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.

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.

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.

Cost effectiveness of clinically appropriate decisions on alternative treatments for angina pectoris: prospective observational study.

OBJECTIVE: To assess whether revascularisation that is considered to be clinically appropriate is also cost effective. DESIGN: Prospective observational study comparing cost effectiveness of coronary artery bypass grafting, percutaneous coronary intervention, or medical management within groups of patients rated as appropriate for revascularisation. SETTING: Three tertiary care centres in London. PARTICIPANTS: Consecutive, unselected patients rated as clinically appropriate (using a nine member Delphi panel) to receive coronary artery bypass grafting only (n=815); percutaneous coronary intervention only (n=385); or both revascularisation procedures (n=520). MAIN OUTCOME MEASURE: Cost per quality adjusted life year gained over six year follow-up, calculated with a National Health Service cost perspective and discounted at 3.5%/year. RESULTS: Coronary artery bypass grafting cost 22,000 pounds sterling (33,000 euros; $43,000) per quality adjusted life year gained compared with percutaneous coronary intervention among patients appropriate for coronary artery bypass grafting only (59% probability of being cost effective at a cost effectiveness threshold of 30,000 pounds sterling per quality adjusted life year) and 19,000 pounds sterling per quality adjusted life year gained compared with medical management among those appropriate for both types of revascularisation (probability of being cost effective 63%). In none of the three appropriateness groups was percutaneous coronary intervention cost effective at a threshold of 30,000 pounds sterling per quality adjusted life year. Among patients rated appropriate for percutaneous coronary intervention only, the cost per quality adjusted life year gained for percutaneous coronary intervention compared with medical management was 47,000, pounds sterling exceeding usual cost effectiveness thresholds; in these patients, medical management was most likely to be cost effective (probability 54%). CONCLUSIONS: Among patients judged clinically appropriate for coronary revascularisation, coronary artery bypass grafting seemed cost effective but percutaneous coronary intervention did not. Cost effectiveness analysis based on observational data suggests that the clinical benefit of percutaneous coronary intervention may not be sufficient to justify its cost.

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.

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.

Virtual outreach: economic evaluation of joint teleconsultations for patients referred by their general practitioner for a specialist opinion.

OBJECTIVES: To test the hypotheses that, compared with conventional outpatient consultations, joint teleconsultation (virtual outreach) would incur no increased costs to the NHS, reduce costs to patients, and reduce absences from work by patients and their carers. DESIGN: Cost consequences study alongside randomised controlled trial. SETTING: Two hospitals in London and Shrewsbury and 29 general practices in inner London and Wales. PARTICIPANTS: 3170 patients identified; 2094 eligible for inclusion and willing to participate. 1051 randomised to virtual outreach and 1043 to standard outpatient appointments. MAIN OUTCOME MEASURES: NHS costs, patient costs, health status (SF-12), time spent attending index consultation, patient satisfaction. RESULTS: Overall six months costs were greater for the virtual outreach consultations ( pound 724 per patient) than for conventional outpatient appointments ( pound 625): difference in means pound 99 ($162; 138) (95% confidence interval pound 10 to pound 187, P=0.03). If the analysis is restricted to resource items deemed "attributable" to the index consultation, six month costs were still greater for virtual outreach: difference in means pound 108 ( pound 73 to pound 142, P < 0.0001). In both analyses the index consultation accounted for the excess cost. Savings to patients in terms of costs and time occurred in both centres: difference in mean total patient cost pound 8 ( pound 5 to pound 10, P < 0.0001). Loss of productive time was less in the virtual outreach group: difference in mean cost pound 11 ( pound 10 to pound 12, P < 0.0001). CONCLUSION: The main hypothesis that virtual outreach would be cost neutral is rejected, but the hypotheses that costs to patients and losses in productivity would be lower are supported.

The effect of alcohol consumption on cost of care in severe psychotic illness: a report from the UK700 study.

OBJECTIVE: Alcohol misuse in psychotic patients is common and leads to poor treatment outcome. This study examines the relationship between alcohol consumption and cost of care in patients with a severe psychotic illness. METHOD: Patient care was evaluated over 2 years for 708 patients. Patient reported alcohol consumption was evaluated at initial interview. The outcome measure was cost of care over 2 years. RESULTS: There was no difference in mean cost of care between non-drinkers, moderate and heavy drinkers. Increased alcohol consumption (measured as a continuous variable, adjusted for baseline characteristics) was associated with lower cost of care. CONCLUSION: Heavier alcohol consumers did not incur more treatment costs and may, indeed, cost less than other patients. This may reflect higher levels of drinking being associated with better overall functioning, poorer engagement with services or exclusion from services.

Neuropsychological performance of psychotic patients in community care: results from the UK700 study.

OBJECTIVE: To compare cognitive performance in chronic schizophrenic and affective psychotic patients maintained in community care. METHOD: We studied a sample of community-based patients (n = 707) with chronic psychotic disorders. Neuropsychological assessment was completed using the National Adult Reading Test (NART) and the Trail Making Test (TMT). RESULTS: Affective psychotic patients had higher premorbid IQ than schizophrenic patients before adjustment for confounding factors (P=0.03); however, after adjustment for ethnic group and social class this became non-significant (P=0.19). There were no significant differences between groups on the TMT, parts A or B. CONCLUSION: Unlike studies suggesting that schizophrenic patients are more cognitively impaired than affective psychotic patients, our study suggests a degree of cognitive homogeneity between those patients who develop a chronic illness. Measures of premorbid IQ suggest that this cognitive homogeneity exists prior to the onset of illness.

Factors that influence the cost of caring for patients with severe psychotic illness: report from the UK 700 trial.

BACKGROUND: Many factors influence the type and quantity of services received by patients and, thus, the total cost of care. Knowledge of these factors can aid budgetary and service-planning decisions. AIMS: To investigate factors that influence the cost of caring for patients with severe psychotic illness. METHOD: Univariate and multivariate analyses were used to examine associations between baseline characteristics and subsequent 2-year total direct costs in 667 patients from the UK 700 case management trial. RESULTS: Significantly more money was spent on younger patients, those with longer duration of illness, those who had spent less time living independently and those who had spent longer in hospital for psychiatric reasons. CONCLUSIONS: Total costs of caring for patients with severe psychotic illness appear to be influenced to a large extent by age, duration of illness and past levels of dependence on statutory services. The strength of these relationships is greater than the impact of illness severity.

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.

Analysis of cost data in randomized trials: an application of the non-parametric bootstrap.

Health economic evaluations are now more commonly being included in pragmatic randomized trials. However a variety of methods are being used for the presentation and analysis of the resulting cost data, and in many cases the approaches taken are inappropriate. In order to inform health care policy decisions, analysis needs to focus on arithmetic mean costs, since these will reflect the total cost of treating all patients with the disease. Thus, despite the often highly skewed distribution of cost data, standard non-parametric methods or use of normalizing transformations are not appropriate. Although standard parametric methods of comparing arithmetic means may be robust to non-normality for some data sets, this is not guaranteed. While the randomization test can be used to overcome assumptions of normality, its use for comparing means is still restricted by the need for similarly shaped distributions in the two groups. In this paper we show how the non-parametric bootstrap provides a more flexible alternative for comparing arithmetic mean costs between randomized groups, avoiding the assumptions which limit other methods. Details of several bootstrap methods for hypothesis tests and confidence intervals are described and applied to cost data from two randomized trials. The preferred bootstrap approaches are the bootstrap-t or variance stabilized bootstrap-t and the bias corrected and accelerated percentile methods. We conclude that such bootstrap techniques can be recommended either as a check on the robustness of standard parametric methods, or to provide the primary statistical analysis when making inferences about arithmetic means for moderately sized samples of highly skewed data such as costs.

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.

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.

'Concerning our national honour': Florence Nightingale and the welfare of aboriginal Australians.

Florence Nightingale was a prolific writer on many subjects from nursing to religion to hospital design and sanitary statistics. Her writing on the indigenous people of Australia is little known but should be of interest especially to those involved in the present desperate search for ways to improve the health of Australia's first settlers. Nightingale's evidence was second-hand, derived largely from missionaries, especially Bishop Salvado of the Benedictine foundation of New Norcia in Western Australia. This paper reviews the attitudes to Australian Aborigines which emerge from Nightingale's and others' writings and argues that their place in modern nursing is to stimulate a reappraisal of current attitudes to Aboriginal health.