Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Prediction of plan adaptation in head and neck cancer proton therapy using clinical, radiographic, and dosimetric features.

PURPOSE: Because proton head and neck (HN) treatments are sensitive to anatomical changes, plan adaptation (re-plan) during the treatment course is needed for a significant portion of patients. We aim to predict re-plan at plan review stage for HN proton therapy with a neural network (NN) model trained with patients' dosimetric and clinical features. The model can serve as a valuable tool for planners to assess the probability of needing to revise the current plan. METHODS AND MATERIALS: Mean beam dose heterogeneity index (BHI), defined as the ratio of the maximum beam dose to the prescription dose, plan robustness features (clinical target volume (CTV), V100 changes, and V100 > 95% passing rates in 21 robust evaluation scenarios), as well as clinical features (e.g., age, tumor site, and surgery/chemotherapy status) were gathered from 171 patients treated at our proton center in 2020, with a median age of 64 and stages from I-IVc across 13 HN sites. Statistical analyses of dosimetric parameters and clinical features were conducted between re-plan and no-replan groups. A NN was trained and tested using these features. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the prediction model. A sensitivity analysis was done to determine feature importance. RESULTS: Mean BHI in the re-plan group was significantly higher than the no-replan group (p < .01). Tumor site (p < .01), chemotherapy status (p < .01), and surgery status (p < .01) were significantly correlated to re-plan. The model had sensitivities/specificities of 75.0%/77.4%, respectively, and an area under the ROC curve of .855. CONCLUSION: There are several dosimetric and clinical features that correlate to re-plans, and NNs trained with these features can be used to predict HN re-plans, which can be used to reduce re-plan rate by improving plan quality.

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study.

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3-13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.

The relationship between sleep, pain,and musculoskeletal injuries in US Army Soldiers.

INTRODUCTION: The purpose of this study was to investigate the relationship between sleep and pain in military personnel and to determine if metrics of sleep and pain intensity differ between the injured and uninjured in this population. METHODS: Active-duty US Army Soldiers (n=308; 26.8±6.5 years, 82% male) from the 2nd Infantry Division, Joint Base Lewis-McChord, Washington, and 101st Airborne Division, Fort Campbell, Kentucky, completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and questionnaires about current musculoskeletal injuries and pain intensity (0=no pain to 10=worst imaginable pain). Pearson correlation coefficients were used to assess the association between pain and sleep. Differences in sleep and pain between injured and uninjured participants were determined using an analysis of covariance. RESULTS: Pain intensity was positively correlated with sleep quality (global PSQI score, r=0.337, p<0.001) and daytime sleepiness (ESS score, r=0.163, p=0.005), and negatively associated with sleep duration (r=-0.118, p=0.039). Injured participants accounted for 37.7% (n=116) of the study population. Injured participants reported greater pain intensity (3.7±2.5 vs 1.3±1.9, p<0.001), were older (28.5±7.4 years vs 25.8±5.7 years, p=0.001) and in the service longer (6.3±6.3 years vs 4.6±4.7 years, p=0.013) than uninjured participants. Injured participants had higher global PSQI scores (9.0±4.1 vs 6.4±3.4, p<0.001), including each of the seven PSQI components (all p<0.050), and reported sleeping less per night than uninjured participants (5.7±1.3 hours vs 6.1±1.2 hours, p=0.026). CONCLUSION: These data demonstrate that pain intensity is associated with sleep in active-duty US Army Soldiers and that those who report a musculoskeletal injury, regardless of age and time in service, report poorer sleep quality, shorter sleep durations, and greater levels of pain than uninjured Soldiers.

Physical sleeping environment is related to insomnia risk and measures of readiness in US army special operations soldiers.

BACKGROUND: US military service members have characteristically poor sleep, even when 'in garrison' or at one's home base. The physical sleeping environment, which is often poor in military-provided housing or barracks, may contribute to poor sleep quality in soldiers. The current study aimed to assess whether the sleeping environment in garrison is related to sleep quality, insomnia risk and military readiness. METHODS: Seventy-four US army special operations soldiers participated in a cross-sectional study. Soldiers were queried on their sleeping surface comfort and the frequency of being awakened at night by excess light, abnormal temperatures and noise. Subjective sleep quality and insomnia symptoms were also queried, via the Pittsburgh Sleep Quality Index and Insomnia Severity Index, respectively. Lastly, measures of soldier readiness, including morale, motivation, fatigue, mood and bodily pain, were assessed. RESULTS: Soldiers reporting temperature-related and light-related awakenings had poorer sleep quality higher fatigue and higher bodily pain than soldiers without those disturbances. Lower ratings of sleeping surface comfort were associated with poorer sleep quality and lower motivation, lower morale, higher fatigue and higher bodily pain. Each 1-point increase in sleeping surface comfort decreased the risk for a positive insomnia screen by 38.3%, and the presence of temperature-related awakenings increased risk for a positive insomnia screen by 78.4%. Those living on base had a poorer sleeping environment than those living off base. CONCLUSION: Optimising the sleep environment-particularly in on-base, military-provided housing-may improve soldier sleep quality, and readiness metrics. Providers treating insomnia in soldiers should rule out environment-related sleep disturbances prior to beginning more resource-intensive treatment.

Cardiopulmonary exercise testing excludes significant disease in patients recovering from COVID-19.

OBJECTIVE: Post-COVID-19 syndrome presents a health and economic challenge affecting ~10% of patients recovering from COVID-19. Accurate assessment of patients with post-COVID-19 syndrome is complicated by health anxiety and coincident symptomatic autonomic dysfunction. We sought to determine whether either symptoms or objective cardiopulmonary exercise testing could predict clinically significant findings. METHODS: 113 consecutive military patients were assessed in a comprehensive clinical pathway. This included symptom reporting, history, examination, spirometry, echocardiography and cardiopulmonary exercise testing (CPET) in all, with chest CT, dual-energy CT pulmonary angiography and cardiac MRI where indicated. Symptoms, CPET findings and presence/absence of significant pathology were reviewed. Data were analysed to identify diagnostic strategies that may be used to exclude significant disease. RESULTS: 7/113 (6%) patients had clinically significant disease adjudicated by cardiothoracic multidisciplinary team (MDT). These patients had reduced fitness (V̇O2 26.7 (±5.1) vs 34.6 (±7.0) mL/kg/min; p=0.002) and functional capacity (peak power 200 (±36) vs 247 (±55) W; p=0.026) compared with those without significant disease. Simple CPET criteria (oxygen uptake (V̇O2) >100% predicted and minute ventilation (VE)/carbon dioxide elimination (V̇CO2) slope <30.0 or VE/V̇CO2 slope <35.0 in isolation) excluded significant disease with sensitivity and specificity of 86% and 83%, respectively (area under the receiver operating characteristic curve (AUC) 0.89). The addition of capillary blood gases to estimate alveolar-arterial gradient improved diagnostic performance to 100% sensitivity and 78% specificity (AUC 0.92). Symptoms and spirometry did not discriminate significant disease. CONCLUSIONS: In a population recovering from SARS-CoV-2, there is reassuringly little organ pathology. CPET and functional capacity testing, but not reported symptoms, permit the exclusion of clinically significant disease.

Rates, costs, return to work and reoperation following spinal surgery in a workers' compensation cohort in New South Wales, 2010-2018: a cohort study using administrative data.

BACKGROUND: Internationally, elective spinal surgery rates in workers' compensation populations are high, as are reoperation rates, while return-to-work rates following spinal surgery are low. Little information is available from Australia. The aim of this study was to describe the rates, costs, return to work and reoperation following elective spinal surgery in the workers' compensation population in New South Wales (NSW), Australia. METHODS: This retrospective cohort study used administrative data from the State Insurance Regulatory Authority, the government organisation responsible for regulating and administering workers' compensation insurance in NSW. These data cover all workers' compensation-insured workers in New South Wales (over 3 million workers/year). We identified a cohort of insured workers who underwent elective spinal surgery (fusion or decompression) between January 1, 2010 and December 31, 2018. People who underwent surgery for spinal fracture or dislocation, or who had sustained a traumatic brain injury were excluded. The main outcome measures were annual spinal surgery rates, cost of the surgical episode, cumulative costs (surgical, hospital, medical and physical therapy) to 2 years post-surgery, and reoperation and return-to-work rates 2 years post-surgery. RESULTS: There were 9343 eligible claims (39.1 % fusion; 59.9 % decompression); claimants were predominantly male (75 %) with a mean age of 43 (range 18 to 75) years. Spinal surgery rates ranged from 15 to 29 surgeries per 100,000 workers per year, fell from 2011-12 to 2014-15 and rose thereafter. The average cost in Australian dollars for a surgical episode was $46,000 for a spinal fusion and $20,000 for a decompression. Two years post-fusion, only 19 % of people had returned to work at full capacity; 39 % after decompression. Nineteen percent of patients underwent additional spinal surgery within 2 years of the index surgery, to a maximum of 5 additional surgeries. CONCLUSION: Rates of workers' compensation-funded spinal surgery did not rise significantly during the study period, but reoperation rates are high and return-to-work rates are low in this population at 2 years post- surgery. In the context of the poor evidence base supporting lumbar fusion surgery, the high cost, increasing rates, and the increased likelihood of poor outcomes in the workers' compensation population, we question the value of this procedure in this setting.

An equivalence study: Are patient-completed and telephone interview equivalent modes of administration for the EuroQol survey?

BACKGROUND: To determine if the EuroQol Health Related Quality of Life survey produces equivalent results when administered by phone interview or patient-completed forms. METHODS: People awaiting hip or knee arthroplasty at a major metropolitan hospital participated. They were randomly assigned to receive the EuroQol Health Related Quality of Life survey via telephone, followed by a patient completed form 1 week later, or vice versa. Equivalence was determined using two one-sided tests (TOST) based on minimal clinically-important differences for the visual analogue scale (VAS) and the summary Utility Index. Cohen's Kappa scores were computed to determine agreement for the individual EuroQoL Likert scale items. RESULTS: Seventy-six from 90 (84%) participants completed the survey twice. Based on limits set at ±7 and ±0.11 for the VAS and Utility Index, respectively, equivalence was established between the two methods of administration for both the VAS (mean difference 0.05 [90% CI -3.76-3.67]) and the Utility Index (mean difference 0.06 [90% CI 0.02-0.11]). Varying levels of agreement, ranging from slight to substantial (κ = 0.17-0.67), were demonstrated for the individual health domains. The order of telephone and patient-completed survey administration had no significant effect on results. CONCLUSIONS: Equivalent results are obtained between telephone and patient-completed administration for the VAS and Utility Index of the EuroQol Survey in people with advanced hip or knee osteoarthritis. The limits of agreement for the individual health domains vary which prevents the accurate interpretation of real change in these items across modes.

Self-administration and behavioral economics of second-generation synthetic cathinones in male rats.

RATIONALE: Synthetic cathinones have become increasingly available as drugs of abuse. Distribution of these drugs is made possible by altering the chemical structures of prohibited cathinones and marketing them under misleading labels. Very little is known about the relative reinforcing effectiveness of new synthetic cathinones relative to known drugs of abuse. OBJECTIVE: We examined self-administration of three second-generation synthetic cathinones: alpha-pyrrolidinopentiophenone (alpha-PVP), 4-methyl-N-ethylcathinone (4-MEC), and 4-methyl-alpha-pyrrolidinopropiophenone (4-MePPP) relative to methamphetamine. METHOD: Male, Sprague-Dawley rats, implanted with intravenous catheters, were trained to self-administer methamphetamine (0.05 mg/kg/injection) under a fixed-ratio schedule. Following training, various doses of methamphetamine (0.006-0.1 mg/kg/injection), alpha-PVP (0.0015-0.1 mg/kg/injection), 4-MEC (0.1-3.2 mg/kg/injection), or 4-MePPP (0.1-0.8 mg/kg/injection) were available for self-administration in separate groups, followed by a behavioral-economics evaluation of the reinforcing effectiveness of each drug. RESULTS: For all drugs, at least one dose functioned as a reinforcer. Alpha-PVP and 4-MePPP maintained the highest numbers of infusions per session and both were more effective reinforcers relative to methamphetamine. 4-MEC and methamphetamine were not significantly different in terms of infusions per session or reinforcing effectiveness. CONCLUSION: Emerging synthetic cathinones whose primary pharmacological mechanism is to block dopamine uptake but with little effects on monoamine release or serotonin uptake may have a greater degree of abuse potential compared with known abused stimulants.

Minimal important improvement thresholds for the six-minute walk test in a knee arthroplasty cohort: triangulation of anchor- and distribution-based methods.

BACKGROUND: The 6-minute walk test (6MWT) is a commonly used metric for measuring change in mobility after knee arthroplasty, however, what is considered an improvement after surgery has not been defined. The determination of important change in an outcome assessment tool is controversial and may require more than one approach. This study, nested within a combined randomised and observational trial, aimed to define a minimal important improvement threshold for the 6MWT in a knee arthroplasty cohort through a triangulation of methods including patient-perceived anchor-based thresholds and distribution-based thresholds. METHODS: Individuals with osteoarthritis performed a 6MWT pre-arthroplasty then at 10 and 26 weeks post-surgery. Each rated their perceived improvement in mobility post-surgery on a 7-point transition scale anchored from "much better" to "much worse". Based on these responses the cohort was dichotomised into 'improved' and 'not improved'. The thresholds for patient-perceived improvements were then identified using two receiver operating curve methods producing sensitivity and specificity indices. Distribution-based change thresholds were determined using two methods utilising effect size (ES). Agreement between the anchor- and distribution-based methods was assessed using kappa. RESULTS: One hundred fifty-eight from 166 participants in the randomised cohort and 222 from 243 in the combined randomised and observational cohort were included at 10 and 26 weeks, respectively. The slightly or more patient-perceived improvement threshold at 26 weeks (an absolute improvement of 26 m) was the only one to demonstrate sensitivity and specificity results both better than chance. At 10- and 26-weeks, the ES based on the mean change score divided by the baseline standard deviation (SD), was an absolute change of 24.5 and 37.9 m, respectively. The threshold based on a moderate ES (a 0.5 SD of the baseline score) was a change of 55.0 and 55.4 m at 10- and 26-weeks, respectively. The level of agreement between the 26-week anchor-based and distribution-based minimal absolute changes was very good (k = 0.88 (95 % CI 0.81 0.95)). CONCLUSION: A valid threshold of improvement for the 6MWT can only be proposed for changes identified from baseline to 26 weeks post-surgery. The level of agreement between anchor- and distribution-based methods indicates that a true minimal or more threshold of meaningful improvement following surgery is likely within the ranges proposed by the triangulation of all four methods, that is, 26 to 55 m.

Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates.

AIMS: To characterize the pharmacology of MEDI0382, a peptide dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptors. MATERIALS AND METHODS: MEDI0382 was evaluated in vitro for its ability to stimulate cAMP accumulation in cell lines expressing transfected recombinant or endogenous GLP-1 or glucagon receptors, to potentiate glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cell lines and stimulate hepatic glucose output (HGO) by primary hepatocytes. The ability of MEDI0382 to reduce body weight and improve energy balance (i.e. food intake and energy expenditure), as well as control blood glucose, was evaluated in mouse models of obesity and healthy cynomolgus monkeys following single and repeated daily subcutaneous administration for up to 2 months. RESULTS: MEDI0382 potently activated rodent, cynomolgus and human GLP-1 and glucagon receptors and exhibited a fivefold bias for activation of GLP-1 receptor versus the glucagon receptor. MEDI0382 produced superior weight loss and comparable glucose lowering to the GLP-1 peptide analogue liraglutide when administered daily at comparable doses in DIO mice. The additional fat mass reduction elicited by MEDI0382 probably results from a glucagon receptor-mediated increase in energy expenditure, whereas food intake suppression results from activation of the GLP-1 receptor. Notably, the significant weight loss elicited by MEDI0382 in DIO mice was recapitulated in cynomolgus monkeys. CONCLUSIONS: Repeated administration of MEDI0382 elicits profound weight loss in DIO mice and non-human primates, produces robust glucose control and reduces hepatic fat content and fasting insulin and glucose levels. The balance of activities at the GLP-1 and glucagon receptors is considered to be optimal for achieving weight and glucose control in overweight or obese Type 2 diabetic patients.

Interventions to reduce vasovagal reactions in blood donors: a systematic review and meta-analysis.

Vasovagal reactions (VVRs) in blood donors have significant implications for the welfare of donors, donor retention and the management of donor sessions. We present a systematic review of interventions designed to prevent or reduce VVRs in blood donors. Electronic databases were searched for eligible randomised trials to March 2015. Data on study design and outcomes were extracted and pooled using random effects meta-analyses. Sixteen trials met the inclusion criteria: five trials (12 042 participants) of pre-donation water, eight trials (3500 participants) of applied muscle tension (AMT) and one trial each of AMT combined with water, caffeine, audio-visual distraction and/or social support. In donors receiving pre-donation water, the relative risk (RR) compared with controls for VVRs was 0·79 [95% confidence interval (CI) 0·70-0·89, P < 0·0001] and the mean difference (MD) in severity of VVRs measured with the Blood Donation Reactions Inventory (BDRI) score was -0·32 (95% CI -0·51 to -0·12, P < 0·0001). Excluding trials with a high risk of selection bias, the RR for VVRs was 0·70 (95% CI 0·45-1·11, P = 0·13). In donors who received AMT, there was no difference in the risk of chair recline in response to donor distress from controls (RR 0·76, 95% CI 0·53-1·10, P = 0·15), although the MD in BDRI score was -0·07 (95% CI -0·11 to -0·03, P = 0·0005). There was insufficient data to perform meta-analysis for other interventions. Current evidence on interventions to prevent or reduce VVRs in blood donors is indeed limited and does not provide strong support for the administration of pre-donation water or AMT during donation. Further large trials are required to reliably evaluate the effect of these and other interventions in the prevention of VVRs.

Deep vein thrombosis and pulmonary embolism in the military patient.

OBJECTIVES: Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, is a common, potentially lethal condition and a cause of long-term morbidity and functional limitation. This paper is a clinical review focused on military epidemiology, evidence-based recommendations for prevention, diagnosis and management of VTE and occupational considerations in a military population. METHODS: A literature review was conducted through Pubmed and Embase for systematic reviews, meta-analyses and clinical trials relating to VTE. Guidelines from the National Institute for Health and Care Excellence, British Thoracic Society and the American College of Chest Physicians were reviewed and recommendations considered. RESULTS: Acute morbidity from VTE can range from limb pain and swelling to life-threatening cardiovascular compromise. Long-term sequelae include postthrombotic syndrome, chronic thrombosis and pulmonary hypertension. Diagnosis should follow a validated pathway depending on the patient's prerest probability. The management of the condition should vary with attention to risk stratification. DISCUSSION: Prompt initiation of anticoagulation reduces symptoms, rates of recurrent VTE and death but treatment must be balanced against the risk of major haemorrhage. Military operations expose personnel to a unique combination of risk factors for VTE and operating in austere environments can increase the challenge of diagnosis, prognostication and management. Furthermore, there are implications for troop attrition, operational readiness and return to work.

A hierarchical model of factors influencing a battery of agility tests.

AIM: The aim of this study was to investigate the hierarchical contributions of anthropometry, strength and cognition to a battery of prescriptive and reactive agility tests. METHODS: Nineteen participants (mean±S.D.; age:22.1±1.9 years; height: 182.9±5.5 cm; body mass: 77±4.9 kg) completed four agility tests: a prescriptive linear sprint, a prescriptive change-of-direction sprint, a reactive change-of-direction sprint, and a reactive linear deceleration test. Anthropometric variables included body fat percentage and thigh girth. Strength was quantified as the peak eccentric hamstring torque at 180, 300, and 60°·s-1. Mean reaction time and accuracy in the Stroop word-colour Test was used to assess perceptual and decision making factors. RESULTS: There was little evidence of intertest correlation with the strongest relationship observed between 10 m sprint and t-test performance (r2=0.49, P<0.01). Anthropometric measures were not strong predictors of agility, accounting for a maximum 23% (P=0.12) in the prescriptive change-of-direction test. Cognitive measures had a stronger correlation with the reactive (rather than prescriptive) agility tests, with a maximum 33% (P=0.04) of variance accounted for in the reactive change-of-direction test. Eccentric hamstring strength accounted for 62% (P=0.01) of the variance in the prescriptive change-of-direction test. Hierarchical ordering of the agility tests revealed that eccentric hamstring strength was the primary predictor in 3 of the 4 tests, with cognitive accuracy the next most common predictor. CONCLUSION: There is little evidence of inter-test correlation across a battery of agility tests. Eccentric hamstring strength and decision making accuracy are the most common predictors of agility performance.

Mail versus telephone administration of the Oxford Knee and Hip Scores.

Telephone and postal methods of administration of the Oxford Knee Score (OKS) and the Oxford Hip Score (OHS) were compared on 85 and 61 patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA), respectively. The test for equivalence was significant for both the knee (P<0.001) and hip participants (P<0.001) indicating that the modes of administration yielded similar results. The ICCs of the OKS and OHS were 0.79 (95% Confidence Interval (CI) 0.70, 0.86) and 0.87 (0.79, 0.92) respectively. The 95% limits of agreement were wide for both scores (OKS LOA, -8.6, 8.2; OHS LOA, -7.7, 5.3). The two modes of administration of the OKS and OHS produce equivalent survey responses at a group level but the same method of administration should be constant for individual monitoring in a clinical setting.

The effect of acute moderate-intensity exercise on the accuracy of air-displacement plethysmography in young adults.

BACKGROUND/OBJECTIVES: Air-displacement plethysmography (ADP) body composition systems utilize a precise pre-test protocol that must be followed for each trial. Previous research has shown that body temperature changes influence the results when using ADP as a measurement. The objective of this study is to determine the effect of post-exercise body temperature changes on body composition results using ADP. SUBJECTS/METHODS: Forty young adults (18-30 years) participated in the study (23 females, 17 males). Resting heart rate was measured to calculate exercise intensity. First, an ADP test was done according to the instructions outlined by the manufacturer. Upon completion of the ADP test, the subject exercised on a treadmill at moderate intensity (∼65% heart rate reserve) for 30 min to increase body temperature. Another ADP measurement followed the physical activity. Chamber temperature (CT) was measured during each of the trials using a thermistor to assess changes. Fat mass (FM), fat-free mass (FFM), percentage body fat (%BF) and CT were compared pre- and post exercise. RESULTS: Paired sample t-tests revealed significant differences (P<0.05) between pre-exercise %BF and post-exercise %BF (21.3 ± 9.8% vs 19.6 ± 10.2%), pre-exercise CT and post-exercise CT (22.7 ± 1.2 vs 23.0 ± 1.1 °C), and pre-exercise FM and post-exercise FM (14.9 ± 7.9 vs 13.8 ± 8.0 kg). FFM showed no significant difference. CONCLUSION: This investigation demonstrates the importance of following the manufacturer's recommended pre-test protocol as the accuracy of the ADP testing may be compromised, resulting in lower FM and %BF estimations.

An unusual case of anaemia and lymphadenopathy in a soldier on deployment.

We describe the case of a British soldier, originally from southeast Africa, who presented to the British military hospital in Helmand Province, southern Afghanistan, with a history of constitutional upset, profound anaemia and diffuse lymphadenopathy with hepatosplenomegaly. Following evacuation to the UK investigations revealed a rare (and a not so rare) diagnosis. This case raises a number of questions regarding the population at risk, the prevalence of endemic diseases in this population and laboratory capabilities in the deployed setting.

Serum D-lactate concentrations in cats with gastrointestinal disease.

BACKGROUND: Increased D-lactate concentrations cause neurological signs in humans with gastrointestinal disease. HYPOTHESIS/OBJECTIVES: To determine if serum D-lactate concentrations are increased in cats with gastrointestinal disease compared to healthy controls, and if concentrations correlate with specific neurological or gastrointestinal abnormalities. ANIMALS: Systematically selected serum samples submitted to the Gastrointestinal Laboratory at Texas A&M University from 100 cats with clinical signs of gastrointestinal disease and abnormal gastrointestinal function tests, and 30 healthy cats. METHODS: Case-control study in which serum D- and L-lactate concentrations and retrospective data on clinical signs were compared between 30 healthy cats and 100 cats with gastrointestinal disease. Association of D-lactate concentration with tests of GI dysfunction and neurological signs was evaluated by multivariate linear and logistic regression analyses, respectively. RESULTS: All 100 cats had a history of abnormal gastrointestinal signs and abnormal gastrointestinal function test results. Thirty-one cats had definitive or subjective neurological abnormalities. D-lactate concentrations of cats with gastrointestinal disease (median 0.36, range 0.04-8.33 mmol/L) were significantly higher than those in healthy controls (median 0.22, range 0.04-0.87 mmol/L; P = .022). L-lactate concentrations were not significantly different between the 2 groups of cats with gastrointestinal disease and healthy controls. D-lactate concentrations were not significantly associated with fPLI, fTLI, cobalamin, folate, or neurological abnormalities (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: D-lactate concentrations can be increased in cats with gastrointestinal disease. These findings warrant additional investigations into the role of intestinal microbiota derangements in cats with gastrointestinal disease, and the association of D-lactate and neurological abnormalities.

Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence.

Emerging preclinical and clinical evidence suggests that pregnenolone may be a promising novel therapeutic candidate in schizophrenia. Pregnenolone is a neurosteroid with pleiotropic actions in rodents that include the enhancement of learning and memory, neuritic outgrowth, and myelination. Further, pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABA(A) receptor responses. In addition, pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. There are thus multiple mechanistic possibilities for pregnenolone as a potential therapeutic agent in schizophrenia, including the amelioration of NMDA receptor hypofunction (via metabolism to pregnenolone sulfate) and the mitigation of GABA dysregulation (via metabolism to allopregnanolone). Additional evidence consistent with a therapeutic role for pregnenolone in schizophrenia includes neurosteroid changes following administration of certain antipsychotics in rodent models. For example, clozapine elevates pregnenolone levels in rat hippocampus, and these increases may potentially contribute to its superior antipsychotic efficacy [Marx et al. (2006a) Pharmacol Biochem Behav 84:598-608]. Further, pregnenolone levels appear to be altered in postmortem brain tissue from patients with schizophrenia compared to control subjects [Marx et al. (2006c) Neuropsychopharmacology 31:1249-1263], suggesting that neurosteroid changes may play a role in the neurobiology of this disorder and/or its treatment. Although clinical trial data utilizing pregnenolone as a therapeutic agent in schizophrenia are currently limited, initial findings are encouraging. Treatment with adjunctive pregnenolone significantly decreased negative symptoms in patients with schizophrenia or schizoaffective disorder in a pilot proof-of-concept randomized controlled trial, and elevations in pregnenolone and allopregnanolone post-treatment with this intervention were correlated with cognitive improvements [Marx et al. (2009) Neuropsychopharmacology 34:1885-1903]. Another pilot randomized controlled trial recently presented at a scientific meeting demonstrated significant improvements in negative symptoms, verbal memory, and attention following treatment with adjunctive pregnenolone, in addition to enduring effects in a small subset of patients receiving pregnenolone longer-term [Savitz (2010) Society of Biological Psychiatry Annual Meeting New Orleans, LA]. A third pilot clinical trial reported significantly decreased positive symptoms and extrapyramidal side effects following adjunctive pregnenolone, in addition to increased attention and working memory performance [Ritsner et al. (2010) J Clin Psychiatry 71:1351-1362]. Future efforts in larger cohorts will be required to investigate pregnenolone as a possible therapeutic candidate in schizophrenia, but early efforts are promising and merit further investigation. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.