Statistical complexity of reasons for encounter in high users of out of hours primary care:analysis of a national service

Background: Managing demand for urgent and unscheduled care is a major problem for health services globally. A particular issue is that some patients appear to make heavy use of services, including primary care out of hours. We hypothesised that greater variation (statistical complexity) in reasons for attending primary care out of hours services may be a useful marker of patients at high risk of ongoing heavy service use. Methods: We analysed an anonymised dataset of contacts with the primary care out of hours care for Scotland in 2011. This contained 120,395 contacts from 13,981 high-using patients who made 5 or more contacts during a calendar year. We allocated the stated reason for each encounter into one of 14 categories. For each patient we calculated measures of statistical complexity of reasons for encounter including the count of different categories, Herfindahl index and statistical entropy of either the categories themselves, or the category transitions. We examined the association of these measures of statistical complexity with patient and healthcare use characteristics. Results: The high users comprised 2.4% of adults using the service and accounted for 15% of all contacts. Statistical complexity (as entropy of categories) increased with number of contacts but was not substantially influenced by either patient age or sex. This lack of association with age was unexpected as with increasing multi-morbidity one would expect greater variability in reason for encounter. Between 5 and 10 consultations, higher entropy was associated with a reduced likelihood of further consultations. In contrast, the occurrence of one or more contacts for a mental health problem was associated with increased likelihood of further consultations. Conclusion: Complexity of reason for encounter can be estimated in an out of hours primary care setting. Similar levels of statistical complexity are seen in younger and older adults (suggesting that it is more to do with consultation behaviour than morbidity) but it is not a predictor of ongoing high use of urgent care.</p

Patterns of symptoms possibly indicative of cancer and associated help-seeking behaviour in a large sample of United Kingdom residents - the USEFUL study

Background.Cancer awareness campaigns aim to increase awareness of the potential seriousness of signs and symptoms of cancer, and encourage their timely presentation to healthcare services. Enhanced understanding of the prevalence of symptoms possibly indicative of cancer in different population subgroups, and associated general practitioner (GP) help-seeking behaviour, will help to target cancer awareness campaigns more effectively.Aim.To determine: i) the prevalence of 21 symptoms possibly indicative of breast, colorectal, lung or upper gastrointestinal cancer in the United Kingdom (UK), including six ‘red flag’ symptoms; ii) whether the prevalence varies among population subgroups; iii) the proportion of symptoms self-reported as presented to GPs; iv) whether GP help-seeking behaviour varies within population subgroups.Methods.Self-completed questionnaire about experience of, and response to, 25 symptoms (including 21 possibly indicative of the four cancers of interest) in the previous month and year; sent to 50,000 adults aged 50 years or more and registered with 21 general practices in Staffordshire, England or across Scotland. Results.Completed questionnaires were received from 16,778 respondents (corrected response rate 34.2%). Almost half (45.8%) of respondents had experienced at least one symptom possibly indicative of cancer in the last month, and 58.5% in the last year. The prevalence of individual symptoms varied widely (e.g. in the last year between near zero% (vomiting up blood) and 15.0% (tired all the time). Red flag symptoms were uncommon. Female gender, inability to work because of illness, smoking, a history of a specified medical diagnosis, low social support and lower household income were consistently associated with experiencing at least one symptom possibly indicative of cancer in both the last month and year. The proportion of people who had contacted their GP about a symptom experienced in the last month varied between 8.1% (persistent cough) and 39.9% (unexplained weight loss); in the last year between 32.8% (hoarseness) and 85.4% (lump in breast). Nearly half of respondents experiencing at least one red flag symptom in the last year did not contact their GP about it. Females, those aged 80+ years, those unable to work because of illness, ex-smokers and those previously diagnosed with a specified condition were more likely to report a symptom possibly indicative of cancer to their GP; and those on high household income less likely.Conclusion.Symptoms possibly indicative of cancer are common among adults aged 50+ years in the UK, although they are not evenly distributed. Help-seeking responses to different symptoms also vary. Our results suggest important opportunities to provide more nuanced messaging and targeting of symptom-based cancer awareness campaigns

Examining the role of Scotland’s telephone advice service (NHS 24) for managing health in the community : analysis of routinely collected NHS 24 data

Date of Acceptance: 15/06/2015 Funding This work was supported by the Chief Scientist Office, ScottishExecutive (grant no. CZH/4/692). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.Peer reviewedPublisher PD

Circulating B-lymphocytes as potential biomarkers of tuberculosis infection activity.

Accurate biomarkers of Mycobacterium tuberculosis infection activity would significantly improve early diagnosis, treatment and management of M. tuberculosis infection. We hypothesised that circulating B-lymphocytes may be useful biomarkers of tuberculosis (TB) infection status in highly TB-endemic settings. Ex-vivo and in-vitro mycobacteria-specific B-cell ELISPOT assays were used to examine the plasmablast (PB) and memory B-cell (MBC) responses in the peripheral blood of adult, healthy, community controls (n = 151) and of active TB patients (n = 48) living in Uganda. Frequencies of mycobacteria-specific PBs were markedly higher in active TB patients compared to healthy controls, and, conversely, MBCs were markedly higher in the healthy controls compared to active TB patients. In addition, the community controls with evidence of latent TB infection had higher peripheral blood PB and MBC responses than those without evidence of TB infection. These data demonstrate that peripheral blood B-cell responses are differentially modulated during latent and active M. tuberculosis infection, and suggest that the PB to MBC ratio may be a useful biomarker of TB infection activity

Post-immunization leucocytosis and its implications for the management of febrile infants.

AIMS: Clinical guidelines for management of infants with fever but no evident focus of infection recommend that those aged 1-3 months with a white cell count >15 × 109/l have a full septic screen and be admitted for parenteral antibiotics. However, there is limited information about leucocyte changes following routine immunization, a common cause of fever. We investigated white cell counts shortly after routine immunization in Ugandan infants under 3 months of age. METHODS: White cell counts were measured in 212 healthy infants following routine immunizations (DTwP-HepB-Hib, oral polio and pneumococcal conjugate 7 vaccines) received prior to 3 months of age. RESULTS: Mean leucocyte counts increased from 9.03 × 109/l (95% confidence interval 8.59-9.47 × 109/l) pre-immunizations to 16.46 × 109/l (15.4-17.52 × 109/l) at one-day post-immunizations at 6 weeks of age, and 15.21 × 109/l (14.07-16.36 × 109/l) at one-day post-immunizations at 10 weeks of age. The leucocytosis was primarily a neutrophilia, with neutrophil percentages one-day post-immunization of 49% at 6 weeks of age and 46% at 10 weeks of age. White cell parameters returned to baseline by two-days post-immunization. No participant received antibiotics when presenting with isolated fever post-immunization and all remained well at follow-up. CONCLUSIONS: In our study almost half the children <3 months old presenting with fever but no evident focus of infection at one-day post-immunization met commonly used criteria for full septic screen and admission for parenteral antibiotics, despite having no serious bacterial infection. These findings add to the growing body of literature that questions the utility of white blood cell measurement in identification of young infants at risk of serious bacterial infections, particularly in the context of recent immunizations, and suggest that further exploration of the effect of different immunization regimes on white cell counts is needed. This observational work was nested within a clinical trial, registration number ISRCTN59683017

Praziquantel for the treatment of schistosomiasis during human pregnancy.

In 2014, an estimated 40 million women of reproductive age were infected with Schistosoma haematobium, S. japonicum and/or S. mansoni. In both 2003 and 2006, the World Health Organization (WHO) recommended that all schistosome-infected pregnant and breastfeeding women be offered treatment, with praziquantel, either individually or during treatment campaigns. In 2006, WHO also stated the need for randomized controlled trials to assess the safety and efficacy of such treatment. Some countries have yet to follow the recommendation on treatment and many programme managers and pregnant women in other countries remain reluctant to follow the recommended approach. Since 2006, two randomized controlled trials on the use of praziquantel during pregnancy have been conducted: one against S. mansoni in Uganda and the other against S. japonicum in the Philippines. In these trials, praziquantel treatment of pregnant women had no significant effect on birth weight, appeared safe and caused minimal side-effects that were similar to those seen in treated non-pregnant subjects. Having summarized the encouraging data, on efficacy, pharmacokinetics and safety, from these two trials and reviewed the safety data from non-interventional human studies, we recommend that all countries include pregnant women in praziquantel treatment campaigns. We identify the barriers to the treatment of pregnant women, in countries that already include such women in individual treatments and mass drug administration campaigns, and discuss ways to address these barriers

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial.

BACKGROUND: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown. METHODS: In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy. RESULTS: Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel. CONCLUSIONS: Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated. TRIAL REGISTRATION: ISRCTN: ISRCTN32849447

Assessing the external validity of a randomized controlled trial of anthelminthics in mothers and their children in Entebbe, Uganda.

BACKGROUND: The 'external validity' of randomized controlled trials is an important measure of quality, but is often not formally assessed. Trials concerning mass drug administration for helminth control are likely to guide public health policy and careful interpretation of their context is needed. We aimed to determine how representative participants in one such trial were of their community. We explore implications for trial interpretation and resulting public health recommendations. METHODS: The trial assessed was the Entebbe Mother and Baby Study (EMaBS), a trial of anthelminthic treatment during pregnancy and early childhood. In a novel approach for assessing external validity, we conducted a two-stage cluster sample community survey within the trial catchment area and compared characteristics of potentially-eligible community children with characteristics of children participating in the trial. RESULTS: A total of 173 children aged three to five-years-old were surveyed from 480 households. Of children surveyed, we estimated that mothers of 60% would have been eligible for recruitment, and of these, 31% had actually been enrolled. Children surveyed were compared to 199 trial children in the same age group reviewed at annual trial visits during the same time period. There were significant differences in ethnicity between the trial participants and the community children, and in socioeconomic status, with those in the trial having, on average, more educated parents and higher maternal employment. Trial children were less likely to have barefoot exposure and more likely to use insecticide-treated bed nets. There were no significant differences in numbers of reported illness events over the last year. CONCLUSIONS: The trial had not enrolled all eligible participants, and those enrolled were of higher socioeconomic status, and had lower risk of exposure to the parasitic infections targeted by the trial interventions. It is possible the trial may have underestimated the absolute effects of anthelminthic treatment during pregnancy and early childhood, although the fact that there were no differences in reported incidence of common infectious diseases (one of the primary outcomes of EMaBS) between the two groups provides reassurance. Concurrent community surveys may be an effective way to test the external validity of trials. EMABS TRIAL REGISTRATION: ISRCTN32849447, registered 22 July 2005

Pharmacist-led management of chronic pain in primary care:results from a randomised controlled exploratory trial

To compare the effectiveness of pharmacist medication review, with or without pharmacist prescribing, with standard care, for patients with chronic pain

The effect of anthelmintic treatment during pregnancy on HIV plasma viral load: results from a randomized, double-blind, placebo-controlled trial in Uganda.

BACKGROUND: To investigate the effect of helminth infections and their treatment during pregnancy on HIV load, we conducted a 2 × 2 factorial randomized controlled trial of albendazole versus placebo and praziquantel versus placebo in pregnant women in Entebbe, Uganda. METHODS: Two hundred sixty-four HIV-infected pregnant women from the Entebbe Mother and Baby Study (ISRCTN 32849447) were included in this analysis. Women were tested for helminth infections at enrollment, and mean HIV load was compared between infected and uninfected groups. The effect of anthelmintic treatment on HIV load was evaluated at 6 weeks after treatment and at delivery using linear regression and adjusting for enrollment viral load. RESULTS: Hookworm and Trichuris infections were associated with higher mean viral load at enrollment [adjusted mean difference 0.24 log10 copies/mL, 95% confidence interval (CI): 0.01 to 0.47, P = 0.03, and 0.37 log(10) copies/mL, 95% CI: 0.00 to 0.74, P = 0.05, respectively]. There were no associations between viral load and other helminth species. There was some evidence that albendazole reduced viral load at 6 weeks after treatment (adjusted mean difference -0.17, 95% CI: -0.36 to 0.01, P = 0.07); however, this effect did not differ according to mother's hookworm infection status and had diminished at delivery (adjusted mean difference -0.11, 95% CI: -0.28 to 0.07, P = 0.23). There was no effect of praziquantel treatment on HIV load at any time point. CONCLUSIONS: Infection with some soil-transmitted helminth species is associated with increased HIV load in pregnancy. Treatment with albendazole causes a small decrease in HIV load; however, this may not represent a direct effect of worm removal