A study protocol of a randomised controlled trial to measure the effects of an augmented prescribed exercise programme (APEP) for frail older medical patients in the acute setting

Background: Older adults experience functional decline in hospital leading to increased healthcare burden and morbidity. The benefits of augmented exercise in hospital remain uncertain. The aim of this trial is to measure the short and longer-term effects of augmented exercise for older medical in-patients on their physical performance, quality of life and health care utilisation. Design and Methods: Two hundred and twenty older medical patients will be blindly randomly allocated to the intervention or sham groups. Both groups will receive usual care (including routine physiotherapy care) augmented by two daily exercise sessions. The sham group will receive stretching and relaxation exercises while the intervention group will receive tailored strengthening and balance exercises. Differences between groups will be measured at baseline, discharge, and three months. The primary outcome measure will be length of stay. The secondary outcome measures will be healthcare utilisation, activity (accelerometry), physical performance (Short Physical Performance Battery), falls history in hospital and quality of life (EQ-5D-5 L). Discussion: This simple intervention has the potential to transform the outcomes of the older patient in the acute setting

Professional Reading

Fire in the Lak

The inter-rater reliability of the Risk Instrument for Screening in the Community

Predicting risk of adverse healthcare outcomes is important to enable targeted delivery of interventions. The Risk Instrument for Screening in the Community (RISC), designed for use by public health nurses (PHNs), measures the one-year risk of hospitalisation, institutionalisation and death in community-dwelling older adults according to a five-point global risk score: from low (score 1,2), medium (3) and high (4,5). We examined the inter-rater reliability (IRR) of the RISC between student PHNs (n=32) and expert raters using six cases (two low, medium and high-risk), scored before and after RISC training. Correlations increased for each adverse outcome, statistically significantly for institutionalisation (r=0.72 to 0.80,p=0.04) and hospitalisation, (r=0.51 to 0.71,p<0.01) but not death. Training improved accuracy for low-risk but not all high-risk cases. Overall, the RISC showed good IRR, which increased after RISC training. That reliability reduced for some high-risk cases suggests that the training programme requires adjustment to further improve IRR

Activity of dalotuzumab, a selective anti-IGF1R antibody, in combination with erlotinib in unselected patients with Non-small-cell lung cancer: a phase I/II randomized trial

BACKGROUND: We investigated the safety and antitumor activity of dalotuzumab, a selective anti-insulin growth factor 1 receptor monoclonal antibody (IGF1R MoAb), plus erlotinib in a sequential phase I/II trial in unselected patients with refractory advanced non-small-cell lung cancer (NSCLC).The phase I trial determined the recommended dose and safety of erlotinib plus dalotuzumab at 5 mg/kg or 10 mg/kg weekly in 20 patients. The phase II trial compared outcomes to erlotinib alone and erlotinib plus dalotuzumab at the mg/kg established in the phase I trial. RESULTS: Erlotinib at 150 mg plus dalotuzumab at 10 mg/kg was safe. The phase II trial included 37 patients in the erlotinib arm and 38 patients in the erlotinib plus dalotuzumab arm. Progression-free survival was 1.6 versus 2.5 months, overall survival was 10.2 and 6.6 months, and the objective response rate was 7.9% and 2.7%, respectively, with no significant differences between the two arms. Grade 3-5 adverse events occurred in 11 (28.9%) versus 13 (35.1%) patients, respectively. The most frequent adverse events were asthenia (36.8% vs. 37.8%), dehydration (5.3% vs. 2.7%), diarrhea (71% vs. 81.1%), hyperglycemia (13.1% vs.18.9%), and skin-related toxicities (92.1% vs. 86.4%). CONCLUSION: The addition of dalotuzumab to erlotinib did not improve efficacy outcome in patients with refractory advanced NSCLC

A systematic review of randomised controlled trials of interventions promoting effective condom use

BACKGROUND: Effective condom use can prevent sexually transmitted infections (STIs) and unwanted pregnancy. We conducted a systematic review and methodological appraisal of randomised controlled trials (RCTs) of interventions to promote effective condom use. METHODS: We searched for all RCTs of interventions to promote effective condom use using the Cochrane Infectious Diseases Group's trials register (Oct 2006), CENTRAL (Issue 4, 2006), MEDLINE (1966 to Oct 2006), EMBASE (1974 to Oct 2006), LILACS (1982 to Oct 2006), IBSS (1951 to Oct 2006) and Psychinfo (1996 to Oct 2006). We extracted data on allocation sequence, allocation concealment, blinding, loss to follow-up and measures of effect. Effect estimates were calculated. RESULTS: We identified 139 trials. Seven out of ten trials reported reductions in 'any STI' with five statistically significant results. Three out of four trials reported reductions in pregnancy, although none was statistically significant. Only four trials met all the quality criteria. Trials reported a median of 11 (IQR 7-17) outcome measures. Few trials used the same outcome measure. Altogether, 10 trials (7%) used the outcome 'any STI', 4 (3%) self-reported pregnancy and 22 (16%) used 'condom use at last sex'. CONCLUSIONS: The results are generally consistent with modest benefits but there is considerable potential for bias due to poor trial quality. Because of the low proportion of trials using the same outcome the potential for bias from selective reporting of outcomes is considerable. Despite the public health importance of increasing condom use there is little reliable evidence on the effectiveness of condom promotion interventions

Preliminary molecular replacement results for a crystalline gene 5 protein–deoxyoligonucleotide complex

Complexes of the gene 5 protein from bacteriophage fd with a variety of oligodeoxynucleotides, ranging in length from two to eight and comprised of several different sequences, have been formed and crystallized for X-ray diffraction analysis. The crystallographic parameters of four different unit cells, all of which are based on hexagonal packing arrangements, indicate that the fundamental unit of the complex is composed of six gene 5 protein dimers. We believe this aggregate has 622 point group symmetry and is a ring formed by end-to-end closure of a linear array of six dimers. From our results we have proposed a double-helix model for the gene 5 protein-DNA complex in which the protein forms a spindle or core around which the DNA is spooled. Currently 5.0-A X-ray diffraction data from one of the crystalline complexes is being analyzed by molecular replacement techniques to obtain a direct image of the protein-nucleic acid complex

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar