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Abstract An index of heart rate variability (HRV), detrended fluctuation analysis (DFA a1) has gathered interest as a surrogate marker of exercise intensity boundaries. The aim of this report was to examine heart rate variability threshold (HRVT) behavior across different ramp incremental (RI) slopes. Seventeen participants completed a series of three RI (15, 30, and 45 W · min−1 slopes) with monitoring of gas exchange parameters, heart rate (HR) and HRV. HRVT1 was defined as the V̇O2 or HR at which DFA a1 reached 0.75 and the HRVT2 at which these values reached 0.5. HRVTs were compared by Pearson's r, Bland–Altman analysis, ICC3,1, ANOVA, and paired t‐testing. An excellent degree of reliability was seen across all three ramps, with an ICC3,1 of 0.93 and 0.88 for the HRVT1 V̇O2 and HR, respectively, and 0.90 and 0.92 for the HRVT2 V̇O2 and HR, respectively. Correlations between HRVT1/2 of the individual ramps were high with r values 0.84–0.95 for both HR and V̇O2. Bland–Altman differences ranged between −1.4 and 1.2 mL · kg−1 · min−1 and −2 and +2 bpm. Paired t‐testing showed no mean differences between any HRVT1/2 ramp comparisons. Cycling ramp slope does not appear to affect either HRVT1 or HRVT2 in terms of HR or V̇O2.

Background. Anticoagulants carry a significant risk of gastrointestinal bleeding. With the increase in use and availability of direct oral anticoagulants (“DOACs”) more data are available regarding the risks of these medications. With diverticular bleeds being common, and hospitalization associated with gastrointestinal bleed increasing 30-day mortality, it is paramount to better understand the potential risks of using DOACs in this population. Methods. A systematic review of the literature was undertaken, using the databases PubMed, EMBASE, Cochrane Library, and CINAHL. Two reviewers independently searched the literature, and initial screening was performed through title and abstract reading. Search terms included “direct” AND “anticoagulant” AND “diverticular bleed” OR “diverticular hemorrhage”. The references of the selected studies were manually reviewed for any further relevant articles. Results. Literature search across the databases garnered 182 articles—157 unique abstracts after duplicate removal. Based on inclusion and exclusion criteria, 6 studies were deemed relevant. The selected studies’ reference lists yielded no further relevant articles. Discussion. Across the 6 studies, the incidence of diverticular bleeding in patients using DOACs was extremely low. Of 23,990 patients taking DOACs identified from two separate institutions, only 60 were found to have diverticular hemorrhage. Similarly, among 15,056 patients with diverticular hemorrhage, only 246 (1.6%) among them were taking DOACs. Generally, the studies found no increased diverticular bleeding rate between patients taking DOACs and those who were taking other anticoagulants, such as warfarin, or the general population. The studies also did not find an increased risk of rebleeding with DOAC continuation. Conclusion. The evidence suggests the risk of diverticular bleed among DOAC users is equivocal to those not taking DOACs, and the overall incidence of diverticular bleed in the DOAC population is low. As it stands, the risk of thrombotic events from not starting DOACs apparently outweighs the risk of diverticular bleed.

Background: Movement of the lower jaw, a common behavior observed among vertebrates, is required for eating and processing food. This movement is controlled by signals sent from the trigeminal motor nerve through neuromuscular junctions (NMJs) to the masticatory muscles. Dysfunctional jaw movements contribute to craniomandibular disorders, yet the pathophysiology of these disorders is not well understood, as limited studies have been conducted on the molecular mechanisms of jaw movement., Results: Using erc1b/kim m533 genetic loss of function mutant, we evaluated lower jaw muscle organization and innervation by the cranial motor nerves in developing zebrafish. Using time-lapse confocal imaging of the erc1b mutant in a transgenic fluorescent reporter line, we found delayed trigeminal nerve growth and disrupted nerve branching architecture during muscle innervation. By automated 3D image analysis of NMJ distribution, we identified an increased number of small, disorganized NMJ clusters in erc1b mutant larvae compared to WT siblings. Using genetic replacement experiments, we determined the Rab GTPase binding domain of Erc1b is required for cranial motor nerve branching, but not NMJ organization or muscle attachment., Conclusions: We identified Erc1b/ERC1 as a novel component of a genetic pathway contributing to muscle organization, trigeminal nerve outgrowth, and NMJ spatial distribution during development that is required for jaw movement., (© 2022 American Association for Anatomy.)

Objective: In utero SMA treatment could improve survival and neurologic outcomes. We investigated the attitudes of patients and parents with SMA regarding prenatal diagnosis, fetal therapies, and clinical trials., Methods: A multidisciplinary team designed a questionnaire that Cure SMA electronically distributed to parents and patients (>18 years old) affected by SMA. Multivariable ordinal logistic regression was used to analyze associations between respondent characteristics and attitudes., Results: Of 114 respondents (60% of whom were patients), only 2 were prenatally diagnosed. However, 91% supported prenatal testing and 81% felt there had been a delay in their diagnosis. Overall, 55% would enroll in a phase I trial for fetal antisense oligonucleotide (ASO) while 79% would choose an established fetal ASO/small molecule therapy. Overall, 61% would enroll in fetal gene therapy trials and 87% would choose fetal gene therapies. Patients were less likely to enroll in a fetal gene therapy trial than parents enrolling a child (OR 0.31, p < 0.05). Older parental age and believing there had been excessive delay in diagnosis were associated with an interest in enrolling in a fetal ASO trial (OR 1.04, 7.38, respectively, p < 0.05)., Conclusion: In utero therapies are promising for severe genetic diseases. Patients with SMA and their parents view prenatal testing and therapies positively, with gene therapy being favored., (© 2022 John Wiley & Sons Ltd.)

Background: Many reports have documented the relationship between previous traumatic experiences, including childhood trauma, and the development of later life psychopathology, including posttraumatic stress disorder (PTSD). Identification of individuals at greatest risk for the development of PTSD could lead to preventative interventions. The present study examined the developmental course of PTSD after trauma exposure, using histories of previous traumatic experiences and the severity of the reaction to the trauma as predictors., Methods: Participants (N = 713) were recruited from Emergency Departments in Miami and Atlanta immediately following a traumatic experience. Histories of previous traumatic experiences and the immediate reaction to the new trauma were examined at baseline. Follow-up assessments of PTSD severity were conducted at 1, 3, and 6 months., Results: Histories of child abuse and pre-existing trauma symptoms predicted the immediate response to stress (R 2  = .21, p < .001) and the initial trauma reaction (p < .005).) A mixed-model repeated-measures analysis of variance found that immediate stress response and a history of prior trauma (p < .001) significantly predicted the course of PTSD symptoms. Area under the curve (AUC) analyses suggested that the presence of PTSD at each successive assessment was predicted most substantially by the severity of PTSD at the immediately prior follow-up assessment (AUC > 0.86)., Conclusions: The current findings suggest that previous traumatic experiences lead to a greater immediate reaction to trauma and combine to predict the development of PTSD, the maintenance of which is not moderated by these earlier experiences. The identification of people likely to develop PTSD may be aided by the assessment of prior experiences and immediate reactions., (© 2020 Wiley Periodicals LLC.)

Background: Diabetes is an emerging public health issue in the US, affecting 11% of Americans over the age of 20, with long-term complications that include cardiovascular disease, retinopathy, neuropathy, and nephropathy. A recent meta-analysis found that bladder cancer incidence was approximately 40% higher in individuals with diabetes; however, few studies considered duration or type of therapy and had limited adjustment for potentially confounding factors., Methods: To further investigate the potential role of diabetes in risk of bladder cancer, the authors analyzed data from a case-control study conducted in New Hampshire in which patients with bladder cancer, and controls sampled from the population, completed an interview regarding history of diabetes, cigarette smoking history, height, weight, and history of urinary tract infections., Results: The study consisted of 331 cases and 263 controls on whom information regarding diabetes was ascertained. History of diabetes was related to an increased bladder cancer risk (adjusted odds ratio = 2.2, 95% CI, 1.3 to 3.8). The association was strongest in those who had diabetes for the longest duration (OR for 16 or more years = 3.6, 1.1 to 11.2) and in those taking oral hypoglycemic medications (OR = 3.3, 1.5 to 7.1)., Conclusions: Our findings support an association between bladder cancer incidence and diabetes, and further suggest that the risk may be greater among patients taking oral hypoglycemics and those with diabetes of longer duration., (Copyright © 2010 American Cancer Society.)

Objectives: To examine the patterns of antibiotic use for acute respiratory tract infections (ARIs) in acute care settings., Methods: Chart reviews were performed retrospectively on a random sample of adult ARI visits to seven Veterans Affairs (VA) and seven non-VA emergency departments (EDs) for the period of November 2003 to February 2004. Visits were limited to those discharged to home and those with primary diagnoses of antibiotic-responsive (pneumonia, acute exacerbation of chronic bronchitis, pharyngitis, sinusitis) and antibiotic-nonresponsive conditions (acute bronchitis, nonspecific upper respiratory tract infection [URI]). Results are expressed as adjusted odds ratios with 95% confidence intervals., Results: Of 2,270 ARI visits, 62% were for antibiotic-nonresponsive diagnoses. Seventy-two percent of acute bronchitis and 38% of URI visits were treated with antibiotics (p < 0.001). Stratified analyses show that antibiotic prescription rates were similar among attending-only and housestaff-associated visits for antibiotic-responsive diagnoses (p = 0.11), and acute bronchitis (76% vs. 59%; p = 0.31). However, the antibiotic prescription rate for URIs was greater for attending-only visits compared with housestaff-associated visits (48% vs. 15%; p = 0.01). Antibiotic prescription rates for total ARIs varied between sites, ranging from 42% to 89%. Patient age, gender, race and ethnicity, smoking status, comorbidities, and clinical setting (VA vs. non-VA) were not independently associated with antibiotic prescribing., Conclusions: Acute care settings are important targets for reducing inappropriate antibiotic prescribing. The mechanisms accounting for lower antibiotic prescription rates observed with housestaff-associated visits merit further study.

Background: The objective of screening mammography is to identify breast carcinoma early, which requires routine screening. Although self-report data indicate that screening utilization is high, the results of this population-based assessment indicated that utilization is lower than reported previously., Methods: The authors compared New Hampshire population data from the 2000 Census with clinical encounter data for the corresponding time obtained from the New Hampshire Mammography Network, a mammography registry that captures approximately 90% of the mammograms performed in participating New Hampshire facilities., Results: The results showed that approximately 36% of New Hampshire women either never had a mammogram or had not had a mammogram in > 27 months (irregular screenees), and older women (80 yrs and older) were less likely to be screened (79% unscreened/underscreened) compared with younger women (ages 40-69 yrs; 28-32% unscreened/underscreened). Of the screened women, 44% were adhering to an interval of 14 months, and 21% were adhering within 15 months and 26 months. The remaining 35% of the women had 1 or 2 mammograms and did not return within 27 months., Conclusions: Routine mammography screening may be occurring less often than believed when survey data alone are used. An important, compelling concern is the reason women had one or two mammograms only and then did not return for additional screening. This area deserves additional research., (Copyright 2005 American Cancer Society)

The aim of this study was to establish the effectiveness of scalp cooling in preventing alopecia for patients with breast cancer who received the trial combination chemotherapy of Epirubicin and Docetaxel. Doubt remains about the general effectiveness of scalp cooling in preventing hair loss for patients receiving chemotherapy. There is very little information available about its specific effectiveness with combinations of Taxanes and Anthracycline drugs. Of the 40 patients who received this drug combination, 10 were included in a pilot study whereas the remaining 30 constituted the main study sample. A randomized controlled study was undertaken whereby the intervention group received scalp cooling via gel cool caps and the control group received no specific preventative intervention. Nurses assessed participants' hair loss using a modified version of the WHO scale at seven time points and also recorded hair loss photographically. Two independent experts rated the photographs using the same scale. Patients self-reported in relation to overall hair loss, hair condition, levels of emotional upset, negativity about appearance, hair re-growth and wig use. Significantly greater hair loss was apparent in the control group during most of the treatment period. However, the level of protection afforded by the cool caps was relatively poor with this chemotherapy combination. The marginal benefits of scalp cooling in this context must be clearly explained to patients.

Since 1983, hospitals in the United States have been receiving prospective payment for their in-hospital patient admissions covered under Medicare. Under such schemes each patient is placed in a group by a classification system, known as the Diagnosis Related Groups (DRG), and the hospital is reimbursed by the Health Care Financing Administration according to some predetermined group average, adjusted for hospital level characteristics, such as size, location and teaching activity. Recent interest has focused on refining the DRG system or considering totally different systems of classification. Studies designed to compare the ability of different systems to account for between-patient variability in resource consumption in the same dataset lead to the problem of model selection between large non-nested regressions, where resource consumption, measured by length of hospital stay or costs, is regressed on dummy-indicator variables representing different patient groups. We use a simple measure of fit to develop a symmetric test of the null hypothesis that the two systems account equally well for variability in resource consumption. With this method, unlike methods such as Akaike's AIC criterion, we can quantify the probability of a false positive, and thereby limit the probability of choosing one system over another when it is no better at accounting for variability in resource consumption.

The effect of short-term caffeine withdrawal on lymphocyte beta-adrenoceptor sensitivity was studied in seven men who had been drinking coffee daily for at least 3 mo before the study. The ratio of cyclic adenosine monophosphate production after in vitro incubation with isoproterenol and a blank was used to assess receptor sensitivity. There was a reduction in sensitivity to isoproterenol but not to prostaglandin E1 3 days after caffeine withdrawal. The mechanism of this effect is not clear, but may represent a biochemical correlate of caffeine-withdrawal syndrome.