Shorter and Longer Courses of Antibiotics for Common Infections and the Association With Reductions of Infection-Related Complications Including Hospital Admissions

BACKGROUND: Antimicrobial resistance is a serious global health concern that emphasizes completing treatment course. Recently, the effectiveness of short versus longer antibiotic courses has been questioned. This study investigated the duration of prescribed antibiotics, their effectiveness, and associated risk of infection-related complications. METHODS: Clinical Practice Research Datalink identified 4 million acute infection episodes prescribed an antibiotic in primary care between January 2014—June 2014, England. Prescriptions were categorized by duration. Risk of infection-related hospitalizations within 30 days was modelled overall and by infection type. Risk was assessed immediately after or within 30 days follow-up to measure confounders given similar and varying exposure, respectively. An interaction term with follow-up time assessed whether hazard ratios (HRs) remained parallel with different antibiotic durations. RESULTS: The duration of antibiotic courses increased over the study period (5.2–19.1%); 6–7 days were most common (66.9%). Most infection-related hospitalizations occurred with prescriptions of 8–15 days (0.21%), accompanied by greater risk of infection-related complications compared to patients who received a short prescription (HR: 1.75 [95% CI: 1.54–2.00]). Comparing HRs in the first 5 days versus remaining follow-up showed longer antibiotic courses were no more effective than shorter courses (1.02 [95% CI: 0.90–1.16] and 0.92 [95% CI: 0.75–1.12]). No variation by infection-type was observed. CONCLUSIONS: Equal effectiveness was found between shorter and longer antibiotic courses and the reduction of infection-related hospitalizations. Stewardship programs should recommend shorter courses of antibiotics for acute infections. Further research is required for treating patients with a complex medical history. Summary Prescribing of longer courses increased over the study period. The majority of hospitalizations occurred for patients receiving longer courses. Risk of developing a complication (immediate vs remaining follow-up) found longer courses were no more effective than shorter courses

Comparing antibiotic prescribing between clinicians in UK primary care: an analysis in a cohort study of eight different measures of antibiotic prescribing

Background There is a need to reduce antimicrobial uses in humans. Previous studies have found variations in antibiotic (AB) prescribing between practices in primary care. This study assessed variability of AB prescribing between clinicians. Methods Clinical Practice Research Datalink, which collects electronic health records in primary care, was used to select anonymised clinicians providing 500+ consultations during 2012-2017. Eight measures of AB prescribing were assessed, such as overall and incidental AB prescribing, repeat AB courses and extent of risk-based prescribing. Poisson regression models with random effect for clinicians were fitted. Results 6111 clinicians from 466 general practices were included. Considerable variability between individual clinicians was found for most AB measures. For example, the rate of AB prescribing varied between 77.4 and 350.3 per 1000 consultations; percentage of repeat AB courses within 30 days ranged from 13.1% to 34.3%; predicted patient risk of hospital admission for infection-related complications in those prescribed AB ranged from 0.03% to 0.32% (5th and 95th percentiles). The adjusted relative rate between clinicians in rates of AB prescribing was 5.23. Weak correlation coefficients (<0.5) were found between most AB measures. There was considerable variability in case mix seen by clinicians. The largest potential impact to reduce AB prescribing could be around encouraging risk-based prescribing and addressing repeat issues of ABs. Reduction of repeat AB courses to prescribing habit of median clinician would save 21 813 AB prescriptions per 1000 clinicians per year. Conclusions The wide variation seen in all measures of AB prescribing and weak correlation between them suggests that a single AB measure, such as prescribing rate, is not sufficient to underpin the optimisation of AB prescribing

Introduction and evaluation of a 'pre-ART care' service in Swaziland: an operational research study

Objective: To implement and evaluate a formal pre-antiretroviral therapy (ART) care service at a district hospital in Swaziland. Design: Operational research. Setting: District hospital in Southern Africa. Participants: 1171 patients with a previous diagnosis of HIV. A baseline patient group consisted of the first 200 patients using the service. Two follow-up groups were defined: group 1 was all patients recruited from April to June 2009 and group 2 was 200 patients recruited in February 2010. Intervention: Introduction of pre-ART care-a package of interventions, including counselling; regular review; clinical staging; timely initiation of ART; social and psychological support; and prevention and management of opportunistic infections, such as tuberculosis. Primary and secondary outcome measures: Proportion of patients assessed for ART eligibility, proportion of eligible patients who were started on ART and proportion receiving defined evidence-based interventions (including prophylactic co-trimoxazole and tuberculosis screening). Results: Following the implementation of the pre-ART service, the proportion of patients receiving defined interventions increased; the proportion of patient being assessed for ART eligibility significantly increased (baseline: 59%, group 1: 64%, group 2: 76%; p=0.001); the proportion of ART-eligible patients starting treatment increased (baseline: 53%, group 1: 81%, group: 2, 81%; p<0.001) and the median time between patients being declared eligible for ART and initiation of treatment significantly decreased (baseline: 61 days, group 1: 39 days, group 2: 14 days; p<0.001). Conclusions: This intervention was part of a shift in the model of care from a fragmented acute care model to a more comprehensive service. The introduction of structured pre-ART was associated with significant improvements in the assessment, management and timeliness of initiation of treatment for patients with HIV

Reviewing progress: 7 Year Trends in Characteristics of Adults and Children Enrolled at HIV Care and Treatment Clinics in the United Republic of Tanzania.

To evaluate the on-going scale-up of HIV programs, we assessed trends in patient characteristics at enrolment and ART initiation over 7 years of implementation. Data were from Optimal Models, a prospective open cohort study of HIV-infected (HIV+) adults (>=15 years) and children (<15 years) enrolled from January 2005 to December 2011 at 44 HIV clinics in 3 regions of mainland Tanzania (Kagera, Kigoma, Pwani) and Zanzibar. Comparative statistics for trends in characteristics of patients enrolled in 2005--2007, 2008--2009 and 2010--2011 were examined. Overall 62,801 HIV+ patients were enrolled: 58,102(92.5%) adults, (66.5% female); 4,699(7.5%) children.Among adults, pregnant women enrolment increased: 6.8%, 2005--2007; 12.1%, 2008--2009; 17.2%, 2010--2011; as did entry into care from prevention of mother-to-child HIV transmission (PMTCT) programs: 6.6%, 2005--2007; 9.5%, 2008--2009; 12.6%, 2010--2011. WHO stage IV at enrolment declined: 27.1%, 2005--2007; 20.2%, 2008--2009; 11.1% 2010--2011. Of the 42.5% and 29.5% with CD4+ data at enrolment and ART initiation respectively, median CD4+ count increased: 210cells/muL, 2005--2007; 262cells/muL, 2008--2009; 266cells/muL 2010--2011; but median CD4+ at ART initiation did not change (148cells/muL overall). Stavudine initiation declined: 84.9%, 2005--2007; 43.1%, 2008--2009; 19.7%, 2010--2011.Among children, median age (years) at enrolment decreased from 6.1(IQR:2.7-10.0) in 2005--2007 to 4.8(IQR:1.9-8.6) in 2008--2009, and 4.1(IQR:1.5-8.1) in 2010--2011 and children <24 months increased from 18.5% to 26.1% and 31.5% respectively. Entry from PMTCT was 7.0%, 2005--2007; 10.7%, 2008--2009; 15.0%, 2010--2011. WHO stage IV at enrolment declined from 22.9%, 2005--2007, to 18.3%, 2008--2009 to 13.9%, 2010--2011. Proportion initiating stavudine was 39.8% 2005--2007; 39.5%, 2008--2009; 26.1%, 2010--2011. Median age at ART initiation also declined significantly. Over time, the proportion of pregnant women and of adults and children enrolled from PMTCT programs increased. There was a decline in adults and children with advanced HIV disease at enrolment and initiation of stavudine. Pediatric age at enrolment and ART initiation declined. Results suggest HIV program maturation from an emergency response

Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne bla KPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014.

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the bla KPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of bla KPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, bla KPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of bla KPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 bla KPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of bla KPC (predominantly bla KPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), bla KPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-bla KPC and bla KPC plasmids and the common presence of multiple replicons within bla KPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control

The perceived meaning of a (w)holistic view among general practitioners and district nurses in Swedish primary care: a qualitative study

BACKGROUND: The definition of primary care varies between countries. Swedish primary care has developed from a philosophic viewpoint based on quality, accessibility, continuity, co-operation and a holistic view. The meaning of holism in international literature differs between medicine and nursing. The question is, if the difference is due to different educational traditions. Due to the uncertainties in defining holism and a holistic view we wished to study, in depth, how holism is perceived by doctors and nurses in their clinical work. Thus, the aim was to explore the perceived meaning of a holistic view among general practitioners (GPs) and district nurses (DNs). METHODS: Seven focus group interviews with a purposive sample of 22 GPs and 20 nurses working in primary care in two Swedish county councils were conducted. The interviews were transcribed verbatim and analysed using qualitative content analysis. RESULTS: The analysis resulted in three categories, attitude, knowledge, and circumstances, with two, two and four subcategories respectively. A professional attitude involves recognising the whole person; not only fragments of a person with a disease. Factual knowledge is acquired through special training and long professional experience. Tacit knowledge is about feelings and social competence. Circumstances can either be barriers or facilitators. A holistic view is a strong motivator and as such it is a facilitator. The way primary care is organised can be either a barrier or a facilitator and could influence the use of a holistic approach. Defined geographical districts and care teams facilitate a holistic view with house calls being essential, particularly for nurses. In preventive work and palliative care, a holistic view was stated to be specifically important. Consultations and communication with the patient were seen as important tools. CONCLUSION: 'Holistic view' is multidimensional, well implemented and very much alive among both GPs and DNs. The word holistic should really be spelt 'wholistic' to avoid confusion with complementary and alternative medicine. It was obvious that our participants were able to verbalise the meaning of a 'wholistic' view through narratives about their clinical, every day work. The possibility to implement a 'wholistic' perspective in their work with patients offers a strong motivation for GPs and DNs

Burden of malaria in pregnancy in Jharkhand State, India

<p>Abstract</p> <p>Background</p> <p>Past studies in India included only symptomatic pregnant women and thus may have overestimated the proportion of women with malaria. Given the large population at risk, a cross sectional study was conducted in order to better define the burden of malaria in pregnancy in Jharkhand, a malaria-endemic state in central-east India.</p> <p>Methods</p> <p>Cross-sectional surveys at antenatal clinics and delivery units were performed over a 12-month period at two district hospitals in urban and semi-urban areas, and a rural mission hospital. Malaria was diagnosed by Giemsa-stained blood smear and/or rapid diagnostic test using peripheral or placental blood.</p> <p>Results</p> <p>2,386 pregnant women were enrolled at the antenatal clinics and 718 at the delivery units. 1.8% (43/2382) of the antenatal clinic cohort had a positive diagnostic test for malaria (53.5% <it>Plasmodium falciparum</it>, 37.2% <it>Plasmodium vivax</it>, and 9.3% mixed infections). Peripheral parasitaemia was more common in pregnant women attending antenatal clinics in rural sites (adjusted relative risk [aRR] 4.31, 95%CI 1.84-10.11) and in those who were younger than 20 years (aRR 2.68, 95%CI 1.03-6.98). Among delivery unit participants, 1.7% (12/717) had peripheral parasitaemia and 2.4% (17/712) had placental parasitaemia. Women attending delivery units were more likely to be parasitaemic if they were in their first or second pregnancy (aRR 3.17, 95%CI 1.32-7.61), had fever in the last week (aRR 5.34, 95%CI 2.89-9.90), or had rural residence (aRR 3.10, 95%CI 1.66-5.79). Malaria control measures including indoor residual spraying (IRS) and untreated bed nets were common, whereas insecticide-treated bed nets (ITN) and malaria chemoprophylaxis were rarely used.</p> <p>Conclusion</p> <p>The prevalence of malaria among pregnant women was relatively low. However, given the large at-risk population in this malaria-endemic region of India, there is a need to enhance ITN availability and use for prevention of malaria in pregnancy, and to improve case management of symptomatic pregnant women.</p

A PALB2 mutation associated with high risk of breast cancer

Introduction: As a group, women who carry germline mutations in partner and localizer of breast cancer 2 susceptibility protein (PALB2) are at increased risk of breast cancer. Little is known about by how much or whether risk differs by mutation or family history, owing to the paucity of studies of cases unselected for family history.Methods: We screened 1,403 case probands for PALB2 mutations in a population-based study of Australian women with invasive breast cancer stratified by age at onset. The age-specific risk of breast cancer was estimated from the cancer histories of first- and second-degree relatives of mutation-carrying probands using a modified segregation analysis that included a polygenic modifier and was conditioned on the carrier case proband. Further screening for PALB2 c.3113G > A (W1038X) was conducted for 779 families with multiple cases of breast cancer ascertained through family cancer clinics in Australia and New Zealand and 764 population-based controls.Results: We found five independent case probands in the population-based sample with the protein-truncating mutation PALB2 c.3113G > A (W1038X); 2 of 695 were diagnosed before age 40 years and 3 of 708 were diagnosed when between ages 40 and 59 years. Both of the two early-onset carrier case probands had very strong family histories of breast cancer. Further testing found that the mutation segregated with breast cancer in these families. No c.3113G > A (W1038X) carriers were found in 764 population-based unaffected controls. The hazard ratio was estimated to be 30.1 (95% confidence interval (CI), 7.5 to 120; P A mutation appears to be associated with substantial risks of breast cancer that are of clinical relevance. © 2010 Southey et al.; licensee BioMed Central Ltd