Introduction Mobile phone technology may be a cost-effective and convenient way to deliver proven weight-loss interventions and thereby prevent or delay onset of type 2 diabetes. The purpose of this ...study was to examine the feasibility and efficacy of a diabetes prevention intervention combined with a mobile app and pedometer in English-speaking overweight adults at risk for type 2 diabetes. Design RCT. Participants Participants included 61 overweight adults with a mean age (SD) of 55.2 (9.0) years. Seventy-seven percent were women, 48% were racial/ethnic minorities, and baseline BMI was 33.3 (6.0). Intervention The curriculum was adapted from the Diabetes Prevention Program, with the frequency of in-person sessions reduced from 16 to six sessions and group exercise sessions replaced by a home-based exercise program. A study-developed mobile phone app and pedometer augmented the intervention and provided self-monitoring tools. Main outcome measure Weight loss. Results Data were collected in 2012 and 2013 and were analyzed in 2014. In intention-to-treat analyses, the intervention group ( n =30) lost an average of 6.2 (5.9) kg (–6.8% 5.7%) between baseline and 5-month follow-up compared to the control group’s ( n =31) gain of 0.3 (3.0) kg (0.3% 5.7%) ( p <0.001). The intervention group’s steps per day increased by 2,551 (4,712) compared to the control group’s decrease of 734 (3,308) steps per day ( p <0.001). In comparison, the intervention group had greater reductions in hip circumference ( p <0.001); blood pressure ( p <0.05); and intake of saturated fat ( p =0.007) and sugar-sweetened beverages ( p =0.02). The intervention had no significant effect on fasting lipid or glucose levels. Conclusions The significant weight loss resulting from this modified combined mobile app and pedometer intervention for overweight adults warrants further investigation in a larger trial.
Summary Background Immunisation of patients with Alzheimer's disease with full-length amyloid-β peptide (Aβ42 ) can clear amyloid plaques from the brain. Our aim was to assess the relation between ...Aβ42 immune response, degree of plaque removal, and long-term clinical outcomes. Methods In June, 2003, consent for long-term clinical follow-up, post-mortem neuropathological examination, or both, was sought from 80 patients (or their carers) who had entered a phase I randomised, placebo-controlled trial of immunisation with Aβ42 (AN1792, Elan Pharmaceuticals) in September, 2000. The follow-up study was completed in September, 2006. Plaques were assessed in terms of the percentage area of the cortex with Aβ immunostaining (Aβ load) and in terms of characteristic histological features reflecting plaque removal. Survival of all 80 individuals until severe dementia or death was assessed with a Cox proportional hazard model. Findings 20 participants—15 in the AN1792 group, five in the placebo group—died before follow-up started. A further 22 patients—19 in the AN1792 group, three in the placebo group—died during follow-up. Nine of the deceased patients, all in the AN1792 group, had given consent for post-mortem analysis; one of these who did not die with Alzheimer's disease was excluded. In the remaining eight participants who received immunisation and who were examined neuropathologically, mean Aβ load was lower than in an unimmunised control group that was matched for age at death (2·1% SE 0·7 in treated participants vs 5·1% 0·9 in controls; mean difference 3·0%, 95% CI 0·6–5·4; p=0·02). Although there was considerable variation in Aβ load and degree of plaque removal among immunised participants, the degree of plaque removal varied significantly with mean antibody response attained during the treatment study period (Kruskal-Wallis p=0·02). Seven of the eight immunised patients who underwent post-mortem assessment, including those with virtually complete plaque removal, had severe end stage dementia before death. In the whole cohort, there was no evidence of improved survival (hazard ratio 0·93, 95% CI 0·43–3·11; p=0·86) or of an improvement in the time to severe dementia (1·18, 0·45–3·11; p=0·73) in the AN1792 group versus the placebo group. Interpretation Although immunisation with Aβ42 resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not prevent progressive neurodegeneration. Funding Alzheimer's Research Trust, Medical Research Council.
Opioid Metabolism Smith, Howard S., MD
Mayo Clinic proceedings,
July 2009, Volume:
84, Issue:
7
Journal Article
Peer reviewed
Open access
Clinicians understand that individual patients differ in their response to specific opioid analgesics and that patients may require trials of several opioids before finding an agent that provides ...effective analgesia with acceptable tolerability. Reasons for this variability include factors that are not clearly understood, such as allelic variants that dictate the complement of opioid receptors and subtle differences in the receptor-binding profiles of opioids. However, altered opioid metabolism may also influence response in terms of efficacy and tolerability, and several factors contributing to this metabolic variability have been identified. For example, the risk of drug interactions with an opioid is determined largely by which enzyme systems metabolize the opioid. The rate and pathways of opioid metabolism may also be influenced by genetic factors, race, and medical conditions (most notably liver or kidney disease). This review describes the basics of opioid metabolism as well as the factors influencing it and provides recommendations for addressing metabolic issues that may compromise effective pain management. Articles cited in this review were identified via a search of MEDLINE, EMBASE, and PubMed. Articles selected for inclusion discussed general physiologic aspects of opioid metabolism, metabolic characteristics of specific opioids, patient-specific factors influencing drug metabolism, drug interactions, and adverse events.
Summary An unprecedented number of humanitarian emergencies of large magnitude and duration is causing the largest number of people in a generation to be forcibly displaced. Yet the existing ...humanitarian system was created for a different time and is no longer fit for purpose. On the basis of lessons learned from recent crises, particularly the Syrian conflict and the Ebola epidemic, I recommend four sets of actions that would make the humanitarian system relevant for future public health responses: (1) operationalise the concept of centrality of protection; (2) integrate affected persons into national health systems by addressing the humanitarian–development nexus; (3) remake, do not simply revise, leadership and coordination; and (4) make interventions efficient, effective, and sustainable. For these recommendations to be implemented, governments, UN agencies, multilateral organisations, and international non-governmental organisations will need to put aside differences and relinquish authority, influence, and funding.
Summary Background Intravenous alteplase is approved for use within 3 h of ischaemic stroke onset, although a meta-analysis of randomised controlled trials suggests treatment benefit up to 4·5 h. We ...compared outcome in patients treated between 3 h and 4·5 h versus those treated within 3 h, who were recorded in the in the Safe Implementation of Treatments in Stroke (SITS), a prospective internet-based audit of the International Stroke Thrombolysis Registry (ISTR). Methods We compared 664 patients presenting with ischaemic stroke and given intravenous altepase (0·9 mg/kg total dose) between 3 h and 4·5 h with 11 865 patients treated within 3 h. All patients were otherwise compliant with European summary of product characteristics criteria and had been documented in the international stroke treatment registry between Dec 25, 2002, and Nov 15, 2007. Outcome measures were symptomatic intracerebral haemorrhage within 24 h (haemorrhage type 2 associated with National Institutes of Health Stroke Scale NIHSS ≥4 points deterioration), and mortality and independence (modified Rankin scale of 0–2) at 3 months. Findings In the 3–4·5-h cohort, treatment was started at a median of 55 min later after symptom onset (195 min IQR 187–210 vs 140 min 115–165, p<0·0001), median age was 3 years younger (65 years 55–73 vs 68 years 58–74, p<0·0001), and stroke severity was lower (NIHSS score 11 7–16 vs 12 8–17, p<0·0001) than in the 3-h cohort. We recorded no significant differences between the 3–4·5-h cohort and the within 3-h cohort for any outcome measure—rate of symptomatic intracerebral haemorrhage: 2·2% (14 of 649) versus 1·6% (183 of 11 681) (odds ratio OR 1·18 95% CI 0·89–1·55, p=0·24; adjusted OR 1·32 1·00–1·75, p=0·052); mortality: 12·7% (70 of 551) versus 12·2% (1263 of 10 368) (OR 1·02 0·90–1·17; p=0·72; adjusted OR 1·15 1·00–1·33; p=0·053); and independence: 58·0% (314 of 541) versus 56·3% (5756 of 10231) (OR 1·04 0·95–1·13, p=0·42; adjusted OR 0·93 0·84–1·03, p=0·18). Interpretation Alteplase remains safe when given at 3–4·5 h after ischaemic stroke, offering an opportunity for patients who cannot be treated within the standard 3-h timeframe. Funding Boehringer-Ingelheim, European Union Public Health Executive Authority.
Summary Background Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up ...to 6·4 years. Methods Women aged 15–25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6·4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov , number NCT00120848. Findings For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95·3% (95% CI 87·4–98·7) and against 12-month persistent infection was 100% (81·8–100). Vaccine efficacy against CIN2+ was 100% (51·3–100) for lesions associated with HPV-16/18 and 71·9% (20·6–91·9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred. Interpretation Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6·4 years. Funding GlaxoSmithKline Biologicals (Belgium).
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