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A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs ('non-evaluables'). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trails in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure. [ABSTRACT FROM AUTHOR]

Background: Persistent low back pain (LBP) is the leading cause of disability, and a major burden on the healthcare system globally. Many people with LBP experience recurrent pain flares and receive repeated appointments and re-referrals to services such as physiotherapy. However, it is not clear what the criteria are for discharging people with LBP from physiotherapy services. This study aims to describe the current practices for discharging people from physiotherapy for LBP in the United Kingdom (UK)., Methods: A cross-sectional study using an anonymous online national (UK) survey was conducted among qualified physiotherapists who treat people with LBP in UK musculoskeletal out-patient services., Results: A total of 104 surveys were completed. The majority of respondents reported using (i) a shared decision-making (77%) and (ii) person-physiotherapist goal attainment (74%) approach to discharging people with LBP. Sixty-three percent of respondents reported using a patient-initiated follow-up (PIFU) approach. Only 8% of respondents reported using a graded discharge approach with 'booster' appointments. A PIFU or graded discharge approach was considered most pertinent for people at higher risk of a pain flare (97%; 86%) and with low self-efficacy to self-manage their LBP., Conclusions: This UK survey established that discharge practices for people with LBP after physiotherapy vary. Whilst the majority of people are currently discharged with a PIFU appointment, a graded discharge approach may be more beneficial for people who are less likely to initiate a PIFU appointment. Further consideration on the development of such a pathway is now required., (© 2023 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Dietary analysis of Academy soccer players highlights that total energy and carbohydrate intakes are less than optimal, especially, on match-days. As UK Academy matches predominantly kick-off at ∼11:00 h, breakfast is likely the last pre-exercise meal and thus may provide an intervention opportunity on match-day. Accordingly, the physiological and performance effects of an increased calorie breakfast consumed ∼135-min before soccer-specific exercise was investigated. English Premier League Academy soccer players (n = 7) repeated a 90-min soccer match simulation on two occasions after consumption of habitual (B hab ; ∼1100 kJ) or increased (B inc ; ∼2100 kJ) energy breakfasts standardised for macronutrient contributions (∼60% carbohydrates, ∼15% proteins and ∼25% fats). Countermovement jump height, sprint velocities (15-m and 30-m), 30-m repeated sprint maintenance, gut fullness, abdominal discomfort and soccer dribbling performances were measured. Blood samples were taken at rest, pre-exercise, half-time and every 15-min during exercise. Although dribbling precision (P = .522; 29.9 ± 5.5 cm) and success (P = .505; 94 ± 8%) were unchanged throughout all time-points, mean dribbling speed was faster (4.3 ± 5.7%) in B inc relative to B hab (P = .023; 2.84 vs 2.75 m s -1 ). Greater feelings of gut fullness (67 ± 17%, P = .001) were observed in B inc without changes in abdominal discomfort (P = .595). All other physical performance measures and blood lactate and glucose concentrations were comparable between trials (all P > .05). Findings demonstrate that Academy soccer players were able to increase pre-match energy intake without experiencing abdominal discomfort; thus, likely contributing to the amelioration of energy deficits on match-days. Furthermore, whilst B inc produced limited benefits to physical performance, increased dribbling speed was identified, which may be of benefit to match-play.

Purpose: Perfluorocarbons (PFCs) can transport 50 times more oxygen than human plasma. Their properties may be advantageous in preservation of tissue viability in oxygen-deprived states, such as in acute lung injury. We hypothesized that an intravenous dose of the PFC emulsion Oxycyte ® would improve tissue oxygenation and thereby mitigate the effects of acute lung injury., Methods: Intravenous oleic acid (OA) was used to induce lung injury in anesthetized and instrumented Yorkshire swine assigned to three experimental groups: (1) PFC post-OA received Oxycyte ® (5 ml/kg) 45 min after oleic acid-induced lung injury (OALI); (2) PFC pre-OA received Oxycyte ® 45 min before OALI; and (3) Controls which received equivalent dose of normal saline. Animals were observed for 3 h after OALI began, and then euthanized., Results: The median survival times for PFC post-OA, PFC pre-OA, and control were 240, 87.5, and 240 min, respectively (p = 0.001). Mean arterial pressure and mean pulmonary arterial pressure were both higher in the PFC post-OA (p < 0.001 for both parameters). Oxygen content was significantly different between PFC post-OA and the control (p = 0.001). Histopathological grading of lung injury indicated that edema and congestion was significantly less severe in the PFC post-OA compared to control (p = 0.001)., Conclusion: The intravenous PFC Oxycyte ® improves blood oxygen content and lung histology when used as a treatment after OALI, while Oxycyte ® used prior to OALI was associated with increased mortality. Further exploration in other injury models is indicated.

This study investigated the changes in indices of acid-base balance during 120 minutes of simulated soccer match play that included a 30 minute extra-time (ET) period. Eight English Premier League academy soccer players participated in a simulated soccer match that required varying intensities of intermittent exercise including 15-m sprints and soccer dribbling throughout. Blood samples were obtained before (i.e., baseline and pre-exercise) and throughout exercise (i.e., 15, 30, 45, 60, 75, 90, 105, and 120 minutes), and at half time. Sprint speeds over 15 m reduced in ET compared to the first half (-0.39 ± 0.37 m·s, -7 ± 6%, p = 0.021) but not the second half (-0.18 ± 0.25 m·s, -3 ± 4%, p = 0.086). At 105 minutes, blood lactate concentrations reduced compared with that in the opening 30 minutes (-0.9 to -1.2 mmol·L, p ≤ 0.05). Blood pH (-0.03 to -0.04 units), base excess (-0.95 to -1.48 mmol·L), and bicarbonate concentrations (-0.9 ± 0.8 mmol·L) were depressed at 120 minutes compared with those at 105 minutes, baseline and half time (all p ≤ 0.05). There were no significant correlations between changes in acid-base balance and sprint speed (all p > 0.05). Although the perturbations in acid-base balance during ET were statistically significant, the decreases in blood pH, lactate, base excess, and bicarbonate concentrations may not represent metabolic acidosis or impairments in buffering capacity that are likely to explain reduced physical performance. Further research is warranted to investigate mechanisms of fatigue during ET and to develop interventions that attenuate decrements in performance.

Objectives: The physiological and performance effects of carbohydrate-electrolyte gels consumed before the 30min extra-time period of prolonged soccer-specific exercise were investigated., Design: Randomised, double-blind, crossover., Methods: Eight English Premier League academy soccer players performed 120min of soccer-specific exercise on two occasions while consuming fluid-electrolyte beverages before exercise, at half-time and 90min. Carbohydrate-electrolyte (0.7±0.1gkg(-1) BM) or energy-free placebo gels were consumed ∼5min before extra-time. Blood samples were taken before exercise, at half-time and every 15min during exercise. Physical (15-m and 30-m sprint speed, 30-m sprint maintenance and countermovement jump height) and technical (soccer dribbling) performance was assessed throughout each trial., Results: Carbohydrate-electrolyte gels improved dribbling precision (+29±20%) and raised blood glucose concentrations by 0.7±0.8mmoll(-1) during extra-time (both p<0.01). Supplementation did not affect sprint velocities (15m and 30m), 30-m sprint maintenance or dribbling speed as reductions compared to 0-15min values occurred at 105-120min irrespective of trial (all p<0.05). Plasma osmolality and blood sodium concentrations increased post-exercise vs. the opening 15min (p<0.05) but no effect of supplementation existed. Selected markers of physical performance (jump height, 30-m sprint velocity and 30-m repeated sprint maintenance) also reduced by >3% during half-time (all p<0.05)., Conclusions: Carbohydrate-electrolyte gel ingestion raised blood glucose concentrations and improved dribbling performance during the extra-time period of simulated soccer match-play. Supplementation did not attenuate reductions in physical performance and hydration status that occurred during extra-time., (Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: Fabric-like hemostatic dressings offer promise for hemorrhage control in noncompressible areas, especially given their similarity in form to standard gauze currently in use. Recently, two such products, Combat Gauze (CBG) and TraumaStat (TMS), were introduced. Their performance is evaluated in two vascular injury models., Materials and Methods: The dressings were evaluated in anesthetized Yorkshire pigs, hemorrhaged by full transection of the femoral vasculature with 2 min free bleeding period (CBG = 6, TMS = 6) or by 4 mm femoral arterial puncture with 45 s free bleeding period (CBG = 8, TMS = 8). After injury, dressings were applied, followed by 5 min of manual compression and then 500 mL resuscitation fluid infused over 30 min. Vital signs, blood pressure, and blood loss were recorded throughout the 3-h experiment. Bleeding control was the primary outcome., Results: All animals had similar pretreatment mean arterial pressure (MAP) (∼ 36.5 mmHg); pretreatment blood loss following injury was similar for both dressing groups in the two models [24% ± 8% estimated blood volume (EBV) 2 min after transection and 17% ± 4% EBV 45 s after puncture. Incidence of post-treatment bleeding, primarily occurring after release of manual compression or restoration of blood pressure, was more frequent in the puncture model (17% with both CBG and TMS) than the transection model (57% with CBG versus 75% with TMS). Post-treatment blood loss not controlled by the dressing was 19% ± 22% and 31% ± 17% EBV, for CBG and TMS, respectively. Survival rate was 100% for both dressings in the transection model, and was 88% for CBG and 50% for TMS in the puncture model., Conclusions: These findings indicated that CBG and TMS were similarly effective in improving hemostasis. These two fabric-like dressings showed easy application and removal, leaving a clean wound for surgical repair., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The Aim of the Study: An ideal hemostatic dressing that would control bleeding and protect the wound from further contamination is still being sought for combat casualty care. The new SilverLeaf™ (SL) bandage was made of material containing active hemostatic property and possible antimicrobial property from silver coating. This study was conducted to compare and ascertain the hemostatic properties of SL and compare it with known hemostatic dressings: Combat Gauze® (CG) and WoundStat™ (WS) in a swine model with punch, vascular injury., Material and Methods: Three hemostatic dressings were evaluated in anesthetized Yorkshire swine hemorrhaged for 45 sec in a femoral arterial puncture model. The hemostatic dressings SL, CG, or WS were applied on an actively bleeding wound, followed by 5 minutes of compression at 200 mm Hg. The pressure was then released to baseline and skin closed with towel clamps. After 15 minutes, 500 ml of (Hextend) resuscitation fluid infused over a period of 30 minutes. The animal's vital signs were monitored for the 3-hour experiment period. Primary outcomes documented were incidence of bleeding after application of the dressing, restoration of MAP and rate of survival.Results. The pre-treatment blood loss for WS was 375.66 ml (16.49%), SL 282.08 ml (12.15%) and CG 307.24 ml (12.68%) and was comparable between groups (p>0.56). The post-treatment blood loss for WS was 286.05 ml (10.65%), SL 386.81 ml (16.92%), and CG 525.76 ml (21.52%). There was no significant difference in post-treatment blood loss (p>0.37) between groups. The Mean Arterial Pressure (MAP) did not significantly differ between the groups at all time points compared. The SL and CG had comparable MAPS during the first hour. The SL had a slight advantage, but didn't reach statistical significance. This suggests that all the bandages were comparable. The two time points at which the post-treatment bleeding occurred in the three groups after the release of manual compression and after restoration of blood pressure. The post-treatment re-bleeding rates were 22.22% (2/9) for WS and SL, 44.44% (4/9) for CG. The survival rates were 100% for WS, 88.89% for SL, and 77.78% for CG., Conclusion: The findings indicate that SilverLeaf, WoundStat and Combat Gauze were comparable in controlling bleeding, preventing re-bleeding, maintenance of mean arterial pressure and improving survival following treatment.

During development of a pig model of neurologic decompression illness (DCI) we noted that treadmill-trained pigs seemed less likely to develop DCI than sedentary pigs. The phenomenon was formally investigated. Twenty-four immature, male, castrated, pure-bred Yorkshire swine were conditioned by treadmill running, while 34 control pigs remained sedentary. All pigs (weight 18.75-21.90 kg) were dived on air to 200 feet of seawater (fsw) in a dry chamber. Bottom time was 24 min. Decompression rate was 60 fsw/min. Pigs that developed neurologic DCI were treated by recompression. Pigs without neurologic signs were considered neurologically normal if they ran on the treadmill without gait disturbance at 1 and 24 h postdive. Of the 24 exercise-conditioned pigs, only 10 (41.7%) developed neurologic DCI, compared to 25 of 34 (73.5%) sedentary pigs (X2 = 5.97; P = < 0.015). Neither mean carcass density (adiposity) nor mean age were significantly different between groups. No patent foramen ovale was detected at necropsy. An additional control group of 24 pigs was dived to clarify the influence of weight. The results suggest that the risk of neurologic DCI is reduced by physical conditioning, and the effect is independent of differences in age, adiposity, and weight.

Peripheral venous access can often be difficult to obtain in infants and young children. Landmark articles in the 1940s showed that the intraosseous (IO) route was a viable one for resuscitation. While anecdotal reports and clinical experience suggest that blood products can be transfused via the IO route, it has not been specifically studied nor documented. We performed a prospective study to document the feasibility of red blood cell transfusion via the IO space. We studied the rapid infusion of 51Cr-labeled red blood cells via the IO space through an 18-gauge IO needle in three normovolemic immature swine. Serial central venous samples were removed at 30 seconds and at 1, 5, 15, 30, and 60 minutes and analyzed for evidence of radiolabeling. Our results revealed rapid delivery of radiolabeled red blood cells into the central circulation with no evidence of early heomolysis. Highest counts were seen in samples taken at 30 seconds to 1 minute. We conclude that the IO route is a viable means for blood transfusion in a nonhemorrhagic model.

Dopamine is a commonly used pressor agent. Frequently recognized side effects other than occasional reports of pedal gangrene respond to reduction of dose. Because a number of compounds interfere with vitamin B6 and dopamine toxicity in animals is modified by B6, we studied the dopamine-vitamin B6 interaction in rabbits. Six animals received 40 mg dopamine/kg and 10 mg pyridoxine injections; 6 received dopamine and saline. Dopamine administration led to an average fall of 20% (p = 0.04) in plasma pyridoxal 5'-phosphate (PLP) levels, which declined 42% by day 5. Three days later, a 25% decrease persisted (p = 0.03). Dopamine with pyridoxine caused a PLP rise of 65% (p = 0.007), but the post-study level was 28% lower than baseline (p = 0.04). We interpret our data to mean that dopamine reduced PLP levels during and 3 days after the study, and that dopamine appeared to increase the requirements for B6. We worry that dopamine given with other drugs, ie gentamicin, digoxin and theophylline which are frequently used in critical care settings, could aggravate alterations of requirements for or body stores of vitamin B6, creating B6 deficiency.

Theophylline overdosage can cause life-threatening symptoms, that include seizures and cardiac arrhythmias, and can be fatal. Neither the onset of toxicity nor the severity of symptoms is well predicted by serum theophylline concentrations. Since depressed vitamin B6 plasma levels can occur in patients receiving theophylline, we explored a B6-theophylline interaction in a rabbit model. Administration of theophylline preparations intraperitoneally (aminophylline) or orally (sustained release anhydrous theophylline) resulted in a 47% depression of plasma pyridoxal 5'-phosphate (PLP) levels. The 87% increase in PLP with pyridoxine administration was only 18% when aminophylline was also given. The mechanism of the theophylline-B6 interaction is obscure. Ethylenediamine in some theophylline preparations binds directly to PLP, potentially increasing the less direct theophylline effect. Pyridoxine supplementation resulted in higher average PLP levels but did not prevent death in animals with profoundly low PLP levels. If these data apply to humans, B6 deficiency may contribute to chronic theophylline toxicity; however, pyridoxine administration in the dosage used may not prevent toxicity. Larger doses may prove beneficial after further investigation.

The renal toxicity of gentamicin is altered by dietary protein modifications, bicarbonate and acetazolamide administration, magnesium supplementation, polyaspartic acid, piperacillin, hypercalcemia and calcium channel blockers. Renal tissue gentamicin levels have an undetermined role. Reduction of renal pyridoxal 5'-phosphate (PLP- by gentamicin has been shown, as has protection from nephrotoxicity by administration of vitamin B6. To explore an interaction between gentamicin and vitamin B6, gentamicin (5 mg/kg) was given to rabbits by ip injection, with either pyridoxine (10 mg) or isovolemic saline for 3 weeks. There was not a difference between gentamicin levels for animals given gentamicin and pyridoxine versus those given gentamicin and saline. Gentamicin administration led to a 47% fall (p = .0001) in plasma PLP levels. Three days after the last gentamicin administration, the animals maintained a 32% decrease from the pre-gentamicin baseline values (p = 0.02). When pyridoxine was administered concurrently with gentamicin, the PLP rise of 49% was significant (p = 0.001). The mean level after the study (6%) was not significantly lower than baseline (p = .6). We believe that gentamicin interfers with vitamin B6 metabolism, but that vitamin B6 status does not affect levels of gentamicin. A number of drugs affect B6 levels, creating the potential for hypovitaminosis B6 to be an important mechanism of drug-drug interaction in seriously ill patients, particularly in sick newborns or the elderly with lower average PLP levels.

Sequential liver biopsies of owl monkeys that had been experimentally infected with one of two strains of hepatitis A virus (HM-175 or PA-33) were examined for histopathologic alterations. Preinoculation biopsies were normal with only occasional minimal mononuclear cell infiltrates in portal tracts and hepatic lobular parenchyma. Histopathologic features that were present in biopsies taken during the period of elevated serum alanine aminotransferase activity (16-43 days after the intravenous inoculation of virus) included infiltration of predominantly mononuclear inflammatory cells into portal tracts and surrounding parenchyma, degeneration and necrosis of hepatocytes, and hypertrophy of Kupffer cells. Changes were similar in monkeys infected with either HM-175 or PA-33 virus strains. Convalescent biopsies (147-186 days after inoculation) showed resolving lesions with mild portal inflammation and occasional focal collections of inflammatory cells in the parenchyma. These histologic changes are similar to those associated with hepatitis A infection in man, chimpanzees, and several species of marmosets, and support the further use of the owl monkey as a model of human hepatitis A.

To determine spontaneous 24-h patterns of growth hormone (GH) plasma levels in unsedated and unrestrained nonhuman primates, a jacket and tethering system were used to study six cynomolgus monkeys. Hourly blood samples were collected, and body temperatures were recorded over 24-h periods. Measurements of GH were made on all samples. In one 24-h study cortisol levels were also measured as well to document a normal circadian rhythm. GH was released at mean intervals of 4.5 +/- 0.47 h (mean +/- SE) over the 24-h studies. There were no day-to-night differences in either the mean interval of GH release (day, 4.6 +/- 0.66 h; night, 4.4 +/- 0.51) or the mean GH values (day, 9.8 +/- 1.7 mU/l; night, 7.9 +/- 0.8). An apparent midday peak in GH in the 24-h studies followed feeding. As expected, body temperature was higher during the day than night, documenting a normal circadian rhythm. Plasma cortisol also showed a normal circadian variation with a low point midday and a progressive rise during the night in the one 24-h cycle in which it was measured. GH in unsedated, unrestrained cynomolgus monkeys was released in 4- to 5-h cycles both day and night without increased nighttime release. This contrasts sharply with the known nocturnal sleep release of GH seen in humans.

A jacket and tethering system was used to maintain chronic catheters in monkeys, which provided catheter access and manipulability without further restraint. Surgical placement of catheters and a temperature probe allowed for a common cutaneous exit and interface with the jacket and tether. Monkeys were fitted in a sterile leather or denim jacket which was attached to a sterilized flexible stainless steel cable. Through this conduit, an indwelling temperature probe, as well as catheters from the internal jugular and femoral veins, were attached to a swivel unit located on the upper portion of the cage. The internal jugular catheter was used for the continuous infusion of support solution. The catheter from the femoral vein was maintained with a heparin lock and used for serial blood sampling. Using this system, it was possible to obtain frequent blood samples and body temperature readings, and to administer a continuous intravenous infusion without chemical or excessive physical restraint. To date, 367 monkeys, 322 cynomolgus (Macaca fasicularis), 16 rhesus (Macaca mulatta), and 21 African green (Cercopithecus aethiops) have been studied using this procedure.

Intraperitoneal injection of a selected radiopharmaceutical results in the diffusion of radioactive material throughout the peritoneum. A diaphragmatic injury should theoretically result in the diffusion of the radioactive material into the chest. To test this hypothesis, Technetium-99m diethylene-triamine pentacetic acid (Tc-99m DTPA) was administered intraperitoneally by either direct needle injection or catheter into 18 rabbits. Four of the rabbits served as controls and did not have any diaphragmatic injury. Fourteen rabbits had surgically induced diaphragmatic tears of varying size (1/4 to 1 cm) after thoracotomy. Four of the 14 rabbits were dropped from the study because they had inadequate peritoneal injections of the radiopharmaceutical. The remaining ten rabbits showed peritoneoscintigraphic evidence of diaphragmatic injury either by showing passage of the radiotracer into the chest, demonstrating the site of injury as a focal region of increased radiotracer uptake, or showing both of these features. Peritoneoscintigraphy appears to be a potentially useful modality in the detection of diaphragmatic injury.

Of 57 patients with panic disorder with agoraphobia, more had their first panic in late spring and summer than in fall and winter, and in warm weather than in cold weather. In the month before the first panic 52% of the patients had prodromal depression or anxiety. Agoraphobic avoidance preceded the first panic in 23%, began within days after the first panic in 32% (without prodromal anxiety or depression in only 20%), and after more than one panic (1 week to 11 years later) in 41%. The site of the first panic was from the agoraphobic cluster (public places) in 81%, at work or school in 11%, and inside the home in 8%. Thirty-eight percent of patients were with a familiar adult at the time. Many features of the syndrome can be explained by an integrated model with several interacting factors contributing in varying degrees to the different routes by which it develops. To the learning and biological factors already suggested we add an evolutionary factor to explain why most first panics occur outside the home and mainly in public places. Certain extraterritorial cues constituting an agoraphobic cluster seem to be prepotent and prepared triggers or modifiers of fear during stress.