of growth factor and immunomodulatory genes in the murine pancreas and human MSC. Phosphorylation of AKT and ERK was analyzed with Western blotting.ResultsThe administration of MSC through IPR ameliorated hyperglycemia in contrast to IVR, STZ, and non-diabetic control in a 30-day window. IPR resulted in a higher number of replicating islet cells, number of islets, islet area, growth factor (EGF), and balancing of the Th1/Th2 response in vivo. Physical contact also provided a superior protection to MIN6-cells from STZ through the AKT and ERK pathway in vitro in comparison with IDC.ConclusionOur study suggests that the physical contact between MSC and pancreatic islet cells is required to fully unfold their protective potential.

3 - A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

3 - A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

Autism and General Developmental Screening Practices Among Primary Care Providers.

Using standardized screening tools increases accuracy in early identification of autism. The American Academy of Pediatrics recommends systematic developmental screening at all 9-, 18-, and 24- or 30-month well-child visits (WCVs) and autism-specific screening at all 18- and 24-month WCVs. The study objectives were to examine the extent to which these guidelines have been adopted in practice among primary care providers (PCPs) and to identify potential provider-level factors associated with screening practices. Participants included 94 PCPs (79% pediatricians) from 13 states enrolled in a study of an autism training program. Self-report and chart-review data collected before training were examined. Screening practices were assessed through chart review of all 9-, 18-, and 24-month WCVs within a 30-day window. Sixty-four percent of PCPs administered developmental screening tools at all 9-month WCVs, and 62% at all 18-month WCVs. Fifty-one percent administered autism screening tools at all 18-month WCVs, and 41% at all 24-month WCVs. Screening practices varied by provider type (pediatrician vs other PCP), self-efficacy in screening and identification, and previous autism training (autism screening only), but not by years of experience. Overall, general developmental and autism-specific screenings are not being consistently administered across recommended WCVs in primary care practices. Provider self-efficacy in autism identification and screening and previous autism training were associated with increased autism screening. As such, these results suggest a need for increased training and dissemination of information on screening implementation for practicing PCPs.

Tiny Bodies, Big Needs: Prospective Biobanking of Neonatal Clinical Remnant Samples.

Repurposing biological samples collected for required diagnostic purposes into suitable biobanking projects is a particularly useful method for enabling research in vulnerable populations. This approach is especially appropriate for the neonate in the neonatal intensive care unit (NICU), where blood volume reductions can quickly increase beyond minimal risk for adverse events, such as iatrogenic anemia, and proxy consent provided by parents or guardians is required. The method described in this study provides a framework to prospectively collect and store blood-derived clinical samples after all clinical and regulatory requirements are fulfilled. The consent approach incorporated a 30-day window to allow parents and guardians ample consideration time with follow-up involvement with NICU embedded study team members. The study enrolled 875 participants over a 3-year period. This established a critically needed biobank to support investigator-initiated research with explicit study aims requiring samples at defined day of life frequencies within the NICU and created a normative control reference bank for case comparisons for premature and full-term neonates with brain injury.

The Mortality Risk of Proton Pump Inhibitors in 1.9 Million US Seniors: An Extended Cox Survival Analysis

Observational studies have linked proton pump inhibitors (PPIs) with increased risk of mortality and other safety outcomes, in contradiction with a recent PPI randomized controlled trial (RCT). Observational studies may be prone to reverse causality, where deaths are attributed to the treatment rather than the conditions that are treated (protopathic bias). We analyzed an incident drug user cohort of 1,930,728 elderly Medicare fee-for-service beneficiaries to evaluate the PPI-associated risk of death with a Cox regression analysis with time-varying covariates and propensity score adjustments. To correct for protopathic bias which occurs when a given drug is associated with prodromal signs of death, we implemented a lag-time approach by which any study drug taken during a 90-day look-back window before each death was disregarded. Among 1,930,728 study individuals, 80,972 (4.2%) died during a median 3.8 years of follow-up, yielding an overall unadjusted death rate/1000 person-years of 9.85; 14.31 for PPI users and 7.93 for non- users. With no lag-time, PPI use (vs no use) was associated with 10% increased mortality risk (adjusted HR=1.10; 95% CI 1.08-1.12). However, with a lag-time of 90 days, mortality risk associated with PPI use was near zero (adjusted HR=1.01; 95% CI 0.99-1.02). Given the usage patterns of PPIs in patients with conditions that may presage death, protopathic bias may explain the association of PPIs with increased risk of death reported in observational studies.

A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102