The APPLE Tree programme: Active Prevention in People at risk of dementia through Lifestyle, bEhaviour change and Technology to build REsiliEnce-randomised controlled trial.

BACKGROUND: Large-scale trials of multidomain interventions show that modifying lifestyle and psychological risk factors can slow cognitive decline. We aim to determine if a lower intensity, personally tailored secondary dementia prevention programme for older people with subjective or mild objective memory decline, informed by behaviour change theory, reduces cognitive decline over 2 years. METHODS: A multi-site, single-blind randomised controlled trial recruiting 704 older adults at high dementia risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Participants are randomised using 1:1 allocation ratio to the APPLE Tree intervention versus control arm (dementia prevention information), stratified by site. The intervention explores and implements strategies to promote healthy lifestyle, increase pleasurable activities and social connections and improve long-term condition self-management. Two facilitators trained and supervised by a clinical psychologist deliver ten, 1-h group video call sessions over 6 months (approximately every fortnight), video-call 'tea breaks' (less structured, facilitated social sessions) in intervening weeks and individual goal-setting phone calls every 2 weeks. From 6 to 12 months, participants meet monthly for 'tea breaks', with those not attending receiving monthly goal-setting phone calls. Participants receive a food delivery, pedometer and website access to cognitive training and information about lifestyle modification. Follow-ups for all outcome measures are at 12 and 24 months. The primary outcome is cognition (Neuropsychological Test Battery (NTB) score) at 24 months. Secondary outcomes are quality of life, cost per quality-adjusted life year (QALY) and wellbeing and lifestyle factors the intervention targets (diet, vascular risk, body weight, activity, sleep, anxiety, depression, social networks and loneliness, alcohol intake and smoking). Participants from purposively selected sites participate in qualitative process evaluation interviews, which will be analysed using thematic analytic methods. DISCUSSION: If effective, the intervention design, involving remote delivery and non-clinical facilitators, would facilitate intervention roll-out to older people with memory concerns. TRIAL REGISTRATION: ISRCTN17325135 . Registration date 27 November 2019.

Comparing physical activity in individuals with overweight/obesity with and without binge eating disorder.

Objective: Differential participation in physical activity (PA) may partially explain the health discrepancies between individuals with or without binge-eating disorder (BED). Yet, little is known about the PA habits of individuals with overweight/obesity and how those patterns may differ based on BED status. PA patterns and exercise self-efficacy were examined in individuals with overweight/obesity, with and without BED. Design: Ninety-seven participants with overweight/obesity self-reported their PA via the Godin Leisure-Time Questionnaire and the Paffenbarger PA Questionnaire. Exercise self-efficacy was assessed with the Marcus 5-item Exercise Self-Efficacy scale. Based on the Eating Disorder Examination, 27.8% (n = 27) of the participants met BED criteria. Participants were primarily female (n = 75, 77.3%), on average 47.5 years old (standard deviation = 10.4), and predominantly White/Not Hispanic (n = 67, 69.1%) or African-American/Not Hispanic (n = 18, 18.6%). Results: Hierarchical regressions, accounting for significant differences in body mass index between those with and without BED, showed that the Marcus 5-item Exercise Self-Efficacy Scale (but not BED status) was significantly related to PA. BED status also was unrelated to likelihood of reaching Centres for Disease Control PA guidelines, and 44.3% of all participants reported no participation in weekly sports/recreation activities. Conclusions: Both groups participated in relatively little purposeful and moderate/strenuous PA. Exercise self-efficacy may be important to assess and address among treatment seeking individuals with and without BED who struggle with excess weight.

Factors associated with healthy and unhealthy workplace eating behaviours in individuals with overweight/obesity with and without binge eating disorder.

Objective: Most Americans spend an average of 8 hours per day in the workplace. Current understanding of eating behaviours in the workplace and their association with overweight, obesity and binge eating disorder (BED) is limited. Workplace eating behaviours and weight-related self-efficacy were examined in a sample of 98 individuals with overweight or obesity, with or without BED. Design: Participants completed the Weight Efficacy Lifestyle Questionnaire, Work and Social Adjustment Scale, Worker's Perception of Environmental Factors, and a Workplace Questionnaire. Results: Eating unplanned food occurred on average 2.43 times per week (SD = 3.37), and eating unplanned food even when meals were brought from home occurred on average 1.28 times per week (SD = 1.84). Individuals with BED purchased lunch even when they brought food from home significantly more frequently than did individuals without BED. Those with BED also reported significantly poorer work and social adjustment related to binge eating as compared with those without BED. The most significant barriers to healthy eating in the workplace were coworker influence, eating more food in general and more junk food in response to stress, eating unplanned food at work and time constraints. Conclusions: These factors may be important to target in weight-loss treatment to increase individuals' weight loss success. As individuals with BED may be the most vulnerable to eating unplanned foods, clinicians may want to focus on this potential barrier in BED treatment.

Marketing small animal theriogenology services--one perspective.

Once a decision is made to add small animal theriogenology services to a practice, marketing strategies must be developed and implemented to attract clients to the new services. Marketing strategies for the niche market of theriogenology include start-up marketing methods, referral programs, internal marketing, and continued marketing. Marketing theriogenology services is a dynamic, ongoing process that never ends.

Characterization of truck-mounted atomization equipment typically used in vector control.

The control of medically important arthropod vectors of human and animal disease is a high priority for both public health and military officials. Because droplet size of pesticide spray material is a critical factor affecting vector control applications, the droplet-size spectra produced by 11 sprayers and 3 spray formulations were evaluated. Droplet-size spectra were measured by a laser diffraction instrument, a hot-wire system, and rotating slides. There were considerable differences in the droplet-size spectra produced by the different sprayers tested. The volume median diameter (Dv0.5) for the water-based sprays ranged from 4.7 to 211 microm, depending on the sprayer, and the percent of spray volume contained in droplets less than 20 microm (%vol <20 microm) ranged between 0.5% and 98.9%. The Dv0.5 measurements for the oil-based sprays ranged from 9.4 to 125.3 microm and the %vol <20 microm ranged between 2.4% and 97.9%. The correlations between the Dv0.5 measured by the laser system (Dv0.5-laser) and the mass median diameter, Sauter diameter, and Dv0.5 measured by the AIMS probe were all significant. Generally, the slide Dv0.5s were numerically similar to the Dv0.5 from the laser system and the Sauter diameter from the Army Insecticide Measuring System probe. There was less consistent agreement between the % <32 microm values obtained from the slides and those from the other 2 samplers. The information presented can be used by applicators to select the sprayer that produces the droplet-size spectra needed for their particular application situation.

Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study.

Interest in lycopene has focused primarily on its use in the chemoprevention of prostate cancer (CaP); there are few clinical trials involving men with established disease. In addition, most data examining its mechanism of action have been obtained from experiments using immortal cell lines. We report the inhibitory effect(s) of lycopene in primary prostate epithelial cell (PEC) cultures, and the results of a pilot phase II clinical study investigating whole-tomato lycopene supplementation on the behavior of established CaP, demonstrating a significant and maintained effect on prostate-specific antigen velocity over 1 year. These data reinforce the justification for a large, randomized, placebo-controlled study.

The effect of pesticide residue on caged mosquito bioassays.

Wind tunnel experiments showed that secondary pickup of insecticide residue by mosquitoes in cage bioassays had a significant effect on mortality. Cage bioassays using adult Ochlerotatus taeniorhynchus (Wiedemann) investigated the effect of exposure time to a contaminated surface. Cages were dosed in a wind tunnel using the LC50 for naled (0.124 mg a.i./ml) and an LC25 (0.0772 mg a.i./ml) for naled. Half of the bioassay mosquitoes were moved directly into clean cages with the other half remaining in the sprayed, hence contaminated, cage. Treatment mortality was assessed at 8, 15, 30, 60, 120, 240, and 1,440 min postapplication. Cage contamination had a significant effect on mosquito mortality for both the LC25 and LC50 between 15 and 30 min postapplication.

Risk of second malignancy after Hodgkin's disease in a collaborative British cohort: the relation to age at treatment.

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin's disease in relation to age at treatment and other factors. PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin's disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete. RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3. 3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55. 9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy). CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin's disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin's disease require detailed investigation.

Lung cancer after Hodgkin's disease: a nested case-control study of the relation to treatment.

PURPOSE: To investigate the causes of the raised risk of lung cancer in patients who have had Hodgkin's disease, and in particular the relationship to treatment. PATIENTS AND METHODS: A nested case-control study was conducted within a cohort of 5,519 patients with Hodgkin's disease treated in Britain during 1963 through 1993. For 88 cases of lung cancer and 176 matched control subjects, information on treatment and other risk factors was extracted from hospital case-notes, and odds ratios for lung cancer in relation to these factors were calculated. RESULTS: Risk of lung cancer was borderline significantly greater in patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy than those who did not receive this treatment (relative risk [RR] = 1.66; 95% confidence interval [CI], 0.99 to 2.82), and increased with number of cycles of MOPP (P =.07). Exclusion of lung cancers for which histologic confirmation was not available strengthened these associations (RR = 2.41; 95% CI, 1.33 to 4.51; P =.004 for any MOPP and P =.007 for trend with number of cycles of MOPP). Risks were not raised, however, after chlorambucil, vinblastine, procarbazine, and prednisone treatment. There was evidence that the raised risk of lung cancer occurring in relation to radiotherapy was restricted to histologies other than adenocarcinoma. CONCLUSION: The results suggest that MOPP chemotherapy may lead to elevated risk of lung cancer, at least in certain subgroups of patients. The role of chemotherapy in the etiology of lung cancer after Hodgkin's disease deserves further investigation.

Expression of the mRNAs for the insulin-like growth factors and their binding proteins during development of porcine ovarian follicles.

We examined the expression of the mRNAs for the insulin-like growth factors (IGFs) and two of their binding proteins (BPs), IGFBP-2 and IGFBP-3, in individual follicles of the porcine ovary. Follicular development was synchronized with a progestin (altrenogest). Individual follicles were isolated on days 1, 3, 5 and 7 after progestin withdrawal. No IGFBP-3 mRNA was detected. While IGF-II mRNA was easily detected, the levels of expression did not change. IGF-I and IGFBP-2 mRNAs increased and decreased, respectively, with follicle development until day 7 when IGF-I expression declined. Regression analysis of IGF-I and IGFBP-2 mRNA expression was performed to assess the relative strength of correlations with day, diameter and steroid concentrations as covariates. IGFBP-2 mRNA was correlated with both day and diameter (r = -.713 and -.705, respectively, n = 24) and neither estrogen (E2) nor progesterone (P4) contributed to the fit. While IGF-I mRNA expression was correlated to both day (r = .483) and diameter (r = .587), the strongest predictor was E2 concentration (r = .694, n = 27). In conclusion, the expression of IGF-I and IGFBP-2 mRNAs in the ovarian follicle are discordantly regulated during follicular growth and maturation. The observed changes in these parameters should result in increased bioavailable IGF-I. This supports a pivotal autocrine/paracrine role for these factors during follicle growth and development.

Porcine ovarian cells express messenger ribonucleic acids for the acid-labile subunit and insulin-like growth factor binding protein-3 during follicular and luteal phases of the estrous cycle.

It has recently been shown that, in follicular fluid, as in the circulation, insulin-like growth factors (IGFs)-I and -II exist in a ternary complex with IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). The current study was designed to determine whether ovarian follicular and luteal cells could synthesize IGFBP-3 and ALS. Ovaries were collected, during the follicular and early luteal phases, from mature pigs whose cycles were synchronized with PGF2alpha. We studied IGFBP-3 and ALS messenger RNA (mRNA) by in situ hybridization. These transcripts were colocalized with aromatase mRNA, a marker of healthy granulosa cells. IGFBP-3 mRNA was equally expressed in granulosa cells of all growing follicles. In contrast, granulosa cell ALS mRNA levels were higher (P < 0.05) in preantral and small antral follicles than in large antral follicles. In thecal cells, expression of mRNA for IGFBP-3, ALS and cyclin D1 (a marker of cell proliferation) was restricted to healthy (aromatase-expressing) follicles. In those follicles, thecal expression of IGFBP-3 mRNA was low or absent in preantral follicles but increased (P < 0.05) in antral follicles. Thecal cell ALS transcripts peaked in small antral follicles (P < 0.05) and then declined. In granulosa cells of atretic follicles, transcripts for aromatase were greatly reduced, whereas IGFBP-3 mRNA levels remained high. In contrast, ALS transcript levels were greatly reduced in both granulosa (P < 0.05) and thecal cells (P < 0.001) of atretic follicles. After ovulation, IGFBP-3 mRNA was moderately expressed in granulosa luteins but strongly detected in a few theca-derived cells and in vascular endothelial cells. This study demonstrates that follicular fluid IGFBP-3 and ALS, like the IGFs, originate (at least in part) from the ovary. The ability of follicular cells to synthesize, assemble, and store all components of the ternary complex may be critical in determining the bioavailability of follicular IGF-I and -II.

Messenger ribonucleic acids for MAC25 and connective tissue growth factor (CTGF) are inversely regulated during folliculogenesis and early luteogenesis.

Cell proliferation, terminal differentiation, and angiogenesis occur during cycles of follicular and luteal development. In other paradigms, mac25, a potent tumor inhibitor is strongly induced in senescent epithelial cells, whereas CTGF stimulates angiogenesis and wound healing. Using in situ hybridization and immunohistochemistry, we have examined the possibilities that mac25 is inhibited, whereas CTGF is induced during active periods of follicular development and luteogenesis. Ovaries were collected during the follicular and early luteal phases from prostaglandin F2alpha-treated mature pigs and from slaughterhouse sows. CTGF transcripts were induced during the late preantral stage in granulosa and theca cells concomitantly with the appearance of endothelial cells in the theca. CTGF mRNA expression increased in granulosa cells to a maximum (P < 0.01) in mid-antral follicles but was down regulated (P < 0.01) in preovulatory follicles. In contrast, granulosa cell mac25 mRNA expression was undetectable between the preantral and mid-antral stage but was strongly induced in terminally differentiated granulosa cells of preovulatory follicles. CTGF mRNA and peptide were also detected in the theca externa/interstitium and in vascular endothelial cells of ovarian blood vessels, whereas mac25 transcripts, which were also abundant in ovarian blood vessels increased in the theca interna with follicular development. Transcripts of cyclin D 1, a marker of cell proliferation, appeared during the early antral stage and were moderate in granulosa cells but abundant in capillary endothelial cells in the theca interna, underneath the basement membrane. Following ovulation, CTGF and cyclin D1 mRNAs were associated with the migration of endothelial cells into the CL. Subsequently, there was a marked up-regulation of CTGF mRNA expression in granulosa luteins concomitantly with an increase in endothelial cell proliferation within the CL. We hypothesize that CTGF may promote ovarian cell growth and blood vessel formation during follicular and luteal development whereas mac25, a tumor inhibitor, may promote terminal differentiation of granulosa cells in preovulatory follicles.

Regulation of insulin-like growth factor I biosynthesis in porcine granulosa cells.

In the present studies we examined the regulation of insulin-like growth factor I (IGF-I) expression in porcine granulosa cells in vitro. Using Northern analysis and ribonuclease protection assays with exon-specific probes, we identified the IGF-I messenger RNA (mRNA) transcripts present in these cells under basal and hormone-stimulated conditions. We also assessed changes in secreted IGF-I using Western blots and correlated the change in protein secretion after hormone treatment with changes in mRNA levels. By analogy to the human IGF-I gene and its transcription, two major transcripts of approximately 1 and 7.5 kilobases, seen in freshly isolated granulosa cells and follicle wall and in single passaged granulosa (MDGp1) cells, most likely correspond to IGF-IA. Minor transcripts of 3-4 kilobases, which appeared after FSH or forskolin treatments or in control cells after long exposure of the autoradiographs, were attributed to incompletely processed RNA precursors. Ribonuclease protection assay analysis using probes to detect alternative use of exon 5 or exon 6 indicated that most, if not all, of the transcripts contained only exon 6 sequence (IGF-IA). Both class 1 and class 2 transcripts were identified using exon 1- and exon 2-specific probes, respectively. GH increased steady state levels of IGF-I mRNA 3-fold, FSH increased it approximately 10-fold, and forskolin maximally increased it 12- to 15-fold. Estradiol had no effect alone or in combination with the other treatments. All treatments that increased IGF-I mRNA coordinately increased both class 1 and class 2 transcripts, with the increase in class 1 greater than that in class 2. Multiple forms of IGF-I protein were seen under basal conditions and after hormone treatment. These were identified based on mRNA analysis and biochemical methods as both glycosylated and nonglycosylated IGF-IA prohormone, incompletely processed forms of prohormone, and the mature peptide. Changes in the levels of total protein were similar to the changes in mRNA (GH, 3-fold; FSH and forskolin, 10- to 20-fold). All forms of the protein changed coordinately, suggesting that these hormones had no major effect on the intracellular processing mechanism. IGF-binding protein-3 was able to bind to all IGF-I forms. These data conclusively demonstrate FSH and GH induction of ovarian IGF-I. The porcine granulosa cell culture system used in these studies should be an excellent system for studying the hormonal regulation of IGF-I expression.

Rat brain glucose and energy metabolites: effect of +Gz (head-to-foot inertial load) exposure in a small animal centrifuge.

A unique small animal centrifuge with on-line physiological monitoring and brain tissue collection (in < 1 s) capability was used to investigate the effect of increasing +Gz levels, exposure duration, number of exposures, and time course of metabolic changes in the rat brain. To determine the +Gz tolerance, rats were exposed to +7.5 to 25 Gz (30 s each) and EEG was monitored. G-induced loss of consciousness (G-LOC) defined as isoelectric EEG (I-EEG) occurred only at +22.5 and 25 Gz within 14.5 +/- 3 s. To study the effect of increasing +Gz levels on metabolism, rats were exposed to either 0.5 (control) or +7.5 to 25 Gz (30 s each), and brains were collected 1 min postcentrifugation by freeze fixation. A significant increase in lactate (> or = +7.5 Gz) and a decrease in glucose, creatine phosphate (Cr-P), and ATP levels were observed at +15 Gz and higher. The effect of exposure duration was investigated by exposing the rats to +22.5 Gz for 15-60 s. Brain lactate levels increased six-fold while glucose decreased (75%) following the 60-s exposure. The level of Cr-P and ATP decreased significantly after the 15- and 30-s exposures with no further changes at longer +Gz exposures. For time course studies, brains were collected both during (5-35 s) and after (1-15 min) a +25 Gz exposure. A significant decrease in Cr-P occurred within 5 s, but changes in glucose, ATP, and lactate required 15 s. All metabolites returned to control levels within 3 min, except lactate and adenosine, which required 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of operative stress on the coagulation profile.

There is a tendency toward hypercoagulability in the postoperative period. This is manifested by changes in a number of coagulation parameters, and if not offset by some protective mechanism, thrombosis may occur. This protection appears to be mediated more through the fibrinolytic mechanism than through the action of antithrombin 3 (AT-3) because AT-3 activity diminishes in the early postoperative period. The introduction of variables such as invasion of the vascular system, intraoperative heparin administration, administration of whole blood, and insertion of a Dacron prosthesis does not appreciably affect the response of the coagulation profile to operative stress.

Recovery from severe dysspermatogenesis in a bull: A case report.

An 18-month-old Holstein bull with a history of producing ejaculates of freezable quality was presented with marked oligozoospermia, teratozoospermia and akinozoospermia. Ejaculates also contained many spheroids and medusa forms. The severe dysspermatogenesis was associated with Haemophilus somnus infection based upon positive semen cultures and serology. The bull was treated systemically with the antibiotic, ceftiofur, for 15 days. Approximately 3 months after initial presentation, the bull was again producing semen of freezable quality. The case presented provides one example in which severe dysspermatogenesis resolved to the point of apparently normal spermatogenesis.

Mummified fetus in a mare.

A 12-year-old Arabian mare with a history of repeated early embryonic losses gave birth to a mummified fetus. The fetus was not the result of a pregnancy with twins. The mare had been given a progestogen throughout gestation and expelled the mummified fetus at about 325 days of gestation, 2 weeks after progestogen treatment was discontinued. We estimate that the size of the fetus was consistent with a fetal age of 5 months. The mare and mummified fetus illustrated that progestogen administration after 100 days of gestation can promote retention of a nonviable fetus. When the fetoplacental unit is incapable of producing progestogens in adequate amounts for pregnancy maintenance at that stage of gestation, then it is also unlikely to provide sufficient oxygen and nutrients to meet the needs of the growing fetus. Monitoring fetal viability would enable practitioners to prevent prolonged retention of a nonviable fetus.

Multiple +Gz exposures cause brain edema in rats.

The most serious effect of high sustained +Gz (head-to-foot inertial load) known to occur in pilots of high performance aircraft is +Gz-induced loss of consciousness (G-LOC), which may result in pilot incapacitation and subsequent loss of life. G-LOC is believed to occur due to a critical reduction in cerebral blood flow (CBF). Recently, using a small animal centrifuge (SAC), we showed that +Gz exposure causes global cerebral ischemia in a rodent animal model. Since ischemia, depending upon the severity and duration, has been associated with increased brain water content or edema, the present study was undertaken. Rats were exposed to six exposures of either +25 Gz (30 s each) or +10 Gz (2 min each) in the SAC at +20 Gz.s-1 G onset rate. The appearance of G-LOC was monitored by the flattening of the electroencephalography (EEG) brain wave recording. G-LOC was observed at 101 +/- 46 and 19.2 +/- 5 s during +10 and +25 Gz exposures, respectively. The brains from these animals were removed 15 min to 24 h after the +Gz exposure and analyzed for edema formation (increase in the percentage of tissue water), metabolites, and cerebral blood volume (CBV). A significant decrease in glucose and an increase in lactate concentration were observed during +Gz exposure. Edema formation was observed 15 min after six exposures of either +10 or +25 Gz. A slight but significant decrease in CBV was also observed in rats exposed to six +10 Gz exposures. Edema formation was transient and resolved within 24 h. We concluded that multiple exposures of either +25 Gz, short duration or +10 Gz, long duration, that resulted in G-LOC, can cause cytotoxic brain edema which probably results from tissue hyperosmolality due to metabolic changes and accumulation of lactate during ischemia.

Effect of pyridostigmine bromide on acceleration tolerance and performance.

Pyridostigmine Bromide (PB) is used as a pre-exposure antidote for the prevention of potentially lethal effects of certain chemical warfare nerve agents by reversibly inhibiting acetylcholinesterase (AChE). This study was designed to determine whether PB has any deleterious effects on acceleration tolerance (+Gz) or performance. Double-blind placebo trials were conducted to evaluate the effects of PB (90 mg) per day on +Gz tolerances and performance. Three types of exposures were used: 1) gradual onset rate (GOR) exposures of 0.1 G/s; 2) a series of rapid onset rate (ROR) exposures of 6.0 G/s; and 3) a simulated aerial combat maneuver (SACM) of 4.5 to 9.0 +Gz. Performance tasks included the Unified Tri-Service Cognitive Performance Assessment Battery (UTC-PAB). The subjects were not able to correlate their symptoms with PB, placebo, or the acceleration exposure itself. Plasma PB individual levels ranged between 6 and 31 ng/ml and AChE levels of inhibition had a range of 12 to 45%. There were no significant effects on +Gz tolerance or performance related to PB. Based on the results of this study, PB does not significantly alter +Gz tolerance or performance. Therefore, we do not expect aircrew taking prophylactic doses of PB to be adversely affected during aerial combat operations.

Analysis and interpretation of cost data in randomised controlled trials: review of published studies.

OBJECTIVE: To review critically the statistical methods used for health economic evaluations in randomised controlled trials where an estimate of cost is available for each patient in the study. DESIGN: Survey of published randomised trials including an economic evaluation with cost values suitable for statistical analysis; 45 such trials published in 1995 were identified from Medline. MAIN OUTCOME MEASURES: The use of statistical methods for cost data was assessed in terms of the descriptive statistics reported, use of statistical inference, and whether the reported conclusions were justified. RESULTS: Although all 45 trials reviewed apparently had cost data for each patient, only 9 (20%) reported adequate measures of variability for these data and only 25 (56%) gave results of statistical tests or a measure of precision for the comparison of costs between the randomised groups. Only 16 (36%) of the articles gave conclusions which were justified on the basis of results presented in the paper. No paper reported sample size calculations for costs. CONCLUSIONS: The analysis and interpretation of cost data from published trials reveal a lack of statistical awareness. Strong and potentially misleading conclusions about the relative costs of alternative therapies have often been reported in the absence of supporting statistical evidence. Improvements in the analysis and reporting of health economic assessments are urgently required. Health economic guidelines need to be revised to incorporate more detailed statistical advice.