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Scoring a polysomnogram is an essential skill for sleep medicine trainees to meet Accreditation Council for Graduate Medical Education Sleep Medicine Milestones. Appraisal is based on faculty evaluation rather than objective competency assessment. We developed a computer-based polysomnogram scoring curriculum, utilizing the mastery learning method, then compared achievement of competency using the new curriculum against standard institutional training.The scoring program consisted of a pretest assessment, sequential acquisition of knowledge utilizing online modules, a posttest, and competency assessment. Fellows needed to demonstrate mastery of each module before moving ahead. Competency was demonstrating ≥ 90% on interscorer reliability assessment on 5 studies (out of up to 10 attempts). Participating fellows were assigned to Mastery Learning Participants (MLP) or Traditional Learning Participants (TLP) groups and completed the program within the first 1-3 months of training.Of 87 fellows enrolled in the program, 75 participants completed the program (40 MLP and 35 TLP). Among completers, there was no difference in the proportion that achieved competency (MLP 90.0% vs TLP 97.1%;We demonstrated similar outcomes utilizing a novel, computer-based modular interactive course compared to traditional methods of teaching polysomnogram scoring. We used a mastery learning paradigm and set specific objective competency levels for this skill.Epstein LJ, Plante DT, Rosen IM. Mastery learning program to teach sleep study scoring.

The coronavirus disease 2019 (COVID-19) pandemic is a reminder that global infectious disease outbreaks are not new and they have the potential to cause catastrophic morbidity and mortality, disrupt health care delivery, demand critical decision making in the absence of scientific certainty, interrupt trainee education, inflict economic damage, and cause a spike in demand for health care services that exceeds societal capacity. In this article, we look back at how the sleep medicine community adapted to challenges imposed by the COVID-19 pandemic. To mitigate viral transmission perhaps the single most effective and efficient adaptation was the rapid adoption of telemedicine. Many additional strategies were taken up virtually overnight, including more home sleep apnea testing, reconsideration of potential risks of positive airway pressure therapy, a reduction or cessation of laboratory services, and deployment of workers to provide frontline care to infected patients. During some periods, critical shortages in essential personal protective equipment, respiratory assist devices, and even oxygen added to logistical challenges, which were exacerbated by persistent financial threats and insufficient staffing. Through ongoing innovation, resiliency, and adaptability, breakthroughs were made in assigning staff responsibilities and designing workflows, using clinical spaces, obtaining legislative support, and achieving professional society collaboration and guidance so that the missions of providing health care, teaching, and academic pursuits could continue. Here we summarize what we have learned through these critical months and highlight key adaptations that deserve to be embraced as we move forward.Khosla S, Beam E, Berneking M, et al. The COVID-19 pandemic and sleep medicine: a look back and a look ahead.

Background and Objective Antimuscarinics, drugs with anticholinergic properties, are frequently prescribed for overactive bladder, and anticholinergic burden is associated with adverse events. The “Polypharmacy: Use of Multiple Anticholinergic Medications in Older Adults” (Poly-ACH) measure was developed by the Pharmacy Quality Alliance and is used by the Centers for Medicare and Medicaid Services. Using the Poly-ACH measure, we assessed the prevalence of anticholinergic polypharmacy among Medicare patients in the USA with overactive bladder and determined associations between polypharmacy and medical conditions, care, and spending. Methods This was a retrospective cohort study of Medicare beneficiaries with overactive bladder (coverage period: 2006–2017). Anticholinergic polypharmacy, measured by the Poly-ACH, was defined as concurrent use of two or more anticholinergics, each with two or more prescription claims on different dates of service for ≥ 30 cumulative days. Change in annual frequency of anticholinergic polypharmacy was assessed using logistic regression. Associations between anticholinergic polypharmacy over 3 years and falls, fractures, mental status, and medical care spending were assessed with longitudinal regression models. Results In total, 226,712 patients contributed 940,201 person-years of follow-up after overactive bladder diagnosis. The share of patients meeting the Poly-ACH definition was 3.3% in 2006 and 1.7% in 2017. Women and nursing home residents had higher risks of anticholinergic polypharmacy. Having 1 year or more of positive Poly-ACH status in the 3 years prior was associated with higher rates of all outcomes. Conclusions Anticholinergic polypharmacy was uncommon among older adults with overactive bladder. Prevalence was higher among women and nursing home residents, and it was associated with negative outcomes, highlighting potential longitudinal implications of anticholinergic burden. Supplementary Information The online version contains supplementary material available at 10.1007/s40266-021-00901-2.

PURPOSE Predicting short-term mortality in patients with advanced cancer remains challenging. Whether digitalized clinical text can be used to build models to enhance survival prediction in this population is unclear. MATERIALS AND METHODS We conducted a single-centered retrospective cohort study in patients with advanced solid tumors. Clinical correspondence authored by oncologists at the first patient encounter was extracted from the electronic medical records. Machine learning (ML) models were trained using narratives from the derivation cohort, before being tested on a temporal validation cohort at the same site. Performance was benchmarked against Eastern Cooperative Oncology Group performance status (PS), comparing ML models alone (comparison 1) or in combination with PS (comparison 2), assessed by areas under receiver operating characteristic curves (AUCs) for predicting vital status at 11 time points from 2 to 52 weeks. RESULTS ML models were built on the derivation cohort (4,791 patients from 2001 to April 2017) and tested on the validation cohort of 726 patients (May 2017-June 2019). In 441 patients (61%) where clinical narratives were available and PS was documented, ML models outperformed the predictivity of PS (mean AUC improvement, 0.039, P < .001, comparison 1). Inclusion of both clinical text and PS in ML models resulted in further improvement in prediction accuracy over PS with a mean AUC improvement of 0.050 ( P < .001, comparison 2); the AUC was > 0.80 at all assessed time points for models incorporating clinical text. Exploratory analysis of oncologist's narratives revealed recurring descriptors correlating with survival, including referral patterns, mobility, physical functions, and concomitant medications. CONCLUSION Applying ML to oncologists' narratives with or without including patient's PS significantly improved survival prediction to 12 months, suggesting the utility of clinical text in building prognostic support tools.

Objective: Menopause is associated with an increased prevalence of sleep difficulties. We evaluated the economic burden of sleep disturbances among working midlife women. Methods: This retrospective, longitudinal cohort study collected data from the US Study of Women's Health Across the Nation (SWAN) database of women age 42-52 years at enrollment. We assessed the association between sleep disturbances (trouble falling asleep, waking early, or nocturnal awakenings) and workplace productivity (employment [yes/no] and work hours/wk) for women who were employed at the baseline visit and had ≥1 follow-up visit. We estimated overall economic burden by multiplying changes in productivity by median age-specific hourly US wages. Each woman's data were compared from visit to visit and were excluded after the first observed unemployment. Regression analysis was used to estimate associations between changes in sleep and changes in workplace productivity while controlling for relevant characteristics that varied over time. Results: The analysis included 2,489 working women (19,707 visits); 31% became unemployed during follow-up. Risk of unemployment was 31% higher for women with versus without new-onset sleep disturbances (P = 0.0474). Onset of sleep disturbances was associated with a 0.44-0.57 hours/wk reduction in work time (not significant). Using the more conservative reduction (0.44 h), sleep problems were associated with an annual loss of $517 to $524 per woman and $2.2 billion/yr in lost productivity among women age 42-64 nationwide. Conclusions: New-onset sleep problems in midlife women are associated with significant increases in risk of unemployment and ∼$2 billion/yr in lost productivity nationwide. Video Summary:.

The human TMPRSS2 gene is pathogenetically implicated in both coronaviral lung infection and prostate cancer, suggesting its potential as a drug target in both contexts. SARS-COV-2 spike polypeptides are primed by the host transmembrane TMPRSS2 protease, triggering virus fusion with epithelial cell membranes followed by an endocytotic internalisation process that bypasses normal endosomal activation of cathepsin-mediated innate immunity; viral co-opting of TMPRSS2 thus favors microbial survivability by attenuating host inflammatory responses. In contrast, most early hormone-dependent prostate cancers express TMPRSS2:ERG fusion genes arising from deletions that eliminate the TMPRSS2 coding region while juxtaposing its androgen-inducible promoter and the open reading frame of ERG, upregulating pro-inflammatory ERG while functionally disabling TMPRSS2. Moreover, inflammatory oxidative DNA damage selects for TMPRSS2:ERG-fused cancers, whereas patients treated with antiinflammatory drugs develop fewer of these fusion-dependent tumors. These findings imply that TMPRSS2 protects the prostate by enabling endosomal bypass of pathogens which could otherwise trigger inflammation-induced DNA damage that predisposes to TMPRSS2:ERG fusions. Hence, the high oncogenic selectability of TMPRSS2:ERG fusions may reflect a unique pro-inflammatory synergy between androgenic ERG gain-of-function and fusogenic TMPRSS2 loss-of-function, cautioning against the use of TMPRSS2-inhibitory drugs to prevent or treat early prostate cancer.

Objectives To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). Methods This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). Results We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115; 69.7%), 1 mg/kg/week (18; 10.9%), 3 mg/kg/week (12; 7.3%) or 1 mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL; P Conclusions One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count

Summary Background Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy. Methods We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years. Findings We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0–75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8–90·9), for 3 years was 97·3% (95·2–98·6), and for 5 years was 98·6% (97·6–100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3–95·9), for 3 years was 97·8% (96·6–99·3), and for 5 years was 96·6% (94·0–98·9). Interpretation These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach. Funding European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d’HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.

The optimal method of fixation of acute Lisfranc injuries is yet to be established. We aim to systematically review the literature to identify the impact of fixation method on postoperative functional outcomes. A systematic review was undertaken using the PRISMA framework to identify all studies reporting postoperative functional outcomes in patients who underwent open-reduction internal fixation of acute Lisfranc injuries. Studies reporting outcomes of numerous fixation methods were divided into fixation subcohorts. Studies comparing bridge plate with transarticular screw fixation were included for meta-analysis, conducted using a random-effects model. Seventeen studies (20 subcohorts) with 462 patients were included. Mean patient age was 29.6 (rang, 15-81) years. Mean follow-up was 38.7 (range 11 to 287) months. American Academy of Orthopaedic Surgeons midfoot score (AOFAS-MF) was the most frequently reported functional outcome (16/20 subcohorts). Overall weighted mean AOFAS-MF was 76.3 ± 9.4 for all cases, with 74.2 ± 9.4 for transarticular screws and 79.2 ± 8.3 for bridge plates. The mean difference between screw and plate was not statistically significant (mean difference = 5.0, 95% confidence interval, -4.8 – 14.8, p = .3). A single study reported AOFAS-MF mean of 92 using suture button fixation. Meta-analysis of the 2 available comparative studies revealed higher postoperative AOFAS-MF with bridge plate fixation (pooled standardized mean difference, 0.51; 95% confidence interval, 0.15-0.87, p = .006). There is scarcity of literature examining the impact of fixation method on postoperative functional outcomes in acute Lisfranc injuries. A small number of studies have reported superior functional outcomes with use of bridge plate fixation. Further evidence is needed to ascertain which injuries are best managed with each fixation method or whether 1 fixation construct is universally superior.

Invasive fungal diseases (IFDs) are common in patients with acute myeloid leukemia (AML), but no recent data on incidence without antifungal prophylaxis are available. We evaluated the incidence of IFDs in patients with AML undergoing induction chemotherapy at Stanford University Hospital from 2012 to 2017, for up to 12 weeks after induction. We also analyzed factors associated with IFD development. Thirty-six of 240 patients (13%) developed at least one proven or probable IFD. Seventy-eight percent of the proven or probable IFDs were due toiCandida/ioriAspergillus/ispecies. Infection due toiFusarium/iandiMucorales/iwas uncommon. Absolute neutrophil count (ANC) oflt;500 µL/L at the start of induction was associated with an increased risk of IFD. One hundred and eighty-seven patients (78%) were started on systemic antifungal drugs, even without microbiologic evidence of an IFD. IFDs remain frequent in AML patients undergoing induction chemotherapy without antifungal prophylaxis.

Background Fungal prostatitis is exceedingly rare with mostly case reports. Methods Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years. Results Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable. Conclusion Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.

Literature and clinical practice around adult-onset hearing loss (HL) has traditionally focused on environmental risk factors, including noise exposure, ototoxic drug exposure, and cardiovascular disease. The most common diagnosis in adult-onset HL is presbycusis. However, the age of onset of presbycusis varies, and patients often describe family history of HL as well as individual variation in progression and severity. In recent years, there has been accumulating evidence of gene-environment interactions underlying adult cases of HL. Susceptibility loci for age-related HL have been identified, and genes related to postlingual nonsyndromic HL continue to be discovered through individual reports and genome-wide association studies. This review will outline main concepts in genetics as related to HL, identify implicated genes, and discuss clinical implications. Laryngoscope, 131:401-409, 2021.

Bronchiolitis obliterans syndrome (BOS)-chronic graft-versus-host disease (cGVHD) affecting the lungs-is an uncommon complication of allogeneic hematopoietic cell transplant (HCT). The epidemiology and complications of lower respiratory tract infections (LRTIs) and community-acquired respiratory viruses (CARVs) in these patients are poorly understood.We aim to characterize the epidemiology of LRTIs in patients with BOS complicating HCT. We also aim to explore the association of LRTIs and CARV detection on lung function in BOS patients.Adult patients with BOS at Stanford Health Care between January 2010 and December 2019 were included in this retrospective cohort study. LRTI diagnosis was based on combined clinical, microbiologic, and radiographic criteria, using consensus criteria where available.Fifty-five patients with BOS were included. BOS was diagnosed at a median of 19.2 (IQR 12.5-24.7) months after HCT, and patients were followed for a median of 29.3 (IQR 9.9-53.2) months from BOS diagnosis. Twenty-two (40%) patients died after BOS diagnosis; 17 patients died from complications of cGVHD (including respiratory failure and infection) and 5 died from relapsed disease. Thirty-four (61.8%) patients developed at least one LRTI. Viral LRTIs were most common, occurring in 29 (52.7%) patients, primarily due to rhinovirus. Bacterial LRTIs-excluding Nocardia and non-tuberculous mycobacteria (NTM)-were the second most common, occurring in 21 (38.2%) patients, mostly due to Pseudomonas aeruginosa. Fungal LRTIs, NTM, and nocardiosis occurred in 14 (25.5%), 10 (18.2%), and 4 (7.3%) patients, respectively. Median time to development of the first LRTI after BOS diagnosis was 15.3 (4.7-44.7) months. Twenty-six (76.5%) of the 34 patients who developed LRTIs had infections due to more than one type of organism-fungi, viruses, Nocardia, NTM, and other bacteria-over the observation period. Patients with at least one LRTI had significantly lower forced expiratory volume in one second percent predicted (FEVLRTIs are common in BOS and associated with lower FEV

To investigate the importance of rare variants in adult-onset hearing loss.Genomic association study.Large biobank from tertiary care center.We investigated rare variants (minor allele frequency5%) in 42 autosomal dominant (DFNA) postlingual hearing loss (HL) genes in 16,657 unselected individuals in the Penn Medicine Biobank. We determined the prevalence of known pathogenic and predicted deleterious variants in subjects with audiometric-proven sensorineural hearing loss. We scanned across known postlingual DFNA HL genes to determine those most significantly contributing to the phenotype. We replicated findings in an independent cohort (UK Biobank).While rare individually, when considering the accumulation of variants in all postlingual DFNA genes, more than 90% of participants carried at least 1 rare variant. Rare variants predicted to be deleterious were enriched in adults with audiometric-proven hearing loss (pure-tone average25 dB;Although prior reports have focused on common variants, we find that rare predicted deleterious variants in DFNA postlingual HL genes are enriched in patients with adult-onset HL in a large health care system population. We show the value of investigating rare variants to uncover hearing loss phenotypes related to implicated genes.

OBJECTIVE: Psychiatric hospitalizations and emergency department (ED) visits occur more frequently for children with autism spectrum disorder (ASD). One mechanism that may reduce the likelihood of these events is the utilization of home and community-based care. Using rich commercial claims data and a rigorous analytical framework, this study examines whether spending on outpatient services for ASD, including occupational, physical, and speech therapies and other behavioral interventions, reduces the likelihood of psychiatric hospitalizations and ED visits. METHODS: The study sample comprised over 100,000 children with ASD and commercial insurance in 50 states between 2008 and 2012. The authors estimated maximum-likelihood complementary log-log link survival models with robust standard errors. The outcomes of interest were a hospitalization or an ED visit with an associated psychiatric diagnosis code (ICD-9-CM 290 through 319) in a given week. RESULTS: A $125 increase in weekly spending on ASD-specific outpatient services 7 to 14 weeks prior to a given week reduced the likelihood of a psychiatric hospitalization by 2% in that week. ASD-specific outpatient spending during the 6 weeks prior to a psychiatric hospitalization did not decrease its risk. Spending on ASD-specific outpatient services did not reduce the likelihood of a psychiatric ED visit. CONCLUSIONS: The financial burden associated with ASD is extensive and psychiatric hospitalizations remain the most expensive type of care, costing over $4,000 per week on average. Identifying the mechanisms by which psychiatric hospitalizations occur can reduce the likelihood of these events.

Introduction Immune-mediated inflammatory diseases (IMIDs) cause significant impairment in quality of life. Although they share similar genetic factors, environmental precipitants, and pathophysiological mechanisms, there is little evidence on the risk of developing subsequent IMIDs after an initial IMID diagnosis. We sought to assess the risk of developing subsequent IMIDs among patients diagnosed with an initial IMID. Methods This retrospective matched cohort study used a large US commercial health insurance claims database (01/01/2006–09/30/2015). The risks of developing secondary IMIDs among patients aged 18–64 years with a diagnosis of one of nine IMIDs of interest (ankylosing spondylitis, celiac disease, hidradenitis suppurativa [HS], inflammatory bowel disease, lupus, psoriatic arthritis [PsA], psoriasis, rheumatoid arthritis, and uveitis) as identified from diagnosis codes on medical claims were compared with up to 1000 matched controls without the primary IMID using Cox proportional hazards models. Results Across the nine IMIDs of interest, there were 398,935 unique case patients matched to 256,795,796 non-unique control patients. Case patients with an initial IMID had higher risks of developing each, any one, and any two of the other eight secondary IMIDs compared to their matched controls. Hazard ratios [95% confidence intervals] for the risk of developing any one secondary IMID ranged from 5.4 [5.0, 5.8] (initial IMID: HS) to 62.2 [59.9, 64.6] (initial IMID: PsA), and hazard ratios for developing any two secondary IMIDs ranged from 3.0 [2.3, 3.8] (HS) to 75.2 [69.3, 81.7] (PsA). Conclusions This study demonstrates that the risk of developing a second IMID is significantly higher for individuals who have already experienced a first IMID in a large and contemporary US claims database. Certain pairs of IMIDs co-occur more frequently than others. The risk of developing subsequent IMIDs may be an important consideration for clinicians when selecting treatment strategies. Funding Abbvie. Electronic Supplementary Material The online version of this article (10.1007/s12325-019-00964-z) contains supplementary material, which is available to authorized users.

Background Worst-case, typical, and best-case scenarios for survival, based on simple multiples of an individual's expected survival time (EST), estimated by their oncologist, are a useful way of formulating and explaining prognosis. We aimed to determine the accuracy and prognostic significance of oncologists’ estimates of EST, and the accuracy of the resulting scenarios for survival time, in advanced gastric cancer. Materials and Methods Sixty-six oncologists estimated the EST at baseline for each of the 152 participants they enrolled in the INTEGRATE trial. We hypothesized that oncologists’ estimates of EST would be unbiased (∼50% would be longer or shorter than the observed survival time [OST]); imprecise ( Results Oncologists’ estimates of EST were unbiased (45% were shorter than the OST, 55% were longer); imprecise (29% were within 0.67–1.33 times observed); moderately discriminative (Harrell's C-statistic 0.62, p = .001); and an independently significant predictor of OS (hazard ratio, 0.89; 95% confidence interval, 0.83–0.95; p = .001) in a Cox model including performance status, number of metastatic sites, neutrophil-to-lymphocyte ratio ≥3, treatment group, age, and health-related quality of life (EORTC-QLQC30 physical function score). Scenarios for survival time derived from oncologists’ estimates were remarkably accurate: 9% of patients died within a quarter of their EST, 57% lived within half to double their EST, and 12% lived three times their EST or longer. Conclusion Oncologists’ estimates of EST were unbiased, imprecise, moderately discriminative, and independently significant predictors of OS. Simple multiples of the EST accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer. Implications for Practice Results of this study demonstrate that oncologists’ estimates of expected survival time for their patients with advanced gastric cancer were unbiased, imprecise, moderately discriminative, and independently significant predictors of overall survival. Simple multiples of the expected survival time accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer.

Evidence suggests that elective primary colon resection (ePCR) in patients with asymptomatic colon tumors and unresectable metastases is not required and may expose patients to unnecessary operative risk.Stage IV colon cancer patients with liver metastases from 2000 to 2011 were identified with SEER-Medicare data. Liver-based therapy or urgent/emergent colectomies were excluded. Chemotherapy alone was compared to ePCR ± chemotherapy. Univariate and multivariate analyses were used to identify predictors of ePCR. Multivariate Cox regression compared survival.5139 patients were identified. The ePCR rate decreased over time; 84% underwent ePCR in 2000, compared to 52% in 2011 (p 0.001). In multivariate analysis, older patients were more likely to undergo ePCR, as were patients from rural areas (OR 1.65, p 0.001). The odds of PCR in high poverty areas (10%) were almost 25% higher than those in low poverty areas (OR 1.23, p = 0.03). African-Americana were less likely to undergo PCR than Caucasians (OR 0.76, p = 0.01). In multivariate survival analysis, PCR was associated with a significant survival benefit (HR 0.59, p 0.001).Although ePCR is not recommended with unresectable metastases and the rate has decreased significantly, over 50% of patients with untreated hepatic metastases underwent ePCR in 2011. Disparities exist in use of ePCR that are likely multifactorial and deserve further study.

Progress in the management of non-muscle invasive bladder cancer has been slow. Despite longstanding use of intravesical therapies (e.g., Bacille Calmette-Guerin; BCG) to complement cystoscopic resection of high-grade lesions, many patients still develop recurrences requiring cystectomy, while others suffer side-effects of BCG without definite benefit. Many questions remain: for example, how many patients receive intravesical prophylaxis without efficacy? Which high-risk patients are best managed with early cystectomy? Could systemic therapies and/or radiotherapy extend bladder preservation times? Such questions may soon be refined by clinicopathologic non-muscle invasive bladder cancer signatures that predict sensitivity to cytotoxic, immune and targeted therapies. Hypothesis-based trials using these signatures should lead to more rational adjuvant treatments, longer bladder preservation times, and better quality of life for patients.

"Cookie-bite" or U-shaped audiograms-specifically, those showing midfrequency sensorineural hearing loss (HL)-are traditionally taught to be associated with genetic HL; however, their utility as a screening tool has not been reported. We aim to determine the performance of a cookie-bite audiogram shape in stratifying patients carrying putative loss-of-function variants in known HL genes from wild-type controls. We merged audiometric and exome sequencing data from adults enrolled in a large biobank at a tertiary care center. Of 321 patients, 50 carried a putative loss-of-function variant in an HL gene. The cookie-bite shape was present in 9 of those patients, resulting in low sensitivity (18%) and positive predictive value (15%) in stratifying genetic carrier status; 84% of patients with a cookie-bite audiogram did not carry a genetic variant. A cookie-bite audiogram should not be used to screen adults for possible genetic testing.

International audience; INTRODUCTION: Evaluating the quality of the care pathway for patients with chronic diseases, such as multiple sclerosis (MS), is an important issue. Process indicators are a recognized method for evaluating professional practices. However, these tools have been little developed in the field of MS, and few data are available. The aim of this study was to describe, retrospectively, with validated indicators, the quality of the care pathway in a population-based cohort of 700 patients with the first manifestations of the disease occurring between January 1, 2000 and December 31, 2001 and during the first 10 years of disease. METHOD: This assessment was based on 48 indicators specific to MS. The information required for the calculation of each indicator was collected from the source files of the 700 patients of the cohort. RESULTS: Data for the 10 years of follow-up were collected for 80% of the patients. In total, 36 indicators were calculated. These results reveal that there is room for improvement, particularly in terms of the initial assessment, access to ophthalmological evaluation, employment, obtaining an evaluation of the need for rehabilitation and access to such care. CONCLUSION: The results of this survey provide access to unprecedented new data in France, that professionals and patients can appropriate to improve the targeting of actions, to improve the quality of care further for patients with MS in France. We propose to continue this process by submitting, for discussion, a targeted list of updated indicators relating to changes in guidelines, and in issues concerning the quality of patient management.

Ability to assess flares in osteoarthritis (OA) of the knee and hip (KHOA) is important in clinical care and research. Using mixed methods, we developed a self-reported instrument measuring flare and assessed its psychometric properties.We constructed questionnaire items from semi-structured interviews and a focus group (patients, clinicians) by using a dual-language (English-French) approach. A Delphi consensus method was used to select the most relevant items. Patients with OA from Australia, France and the United States completed the preliminary Flare-OA, HOOS, KOOS and Mini-OAKHQOL questionnaires online. We used a factor analysis and content approach to reduce items and determine structural validity. We tested the resulting questionnaire (score 0-100) for internal consistency, convergent and known-groups validity.Initially, 180 statements were generated and reduced to 33 items in five domains (response 0 = not at all, to 10 = absolutely) by Delphi consensus (50 patients, 116 professionals) and an expert meeting. After 398 patients (mean [SD] age 64 [8.5] years, 70.4% female, 86.7% knee OA) completed the questionnaire, it was reduced to 19 items by factor analysis and a content approach (RMSEA = 0.06; CFI = 0.96; TLI = 0.94). The Cronbach's alpha was0.9 for the five domains and the whole questionnaire. Correlation coefficients between Flare-OA and other instrument scores were as predicted, supporting construct validity. The difference in Flare-OA score between patients with and without flare (31.8) largely exceeded 2 SEM (10.2).Flare-OA is a valid and reliable patient-reported instrument for assessing the occurrence and severity of flare in patients with KHOA in clinical research.

The COVID-19 pandemic led to widespread use of telemedicine and highlighted its importance in improving access to sleep care and advocating for sleep health. This update incorporates the lessons learned from such widespread utilization of telehealth to build on the American Academy of Sleep Medicine’s 2015 position paper on the use of telemedicine for diagnosing and treating sleep disorders. Important key factors in this update include an emphasis on quality and value, privacy and safety, health advocacy through sleep telemedicine, and future directions. CITATION: Shamim-Uzzaman QA, Bae CJ, Ehsan Z, et al. The use of telemedicine for the diagnosis and treatment of sleep disorders: an American Academy of Sleep Medicine update. J Clin Sleep Med. 2021;17(5):1103–1107.

Telemedicine has been widely implemented during the coronavirus disease 2019 (COVID-19) pandemic; however, its impact on those providing care remains largely understudied. Provider documentation data collected by the electronic health record (EHR) represents an underutilized tool for assessing the provider experience. Through Epic Signal, we collected data regarding the actions logged in the EHR by health care providers of the Montefiore Health System (Bronx, NY) before and after the implementation of telemedicine during the pandemic. Focusing on five metrics (appointments per day, visits closed same day, time spent outside 7 AM-7 PM, time spent on unscheduled days, and pajama time), we performed a preliminary analysis of providers across the institution, by specialty, and according to demographic characteristics such as gender and years since graduation. We observed that after telemedicine implementation, a greater proportion of providers had fewer appointments per day, closed more notes same day, and spent less time in the EHR outside of normal working hours for each of the time-related metrics. We additionally found that providers who graduated longer ago as well as female providers spent more time documenting in the EHR after hours. This brief analysis highlights the potential of using EHR data to inform decisions based on provider well-being, specifically in the setting of telemedicine implementation.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep–wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

Background Patient reported outcomes (PROs) are critical for delivering high quality surgical care yet they are seldom collected in routine clinical practice. The objective of this quality improvement study was to improve routine PROs collection in a thoracic surgery clinic. Methods Thoracic surgery patients at a single academic institution were prospectively followed from April 2019 to March 2020. The National Institutes of Health (NIH)-validated Patient-Reported Outcomes Measurement Information System (PROMIS) was employed. Using a Model for Improvement design and through multidisciplinary participant observation, multiple plan-do-study-act (PDSA) cycles (an iterative, four-stage model for rapidly testing interventions) were performed to improve routine collection reliability. Results Over the study period, a total of 2,315 patient visits occurred. The baseline PROMIS assessment collection rate was 53%. After convening a multidisciplinary stakeholder team, the key drivers for PROMIS collection were having engaged staff, engaged patients, adequate technological capacity, and adequate time for survey completion (including when to complete the survey during the patient visits). Regular meetings between stakeholders were initiated to promote these key drivers. Several PDSA cycles were then employed to test different interventions, resulting in several positive system shifts as demonstrated on statistical process control (SPC) chart. Adherence to survey collection reached 91% of office visits by approximately 7 months, a 72% relative improvement, which was sustained. Conclusions Routine collection of PROs, such as PROMIS, are critical for improving thoracic surgical care. Our study shows that reliably collecting these data is possible in a clinical setting with minimal additional hospital resources.

In mammals, sound is detected by mechanosensory hair cells that are activated in response to vibrations at frequency-dependent positions along the cochlear duct. We demonstrate that inner ear supporting cells provide a structural framework for transmitting sound energy through the cochlear partition. Humans and mice with mutations in GAS2, encoding a cytoskeletal regulatory protein, exhibit hearing loss due to disorganization and destabilization of microtubule bundles in pillar and Deiters' cells, two types of inner ear supporting cells with unique cytoskeletal specializations. Failure to maintain microtubule bundle integrity reduced supporting cell stiffness, which in turn altered cochlear micromechanics in Gas2 mutants. Vibratory responses to sound were measured in cochleae from live mice, revealing defects in the propagation and amplification of the traveling wave in Gas2 mutants. We propose that the microtubule bundling activity of GAS2 imparts supporting cells with mechanical properties for transmitting sound energy through the cochlea.

Aims To study the association between initiation of first adjunctive therapy with eslicarbazepine acetate (ESL) vs. brivaracetam (BRV) on healthcare resource utilization (HCRU) and charges among patients with treated focal seizures (FS). Materials and methods Symphony Health's Integrated Dataverse (IDV) claims data (1 April 2015 to 30 June 2018) were used to identify two cohorts as first adjunctive therapy with ESL or BRV following a generic anti-seizure drug (ASD). The index date was the earliest claim for a new ESL or BRV prescription. Key inclusion criteria were only 1 generic ASD in the 12 months before the index date; ≥1 medical claim with an FS diagnosis. Unit of analysis was the 90-day person-time-block. Changes in HCRU and charges were assessed using a difference-in-differences framework. Both unadjusted and adjusted analyses were performed. The adjusted model utilized person-specific fixed effects and propensity score-based weighting to control for differences in baseline covariates. Bias-corrected bootstrap confidence intervals (CIs) were calculated for charge outcomes. Results 208 and 137 patients initiated first adjunctive therapy with ESL (43.7 years, 51.9% female) or BRV (39.3 years, 51.8% female). Patients in the ESL cohort had numerically larger reductions in all-cause and FS-related inpatient hospitalizations and outpatient visits and FS-related emergency department visits. Compared to patients initiating BRV, patients treated with ESL had significantly larger reductions in total charges (-$3,446, CI: -$13,716, -$425), all-cause (-$3,166, CI: -$13,991, -$323) and FS-related (-$2,969, CI: -$21,547, -$842) medical charges, all-cause (-$3,397, CI: -$15,676, -$818) and FS-related (-$2,863, CI: -$19,707, -$787) outpatient charges, and non-ASD-related prescription charges (-$420, CI: -$1,058, -$78). Limitations Claims may be missing, or miscoded; outcomes may be influenced by variables not accounted for in the analysis; only information on submitted charges was included. Conclusions Among patients with FS, initiation of first adjunctive therapy with ESL was associated with significantly larger reductions in medical and non-ASD-related prescriptions charges compared to BRV.

While newborns and children with hearing loss are routinely offered genetic testing, adults are rarely clinically tested for a genetic etiology. One clinically actionable result from genetic testing in children is the discovery of variants in syndromic hearing loss genes. EYA4 is a known hearing loss gene which is also involved in important pathways in cardiac tissue. The pleiotropic effects of rare EYA4 variants are poorly understood and their prevalence in a large cohort has not been previously reported. We investigated cardio-auditory phenotypes in 11,451 individuals in a large biobank using a rare variant, genome-first approach to EYA4. We filtered 256 EYA4 variants carried by 6737 participants to 26 rare and predicted deleterious variants carried by 42 heterozygotes. We aggregated predicted deleterious EYA4 gene variants into a combined variable (i.e. "gene burden") and performed association studies across phenotypes compared to wildtype controls. We validated findings with replication in three independent cohorts and human tissue expression data. EYA4 gene burden was significantly associated with audiometric-proven HL (p = [Formula: see text], Mobitz Type II AV block (p = [Formula: see text]) and the syndromic presentation of HL and primary cardiomyopathy (p = 0.0194). Analyses on audiogram, echocardiogram, and electrocardiogram data validated these associations. Prior reports have focused on identifying variants in families with severe or syndromic phenotypes. In contrast, we found, using a genotype-first approach, that gene burden in EYA4 is associated with more subtle cardio-auditory phenotypes in an adult medical biobank population, including cardiac conduction disorders which have not been previously reported. We show the value of using a focused approach to uncover human disease related to pleiotropic gene variants and suggest a role for genetic testing in adults presenting with hearing loss.

BACKGROUND: eConsult programs have been instituted to increase access to specialty expertise. Opt-in choice eConsult programs maintain primary care physician (PCP) autonomy to decide whether to utilize eConsults versus traditional specialty referrals, but little is known about how this intervention may impact PCP eConsult adoption and traditional referral demand. OBJECTIVE: We assessed the feasibility of implementing an opt-in choice eConsult program and examined whether this intervention reduces demand for in-person visits for primary care patients requiring specialty expertise. DESIGN: Stepped-wedge, cluster randomized trial conducted from July 2018 to June 2019. PARTICIPANTS: Sixteen primary care practices in a large, urban academic health care system. INTERVENTION: Our intervention was an opt-in choice eConsult available in addition to traditional specialty referral; our implementation strategy included in-person training, audit and feedback, and incentive payments. MAIN MEASURES: Our implementation outcome measure was the eConsult rate: weekly proportion of eConsults per PCP visit at each site. Our intervention outcome measure was traditional referral rate: weekly proportion of referrals per PCP visit at each site. We also assessed PCP experiences with questionnaires. KEY RESULTS: Of 305,915 in-person PCP visits, there were 31,510 traditional referrals to specialties participating in the eConsult program, and 679 eConsults. All but one primary care site utilized the opt-in choice eConsult program, with a weekly rate of 0.05 eConsults per 100 PCP visits by the end of the study period. The weekly rate of traditional referrals was 11 per 100 PCP visits at the end of the study period; this represents a significant increase in traditional referral rate after implementation of eConsults. PCPs were generally satisfied with the eConsult program and valued prompt provider-to-provider communication. CONCLUSIONS: Implementation of an opt-in choice eConsult program resulted in widespread PCP adoption; however, this did not decrease the demand for traditional referrals. Future studies should evaluate different strategies to incentivize and increase eConsult utilization while maintaining PCP choice.

ObjectiveWe sought to assess the prevalence, correlates, and consequences of periodic limb movements of sleep (PLMS) in persons with obstructive sleep apnea (OSA) and the effect (worsening or improvement) of continuous positive airway pressure (CPAP) therapy on PLMS in a large prospective multicenter randomized controlled trial.MethodsWe performed retrospective analyses of data from the Apnea Positive Pressure Long-term Efficacy Study, a prospective multicenter randomized controlled trial. A total of 1,105 persons with OSA enrolled in this study underwent a polysomnographic investigation at baseline, another one for CPAP titration, and another study 6 months after randomization to either active CPAP or sham CPAP.ResultsOf all participants, 19.7% had PLM index (PLMI) ≥10/hour, 14.8% had PLMI ≥15/hour, 12.1% had PLMI ≥20/hour, 9.3% had PLMI ≥25/hour, and 7.5% had PLMI ≥30/hour. The odds of having a PLMI ≥10 were higher in older participants (odds ratio [OR] 1.03, p < 0.001), men (OR 1.63. p = 0.007), those using antidepressants (OR 1.48. p = 0.048), and those with higher caffeine use (OR 1.01, p = 0.04). After controlling for OSA and depression, PLMS were associated with increased sleep latency, reduced sleep efficiency, and reduced total sleep time. No significant relationships were noted between PLMS frequency and subjective sleepiness (Epworth Sleepiness Scale score) or objective sleepiness (Maintenance of Wakefulness Test). There was no differential effect of CPAP in comparison to sham CPAP on PLMS after 6 months of therapy.ConclusionsPLMS are common in patients with OSA and are associated with a significant reduction in sleep quality over and above that conferred by OSA. Treatment with CPAP does not affect the severity of PLMS.

The path for physicians to become credentialed sleep medicine specialists has changed in many ways in the last few decades. Currently, sleep medicine is recognized as an independent subspecialty with appropriately rigorous and comprehensive training required to become a board-certified sleep medicine physician. However, added time for requisite fellowship training, coupled with an aging sleep medicine physician workforce, have had the unintended consequence of decreasing the number of sleep medicine physicians at a time when the demands for sleep medicine care continue to rise. Thus, new training pathways that provide flexibility to trainees, while ensuring high-quality, comprehensive, and multidisciplinary sleep medicine training are needed to maintain a workforce that can meet the sleep health needs of the present and future. Here, we describe two pilot programs that apply principles of competency-based medical education to sleep medicine fellowship training. These novel models are likely to attract additional well-qualified physicians to the field who might otherwise not pursue a career in sleep medicine. CITATION: Plante DT, Epstein LJ, Fields BG, Shelgikar AV, Rosen IM. Competency-based sleep medicine fellowships: addressing workforce needs and enhancing educational quality. J Clin Sleep Med. 2020;16(1):137–141.

To evaluate terpinen-4-ol lid scrubs (Cliradex) with Microblepharoexfoliation (MBE) (BlephEx) in the treatment of Demodex blepharitis.An Institutional Review Board (IRB) approved the randomized prospective double-masked trial of 50 patients with Demodex positive blepharitis. All subjects were given an in-office MBE treatment and randomized to masked lid scrubs (terpinen-4-ol or sham) twice daily for 1 month. All subjects then returned for an additional MBE treatment and received open-label terpinen-4-ol scrubs twice daily for 1 month.Demodex levels, Ocular Surface Disease Index, tear osmolarity, MMP-9, Schirmer 1 and grading of the lid margin appearance, meibomian gland dropout, and meibomian gland secretions.Forty-six subjects (23 per group) were included for the analysis; 4 lost to follow up. Total Demodex folliculorum levels in the Cliradex group improved: 4.7 to 3.6 (first month interval P = 0.266) to 2.6 (second month interval P = 0.279), overall P0.05 over 2 months. Total levels in the sham group improved: 5.1 to 3.0 (first month interval P0.05) to 2.5 (second month interval P = 0.496), overall P0.05 over 2 months. No clear statistically meaningful improvements in other dry eye and blepharitis data metrics were observed.In-office MBE treatments combined with either Cliradex terpinen-4-ol medicated lid scrubs or sham scrubs showed a statistically significant reduction in D. folliculorum infestation levels; however, conclusions on clinical significance could not be made. In-office MBE with terpinen-4-ol lid scrubs showed no significant improvement over sham scrubs.

Summary Objectives To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS). Methods Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death). Time to failure and survival were calculated by Kaplan–Meier analysis. Results From March 2011 to May 2016, 113 patients who received at least 2 doses of prophylaxis were analyzed (58 patients randomized to micafungin and 55 to posaconazole). Prophylaxis failure occurred in 34.5% and 52.7% of patients on micafungin and posaconazole, respectively (P = 0.0118). The median number of days on prophylaxis was 16 [interquartile range (IQR) 12–20] for micafungin and 13 [IQR 6–16] for posaconazole (P = 0.01). Micafungin failures were largely due to antifungal treatment; posaconazole failures were mostly due to gastrointestinal intolerance or adverse effects. IFI incidence and survival were similar between study arms. Conclusions Our data support micafungin as alternative antifungal prophylaxis in patients with AL and MDS.

Physicians are increasingly being held accountable for patient outcomes, yet their specific contribution to the outcomes remains uncertain.To determine variation in outcomes of mechanically ventilated patients among intensivists, as well as associations between intensivist experience and patient outcomes.We performed a retrospective cohort study of mechanically ventilated Medicare fee-for-service patients in acute care hospitals in Pennsylvania using administrative, clinical, and physician data from Centers for Medicare and Medicaid Services and the American Medical Association from 2008 and 2009. We identified intensivists by training background, board certification, and claims for services provided to patients admitted to an intensive care unit. We assigned patients to intensivists for outcome attribution based on submitted claims for critical care and in-patient services. We estimated the physician-specific adjusted odds ratios (ORs) for 30-day mortality using a hierarchical model with a random effect for physician, adjusted for patient and hospital characteristics. We tested for independent association of physician experience with patient outcomes using mixed-effects regression for the primary outcome of 30-day mortality. We defined physician experience in two ways: years since training completion ("duration") and annual number of mechanically ventilated patients ("volume").We assigned 345 physicians to 11,268 patients. The 30-day mortality was 43% and median hospital length of stay was 11 days (interquartile range = 6-18). The physician adjusted OR varied from 0.72 to 1.64 (median = 0.99; interquartile range = 0.92-1.09). A total of 48% of physicians was outliers, with an adjusted OR significantly different from 1. However, among intensivists, physician experience was not associated with 30-day mortality (duration OR = 1.00 per additional year; 95% confidence interval = 1.00-1.01; volume OR = 1.00 per additional patient; 95% confidence interval = 1.00-1.00).Intensivists independently contribute to outcomes of Medicare patients who undergo mechanical ventilation, as evidenced by the variation in risk-adjusted mortality across intensivists. However, physician experience does not underlie this relationship between intensivists, suggesting the need to identify modifiable physician factors to improve outcomes.

OBJECTIVES: There is substantial variation in treatment intensity among children with autism spectrum disorder (ASD). This study asks whether policies that target health care utilization for ASD affect children differentially based on this variation. Specifically, we examine the impact of state-level insurance mandates that require commercial insurers to cover certain treatments for ASD for any fully-insured plan. METHODS: Using insurance claims between 2008 and 2012 from three national insurers, we used a difference-in-differences approach to compare children with ASD who were subject to mandates to children with ASD who were not. To allow for differential effects, we estimated quantile regressions that evaluate the impact of mandates across the spending distributions of three outcomes: (1) monthly spending on ASD-specific outpatient services, (2) monthly spending on ASD-specific inpatient services, and (3) quarterly spending on psychotropic medications. RESULTS: The change in spending on ASD-specific outpatient services attributable to mandates varied based on the child’s level of spending. For those children with ASD who were subject to the mandate, monthly spending for a child in the 95(th) percentile of the ASD-specific outpatient spending distribution increased by $1,460 (p

Objective Many states with mandates requiring commercial insurers to cover autism spectrum disorder (ASD) health services specify upper age limits above which coverage is no longer mandated. It is unknown what effects these age caps have on health service use and spending among adolescents who have exceeded the age cap. Method Using administrative claims data from 3 national commercial insurers, a difference-in-differences approach was used to estimate effects of age caps on health service use and spending among adolescents with ASD. Statistical models compared changes in use and spending between those above versus below the age cap among individuals eligible versus ineligible for mandated coverage. The analytic sample included data from 2008 through 2012 on 7,845 individuals (151,976 person-months) ages 10 to 21 years in 11 states imposing mandate age caps going into effect during adolescence. Results Age caps were associated with 4.2 percentage point (95% CI = −7.0, −1.5) lower probability of any ASD-specific service use in a month and $69 less (95% CI = −112, −$26) in average monthly spending on ASD-specific services than would have been expected given concomitant pre−post age cap differences among individuals in the same states who were never eligible for mandate-covered services. In addition, age caps were associated with $99 (95% CI = −$168, −$30) lower average monthly spending on all health care services. Conclusion Insurance mandates that include age caps going into effect during adolescence reduce health service use and spending among individuals with ASD during a critical phase of the life course.

Antifungal prophylaxis is the standard of care for patients undergoing intensive chemotherapy for haematological malignancy or haematopoietic cell transplantation (HCT). Prophylaxis with azoles reduces invasive fungal infections and may reduce mortality. However, breakthrough infections still occur, and the use of azoles is sometimes complicated by pharmacokinetic variability, drug interactions, adverse events and other issues. Echinocandins are highly active against Candida species, including some organisms resistant to azoles, and have some clinical activity against Aspergillus species as well. Although currently approved echinocandins require daily intravenous administration, the drugs have a favourable safety profile and more predictable pharmacokinetics than mould-active azoles. Clinical data support the efficacy and safety of echinocandins for antifungal prophylaxis in haematology and HCT patients, though data are less robust than for azoles. Notably, sparse evidence exists supporting the use of echinocandins as antifungal prophylaxis for patients with significant graft-versus-host disease (GvHD) after HCT. Two drugs that target (1,3)-β-d-glucan are in development, including an oral glucan synthase inhibitor and an echinocandin with unique pharmacokinetics permitting subcutaneous and weekly administration. Echinocandins are a reasonable alternative to azoles and other agents for antifungal prophylaxis in patients undergoing intensive chemotherapy for haematological malignancy or those receiving HCT, excluding those with significant GvHD.

Citation:Sullivan S, Anastasi M, Beam E, et al. Opportunities and unknowns in adapting pediatric sleep practices to a pandemic world. J Clin Sleep Med. 2021;17(3):361–362.

Introduction We sought to characterize changes in healthcare spending associated with the onset of 22 endometriosis-related comorbidities. Methods Women aged 18–49 years with endometriosis (N = 180,278) were extracted from 2006–2015 de-identified Clinformatics® DataMart claims data. For 22 comorbidities, comorbidity patients were identified on the basis of having a first comorbidity diagnosis after their initial endometriosis diagnosis. Controls were identified on the basis of having no comorbidity diagnosis and were matched 1:1 to comorbidity patients on demographics and baseline spending. Total medical and pharmacy spending was measured during 12 months before and after each patient’s index date (first comorbidity diagnosis for comorbidity patients, and equal number of days after earliest endometriosis claim for controls). Pre–post spending differences were compared using difference-in-differences linear regression. Total and comorbidity-related cumulative spending per patient for all endometriosis patients were calculated annually for the 5 years following endometriosis diagnosis. Results The number of endometriosis patients with each comorbidity varied between 121 for endometrial cancer and 16,177 for fatigue. Healthcare spending increased significantly with the onset of eight comorbidities: breast cancer, ovarian cancer, pregnancy complications, systemic lupus erythematosus/rheumatoid arthritis/Sjogren’s/multiple sclerosis, infertility, uterine fibroids, ovarian cyst, and headache [p

Forty-six states and the District of Columbia have enacted insurance mandates that require commercial insurers to cover treatment for children with autism spectrum disorder (ASD). This study examined whether implementing autism mandates altered service use or spending among commercially insured children with ASD. We compared children age twenty-one or younger who were eligible for mandates to children not subject to mandates using 2008-12 claims data from three national insurers. Increases in service use and spending attributable to state mandates were detected for all outcomes. Mandates were associated with a 3.4-percentage-point increase in monthly use and a $77 increase in monthly spending on ASD-specific services. Effects were larger for younger children and increased with the number of years since mandate implementation. These increases suggest that state mandates are an effective tool for broadening access to autism treatment under commercial insurance.

The objective of this study was to measure internal medicine resident engagement with an electronic medical record-based dashboard providing feedback on their use of routine laboratory tests relative to service averages. From January 2016 to June 2016, residents were e-mailed a snapshot of their personalized dashboard, a link to the online dashboard, and text summarizing the resident and service utilization averages. We measured resident engagement using e-mail read-receipts and web-based tracking. We also conducted 3 hour-long focus groups with residents. Using grounded theory approach, the transcripts were analyzed for common themes focusing on barriers and facilitators of dashboard use. Among 80 residents, 74% opened the e-mail containing a link to the dashboard and 21% accessed the dashboard itself. We did not observe a statistically significant difference in routine laboratory ordering by dashboard use, although residents who opened the link to the dashboard ordered 0.26 fewer labs per doctor-patient-day than those who did not (95% confidence interval, -0.77 to 0.25; 𝑃 = 0 .31). While they raised several concerns, focus group participants had positive attitudes toward receiving individualized feedback delivered in real time.

Vast amounts of clinically relevant text-based variables lie undiscovered and unexploited in electronic medical records (EMR). To exploit this untapped resource, and thus facilitate the discovery of informative covariates from unstructured clinical narratives, we have built a novel computational pipeline termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator discovery (TEPAPA). This pipeline combines semantic-free natural language processing (NLP), regular expression induction, and statistical association testing to identify conserved text patterns associated with outcome variables of clinical interest. When we applied TEPAPA to a cohort of head and neck squamous cell carcinoma patients, plausible concepts known to be correlated with human papilloma virus (HPV) status were identified from the EMR text, including site of primary disease, tumour stage, pathologic characteristics, and treatment modalities. Similarly, correlates of other variables (including gender, nodal status, recurrent disease, smoking and alcohol status) were also reliably recovered. Using highly-associated patterns as covariates, a patient’s HPV status was classifiable using a bootstrap analysis with a mean area under the ROC curve of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping tasks. These data support using this integrative approach to efficiently identify disease-associated factors from unstructured EMR narratives, and thus to efficiently generate testable hypotheses.

Introduction The International Immune Tolerance Study (I-ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time-to-treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI. Aim and Methods An economic model was developed to compare high dose ITI to low dose ITI with BAP. All model inputs were derived from clinical trials. The I-ITI study indicated a median time to negative inhibitor titre of 4.6 and 9.2 months and average number of bleeds/patient of 4.2 and 9.9 for the high and low dose regimens respectively. Based on the BAP trials, aPCC (85 U/kg/TIW) and rFVIIa (90 μg/kg/day) achieved a 62% and 45% reduction in bleeding frequency respectively. Cost analysis was from a US third party payer perspective and limited to drug costs. One-way, two-way and probabilistic sensitivity analyses were performed. Results Costs of low dose ITI with aPCC prophylaxis until negative inhibitor titre is achieved was 24.0% less compared to high dose ITI. Low dose ITI with rFVIIa prophylaxis cost 46.5% more compared to high dose ITI. Model results were robust in the majority of the sensitivity analyses. Conclusion A low dose ITI regimen with aPCC prophylaxis may be cost saving compared to a high dose ITI regimen with the potential to reduce morbidity by lowering the risk for breakthrough bleeds.

A 41-year-old man presented 10 years after uneventful laser in situ keratomileusis (LASIK) with symptomatic post-LASIK ectasia. He had treatment with the classic Dresden epithelium-off technique and presented 4 years later with progression of the ectasia. He was subsequently retreated with conductive keratoplasty (CK) followed by a new proprietary epithelium-on corneal collagen crosslinking (CXL) procedure using a proprietary transepithelial riboflavin formulation and delivery system on the following day. One year after retreatment, the patient noted stable vision in the treated eye with a corrected distance visual acuity (CDVA) of 20/60 + . Thus, epithelium-on CXL, if performed with appropriate formulations and delivery technology as well as careful attention to appropriate riboflavin loading of the stroma, can stabilize an ectatic cornea. In addition, when performed prior to CXL, CK can induce a significant, lasting improvement in corneal shape and CDVA. This technique merits further study.

To present a case of microsporidial keratitis in a femtosecond laser-created astigmatic keratotomy (AK) incision.Case report.A 65-year-old Middle Eastern man presented 2 months after uncomplicated femtosecond laser-assisted cataract surgery (FLACS) and AK with mildly decreased vision and corneal edema in the operative eye. Shortly after treatment with topical corticosteroids, a fulminant corneal infiltrate manifested along the temporal arcuate incision. Multiple corneal scrapings sent for laboratory analysis were inconclusive. Two weeks after the initial presentation, a deep tissue sample was obtained using a 27-gauge cannula passed within the arcuate incision. The gram stain was directly observed, revealing intracellular microsporidial spores. The patient was treated with oral albendazole 400 mg once daily over 2 weeks and topical voriconazole 1% and fumagillin 3 mg/mL eye drops over 10 weeks. During this course, visual function steadily recovered as the infiltrate coalesced and ocular inflammation subsided.This is the first reported case of microsporidial keratitis presenting as a late-onset infection after femtosecond laser-assisted AK.

Introduction: Endometriosis is a burdensome chronic condition for which conservative management is often recommended when indicated. Nonetheless, some women seek care for endometriosis in the emerg...

Hematopoietic cell transplantation (HCT) is potentially curative for patients with hematologic disorders, but carries significant risks of infection-related morbidity and mortality. Infectious diseases are the second most common cause of death in HCT recipients, surpassed only by progression of underlying disease. Many infectious diseases are difficult to diagnose and treat, and may only be first identified by autopsy. However, autopsy rates are decreasing despite their value. The clinical and autopsy records of adult HCT recipients at our center who underwent autopsy between 1 January 2000 and 31 December 2017 were reviewed. Discrepancies between premortem clinical diagnoses and postmortem autopsy diagnoses were evaluated. Of 185 patients who underwent autopsy, 35 patients (18.8%) had a total of 41 missed infections. Five patients (2.7%) had >1 missed infection. Of the 41 missed infections, 18 (43.9%) were viral, 16 (39.0%) were fungal, 5 (12.2%) were bacterial, and 2 (4.9%) were parasitic. According to the Goldman criteria, 31 discrepancies (75.6%) were class I, 5 (12.2%) were class II, 1 (2.4%) was class III, and 4 (9.8%) were class IV. Autopsies of HCT recipients frequently identify clinically significant infectious diseases that were not suspected premortem. Had these infections been suspected, a change in management might have improved patient survival in many of these cases. Autopsy is underutilized and should be performed regularly to help improve infection-related morbidity and mortality. Illustrative cases are presented and the lessons learned from them are also discussed.