Analgesia and Sedation Use During Noninvasive Ventilation for Acute Respiratory Failure.

OBJECTIVES: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death. DESIGN: A retrospective multicenter cohort study. SETTING: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States. PATIENTS: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40). CONCLUSIONS: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice.

Prevalence of and Spending on Ear, Nose, Throat, and Respiratory Infections Among Children With Chronic Complex Conditions.

OBJECTIVE: Ear, nose, throat, and respiratory infections (ENTRI) may affect children with complex chronic conditions (CCC) differently than their peers. We compared ENTRI prevalence and spending in children with and without CCCs. METHODS: Retrospective analysis of 3,880,456 children ages 0-to-18 years enrolled in 9 US state Medicaid programs in 2018 contained in the IBM Watson Marketscan Database. Type and number of CCCs were distinguished with Feudtner's system. ENTRI prevalence, defined as ≥1 healthcare encounters for ENTRI, and Medicaid spending on ENTRI were compared by CCC using chi-square tests and logistic regression. RESULTS: ENTRIs were greater in children with vs. without a CCC (57.7% vs 43.5% [P < .001]). Children with a CCC (5.5%, n = 213,425) accounted for nearly one-fourth ($145.8 million [US]) of total spending on ENTRI. Aside from throat and sinus infection, ENTRI prevalence increased with number of CCCs (P < .001). For example, as number of CCCs increased from zero to ≥3, lower-airway infection increased from 12.5% to 37.5%, P < .001 (OR 4.10; 95% CI 3.95-4.26). ENTRI spending attributable to inpatient care increased from 9.7% to 92.8% (P < .001) as the number of CCCs increased from zero to ≥3. CONCLUSION: Most children with a CCC pursued care for ENTRI in 2018 and these children accounted for a disproportionate share of ENTRI spending. Children with multiple CCCs had a high prevalence of lower-airway infection; most of their ENTRI spending was for inpatient care. Providers can use these findings to counsel patients and families and to inform future investigations on how best to manage ENTRI in children with CCCs.

Reduced ER-mitochondria connectivity promotes neuroblastoma multidrug resistance.

Most cancer deaths result from progression of therapy resistant disease, yet our understanding of this phenotype is limited. Cancer therapies generate stress signals that act upon mitochondria to initiate apoptosis. Mitochondria isolated from neuroblastoma cells were exposed to tBid or Bim, death effectors activated by therapeutic stress. Multidrug-resistant tumor cells obtained from children at relapse had markedly attenuated Bak and Bax oligomerization and cytochrome c release (surrogates for apoptotic commitment) in comparison with patient-matched tumor cells obtained at diagnosis. Electron microscopy identified reduced ER-mitochondria-associated membranes (MAMs; ER-mitochondria contacts, ERMCs) in therapy-resistant cells, and genetically or biochemically reducing MAMs in therapy-sensitive tumors phenocopied resistance. MAMs serve as platforms to transfer Ca2+ and bioactive lipids to mitochondria. Reduced Ca2+ transfer was found in some but not all resistant cells, and inhibiting transfer did not attenuate apoptotic signaling. In contrast, reduced ceramide synthesis and transfer was common to resistant cells and its inhibition induced stress resistance. We identify ER-mitochondria-associated membranes as physiologic regulators of apoptosis via ceramide transfer and uncover a previously unrecognized mechanism for cancer multidrug resistance.

What Types of Hospitals Do Adolescents and Young Adults With Complex Chronic Conditions Use?

BACKGROUND AND OBJECTIVE: Hospitalizations for children with complex chronic conditions (CCC) at pediatric hospitals have risen over time. Little is known about what hospital types, pediatric or adult, adolescents, and young adults (AYA) with CCCs use. We assessed the types of hospitals used by AYAs with CCCs. METHODS: We performed a cross-sectional study of 856,120 hospitalizations for AYAs ages 15-to-30 years with ≥1 CCC in the 2017 National Inpatient Sample. We identified AYA with CCC by ICD-10-CM diagnosis codes using the pediatric CCC classification system version 2. Hospital types included pediatric hospitals (n = 70), adult hospitals with pediatric services (n = 277), and adult hospitals without pediatric services (n = 3975). We analyzed age trends by hospital type and CCC count in 1-year intervals and dichotomously (15-20 vs 21-30 years) with the Cochran-Armitage test. RESULTS: The largest change in pediatric hospitals used by AYA with CCCs occurred between 15 and 20 years with 39.7% versus 7.7% of discharges respectively (P< 0.001). For older AYA (21 to 30 years), 1.0% of discharges occurred at pediatric hospitals, compared with 65.6% at adult hospitals without pediatric services (P < 0.001). Older AYA at pediatric hospitals had more technology dependence (42.5%) versus younger AYA (27.6%, p < 0.001). CONCLUSIONS: Most discharges for AYAs ≥21 years with CCCs were from adult hospitals without pediatric services. Higher prevalence of technology dependence and neuromuscular CCCs, as well as multiple CCCs, for AYA 21-to-30 years discharged from pediatric hospitals may be related to specific care needs only found in pediatric settings and challenges transferring into adult hospital care.

The Effectiveness of Thermal Neuromodulation Using Precise Heat in the Treatment of Chronic Low Back Pain Over 60 Days: An In-Home User Trial.

PURPOSE: Two previous independent double-blind randomized studies demonstrated that thermal neuromodulation using high temperature pulsed heat reduced pain in subjects with chronic low back pain. The present study examined the effects of high temperature pulsed heat via an experimental device in a real-world In-Home Use Trial (IHUT) over a sixty-day period. MATERIALS AND METHODS: This in-home study recruited 34 subjects with chronic low back pain, provided them with an experimental device that delivered treatment session of high temperature pulsed heat up to 45°C, and followed them for eight weeks. Subjects were allowed to use the device as needed. Primary outcome was pain rating as measured by the 11-point Numeric Pain Scale at baseline, four and eight weeks of treatment. The secondary outcome measures were the interference with daily living components of the Brief Pain Inventory at baseline versus eight weeks of treatment. RESULTS: Thirty-two subjects completed the study. Pain levels were 5.81 at baseline, 2.79 at four weeks and 2.25 at eight weeks. All changes in pain levels between baseline and four weeks, baseline, and eight weeks and between four and eight weeks were statistically significant (p < 0.05). At eight weeks, the seven components of pain interference with activities of daily living and pain interference with walking were statistically reduced (P < 0.05). About 72% of subjects reported a single 30-minute treatment session produced over 3 hours of pain relief. CONCLUSION: An eight-week in-home trial of high-temperature thermal modulation devices produced significant reductions in pain and pain interference with activities of daily living, an important measure of function. Efforts were made to control and reduce study contamination. This study provides important initial data for long-term outcome studies of thermal neuromodulation using high temperature pulsed heat to treat low back pain and to improve subject function and demonstrated that individuals with chronic pain can effectively self-manage pain.

Properties of Thermal Analgesia in a Human Chronic Low Back Pain Model.

PURPOSE: For years, heat has been used for comfort and analgesia is recommended as a first-line therapy in many clinical guidelines. Yet, there are questions that remain about the actual effectiveness of heat for a condition as common as chronic low back pain, and factors such as time of onset, optimal temperature, and duration of effect. MATERIALS AND METHODS: A randomized double-blinded controlled trial was designed to compare the analgesic response to heat delivered via pulses at 45°C (experimental group, N=49) to steady heat at 37°C (control group, N=51) in subjects with longstanding low back pain. Treatment lasted 30 minutes with follow-up out to four hours. The hypothesis was that the experimental group would experience a higher degree of analgesia compared to the control group. Time of onset and duration of effect were also measured. RESULTS: Both groups were similar in average duration of pain (10.3 years). The primary outcome measure was pain reduction at 30 minutes after the end of treatment, using a 10-points numeric pain scale. Reduction in pain was greater for the experimental group than the control group (difference in mean reduction = 0.72, 95% CI 0.15-1.29, p = 0.014). Statistically significant differences in pain levels were observed from the first measure at 5 minutes of treatment through 120 minutes after completion of treatment. Reduction in pain associated movement was greater in the active heat group than the placebo group (p = 0.04). CONCLUSION: High-level pulsed heat (45°C) produced significantly more analgesia as compared to steady heat at 37°C at the primary end point and for an additional 2 hours after treatment. The onset of analgesia was rapid, <5 minutes of treatment. The results of this trial provide insight into the mechanisms and properties of thermal analgesia that are not well understood in a chronic low back pain model.

Hospital Readmission of Adolescents and Young Adults With Complex Chronic Disease.

Importance: Adolescents and young adults (AYA) who have complex chronic disease (CCD) are a growing population that requires hospitalization to treat severe, acute health problems. These patients may have increased risk of readmission as demands on their self-management increase and as they transfer care from pediatric to adult health care practitioners. Objective: To assess variation across CCDs in the likelihood of readmission for AYA with increasing age. Design, Setting, and Participants: Retrospective 1-year cross-sectional study of the 2014 Agency for Healthcare Research and Quality Nationwide Readmissions Database for all US hospitals. Participants were 215 580 hospitalized individuals aged 15 to 30 years with cystic fibrosis (n = 15 213), type 1 diabetes (n = 86 853), inflammatory bowel disease (n = 48 073), spina bifida (n = 7819), and sickle cell anemia (n = 57 622) from January 1, 2014, to December 1, 2014. Exposures: Increasing age at index admission. Main Outcomes and Measures: Unplanned 30-day hospital readmission. Readmission odds were compared by patients' ages in 2-year epochs (with age 15-16 years as the reference) using logistic regression, accounting for confounding patient characteristics and data clustering by hospital. Results: Of 215 580 participants, 115 982 (53.8%) were female; the median (interquartile range) age was 24 (20-27) years. Across CCDs, multimorbidity was common; the percentages of index hospitalizations with 4 or more coexisting conditions ranged from to 33.4% for inflammatory bowel disease to 74.2% for spina bifida. Thirty-day hospital readmission rates varied significantly across CCDs: 20.2% (cystic fibrosis), 19.8% (inflammatory bowel disease), 20.4% (spina bifida), 22.5% (type 1 diabetes), and 34.6% (sickle cell anemia). As age increased from 15 to 30 years, unadjusted, 30-day, unplanned hospital readmission rates increased significantly for all 5 CCD cohorts. In multivariable analysis, age trends in the adjusted odds of readmission varied across CCDs. For example, for AYA who had cystic fibrosis, the adjusted odds of readmission increased to 1.9 (95% CI, 1.5-2.3) by age 21 years and remained elevated through age 30 years. For AYA who had type 1 diabetes, the adjusted odds of readmission peaked at ages 23 to 24 years (odds ratio, 2.3; 95% CI, 2.1-2.6) and then declined through age 30 years. Conclusions and Relevance: These findings suggest that hospitalized AYA who have CCDs have high rates of multimorbidity and 30-day readmission. The adjusted odds of readmission for AYA varied significantly across CCDs with increasing age. Further attention is needed to hospital discharge care, self-management, and prevention of readmission in AYA with CCD.

A multi-laboratory comparison of blood dendritic cell populations.

HLDA10 collated a panel of monoclonal antibodies (mAbs) that primarily recognised molecules on human myeloid cell and dendritic cell (DC) populations. As part of the studies, we validated a backbone of mAbs to delineate monocyte and DC populations from peripheral blood. The mAb backbone allowed identification of monocyte and DC subsets using fluorochromes that were compatible with most 'off the shelf' or routine flow cytometers. Three laboratories used this mAb backbone to assess the HLDA10 panel on blood monocytes and DCs. Each laboratory was provided with enough mAbs to perform five repeat experiments. The data were collated and analysed using Spanning-tree Progression Analysis of Density-normalised Events (SPADE). The data were interrogated for inter- and intra-laboratory variability. The results highlight the definition of DC populations using current readily available reagents. This collaborative process provides the broader scientific community with an invaluable data set that validates mAbs to leucocyte surface molecules.

Two-way text messaging for health behavior change among human immunodeficiency virus-positive individuals.

BACKGROUND: text-messaging systems have been used to promote a range of health behaviors, including medication adherence among human immunodeficiency virus-positive individuals. However, little is currently known about the specific characteristics of messaging systems that promote user engagement. OBJECTIVE: using data from a randomized controlled trial involving a pager-based text messaging system, this study sought to examine the overall usability of the system, user evaluation of the system, demographic and psychosocial correlates of usability, and its performance as an adherence assessment tool. MATERIALS AND METHODS: the messaging system consisted of an alphanumeric pager capable of sending and receiving individualized text messages and the software necessary to program and track communication. The system was evaluated using behavioral outcomes (pager message response rate), self-report survey responses, focus group discussions, and data from electronic medication monitoring pill bottles. RESULTS: Although the majority of participants reported that the system was effective in reminding them to take medication doses, the overall response rate to system messages was relatively low (42.8%) and dropped significantly over the course of the 3-month intervention period. In addition, user engagement did not differ significantly by most demographic and psychosocial variables. CONCLUSIONS: the pager-based text messaging system was received well by participants and appears to be applicable to a broad population; however, the system did not actively engage all participants over the course of the trial. Future research should determine whether systems customized to personal preference in notification style, frequency, and user device can increase use and provide further assistance to achieve optimal medication adherence.

Key concepts for estimating the burden of surgical conditions and the unmet need for surgical care.

BACKGROUND: Surgical care is emerging as a crucial issue in global public health. Methodology is needed to assess the impact of surgical care from a public health perspective. METHODS: A consensus opinion of a group of surgeons, anesthesiologists, and public health experts was established regarding the methodology for estimating the burden of surgical conditions and the unmet need for surgical care. RESULTS: For purposes of analysis, we define surgical conditions as any disease state requiring the expertise of a surgically trained provider. Abnormalities resulting from a surgical condition or its treatment are termed surgical sequelae. Surgical care is defined as any measure that reduces the rates of physical disability or premature death associated with a surgical condition. To measure the burden of surgical conditions and unmet need for surgical care we propose using cumulative disability-adjusted life-year (DALY) curves generated from age-specific population-based data. This conceptual framework is based on the premise that surgically associated disability and death is determined by the incidence of surgical conditions and the quantity and quality of surgical care. The burden of surgical conditions is defined as the total disability and premature deaths that would occur in a population should there be no surgical care; the unmet need for surgical care is defined as the potentially treatable disability and premature deaths due to surgical conditions. Burden of surgical conditions should be expressed as DALYs and unmet need as potential DALYs avertable. CONCLUSIONS: Methodology is described for estimating the burden of surgical conditions and unmet need for surgical care. Using this approach it will be feasible to estimate the global burden of surgical conditions and help clarify where surgery fits among other global health priorities. These methods need to be validated using population-based data.

Peer support and pager messaging to promote antiretroviral modifying therapy in Seattle: a randomized controlled trial.

OBJECTIVE: To determine the relative efficacy of peer support and pager messaging strategies versus usual care to improve medication adherence and clinical outcomes among HIV-positive outpatients initiating or switching to a new highly active antiretroviral therapy regimen. DESIGN: A 2 3 2 factorial randomized controlled trial of a 3-month intervention with computer-assisted self-interviews and blood draws administered at baseline, 3, 6, and 9 months. METHODS: HIV-positive patients at a public HIV specialty clinic in Seattle,WA (N = 224) were randomly assigned to peer support, pager messaging, both strategies, or usual care. The main outcomes were adherence according to self-report and electronic drug monitoring, CD4 count, and HIV-1 RNA viral load. RESULTS: Intent-to-treat analyses suggested the peer intervention was associated with greater self-reported adherence at immediate postintervention. However, these effects were not maintained at follow-up assessment; nor were there significant differences in biological outcomes. The pager intervention, on the other hand, was not associated with greater adherence but was associated with improved biological outcomes at postintervention that were sustained at follow-up. CONCLUSIONS: Analyses indicate the potential efficacy of peer support and pager messaging to promote antiretroviral adherence and biological outcomes, respectively. More potent strategies still are needed.

University of Washington orthopedic resident experience and interest in developing an international humanitarian rotation.

An academic orthopedic residency program can have a significant impact on the burden of musculoskeletal disease in low- and middle-income countries. Such an exposure may also enhance the education of a resident. A 17-question electronic survey was developed to quantify the interest of orthopedic residents in pursuing an elective international rotation. The survey, which gathered resident demographic data and interest in pursuing an elective international orthopedic rotation, was sent to (and completed by) all 38 University of Washington orthopedic residents during academic year 2007-2008. More than 60% (23/38) of residents indicated they would be willing to commit to an international rotation; an additional 24% (9/38) indicated they would be very interested. Almost 40% of residents had participated in international medical volunteerism before entering residency. Among residents, there is a clear interest in pursuing an international rotation to complement their education in the United States.

Population health metrics for surgery: effective coverage of surgical services in low-income and middle-income countries.

BACKGROUND: Access to surgical services is emerging as a crucial issue in global public health. "Effective coverage" is a health metric used to evaluate essential health services in low- and middle-income countries. It measures the fraction of potential health gained that is actually realized for a given intervention by integrating the concepts of need, use, and quality. METHODS: This study applies the concept of effective coverage to surgical services by considering injuries and obstetric complications as high-priority surgical conditions in low- and middle-income countries. RESULTS: Effective coverage for both is poor, but it is less well defined for traumatic conditions compared to obstetric conditions owing to a lack of data. CONCLUSIONS: More primary and secondary data are critical to measure effective coverage and to estimate the resources required to improve access to surgical services in low- and middle-income countries.

Development of a multi-jurisdictional syndromic surveillance system.

We have identified several potential barriers to shared public health informatics systems in the context of developing a syndromic surveillance. A formal charter process successfully navigated these barriers. A flexible development process enabled building of system to proceed while policy issues were addressed.

Pain management.

This article provides information regarding treatments for the management of moderate to severe pain in patients who are at the end of life. Discussion focuses on the use of strong opioids and adjuvant analgesics. Special attention also is given to the most frequently used forms of interventional pain management. Although pain in terminally ill patients is not always related to cancer, many of the studies cited in this article were performed in cancer patients, a model that informs much of what is presented.