Implications of the problem orientated medical record (POMR) for research using electronic GP databases: a comparison of the Doctors Independent Network Database (DIN) and the General Practice Research Database (GPRD).

Background The General Practice Research Database (GPRD) and Doctor's Independent Network Database (DIN), are large electronic primary care databases compiled in the UK during the 1990s. They provide a valuable resource for epidemiological and health services research. GPRD (based on VAMP) presents notes as a series of discrete episodes, whereas DIN is based on a system (MEDITEL) that used a Problem Orientated Medical Record (POMR) which links prescriptions to diagnostic problems. We have examined the implications for research of these different underlying philosophies. Methods Records of 40,183 children from 141 practices in DIN and 76,310 from 464 practices in GRPD who were followed to age 5 were used to compare the volume of recording of prescribing and diagnostic codes in the two databases. To assess the importance and additional value of the POMR within DIN, the appropriateness of diagnostic linking to skin emollient prescriptions was investigated. Results Variation between practices for both the number of days on which prescriptions were issued and diagnoses were recorded was marked in both databases. Mean number of "prescription days" during the first 5 years of life was similar in DIN (19.5) and in GPRD (19.8), but the average number of "diagnostic days" was lower in DIN (15.8) than in GPRD (22.9). Adjustment for linkage increased the average "diagnostic days" to 23.1 in DIN. 32.7% of emollient prescriptions in GPRD appeared with an eczema diagnosis on the same day compared to only 19.4% in DIN; however, 86.4% of prescriptions in DIN were linked to an earlier eczema diagnosis. More specifically 83% of emollient prescriptions appeared under a problem heading of eczema in the 121 practices that were using problem headings satisfactorily. Conclusion Prescribing records in DIN and GPRD are very similar, but the usage of diagnostic codes is more parsimonious in DIN because of its POMR structure. Period prevalence rates will be underestimated in DIN unless this structure is taken into account. The advantage of the POMR is that in 121 of 141 practices using problem headings as intended, most prescriptions can be linked to a problem heading providing a specific reason for their issue

'I'm sure we made it a better study…': Experiences of adults with intellectual disabilities and parent carers of patient and public involvement in a health research study.

Patient and public involvement is considered integral to health research in the United Kingdom; however, studies documenting the involvement of adults with intellectual disabilities and parent carers in health research studies are scarce. Through group interviews, this study explored the perspectives and experiences of a group of adults with intellectual disabilities and a group of parent carers about their collaborative/participatory involvement in a 3-year study which explored the effectiveness of annual health checks for adults with intellectual disabilities. Thematic analysis identified five key themes consistent across both groups; authenticity of participation, working together, generating new outcome measures, dissemination of findings and involvement in future research. Although reported anecdotally rather than originating from the analysis, increased self-confidence is also discussed. The groups' unique perspectives led to insights not previously considered by the research team which led to important recommendations to inform healthcare practice

Effect of a primary care walking intervention with and without nurse support on physical activity levels in 45- to 75-year-olds: The pedometer and consultation evaluation (PACE-UP) cluster randomised clinical trial

Background Pedometers can increase walking and moderate-to-vigorous physical activity (MVPA) levels, but their effectiveness with or without support has not been rigorously evaluated. We assessed the effectiveness of a pedometer-based walking intervention in predominantly inactive adults, delivered by post or through primary care nurse-supported physical activity (PA) consultations. Methods and Findings A parallel three-arm cluster randomised trial was randomised by household, with 12-mo follow-up, in seven London, United Kingdom, primary care practices. Eleven thousand fifteen randomly selected patients aged 45–75 y without PA contraindications were invited. Five hundred forty-eight self-reporting achieving PA guidelines were excluded. One thousand twenty-three people from 922 households were randomised between 2012–2013 to one of the following groups: usual care (n = 338); postal pedometer intervention (n = 339); and nurse-supported pedometer intervention (n = 346). Of these, 956 participants (93%) provided outcome data (usual care n = 323, postal n = 312, nurse-supported n = 321). Both intervention groups received pedometers, 12-wk walking programmes, and PA diaries. The nurse group was offered three PA consultations. Primary and main secondary outcomes were changes from baseline to 12 mo in average daily step-counts and time in MVPA (in ≥10-min bouts), respectively, measured objectively by accelerometry. Only statisticians were masked to group. Analysis was by intention-to-treat. Average baseline daily step-count was 7,479 (standard deviation [s.d.] 2,671), and average time in MVPA bouts was 94 (s.d. 102) min/wk. At 12 mo, mean steps/d, with s.d. in parentheses, were as follows: control 7,246 (2,671); postal 8,010 (2,922); and nurse support 8,131 (3,228). PA increased in both intervention groups compared with the control group; additional steps/d were 642 for postal (95% CI 329–955) and 677 for nurse support (95% CI 365–989); additional MVPA in bouts (min/wk) were 33 for postal (95% CI 17–49) and 35 for nurse support (95% CI 19–51). There were no significant differences between the two interventions at 12 mo. The 10% (1,023/10,467) recruitment rate was a study limitation. Conclusions A primary care pedometer-based walking intervention in predominantly inactive 45- to 75-y-olds increased step-counts by about one-tenth and time in MVPA in bouts by about one-third. Nurse and postal delivery achieved similar 12-mo PA outcomes. A primary care pedometer intervention delivered by post or with minimal support could help address the public health physical inactivity challenge.The PACE-UP trial was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project number HTA 10/32/02 ISRCTN42122561) and will be published in full in Health Technology Assessment. The funders had no role in study design (beyond the commissioned call outline), data collection and analysis, decision to publish, or preparation of the manuscript

Physical activity levels in adults and older adults 3–4 years after pedometer-based walking interventions: Long-term follow-up of participants from two randomised controlled trials in UK primary care

Background Physical inactivity is an important cause of noncommunicable diseases. Interventions can increase short-term physical activity (PA), but health benefits require maintenance. Few interventions have evaluated PA objectively beyond 12 months. We followed up two pedometer interventions with positive 12-month effects to examine objective PA levels at 3–4 years. Methods and findings Long-term follow-up of two completed trials: Pedometer And Consultation Evaluation-UP (PACE-UP) 3-arm (postal, nurse support, control) at 3 years and Pedometer Accelerometer Consultation Evaluation-Lift (PACE-Lift) 2-arm (nurse support, control) at 4 years post-baseline. Randomly selected patients from 10 United Kingdom primary care practices were recruited (PACE-UP: 45–75 years, PACE-Lift: 60–75 years). Intervention arms received 12-week walking programmes (pedometer, handbooks, PA diaries) postally (PACE-UP) or with nurse support (PACE-UP, PACE-Lift). Main outcomes were changes in 7-day accelerometer average daily step counts and weekly time in moderate-to-vigorous PA (MVPA) in ≥10-minute bouts in intervention versus control groups, between baseline and 3 years (PACE-UP) and 4 years (PACE-Lift). PACE-UP 3-year follow-up was 67% (681/1,023) (mean age: 59, 64% female), and PACE-Lift 4-year follow-up was 76% (225/298) (mean age: 67, 53% female). PACE-UP 3-year intervention versus control comparisons were as follows: additional steps/day postal +627 (95% CI: 198–1,056), p = 0.004, nurse +670 (95% CI: 237–1,102), p = 0.002; total weekly MVPA in bouts (minutes/week) postal +28 (95% CI: 7–49), p = 0.009, nurse +24 (95% CI: 3–45), p = 0.03. PACE-Lift 4-year intervention versus control comparisons were: +407 (95% CI: −177–992), p = 0.17 steps/day, and +32 (95% CI: 5–60), p = 0.02 minutes/week MVPA in bouts. Neither trial showed sedentary or wear-time differences. Main study limitation was incomplete follow-up; however, results were robust to missing data sensitivity analyses. Conclusions Intervention participants followed up from both trials demonstrated higher levels of objectively measured PA at 3–4 years than controls, similar to previously reported 12-month trial effects. Pedometer interventions, delivered by post or with nurse support, can help address the public health physical inactivity challenge

Measuring change in trials of physical activity interventions: a comparison of self-report questionnaire and accelerometry within the PACE-UP trial

Background: Few trials have compared estimates of change in physical activity (PA) levels using self-reported and objective PA measures when evaluating trial outcomes. The PACE-UP trial offered the opportunity to assess this, using the self-administered International Physical Activity Questionnaire (IPAQ) and waist-worn accelerometry. Methods: The PACE-UP trial (N=1023) compared usual care (n=338) with two pedometer-based walking interventions, by post (n=339) or with nurse support (n=346). Participants wore an accelerometer at baseline and 12months and completed IPAQ for the same 7-day periods. Main outcomes were weekly minutes, all in ≥10min bouts as per UK PA guidelines of: i) accelerometer moderate-to-vigorous PA (Acc-MVPA) ii) IPAQ moderate+vigorous PA (IPAQ-MVPA) and iii) IPAQ walking (IPAQ-Walk). For each outcome, 12month values were regressed on baseline to estimate change. Results: Analyses were restricted to 655 (64%) participants who provided data on all outcomes at baseline and 12 months. Both intervention groups significantly increased their accelerometry MVPA minutes/week compared with control: postal group 42 (95% CI 22, 61), nurse group 43 (95% CI 24, 63). IPAQ-Walk minutes/week also increased: postal 57 (95% CI 2, 112), nurse 43 (95% CI -11, 97) but IPAQ-MVPA minutes/week showed non-significant decreases: postal -11 (95% CI -65, 42), nurse -34 (95% CI -87, 19). Conclusions: Our results demonstrate the necessity of using a questionnaire focussing on the activities being altered, as with IPAQ-Walk questions. Even then, the change in PA was estimated with far less precision than with accelerometry. Accelerometry is preferred to self-report measurement, minimising bias and improving precision when assessing effects of a walking intervention

Targeting Neuropilin-1 with Nanobodies Reduces Colorectal Carcinoma Development

Neuropilin-1 (NRP-1) is a co-receptor for semaphorins and vascular endothelial growth factor (VEGF) family members that can be expressed on cancer cells and tumor-infiltrating myeloid, endothelial and lymphoid cells. It has been linked to a tumor-promoting environment upon interaction with semaphorin 3A (Sema3A). Nanobodies (Nbs) targeting NRP-1 were generated for their potential to hamper the NRP-1/Sema3A interaction and their impact on colorectal carcinoma (CRC) development was evaluated in vivo through the generation of anti-NRP-1-producing CRC cells. We observed that tumor growth was significantly delayed and survival prolonged when the anti-NRP-1 Nbs were produced in vivo. We further analyzed the tumor microenvironment and observed that the pro-inflammatory MHC-IIhigh/trophic MHC-IIlow macrophage ratio was increased in tumors that produce anti-NRP-1 Nbs. This finding was corroborated by an increase in the expression of genes associated with MHC-IIhigh macrophages and a decrease in the expression of MHC-IIlow macrophage-associated genes in the macrophage pool sorted from anti-NRP-1 Nb-producing tumors. Moreover, we observed a significantly higher percentage of tumor-associated antigen-specific CD8+ T cells in tumors producing anti-NRP-1 Nbs. These data demonstrate that an intratumoral expression of NRP-1/Sema3A blocking biologicals increases anti-tumor immunity

Baseline characteristics of 1,023 randomised participants.

<p>Baseline characteristics of 1,023 randomised participants.</p

Ancillary outcomes.

<p>Ancillary outcomes.</p