A prospective study to assess the value of MMP-9 in improving the appropriateness of urgent referrals for colorectal cancer

Background Bowel cancer is common and is a major cause of death. Most people with bowel symptoms who meet the criteria for urgent referral to secondary care will not be found to have bowel cancer, and some people who are found to have cancer will have been referred routinely rather than urgently. If general practitioners could better identify people who were likely to have bowel cancer or conditions that may lead to bowel cancer, the pressure on hospital clinics may be reduced, enabling these patients to be seen more quickly. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with such conditions, and this can be measured from a blood sample. This study aims to find out whether measuring MMP-9 levels could improve the appropriateness of urgent referrals for patients with bowel symptoms. Methods People aged 18 years or older referred to a colorectal clinic will be asked to complete a questionnaire about symptoms, recent injuries or chronic illnesses (these can increase the level of matrix metalloproteinases) and family history of bowel cancer. A blood sample will be taken from people who consent to take part to assess MMP-9 levels, and the results of examination at the clinic and/or investigations arising from the clinic visit will be collected from hospital records. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the resulting diagnosis. The combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined. Discussion Although guidelines are in place to facilitate referrals to colorectal clinics, symptoms alone do not adequately distinguish people with malignancy from people with benign conditions. This study will establish whether MMP-9 could assist this process. If this were the case, measurement of MMP-9 levels could be used by general practitioners to assist in the identification of people who were most likely to have bowel cancer or conditions that may lead to bowel cancer, and who should, therefore, be referred most urgently to secondary car

Challenges and priorities for pediatric critical care clinician-researchers in low- and middle-income countries

IntroductionThere is need for more data on critical care outcomes and interventions from low- and middle-income countries (LMIC). Global research collaborations could help improve health-care delivery for critically ill children in LMIC where child mortality rates remain high.Materials and methodsTo inform the role of collaborative research in health-care delivery for critically ill children in LMIC, an anonymous online survey of pediatric critical care (PCC) physicians from LMIC was conducted to assess priorities, major challenges, and potential solutions to PCC research. A convenience sample of 56 clinician-researchers taking care of critically ill children in LMIC was targeted. In addition, the survey was made available on a Latin American PCC website. Descriptive statistics were used for data analysis.ResultsThe majority of the 47 survey respondents worked at urban, public teaching hospitals in LMIC. Respondents stated their primary PCC research motivations were to improve clinical care and establish guidelines to standardize care. Top challenges to conducting research were lack of funding, high clinical workload, and limited research support staff. Respondent-proposed solutions to these challenges included increasing research funding options for LMIC, better access to mentors from high-income countries, research training and networks, and higher quality medical record documentation.ConclusionLMIC clinician-researchers must be better empowered and resourced to lead and influence the local and global health research agenda for critically ill children. Increased funding options, access to training and mentorship in research methodology, and improved data collection systems for LMIC PCC researchers were recognized as key needs for success

Implementation fidelity of a voluntary sector-led diabetes education programme

© 2018, © Michele S.Y. Kok, Mat Jones, Emma Solomon-Moore and Jane R. Smith. Purpose: The quality of voluntary sector-led community health programmes is an important concern for service users, providers and commissioners. Research on the fidelity of programme implementation offers a basis for assessing and further enhancing practice. The purpose of this paper is to report on the fidelity assessment of Living Well Taking Control (LWTC) – a voluntary sector-led, community-based education programme in England focussing on the prevention and management of type 2 diabetes. Design/methodology/approach: This fidelity of implementation (FoI) study was conducted with the Devon-based LWTC programme. A fidelity checklist was developed to analyse audio records of group-based lifestyle education sessions – implementation was rated in terms of adherence to protocol and competence in delivery; the influence of wider contextual factors was also assessed. Kappa statistics (κ) were used to test for inter-rater agreement. Course satisfaction data were used as a supplementary indicator of facilitator competence. Findings: Analysis of 28 sessions, from five diabetes prevention and two diabetes management groups (total participants, n=49), yielded an overall implementation fidelity score of 77.3 per cent for adherence (moderate inter-rater agreement, κ=0.60) and 95.1 per cent for competence (good inter-rater agreement, κ=0.71). The diabetes prevention groups consistently achieved higher adherence scores than the diabetes management groups. Facilitator competence was supported by high participant satisfaction ratings. Originality/value: An appropriate level of implementation fidelity was delivered for the LWTC group-based education programme, which provides some confidence that outcomes from the programme reflected intervention effectiveness. This study demonstrates the viability of assessing the FoI in a voluntary sector-led public health initiative and the potential of this method for assuring quality and informing service development

High Reported Rates of Antimicrobial Resistance in Indian Neonatal and Pediatric Blood Stream Infections.

Background.: There is real shortage of national data on antimicrobial resistance rates in Indian neonates and children. A descriptive review was conducted to determine the patterns of antimicrobial resistance in isolates of blood stream infection among hospitalized children in India. Methods.: Published and gray literature on antibiotic resistance in children was searched using "Google Scholar", "Scopus", and "PubMed" databases between January 2000 and July 2015. Studies were included if they were original articles that reported a minimum of 10 pathogenic bacterial isolates from the bloodstream within a pediatric population in India, and studies were excluded if they reported studies done during an outbreak or epidemic. Results.: A total of 1179 studies were screened, and 82 papers were identified as eligible for inclusion. Most studies (78.7%) were reported from neonatal intensive care units. Among a total of 50545 reported blood cultures, 14704 (29.1%) were positive. Staphylococcus aureus (median, 14.7%; IQR, 7.4%-25.6%) and Klebsiella pneumoniae (median, 26%; IQR, 16.7%-35.4%) were the commonest reported Gram-positive and Gram-negative pathogens, respectively. Approximately half of all S aureus isolates were reported as methicillin-resistant S aureus (median, 50%; IQR, 31.4%-65.1%). After age stratification, the median rate of resistance of common Gram-negative pathogens to ampicillin and gentamicin/amikacin were extremely high (K pneumoniae/ampicillin 95.9%; K pneumoniae/gentamicin 75%; Escherichia coli/ampicillin 92.9%; E coli/gentamicin 55.6%). Likewise, the median resistance of common Gram-negative blood stream isolates to cephalosporins were also high (K pneumoniae/cefotaxime 62.6%; E coli/cefotaxime 47.5%). Conclusions.: High rates of resistance to World Health Organization-recommended first-line treatment options for neonates and children have been identified in blood stream infections across India. There is an urgent need to both enhance antibiotic stewardship and infection prevention and control measures and consider urgently how to repurpose older antibiotics back into routine care in India

C-reactive protein: associations with haematological variables, cardiovascular risk factors and prevalent cardiovascular disease

C-reactive protein (CRP) has been proposed as a risk factor for cardiovascular disease; however, this association is confounded by mutual relationships with both classical and haematological cardiovascular risk factors. We, therefore, measured CRP with a high-sensitivity assay in stored plasma samples from 414 men and 515 women in the north Glasgow MONICA (MONItoring trends in CArdiovascular diseases) survey, to study its correlation with haematological variables, classical risk factors and prevalent cardiovascular disease. CRP correlated with age, oral contraceptive use, menopause and most classical cardiovascular risk factors (except blood pressure). CRP also correlated with plasma levels of the pro-inflammatory cytokine interleukin 6, and haematocrit, viscosity, red cell aggregation, white cell count, and coagulation factors [fibrinogen, factor (F) VII in women, FVIII, FIX] and inhibitors (antithrombin and protein C in women; protein S) but not coagulation activation markers. CRP was significantly associated with prevalent cardiovascular disease in both men (P = 0.03) and women (P = 0.009), however, the association became non-significant after adjustment for firstly classical risk factors, then fibrinogen. We conclude that correlations with classical and haematological risk factors account for a substantial component of the association of CRP with prevalent cardiovascular disease, but there is evidence of a residual, independent effect among women

European active surveillance study of women taking HRT (EURAS-HRT): study protocol [NCT00214903]

BACKGROUND: The post marketing safety surveillance program for a drug containing a new chemical entity should assess both, the safety outcomes that relate specifically to the targeted population, as well as those that could potentially be related to special pharmacological characteristics of the drug. Active safety surveillance using valid epidemiological study designs has been proven to be a pertinent and reliable method to approach this endeavor. METHODS/DESIGN: The primary objective of the study is to compare incidence rates of serious adverse events in users of all types of newly prescribed oral HRT products. This active surveillance study will assess pertinent cardiovascular outcomes - in particular venous and arterial thromboembolism - and other serious adverse events (SAEs) in new HRT users over a period of several years. One product under surveillance is Angeliq(®), which contains the novel progestagen drospirenone (DRSP) combined with estradiol. In addition, all other oral combined HRT products with a novel progestagen or estrogen that will be newly marketed during the study period will be studied. These new HRT products will be compared with established HRT products. The combined cohort will include at least 30,000 women recruited in several European countries. At least 90,000 years of observation are expected from the field work which started in early 2002 and will end around 2008. The participating women will complete a baseline survey using a self-administered questionnaire to describe the baseline risk. After 6 months, 12 months, and then on an annual basis, they will fill out a questionnaire in which they record complaints and events during the use of the prescribed HRTs. All adverse outcomes occurring during the observational period will be evaluated. DISCUSSION: A complete lifetime medical history, individually validated SAEs over time, and a low loss to follow-up rate are essential for a robust safety assessment. Therefore, the lifetime history of diseases and relevant medications will be documented. Reported SAEs will be validated and analyzed. A four level, multi-faceted follow-up process was established to ensure low loss to follow-up rates (e.g., 3–5% after three years of follow up). Multivariate methods will be used to adjust for confounding

Expanding the perspective of translational medicine: the value of observational data

In 2003, the Journal of Translational Medicine was launched to foster the publication of high quality research in both "bench-to-bedside" as well as ex vivo human observation. In spite of the success of several large-scale observational studies, e.g. Framingham Heart Study, the opportunity to expand upon the ex vivo human observation has remained limited within the field of translational medicine. We believe that this presents a significant opportunity that merits consideration in both the planning and analysis of large scale observational studies and can contribute greatly to expanding our approaches in translational medicin

International differences in self-reported health measures in 33 major metropolitan areas in Europe.

The increasing concentration of populations into large conurbations in recent decades has not been matched by international health assessments, which remain largely focused at the country level. We aimed to demonstrate the use of routine survey data to compare the health of large metropolitan centres across Europe and determine the extent to which differences are due to socio-economic factors

Efficacy and safety of cannabidiol plus standard care vs standard care alone for the treatment of emotional exhaustion and burnout among frontline health care workers during the COVID-19 pandemic : a randomized clinical trial

IMPORTANCE Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms. OBJECTIVE To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This prospective open-label single-site randomized clinical trial used a 1:1 block randomization design to examine emotional exhaustion and burnout symptoms among frontline health care professionals (physicians, nurses, and physical therapists) working with patients with COVID-19 at the Ribeirão Preto Medical School University Hospital in São Paulo, Brazil. Participants were enrolled between June 12 and November 12, 2020. A total of 214 health care professionals were recruited and assessed for eligibility, and 120 participants were randomized in a 1:1 ratio by a researcher who was not directly involved with data collection. INTERVENTIONS Cannabidiol, 300mg (150mg twice per day), plus standard care or standard care alone for 28 days. MAIN OUTCOMES AND MEASURES The primary outcome was emotional exhaustion and burnout symptoms, whichwere assessed for 28 days using the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory–Human Services Survey for Medical Personnel. RESULTS A total of 120 participants were randomized to receive either CBD, 300mg, plus standard care (treatment arm; n = 61) or standard care alone (control arm; n = 59) for 28 days. Of those, 118 participants (59 participants in each arm; 79 women [66.9%]; mean age, 33.6 years [95%CI, 32.3- 34.9 years]) received the intervention and were included in the efficacy analysis. In the treatment arm, scores on the emotional exhaustion subscale of the Maslach Burnout Inventory significantly decreased at day 14 (mean difference, 4.14 points; 95%CI, 1.47-6.80 points; partial eta squared [ηp 2] = 0.08), day 21 (mean difference, 4.34 points; 95%CI, 0.94-7.73 points; ηp 2 = 0.05), and day 28 (mean difference, 4.01 points; 95%CI, 0.43-7.59 points; ηp 2 = 0.04). However, 5 participants, all of whomwere in the treatment group, experienced serious adverse events: 4 cases of elevated liver enzymes (1 critical and 3 mild, with the mild elevations reported at the final 28-day assessment) and 1 case of severe pharmacodermia. In 2 of those cases (1 with critical elevation of liver enzymes and 1 with severe pharmacodermia), CBD therapy was discontinued, and the participants had a full recovery. CONCLUSIONS AND RELEVANCE In this study, CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic. However, it is necessary to balance the benefits of CBD therapy with potential undesired or adverse effects. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings