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The paper develops the theme that cues for appropriate changes in nursing care and organization can be detected from the immediate socio-political environment. Taking an historical perspective, changes in nursing care and organization are traced and the split between technology and care is discussed. A return to the model of hippocratic medicine is suggested by the introduction of a new role, that of the nurse practitioner. This model is considered in the light of nursing redefining its role vis-à-vise-present day social needs of health care delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: Retraction is a mechanism for correcting the scientific record and alerts readers when a study contains unreliable or flawed data. Such data may arise from error or research misconduct. Studies examining the landscape of retracted publications provide insight into the extent of unreliable data and its effect on a medical discipline. We aimed to explore the extent and characteristics of retracted publications in pain research. We searched the EMBASE, PubMed, CINAHL, PsycINFO, and Retraction Watch databases to December 31, 2022. We included retracted articles that (1) investigated mechanisms of painful conditions, (2) tested treatments that aimed to reduce pain, or (3) measured pain as an outcome. Descriptive statistics were used to summarise the included data. We included 389 pain articles published between 1993 and 2022 and retracted between 1996 and 2022. There was a significant upward trend in the number of retracted pain articles over time. Sixty-six percent of articles were retracted for reasons relating to misconduct. The median (interquartile range) time from article publication to retraction was 2 years (0.7-4.3). The time to retraction differed by reason for retraction, with data problems, comprising data falsification, duplication, and plagiarism, resulting in the longest interval (3 [1.2-5.2] years). Further investigations of retracted pain articles, including exploration of their fate postretraction, are necessary to determine the impact of unreliable data on pain research., (Copyright © 2023 International Association for the Study of Pain.)

For individuals experiencing pain, the decision to engage in clinical trials may be influenced by a number of factors including current and past care, illness severity, physical functioning, financial stress, and caregiver support. Co-occurring depression and anxiety may add to these challenges. The aim of this scoping review was to describe perspectives about clinical trial participation, including recruitment and retention among individuals with pain and pain comorbidities, including depression and/or anxiety. We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL databases. Study features, sample demographics, perspectives, barriers and/or motivations were collected and described. A total of 35 assessments were included in this scoping review with 24 focused on individuals with pain (24/35, 68.6%), 9 on individuals with depression and/or anxiety (9/35, 25.7%), and 2 on individuals with pain and co-occurring depression/anxiety (2/35, 5.7%). Barriers among participants with pain and those with depression included: research team's communication of information, fear of interventional risks, distrust (only among respondents with pain), too many procedures, fear of inadequate treatment, disease-life stressors, and embarrassment with study procedures (more commonly reported in participants with depression). Facilitators in both groups included: altruism and supportive staff, better access to care, and the ability to have outcome feedback (more commonly among individuals with depression). Individuals with pain and depression experience challenges that affect trial recruitment and retention. Engaging individuals with pain within research planning may assist in addressing these barriers and the needs of individuals affected by pain and/or depression. PERSPECTIVE: This review highlights the need to address barriers and facilitators to participation in clinical trials, including the need for an assessment of perspectives from underserved or marginalized populations., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Prospective trial registration can increase research integrity. This Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) review was designed to compare the primary outcomes (PO) reported in registries with associated publications for opioid use disorder (OUD) clinical trials., Design: The World Health Organization's International Clinical Trials Registry Platform (ICTRP) was searched for completed trials (2010 through 2019). Associated publications were identified and paired with trial registry data based on the publication date., Measurements: Reviewers independently rated the occurrence of discrepancies between the POs in the registry compared to the publication. An analysis of prospective versus retrospective registration was also completed., Findings: One-hundred and forty trials were identified in the search, and 43 registry-publication pairs evaluated. Only 34 of the 43 pairs could be examined for discrepancies because nine did not report a PO in registry and publication. Of the 34 pairs, only four met rigorous criteria for prospective trial registration and had an exact match of POs. In contrast, the majority of the 34 trials, or 80%, had inconsistent POs (e.g., registered secondary outcomes published as primary; the timing of PO not specified) and/or were retrospectively registered., Conclusions: Many clinical trials focused on OUD have not met the standards of trial registration, such as consistent reporting of POs and prospective registration. Failure to properly register trial characteristics undermines the validity of research findings and can delay the development of life-saving treatments. Recommendations for improving prospective trial reporting practices are provided., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Many schools have been cutting physical education (PE) classes due to budget constraints, which raises the question of whether policymakers should require schools to offer PE classes. Evidence suggests that PE classes can help address rising physical inactivity and obesity prevalence. However, it would be helpful to determine if requiring PE is cost-effective., Methods: We developed an agent-based model of youth in Mexico City and the impact of all schools offering PE classes on changes in weight, weight-associated health conditions and the corresponding direct and indirect costs over their lifetime., Results: If schools offer PE without meeting guidelines and instead followed currently observed class length and time active during class, overweight and obesity prevalence decreased by 1.3% (95% CI: 1.0%-1.6%) and was cost-effective from the third-party payer and societal perspectives ($5,058 per disability-adjusted life year [DALY] averted and $5,786/DALY averted, respectively, assuming PE cost $50.3 million). When all schools offered PE classes meeting international guidelines for PE classes, overweight and obesity prevalence decreased by 3.9% (95% CI: 3.7%-4.3%) in the cohort at the end of five years compared to no PE. Long-term, this averted 3,183 and 1,081 obesity-related health conditions and deaths, respectively and averted ≥$31.5 million in direct medical costs and ≥$39.7 million in societal costs, assuming PE classes cost ≤$50.3 million over the five-year period. PE classes could cost up to $185.5 million and $89.9 million over the course of five years and still remain cost-effective and cost saving respectively, from the societal perspective., Conclusion: Requiring PE in all schools could be cost-effective when PE class costs, on average, up to $10,340 per school annually. Further, the amount of time students are active during class is a driver of PE classes' value (e.g., it is cost saving when PE classes meet international guidelines) suggesting the need for specific recommendations., Competing Interests: NO authors have competing interests

Background: Face mask wearing has been an important part of the response to the COVID-19 pandemic. As vaccination coverage progresses in countries, relaxation of such practices is increasing. Subsequent COVID-19 surges have raised the questions of whether face masks should be encouraged or required and for how long. Here, we aim to assess the value of maintaining face masks use indoors according to different COVID-19 vaccination coverage levels in the USA., Methods: In this computational simulation-model study, we developed and used a Monte Carlo simulation model representing the US population and SARS-CoV-2 spread. Simulation experiments compared what would happen if face masks were used versus not used until given final vaccination coverages were achieved. Different scenarios varied the target vaccination coverage (70-90%), the date these coverages were achieved (Jan 1, 2022, to July 1, 2022), and the date the population discontinued wearing face masks., Findings: Simulation experiments revealed that maintaining face mask use (at the coverage seen in the USA from March, 2020, to July, 2020) until target vaccination coverages were achieved was cost-effective and in many cases cost saving from both the societal and third-party payer perspectives across nearly all scenarios explored. Face mask use was estimated to be cost-effective and usually cost saving when the cost of face masks per person per day was ≤US$1·25. In all scenarios, it was estimated to be cost-effective to maintain face mask use for about 2-10 weeks beyond the date that target vaccination coverage (70-90%) was achieved, with this added duration being longer when the target coverage was achieved during winter versus summer. Factors that might increase the transmissibility of the virus (eg, emergence of the delta [B.1.617.2] and omicron [B.1.1.529] variants), or decrease vaccine effectiveness (eg, waning immunity or escape variants), or increase social interactions among certain segments of the population, only increased the cost savings or cost-effectiveness provided by maintaining face mask use., Interpretation: Our study provides strong support for maintaining face mask use until and a short time after achieving various final vaccination coverage levels, given that maintaining face mask use can be not just cost-effective, but even cost saving. The emergence of the omicron variant and the prospect of future variants that might be more transmissible and reduce vaccine effectiveness only increases the value of face masks., Funding: The Agency for Healthcare Research and Quality, the National Institute of General Medical Sciences, the National Science Foundation, the National Center for Advancing Translational Sciences, and the City University of New York., Competing Interests: Declaration of interests PJH and MEB codirect the Texas Children's Center for Vaccine Development and with US are codevelopers of vaccines against emerging and neglected diseases including coronaviruses such as COVID-19. Baylor College of Medicine non-exclusively licensed a COVID-19 vaccine construct to Biological E, an India-based manufacturing company. These authors have no financial stakes in any COVID-19 vaccine candidates under development. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: This systematic review was designed to evaluate the presence of comorbid conditions among patients with temporomandibular disorders (TMDs)., Types of Studies Reviewed: The authors reviewed studies that reported the prevalence or incidence of chronic pain conditions or psychiatric disorders (anxiety, mood, personality disorders) among patients with any type of TMD. The authors calculated sample size-weighted prevalence estimates when data were reported in 2 or more studies for the same comorbid condition., Results: A total of 9 prevalence studies and no incidence studies were eligible for review; 8 of the studies examined chronic pain comorbidities. Weighted estimates showed high prevalence of pain comorbidities across studies, including current chronic back pain (66%), myofascial syndrome (50%), chronic stomach pain (50%), chronic migraine headache (40%), irritable bowel syndrome (19%), and fibromyalgia (14%). A single study examined psychiatric disorders and found that current depression was the most prevalent disorder identified (17.5%)., Conclusions and Practical Implications: There is a high prevalence of comorbid chronic pain conditions among patients with TMDs, with more than 50% of patients reporting chronic back pain, myofascial syndrome, and chronic stomach pain. Psychiatric disorders among patients with different types of TMDs were studied less commonly in this pain population. Knowledge of the distribution of these and other comorbid disease conditions among patients with different types of TMDs can help dentists and other health care providers to identify personalized treatment strategies, including the coordination of care across medical specialties., (Copyright © 2022 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Teaching caregivers to respond to normal infant night awakenings in ways other than feeding is a common obesity prevention effort. Models can simulate caregiver feeding behavior while controlling for variables that are difficult to manipulate or measure in real life., Methods: We developed a virtual infant model representing an infant with an embedded metabolism and his/her daily sleep, awakenings, and feeds from their caregiver each day as the infant aged from 6 to 12 months (recommended age to introduce solids). We then simulated different night feeding interventions and their impact on infant body mass index (BMI)., Results: Reducing the likelihood of feeding during normal night wakings from 79% to 50% to 10% lowered infant BMI from the 84th to the 75th to the 62nd percentile by 12 months, respectively, among caregivers who did not adaptively feed (e.g., adjust portion sizes of solid foods with infant growth). Among caregivers who adaptively feed, all scenarios resulted in relatively stable BMI percentiles, and progressively reducing feeding probability by 10% each month showed the least fluctuations., Conclusions: Reducing night feeding has the potential to impact infant BMI, (e.g., 10% lower probability can reduce BMI by 20 percentile points) especially among caregivers who do not adaptively feed., Impact: Teaching caregivers to respond to infant night waking with other soothing behaviors besides feeding has the potential to reduce infant BMI. When reducing the likelihood of feeding during night wakings from 79% to 50% to 10%, infants dropped from the 84th BMI percentile to the 75th to the 62nd by 12 months, respectively, among caregivers who do not adaptively feed. Night-feeding interventions have a greater impact when caregivers do not adaptively feed their infant based on their growth compared to caregivers who do adaptively feed. Night-feeding interventions should be one of the several tools in a multi-component intervention for childhood obesity prevention., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: Due to shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic, it is necessary to estimate the number of N95s required for healthcare workers (HCWs) to inform manufacturing targets and resource allocation., Methods: We developed a model to determine the number of N95 respirators needed for HCWs both in a single acute-care hospital and the United States., Results: For an acute-care hospital with 400 all-cause monthly admissions, the number of N95 respirators needed to manage COVID-19 patients admitted during a month ranges from 113 (95% interpercentile range [IPR], 50-229) if 0.5% of admissions are COVID-19 patients to 22,101 (95% IPR, 5,904-25,881) if 100% of admissions are COVID-19 patients (assuming single use per respirator, and 10 encounters between HCWs and each COVID-19 patient per day). The number of N95s needed decreases to a range of 22 (95% IPR, 10-43) to 4,445 (95% IPR, 1,975-8,684) if each N95 is used for 5 patient encounters. Varying monthly all-cause admissions to 2,000 requires 6,645-13,404 respirators with a 60% COVID-19 admission prevalence, 10 HCW-patient encounters, and reusing N95s 5-10 times. Nationally, the number of N95 respirators needed over the course of the pandemic ranges from 86 million (95% IPR, 37.1-200.6 million) to 1.6 billion (95% IPR, 0.7-3.6 billion) as 5%-90% of the population is exposed (single-use). This number ranges from 17.4 million (95% IPR, 7.3-41 million) to 312.3 million (95% IPR, 131.5-737.3 million) using each respirator for 5 encounters., Conclusions: We quantified the number of N95 respirators needed for a given acute-care hospital and nationally during the COVID-19 pandemic under varying conditions.

Background: With multiple coronavirus disease 2019 (COVID-19) vaccines available, understanding the epidemiologic, clinical, and economic value of increasing coverage levels and expediting vaccination is important., Methods: We developed a computational model (transmission and age-stratified clinical and economics outcome model) representing the United States population, COVID-19 coronavirus spread (February 2020-December 2022), and vaccination to determine the impact of increasing coverage and expediting time to achieve coverage., Results: When achieving a given vaccination coverage in 270 days (70% vaccine efficacy), every 1% increase in coverage can avert an average of 876 800 (217 000-2 398 000) cases, varying with the number of people already vaccinated. For example, each 1% increase between 40% and 50% coverage can prevent 1.5 million cases, 56 240 hospitalizations, and 6660 deaths; gain 77 590 quality-adjusted life-years (QALYs); and save $602.8 million in direct medical costs and $1.3 billion in productivity losses. Expediting to 180 days could save an additional 5.8 million cases, 215 790 hospitalizations, 26 370 deaths, 206 520 QALYs, $3.5 billion in direct medical costs, and $4.3 billion in productivity losses., Conclusions: Our study quantifies the potential value of decreasing vaccine hesitancy and increasing vaccination coverage and how this value may decrease with the time it takes to achieve coverage, emphasizing the need to reach high coverage levels as soon as possible, especially before the fall/winter., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs)., Objectives: To assess the analgesic efficacy and adverse effects of single-dose intravenous (IV) ibuprofen, compared with placebo or an active comparator, for moderate-to-severe postoperative pain in adults., Search Methods: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 10 June 2021. We checked clinical trials registers and reference lists of retrieved articles for additional studies., Selection Criteria: We included randomized trials that compared a single postoperative dose of intravenous (IV) ibuprofen with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data. Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a 4- and 6-hour period. Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants reporting or experiencing any AE, serious AEs (SAEs), and specific NSAID-related or opioid-related AEs. We were not able to carry out any planned meta-analysis. We assessed the certainty of the evidence using GRADE., Main Results: Only one study met our inclusion criteria, involving 201 total participants, mostly female (mean age 42 years), undergoing primary, unilateral, distal, first metatarsal bunionectomy (with osteotomy and internal fixation). Ibuprofen 300 mg, placebo or acetaminophen 1000 mg was administered intravenously to participants reporting moderate pain intensity the day after surgery. Since we identified only one study for inclusion, we did not perform any quantitative analyses. The study was at low risk of bias for most domains. We downgraded the certainty of the evidence due to serious study limitations, indirectness and imprecision. Ibuprofen versus placebo Findings of the single study found that at both the 4-hour and 6-hour assessment period, the proportion of participants with at least 50% pain relief was 32% (24/76) for those assigned to ibuprofen and 22% (11/50) for those assigned to placebo. These findings produced a risk ratio (RR) of 1.44 (95% confidence interval (CI) 0.77 to 2.66 versus placebo for at least 50% of maximum pain relief over the 4-hour and 6-hour period (very low-certainty evidence). Median time to rescue medication was 101 minutes for ibuprofen and 71 minutes for placebo (1 study, 126 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study (1 study, 126 participants), 58/76 (76%) of participants assigned to ibuprofen and 39/50 (78%) assigned to placebo reported or experienced any adverse event (AE), (RR 0.98, 95% CI 0.81 to 1.19; low-certainty evidence). No serious AEs (SAEs) were experienced (1 study, 126 participants; very low-certainty evidence). Ibuprofen versus active comparators Ibuprofen (300 mg) was similar to the active comparator, IV acetaminophen (1000 mg) at 4 hours and 6 hours (1 study, 126 participants). For those assigned to active control (acetaminophen), the proportion of participants with at least 50% pain relief was 35% (26/75) at 4 hours and 31% (23/75) at 6 hours. At 4 hours, these findings produced a RR of 0.91 (95% CI 0.58 to 1.43; very low-certainty evidence) versus active comparator (acetaminophen). At 6 hours, these findings produced a RR of 1.03 (95% CI 0.64 to 1.66; very low-certainty evidence) versus active comparator (acetaminophen). Median time to rescue medication was 101 minutes for ibuprofen and 125 minutes for the active comparator, acetaminophen (1 study, 151 participants; very low-certainty evidence). The number of participants using rescue medication was not reported within the included study. During the study, 8/76 (76%) of participants assigned to ibuprofen and 45/75 (60%) assigned to active control (acetaminophen) reported or experienced any AE, (RR 1.27, 95% CI 1.02 to 1.59; very low-certainty evidence). No SAEs were experienced (1 study, 151 participants; very low-certainty evidence)., Authors' Conclusions: There is insufficient evidence to support or refute the suggestion that IV ibuprofen is effective and safe for acute postoperative pain in adults., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Single-dose rotavirus vaccines, which are used by a majority of countries, are some of the largest-sized vaccines in immunization programs, and have been shown to constrain supply chains and cause bottlenecks. Efforts have been made to reduce the size of the single-dose vaccines; however, with two-dose, five-dose and ten-dose options available, the question then is whether using multi-dose instead of single-dose rotavirus vaccines will improve vaccine availability., Methods: We used HERMES-generated simulation models of the vaccine supply chains of the Republic of Benin, Mozambique, and Bihar, a state in India, to evaluate the operational and economic impact of implementing each of the nine different rotavirus vaccine presentations., Results: Among single-dose rotavirus vaccines, using Rotarix RV1 MMP (multi-monodose presentation) led to the highest rotavirus vaccine availability (49-80%) and total vaccine availability (56-79%), and decreased total costs per dose administered ($0.02-$0.10) compared to using any other single-dose rotavirus vaccine. Using two-dose ROTASIIL decreased rotavirus vaccine availability by 3-6% across each supply chain compared to Rotarix RV1 MMP, the smallest single-dose vaccine. Using a five-dose rotavirus vaccine improved rotavirus vaccine availability (52-92%) and total vaccine availability (60-85%) compared to single-dose and two-dose vaccines. Further, using the ten-dose vaccine led to the highest rotavirus vaccine availability compared to all other rotavirus vaccines in both Benin and Bihar., Conclusion: Our results show that countries that implement five-dose or ten-dose rotavirus vaccines consistently reduce cold chain constraints and achieve higher rotavirus and total vaccine availability compared to using either single-dose or two-dose rotavirus vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs)., Objectives: To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults., Search Methods: We searched the following databases without language restrictions: CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies., Selection Criteria: Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane.  Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period. Our secondary outcomes were time to and number of participants using rescue medication; withdrawals due to lack of efficacy, adverse events (AEs), and for any other cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related or opioid-related AEs. For subgroup analysis, we planned to analyze different doses of parenteral ketorolac separately and to analyze results based on the type of surgery performed. We assessed the certainty of evidence using GRADE., Main Results: We included 12 studies, involving 1905 participants undergoing various surgeries (pelvic/abdominal, dental, and orthopedic), with 17 to 83 participants receiving intravenous ketorolac in each study. Mean study population ages ranged from 22.5 years to 67.4 years. Most studies administered a dose of ketorolac of 30 mg; one study assessed 15 mg, and another administered 60 mg. Most studies had an unclear risk of bias for some domains, particularly allocation concealment and blinding, and a high risk of bias due to small sample size. The overall certainty of evidence for each outcome ranged from very low to moderate. Reasons for downgrading certainty included serious study limitations, inconsistency and imprecision. Ketorolac versus placebo Very low-certainty evidence from eight studies (658 participants) suggests that ketorolac results in a large increase in the number of participants achieving at least 50% pain relief over four hours compared to placebo, but the evidence is very uncertain (risk ratio (RR) 2.81, 95% confidence interval (CI) 1.80 to 4.37). The number needed to treat for one additional participant to benefit (NNTB) was 2.4 (95% CI 1.8 to 3.7). Low-certainty evidence from 10 studies (914 participants) demonstrates that ketorolac may result in a large increase in the number of participants achieving at least 50% pain relief over six hours compared to placebo (RR 3.26, 95% CI 1.93 to 5.51). The NNTB was 2.5 (95% CI 1.9 to 3.7). Among secondary outcomes, for time to rescue medication, moderate-certainty evidence comparing intravenous ketorolac versus placebo demonstrated a mean median of 271 minutes for ketorolac versus 104 minutes for placebo (6 studies, 633 participants). For the number of participants using rescue medication, very low-certainty evidence from five studies (417 participants) compared ketorolac with placebo. The RR was 0.60 (95% CI 0.36 to 1.00), that is, it did not demonstrate a difference between groups. Ketorolac probably results in a slight increase in total adverse event rates compared with placebo (74% versus 65%; 8 studies, 810 participants; RR 1.09, 95% CI 1.00 to 1.19; number needed to treat for an additional harmful event (NNTH) 16.7, 95% CI 8.3 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from eight studies (703 participants) did not demonstrate a difference in rates between ketorolac and placebo (RR 0.62, 95% CI 0.13 to 3.03). Ketorolac versus NSAIDs  Ketorolac was compared to parecoxib in four studies and diclofenac in two studies. For our primary outcome, over both four and six hours there was no evidence of a difference between intravenous ketorolac and another NSAID (low-certainty and moderate-certainty evidence, respectively). Over four hours, four studies (337 participants) produced an RR of 1.04 (95% CI 0.89 to 1.21) and over six hours, six studies (603 participants) produced an RR of 1.06 (95% CI 0.95 to 1.19). For time to rescue medication, low-certainty evidence from four studies (427 participants) suggested that participants receiving ketorolac waited an extra 35 minutes (mean median 331 minutes versus 296 minutes). For the number of participants using rescue medication, very low-certainty evidence from three studies (260 participants) compared ketorolac with another NSAID. The RR was 0.90 (95% CI 0.58 to 1.40), that is, there may be little or no difference between groups.   Ketorolac probably results in a slight increase in total adverse event rates compared with another NSAID (76% versus 68%, 5 studies, 516 participants; RR 1.11, 95% CI 1.00 to 1.23; NNTH 12.5, 95% CI 6.7 to infinite, moderate-certainty evidence). Serious AEs were rare. Low-certainty evidence from five studies (530 participants) did not demonstrate a difference in rates between ketorolac and another NSAID (RR 3.18, 95% CI 0.13 to 76.99). Only one of the five studies reported a single serious AE., Authors' Conclusions: The amount and certainty of evidence for the use of intravenous ketorolac as a treatment for postoperative pain varies across efficacy and safety outcomes and amongst comparators, from very low to moderate. The available evidence indicates that postoperative intravenous ketorolac administration may offer substantial pain relief for most patients, but further research may impact this estimate. Adverse events appear to occur at a slightly higher rate in comparison to placebo and to other NSAIDs. Insufficient information is available to assess whether intravenous ketorolac has a different rate of gastrointestinal or surgical-site bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was a lack of studies in cardiovascular surgeries and in elderly populations who may be at increased risk for adverse events., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: During a pandemic, there are many situations in which the first available vaccines may not have as high effectiveness as vaccines that are still under development or vaccines that are not yet ready for distribution, raising the question of whether it is better to go with what is available now or wait., Methods: In 2020, the team developed a computational model that represents the U.S. population, COVID-19 coronavirus spread, and vaccines with different possible efficacies (to prevent infection or to reduce severe disease) and vaccination timings to estimate the clinical and economic value of vaccination., Results: Except for a limited number of situations, mainly early on in a pandemic and for a vaccine that prevents infection, when an initial vaccine is available, waiting for a vaccine with a higher efficacy results in additional hospitalizations and costs over the course of the pandemic. For example, if a vaccine with a 50% efficacy in preventing infection becomes available when 10% of the population has already been infected, waiting until 40% of the population are infected for a vaccine with 80% efficacy in preventing infection results in 15.6 million additional cases and 1.5 million additional hospitalizations, costing $20.6 billion more in direct medical costs and $12.4 billion more in productivity losses., Conclusions: This study shows that there are relatively few situations in which it is worth foregoing the first COVID-19 vaccine available in favor of a vaccine that becomes available later on in the pandemic even if the latter vaccine has a substantially higher efficacy., (Copyright © 2021. Published by Elsevier Inc.)

Eight years of passive acoustic data (2007-2014) from the Beaufort Sea were used to estimate the mean cue rate (calling rate) of individual bowhead whales (Balaena mysticetus) during their fall migration along the North Slope of Alaska. Calls detected on directional acoustic recorders (DASARs) were triangulated to provide estimates of locations at times of call production, which were then translated into call densities (calls/h/km 2 ). Various assumptions were used to convert call density into animal cue rates, including the time for whales to cross the arrays of acoustic recorders, the population size, the fraction of the migration corridor missed by the localizing array system, and the fraction of the seasonal migration missed because recorders were retrieved before the end of the migration. Taking these uncertainties into account in various combinations yielded up to 351 cue rate estimates, which summarize to a median of 1.3 calls/whale/h and an interquartile range of 0.5-5.4 calls/whale/h.

Introduction: With norovirus vaccine candidates currently under development, now is the time to identify the vaccine characteristics and implementation thresholds at which vaccination becomes cost effective and cost saving in a community setting., Methods: In 2020, a norovirus transmission, clinical, and economics computational simulation model representing different U.S. population segments was developed to simulate the spread of norovirus and the potential impact of vaccinating children aged <5 years and older adults (aged ≥65 years)., Results: Compared with no vaccination, vaccinating preschool-aged children averted 8%-72% of symptomatic norovirus cases in a community, whereas vaccinating older adults averted 2%-29% of symptomatic cases (varying with vaccine efficacy [25%-75%] and vaccination coverage [10%-80%]). Vaccination with a 25% vaccine efficacy was cost effective (incremental cost-effectiveness ratio ≤$50,000 per quality-adjusted life year) when vaccination cost ≤$445 and cost saving at ≤$370 when vaccinating preschool-aged children and ≤$42 and ≤$30, respectively, when vaccinating older adults. With a 50% vaccine efficacy, vaccination was cost effective when it cost ≤$1,190 and cost saving at ≤$930 when vaccinating preschool-aged children and ≤$110 and ≤$64, respectively, when vaccinating older adults. These cost thresholds (cost effective and cost saving, respectively) further increased with a 75% vaccine efficacy to ≤$1,600 and ≤$1,300 for preschool-aged children and ≤$165 and ≤$100 for older adults., Conclusions: This study outlines thresholds at which a norovirus vaccine would be cost effective and cost saving in the community when vaccinating children aged <5 years and older adults. Establishing these thresholds can help provide decision makers with targets to consider when developing and implementing a norovirus vaccine., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Fibromyalgia (FM) is a chronic widespread pain condition that overlaps with multiple comorbid health conditions and contributes to considerable patient distress. The aim of this review was to provide a systematic overview of psychiatric and chronic pain comorbidities among patients diagnosed with FM and to inform the development of recommendations for the design of clinical trials. Thirty-one, cross-sectional, clinical epidemiology studies that evaluated patients diagnosed with FM were included for review. None of the reviewed studies reported on the incidence of these comorbidities. Sample size-weighted prevalence estimates were calculated when prevalence data were reported in 2 or more studies for the same comorbid condition. The most prevalent comorbidity across all studies reviewed was depression/major depressive disorder (MDD) with over half of the patients included having this diagnosis in their lifetime (weighted prevalence up to 63%). In addition, nearly one-third of FM patients examined had current or lifetime bipolar disorder, panic disorder, or post-traumatic stress disorder. Less common psychiatric disorders reported included generalized anxiety disorder, obsessive compulsive disorder, and specific phobias (agoraphobia, social phobia). There were fewer studies that examined chronic pain comorbidities among FM patients, but when evaluated, prevalence was also high ranging from 39% to 76% (i.e., chronic tension-type or migraine headache, irritable bowel syndrome, myofascial pain syndrome, and temporomandibular disorders). The results of the review suggest that depression and chronic pain conditions involving head/jaw pain and IBS were elevated among FM patients compared to other conditions in the clinic-based studies. In contrast, anxiety-related disorders were much less common. Addressing the presence of these comorbid health conditions in clinical trials of treatments for FM would increase the generalizability and real-world applicability of FM research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Finding medications or vaccines that may decrease the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could potentially reduce transmission in the broader population. We developed a computational model of the U.S. simulating the spread of SARS-CoV-2 and the potential clinical and economic impact of reducing the infectious period duration. Simulation experiments found that reducing the average infectious period duration could avert a median of 442,852 [treating 25% of symptomatic cases, reducing by 0.5 days, reproductive number (R0) 3.5, and starting treatment when 15% of the population has been exposed] to 44.4 million SARS-CoV-2 cases (treating 75% of all infected cases, reducing by 3.5 days, R0 2.0). With R0 2.5, reducing the average infectious period duration by 0.5 days for 25% of symptomatic cases averted 1.4 million cases and 99,398 hospitalizations; increasing to 75% of symptomatic cases averted 2.8 million cases. At $500/person, treating 25% of symptomatic cases saved $209.5 billion (societal perspective). Further reducing the average infectious period duration by 3.5 days averted 7.4 million cases (treating 25% of symptomatic cases). Expanding treatment to 75% of all infected cases, including asymptomatic infections (R0 2.5), averted 35.9 million cases and 4 million hospitalizations, saving $48.8 billion (societal perspective and starting treatment after 5% of the population has been exposed). Our study quantifies the potential effects of reducing the SARS-CoV-2 infectious period duration., Competing Interests: The authors have declared that no competing interests exist.

Background: Studies show that by 3 months, over half of US infants receive formula, and guidelines play a key role in formula feeding. The question then is, what might happen if caregivers follow guidelines and, more specifically, are there situations where following guidelines can result in infants who are overweight/have obesity?, Methods: We used our "Virtual Infant" agent-based model representing infant-caregiver pairs that allowed caregivers to feed infants each day according to guidelines put forth by Johns Hopkins Medicine (JHM), Children's Hospital of Philadelphia (CHOP), Children's Hospital of the King's Daughters (CHKD), and Women, Infants, and Children (WIC). The model simulated the resulting development of the infants from birth to 6 months. The two sets of guidelines vary in their recommendations, and do not provide studies that support amounts at given ages., Results: Simulations identified several scenarios where caregivers followed JHM/CHOP/CHKD and WIC guidelines, but infants still became overweight/with obesity by 6 months. For JHM/CHOP/CHKD guidelines, this occurred even when caregivers adjusted feeding based on infant's weight. For WIC guidelines, when caregivers adjusted formula amounts, infants maintained healthy weight., Conclusions: WIC guidelines may be a good starting point for caregivers who adjust as their infant grows, but the minimum amounts for JHM/CHKD/CHOP recommendations may be too high., Impact: Our virtual infant simulation study answers the question: can caregivers follow current formula-feeding guidelines and still end up with an infant who is overweight or has obesity? Our study identified several situations in which unhealthy weight gain and/or weight loss could result from following established formula-feeding recommendations. Our study also suggests that the minimum recommended amount of daily formula feeding should be lower for JHM/CHOP/CHKD guidelines to give caregivers more flexibility in adjusting daily feeding levels in response to infant weight. WIC guidelines may be a good starting point for caregivers who adjust as their infant grows. In order to understand how to adjust guidelines, we can use computational simulation models, which serve as "virtual laboratories" to help overcome the logistical and ethical issues of clinical trials.

Introduction: Given the continuing COVID-19 pandemic and much of the U.S. implementing social distancing owing to the lack of alternatives, there has been a push to develop a vaccine to eliminate the need for social distancing., Methods: In 2020, the team developed a computational model of the U.S. simulating the spread of COVID-19 coronavirus and vaccination., Results: Simulation experiments revealed that to prevent an epidemic (reduce the peak by >99%), the vaccine efficacy has to be at least 60% when vaccination coverage is 100% (reproduction number=2.5-3.5). This vaccine efficacy threshold rises to 70% when coverage drops to 75% and up to 80% when coverage drops to 60% when reproduction number is 2.5, rising to 80% when coverage drops to 75% when the reproduction number is 3.5. To extinguish an ongoing epidemic, the vaccine efficacy has to be at least 60% when coverage is 100% and at least 80% when coverage drops to 75% to reduce the peak by 85%-86%, 61%-62%, and 32% when vaccination occurs after 5%, 15%, and 30% of the population, respectively, have already been exposed to COVID-19 coronavirus. A vaccine with an efficacy between 60% and 80% could still obviate the need for other measures under certain circumstances such as much higher, and in some cases, potentially unachievable, vaccination coverages., Conclusions: This study found that the vaccine has to have an efficacy of at least 70% to prevent an epidemic and of at least 80% to largely extinguish an epidemic without any other measures (e.g., social distancing)., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The study aim was to help the Girl Scouts of Central Maryland evaluate, quantify, and potentially modify the Girl Scouts Fierce & Fit program., Methods: From 2018 to 2019, our Public Health Informatics, Computational, and Operations Research team developed a computational simulation model representing the 250 adolescent girls participating in the Fierce & Fit program and how their diets and physical activity affected their BMI and subsequent outcomes, including costs., Results: Changing the Fierce & Fit program from a 6-week program meeting twice a week, with 5 minutes of physical activity each session, to a 12-week program meeting twice a week with 30 minutes of physical activity saved an additional $84,828 ($80,130-$89,526) in lifetime direct medical costs, $81,365 ($76,528-$86,184) in lifetime productivity losses, and 7.85 (7.38-8.31) quality-adjusted life-years. The cost-benefit of implementing this program was $95,943. Based on these results, the Girl Scouts of Central Maryland then implemented these changes in the program., Conclusions: This is an example of using computational modeling to help evaluate and revise the design of a program aimed at increasing physical activity among girls., (© 2020 The Obesity Society.)

With the coronavirus disease 2019 (COVID-19) pandemic, one of the major concerns is the direct medical cost and resource use burden imposed on the US health care system. We developed a Monte Carlo simulation model that represented the US population and what could happen to each person who got infected. We estimated resource use and direct medical costs per symptomatic infection and at the national level, with various "attack rates" (infection rates), to understand the potential economic benefits of reducing the burden of the disease. A single symptomatic COVID-19 case could incur a median direct medical cost of $3,045 during the course of the infection alone. If 80 percent of the US population were to get infected, the result could be a median of 44.6 million hospitalizations, 10.7 million intensive care unit (ICU) admissions, 6.5 million patients requiring a ventilator, 249.5 million hospital bed days, and $654.0 billion in direct medical costs over the course of the pandemic. If 20 percent of the US population were to get infected, there could be a median of 11.2 million hospitalizations, 2.7 million ICU admissions, 1.6 million patients requiring a ventilator, 62.3 million hospital bed days, and $163.4 billion in direct medical costs over the course of the pandemic.

Introduction: There are several recommendations advising caregivers when and how to introduce solid food to infants. These complementary feeding guides vary in terms of the recommendations for timing and portions. The objective of this study is to determine the impact of following different guidelines on weight trajectories of infants., Methods: In 2018, the study team developed a computational simulation model to capture feeding behaviors, activity levels, metabolism, and body size of infants from 6 months to 1 year. Daily food intake of virtual infants based on feeding recommendations translated to changes in body weight. Next, simulations tested the impact of the following complementary feeding recommendations that provided amount, type, and timing of foods: Children's Hospital of Philadelphia, Johns Hopkins Medicine, Enfamil, and Similac., Results: When virtual caregivers fed infants according to the four different guides, none of the simulated situations resulted in normal weight at 12 months when infants were also being breastfed along average observed patterns. Reducing breast milk portions in half while caregivers fed infants according to complementary feeding guidelines resulted in overweight BMIs between 9 and 11 months for Children's Hospital of Philadelphia, Johns Hopkins Medicine, and Enfamil guidelines. Cutting breast milk portions in half also led to infants reaching unhealthy underweight BMI percentiles between 7 and 11 months for female and male infants when caregivers followed Children's Hospital of Philadelphia, Johns Hopkins Medicine, and Similac guidelines., Conclusions: This study identified situations in which infants could reach unhealthy weights, even while following complementary feeding guidelines, suggesting that current recommended portion sizes should be tightened., (Copyright © 2019 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, reduces the incidence and severity of opioid-induced adverse events (AEs)., Objectives: To assess the analgesic efficacy and adverse effects of single-dose intravenous diclofenac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults., Search Methods: We searched the following databases without language restrictions: the Cochrane Central Register of Controlled Trials (Cochrane Register of Studies Online), MEDLINE, and Embase on 22 May 2018. We checked clinical trials registers and reference lists of retrieved articles for additional studies., Selection Criteria: We included randomized trials that compared a single postoperative dose of intravenous diclofenac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data.Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period.Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, AEs, and for any cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related AEs. We performed a post hoc analysis of opioid-related AEs, to enable indirect comparisons with other analyses of postoperative analgesics.For subgroup analysis, we planned to analyze different doses and formulations of parenteral diclofenac separately.We assessed the overall quality of the evidence for each outcome using GRADE and created two 'Summary of findings' tables., Main Results: We included eight studies, involving 1756 participants undergoing various surgeries (dental, mixed minor, abdominal, and orthopedic), with 20 to 175 participants receiving intravenous diclofenac in each study. Mean study population ages ranged from 24.5 years to 54.5 years. Intravenous diclofenac doses varied among and within studies, ranging from 3.75 mg to 75 mg. Five studies assessed newer formulations of parenteral diclofenac that could be administered as an undiluted intravenous bolus. Most studies had an unclear risk of bias for several domains and a high risk of bias due to small sample size. The overall quality of evidence for each outcome was generally low for reasons including unclear risk of bias in studies, imprecision, and low event numbers.Primary outcomeThree studies (277 participants) produced a number needed to treat for an additional beneficial outcome (NNTB) for at least 50% of maximum pain relief versus placebo of 2.4 (95% confidence interval (CI) 1.9 to 3.1) over four hours (low-quality evidence). Four studies (436 participants) produced an NNTB of 3.8 versus placebo (95% CI 2.9 to 5.9) over six hours (low-quality evidence). No studies provided data for the comparison of intravenous diclofenac with another NSAID over four hours. At six hours there was no difference between intravenous diclofenac and another NSAID (low-quality evidence).Secondary outcomesFor secondary efficacy outcomes, intravenous diclofenac was generally superior to placebo and similar to other NSAIDs.For time to rescue medication, comparison of intravenous diclofenac versus placebo demonstrated a median of 226 minutes for diclofenac versus 80 minutes for placebo (5 studies, 542 participants, low-quality evidence). There were insufficient data for pooled analysis for comparisons of diclofenac with another NSAID (very low-quality evidence).For the number of participants using rescue medication, two studies (235 participants) compared diclofenac with placebo. The number needed to treat to prevent one additional harmful event (NNTp) (here, the need for rescue medication) compared with placebo was 3.0 (2.2 to 4.5, low-quality evidence). The comparison of diclofenac with another NSAID included only one study (98 participants). The NNTp was 4.5 (2.5 to 33) for ketorolac versus diclofenac (very low-quality evidence).The numbers of participants withdrawing were generally low and inconsistently reported (very low-quality evidence). Participant withdrawals were: 6% (8/140) diclofenac versus 5% (7/128) placebo, and 9% (8/87) diclofenac versus 7% (6/82) another NSAID for lack of efficacy; 2% (4/211) diclofenac versus 0% (0/198) placebo, and 3% (4/138) diclofenac versus 2% (2/129) another NSAID due to AEs; and 11% (21/191) diclofenac versus 17% (30/179) placebo, and 18% (21/118) diclofenac versus 15% (17/111) another NSAID for any cause.Overall adverse event rates were similar between intravenous diclofenac and placebo (71% in both groups, 2 studies, 296 participants) and between intravenous diclofenac and another NSAID (55% and 58%, respectively, 2 studies, 265 participants) (low-quality evidence for both comparisons). Serious and specific AEs were rare, preventing meta-analysis.There were sufficient data for a dose-effect analysis for our primary outcome for only one alternative dose, 18.75 mg. Analysis of the highest dose employed in each study demonstrated a relative benefit compared with placebo of 1.9 (1.4 to 2.4), whereas for the group receiving 18.75 mg, the relative benefit versus placebo was 1.6 (1.2 to 2.1, 2 studies). Compared to another NSAID, the high-dose analysis demonstrated a relative benefit of 0.9 (0.8 to 1.1), for the group receiving 18.75 mg, the relative benefit was 0.78 (0.65 to 0.93). For direct comparison of high dose versus 18.75 mg, the proportion of participants with at least 50% pain relief was 66% (90/137) for the high-dose arm versus 57% (77/135) in the low-dose arm. There were insufficient data for subgroup meta-analysis of different diclofenac formulations., Authors' Conclusions: The amount and quality of evidence for the use of intravenous diclofenac as a treatment for postoperative pain is low. The available evidence indicates that postoperative intravenous diclofenac administration offers good pain relief for the majority of patients, but further research may impact this estimate. Adverse events appear to occur at a similar rate to other NSAIDs. Insufficient information is available to assess whether intravenous diclofenac has a different rate of bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was insufficient information to evaluate the efficacy and safety of newer versus traditional formulations of intravenous diclofenac. There was a lack of studies in major and cardiovascular surgeries and in elderly populations, which may be at increased risk for adverse events.

Introduction: A number of locations have been considering sugar-sweetened beverage point-of-purchase warning label policies to help address rising adolescent overweight and obesity prevalence., Methods: To explore the impact of such policies, in 2016 detailed agent-based models of Baltimore, Philadelphia, and San Francisco were developed, representing their populations, school locations, and food sources, using data from various sources collected between 2005 and 2014. The model simulated, over a 7-year period, the mean change in BMI and obesity prevalence in each of the cities from sugar-sweetened beverage warning label policies., Results: Data analysis conducted between 2016 and 2017 found that implementing sugar-sweetened beverage warning labels at all sugar-sweetened beverage retailers lowered obesity prevalence among adolescents in all three cities. Point-of-purchase labels with 8% efficacy (i.e., labels reducing probability of sugar-sweetened beverage consumption by 8%) resulted in the following percentage changes in obesity prevalence: Baltimore: -1.69% (95% CI= -2.75%, -0.97%, p<0.001); San Francisco: -4.08% (95% CI= -5.96%, -2.2%, p<0.001); Philadelphia: -2.17% (95% CI= -3.07%, -1.42%, p<0.001)., Conclusions: Agent-based simulations showed how warning labels may decrease overweight and obesity prevalence in a variety of circumstances with label efficacy and literacy rate identified as potential drivers. Implementing a warning label policy may lead to a reduction in obesity prevalence. Focusing on warning label design and store compliance, especially at supermarkets, may further increase the health impact., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to quantify the impact of crime on physical activity location accessibility, leisure-time physical activity (LTPA), and obesity among African American women., Methods: An agent-based model was developed in 2016 to represent resource-limited Washington, DC, communities and their populations to simulate the impact of crime on LTPA and obesity among African American women under different circumstances., Results: Data analysis conducted between 2016 and 2017 found that in the baseline scenario, African American women had a 25% probability of exercising. Reducing crime so more physical activity locations were accessible (increasing from 10% to 50%) decreased the annual rise in obesity prevalence by 2.69%. Increasing the probability of African American women to exercise to 37.5% further increased the impact of reducing crime on obesity (2.91% annual decrease in obesity prevalence)., Conclusions: These simulations showed that crime may serve as a barrier to LTPA. Reducing crime and increasing propensity to exercise through multilevel interventions (i.e., economic development initiatives to increase time available for physical activity and subsidized health care) may promote greater than linear declines in obesity prevalence. Crime prevention strategies alone can help prevent obesity, but combining such efforts with other ways to encourage physical activity can yield even greater benefits., (© 2017 The Obesity Society.)

Background: This review replaces an earlier review, "Methadone for chronic non-cancer pain in adults". This review serves to update the original and includes only studies of neuropathic pain. Methadone belongs to a class of analgesics known as opioids, that are considered the cornerstone of therapy for moderate-to-severe postsurgical pain and pain due to life-threatening illnesses; however, their use in neuropathic pain is controversial. Methadone has many characteristics that differentiate it from other opioids, which suggests that it may have a different efficacy and safety profile., Objectives: To assess the analgesic efficacy and adverse events of methadone for chronic neuropathic pain in adults., Search Methods: We searched the following databases: CENTRAL (CRSO), MEDLINE (Ovid), and Embase (Ovid), and two clinical trial registries. We also searched the reference lists of retrieved articles. The date of the most recent search was 30 November 2016., Selection Criteria: We included randomised, double-blind studies of two weeks' duration or longer, comparing methadone (in any dose, administered by any route, and in any formulation) with placebo or another active treatment in chronic neuropathic pain., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. There were insufficient data to perform pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE and created a 'Summary of findings' table., Main Results: We included three studies, involving 105 participants. All were cross-over studies, one involving 19 participants with diverse neuropathic pain syndromes, the other two involving 86 participants with postherpetic neuralgia. Study phases ranged from 20 days to approximately eight weeks. All administered methadone orally, in doses ranging from 10 mg to 80 mg daily. Comparators were primarily placebo, but one study also included morphine and tricyclic antidepressants.The included studies had several limitations related to risk of bias, particularly incomplete reporting, selective outcome reporting, and small sample sizes.There were very limited data for our primary outcomes of participants with at least 30% or at least 50% pain relief. Two studies reported that 11/29 participants receiving methadone achieved 30% pain relief versus 7/29 participants receiving placebo. Only one study presented data in a manner that allowed us to calculate the number of participants with at least 50% pain relief. None of the 19 participants achieved a 50% reduction in pain intensity, either when receiving methadone or when receiving placebo. No study provided data for our other primary outcomes of Patient Global Impression of Change scale (PGIC) much or very much improved (equivalent to at least 30% pain relief) and PGIC very much improved (equivalent to at least 50% pain relief).For secondary efficacy outcomes, one study reported maximum and mean pain intensity and pain relief, and reported statistically significant improvements versus placebo for all outcomes with 20 mg daily doses of methadone, but not with 10 mg daily doses. The second study reported differences in pain reduction between methadone (n = 26) and morphine (n = 38) and found morphine to be statistically superior. The third study reported the number of responders (variously defined) for several pain and functional outcomes and found methadone to be statistically superior to placebo for the outcomes of categorical pain intensity and evoked pain. In the two studies that reported data, 0/29 participants withdrew due to lack of efficacy, whereas 4/29 participants withdrew due to adverse events while taking methadone versus 3/29 while taking placebo.One study reported incidences for several individual adverse events, but found a statistically significant increased incidence for methadone over placebo for only one event, dizziness. The other studies did not report data in a manner that enabled us to analyze adverse events. There were no serious adverse events or deaths reported.We assessed the quality of the evidence as very low for all efficacy and safety outcomes using GRADE, primarily because of the heterogeneity of study designs and populations, short durations, cross-over methodology, and few participants and events., Authors' Conclusions: The three studies provide very limited, very low quality evidence of the efficacy and safety of methadone for chronic neuropathic pain, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. No conclusions can be made regarding differences in efficacy or safety between methadone and placebo, other opioids, or other treatments.

Increasing physical activity among children is a potentially important public health intervention. Quantifying the economic and health effects of the intervention would help decision makers understand its impact and priority. Using a computational simulation model that we developed to represent all US children ages 8-11 years, we estimated that maintaining the current physical activity levels (only 31.9 percent of children get twenty-five minutes of high-calorie-burning physical activity three times a week) would result each year in a net present value of $1.1 trillion in direct medical costs and $1.7 trillion in lost productivity over the course of their lifetimes. If 50 percent of children would exercise, the number of obese and overweight youth would decrease by 4.18 percent, averting $8.1 billion in direct medical costs and $13.8 billion in lost productivity. Increasing the proportion of children who exercised to 75 percent would avert $16.6 billion and $23.6 billion, respectively., (Project HOPE—The People-to-People Health Foundation, Inc.)

Introduction: For a patient who is deaf, providing patient care can be more difficult due to communication barriers. This study was conducted in order to better understand pharmacists' current means of communicating with deaf patients as well as investigating pharmacists' knowledge of their legal responsibility to these patients., Methods: Surveys were used to gather information from pharmacists and were distributed in areas with a large population of deaf patients., Results: Of the 73 pharmacists who completed surveys, 50 (68.5%) of them interact with at least 1 to 5 deaf patients monthly. Pharmacists responded that accessibility of interpreters is the most significant barrier to communication and providing written material is the method most used to communicate with deaf patients. None of the 73 pharmacists who completed the survey felt that they have a legal obligation to provide and pay for an interpreter., Conclusion: When interacting with a deaf patient, pharmacists may experience communication barriers. Pharmacists should strive to appropriately communicate with the deaf as well as familiarize themselves with legal obligations to this patient population., (© The Author(s) 2015.)

Background: This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear., Objectives: To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children., Search Methods: We ran the search for the previous review in May 2010. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 1), MEDLINE (May 2010 to 16 February 2016), EMBASE (May 2010 to 16 February 2016), LILACS (2010 to 2016), a clinical trials registry, and reference lists of reviews for randomized controlled trials (RCTs) in any language and we retrieved articles., Selection Criteria: Randomized, double-blind, placebo- or active-controlled single dose clinical trials of IV paracetamol or IV propacetamol for acute postoperative pain in adults or children., Data Collection and Analysis: Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We contacted study authors for additional information. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence., Main Results: We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants.Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours.For secondary outcomes, participants receiving IV paracetamol/propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events.Meta-analysis of efficacy comparisons between IV paracetamol/propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both.Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event., Authors' Conclusions: Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.

Unlabelled: Semliki Forest virus (SFV) provides a well-characterized model system to study the pathogenesis of virus encephalitis. Several studies have used virus derived from the molecular clone SFV4. SFV4 virus does not have the same phenotype as the closely related L10 or the prototype virus from which its molecular clone was derived. In mice, L10 generates a high-titer plasma viremia, is efficiently neuroinvasive, and produces a fatal panencephalitis, whereas low-dose SFV4 produces a low-titer viremia, rarely enters the brain, and generally is avirulent. To determine the genetic differences responsible, the consensus sequence of L10 was determined and compared to that of SFV4. Of the 12 nucleotide differences, six were nonsynonymous; these were engineered into a new molecular clone, termed SFV6. The derived virus, SFV6, generated a high-titer viremia and was efficiently neuroinvasive and virulent. The phenotypic difference mapped to a single amino acid residue at position 162 in the E2 envelope glycoprotein (lysine in SFV4, glutamic acid in SFV6). Analysis of the L10 virus showed it contained different plaque phenotypes which differed in virulence. A lysine at E2 247 conferred a small-plaque avirulent phenotype and glutamic acid a large-plaque virulent phenotype. Viruses with a positively charged lysine at E2 162 or 247 were more reliant on glycosaminoglycans (GAGs) to enter cells and were selected for by passage in BHK-21 cells. Interestingly, viruses with the greatest reliance on binding to GAGs replicated to higher titers in the brain and more efficiently crossed an in vitro blood-brain barrier (BBB)., Importance: Virus encephalitis is a major disease, and alphaviruses, as highlighted by the recent epidemic of chikungunya virus (CHIKV), are medically important pathogens. In addition, alphaviruses provide well-studied experimental systems with extensive literature, many tools, and easy genetic modification. In this study, we elucidate the genetic basis for the difference in phenotype between SFV4 and the virus stocks from which it was derived and correct this by engineering a new molecular clone. We then use this clone in one comprehensive study to demonstrate that positively charged amino acid residues on the surface of the E2 glycoprotein, mediated by binding to GAGs, determine selective advantage and plaque size in BHK-21 cells, level of viremia in mice, ability to cross an artificial BBB, efficiency of replication in the brain, and virulence. Together with studies on Sindbis virus (SINV), this study provides an important advance in understanding alphavirus, and probably other virus, encephalitis., (Copyright © 2015 Ferguson et al.)

Background: This is an updated version of the original Cochrane review published in Issue 4, 2006. Patients may control postoperative pain by self administration of intravenous opioids using devices designed for this purpose (patient controlled analgesia or PCA). A 1992 meta-analysis by Ballantyne et al found a strong patient preference for PCA over non-patient controlled analgesia, but disclosed no differences in analgesic consumption or length of postoperative hospital stay. Although Ballantyne's meta-analysis found that PCA did have a small but statistically significant benefit upon pain intensity, a 2001 review by Walder et al did not find statistically significant differences in pain intensity or pain relief between PCA and groups treated with non-patient controlled analgesia., Objectives: To evaluate the efficacy and safety of patient controlled intravenous opioid analgesia (termed PCA in this review) versus non-patient controlled opioid analgesia of as-needed opioid analgesia for postoperative pain relief., Search Methods: We ran the search for the previous review in November 2004. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 12), MEDLINE (1966 to 28 January 2015), and EMBASE (1980 to 28 January 2015) for randomized controlled trials (RCTs) in any language, and reference lists of reviews and retrieved articles., Selection Criteria: We selected RCTs that assessed pain intensity as a primary or secondary outcome. These studies compared PCA without a continuous background infusion with non-patient controlled opioid analgesic regimens. We excluded studies that explicitly stated they involved patients with chronic pain., Data Collection and Analysis: Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. We performed meta-analysis of outcomes that included pain intensity assessed by a 0 to 100 visual analog scale (VAS), opioid consumption, patient satisfaction, length of stay, and adverse events., Main Results: Forty-nine studies with 1725 participants receiving PCA and 1687 participants assigned to a control group met the inclusion criteria. The original review included 55 studies with 2023 patients receiving PCA and 1838 patients assigned to a control group. There were fewer included studies in our updated review due to the revised exclusion criteria. For the primary outcome, participants receiving PCA had lower VAS pain intensity scores versus non-patient controlled analgesia over most time intervals, e.g., scores over 0 to 24 hours were nine points lower (95% confidence interval (CI) -13 to -5, moderate quality evidence) and over 0 to 48 hours were 10 points lower (95% CI -12 to -7, low quality evidence). Among the secondary outcomes, participants were more satisfied with PCA (81% versus 61%, P value = 0.002) and consumed higher amounts of opioids than controls (0 to 24 hours, 7 mg more of intravenous morphine equivalents, 95% CI 1 mg to 13 mg). Those receiving PCA had a higher incidence of pruritus (15% versus 8%, P value = 0.01) but had a similar incidence of other adverse events. There was no difference in the length of hospital stay., Authors' Conclusions: Since the last version of this review, we have found new studies providing additional information. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides moderate to low quality evidence that PCA is an efficacious alternative to non-patient controlled systemic analgesia for postoperative pain control.

Objective: To develop and evaluate adjustment factors to convert parent-reported time in bed to an estimate of child sleep time consistent with objective measurement., Methods: A community sample of 217 children aged 4-9 years (mean age = 6.6 years) wore actigraph wristwatches to objectively measure sleep for 7 days while parents completed reports of child sleep each night. After examining the moderators of the discrepancy between parent reports and actigraphy, 3 adjustment factors were evaluated., Results: Parent report of child sleep overestimated nightly sleep duration by ∼24 min per night relative to actigraphy. Child age, gender, and sleep quality all had small or nonsignificant associations with correspondence between parent report and actigraph. Empirically derived adjustment factors significantly reduced the discrepancy between parent report and objective measurement., Conclusions: Simple adjustment factors can enhance the correspondence and utility of parent reports of child sleep duration for clinical and research purposes., (© The Author 2014. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clinical observations have suggested that antagonism of 5-HT2A receptors may benefit patients with parkinsonian symptomatology. The mechanism of the antiparkinsonian effects of 5-HT2A receptor antagonists has not been fully elucidated. We have shown that the selective 5-HT2A receptor antagonist M100907 [R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenethyl)]-4-piperidinemethanol] improved motor impairments in mice treated with the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In Parkinson's disease (PD) patients and animal models of parkinsonism dopamine denervation is associated with increased cortico-striatal glutamatergic transmission. We hypothesized that 5-HT2A receptor antagonists may exert their antiparkinsonian effects by decreasing striatal glutamate. Here, using in vivo microdialysis, we have shown an increased basal level of extracellular striatal glutamate when measured 3weeks after MPTP administration. The local administration of M100907 to the striatum significantly decreased striatal extracellular glutamate levels in MPTP-treated and saline treated mice. Basal extracellular serotonin (5-HT) levels were also elevated, whereas dopamine (DA) levels were significantly reduced in the striatum of MPTP-treated mice. Infusion of M100907 into the striatum produced no effect on dopamine or 5-HT levels. Local application of tetrodotoxin suppressed glutamate, 5-HT and DA concentrations in striatal dialysates in the presence or absence of M100907. The striatal expression of the glutamate transporter GLT1 was unchanged. However, there was an upregulation of the expression of 5-HT2A receptors in the striatum of MPTP-treated animals. Our data provide further evidence of enhanced glutamatergic neurotransmission in parkinsonism and demonstrate that blocking 5-HT2A receptors in the striatum will normalize glutamatergic neurotransmission., (Copyright © 2014 Elsevier Ltd. All rights reserved.)