Effect of case management on neonatal mortality due to sepsis and pneumonia.

BACKGROUND: Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST). METHODS: We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness. RESULTS: Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies) and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies). Two studies (1 RCT, 1 observational study), evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR = 0.56, 95% CI 0.41-0.77) and 34% (RR = 0.66, 95% CI 0.47-0.93), but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents) effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were identified assessing effect of hospital management for neonatal infections and Delphi consensus suggested 80%, and 90% reductions for sepsis and pneumonia-specific mortality respectively. CONCLUSION: Oral antibiotics administered in the community are effective for neonatal pneumonia mortality reduction based on a meta-analysis, but expert opinion suggests much higher impact from injectable antibiotics in the community or primary care level and even higher for facility-based care. Despite feasibility and low cost, these interventions are not widely available in many low income countries. FUNDING: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US

Workplace Incivility and Employee Sleep: The Role of Rumination and Recovery Experiences

This study examines the role of negative work rumination and recovery experiences in explaining the association between workplace incivility and employee insomnia symptoms. Drawing on the perseverative cognition model of stress and the effort–recovery model, we hypothesize a moderated mediation model in which workplace incivility is associated with insomnia symptoms via negative work rumination. This indirect effect is proposed to be conditional on employees’ reported level of recovery experiences (i.e., psychological detachment from work and relaxation during nonwork time). In examining this model, we further establish a link between workplace incivility and sleep and identify one pathway to explain this relationship, as well as resources that may be used to halt the negative spillover of workplace incivility on sleep. Based on a sample of 699 U.S. Forest Service employees, we find support for a moderated mediation model in which the association between workplace incivility and increased insomnia symptoms via increased negative work rumination was weakest for employees reporting high levels of recovery experiences during nonwork time. Findings from the current study contribute to our understanding of why workplace incivility is associated with nonwork outcomes, as well as point to implications for interventions aimed at promoting employees’ recovery from work

Alma-Ata: Rebirth and revision 8 - Primary health care: making Alma-Ata a reality

The principles agreed at Alma-Ata 30 years ago apply just as much now as they did then. Health for all by the year 2000 was not achieved, and the Millennium Development Goals (MDGs) for 2015 will not be met in most low-income countries without substantial acceleration of primary health care. Factors have included insufficient political prioritisation of health, structural adjustment policies, poor governance, population growth, inadequate health systems, and scarce research and assessment on primary health care. We propose the following priorities for revitalising primary health care. Health-service infrastructure, including human resources and essential drugs, needs strengthening, and user fees should be removed for primary health-care services to improve use. A continuum of care for maternal, newborn, and child health services, including family planning, is needed. Evidence-based, integrated packages of community and primary curative and preventive care should be adapted to country contexts, assessed, and scaled up. Community participation and community health workers linked to strengthened primary-care facilities and first-referral services are needed. Furthermore, intersectoral action linking health and development is necessary, including that for better water, sanitation, nutrition, food security, and HIV control. Chronic diseases, mental health, and child development should be addressed. Progress should be measured and accountability assured. We prioritise research questions and suggest actions and measures for stakeholders both locally and globally, which are required to revitalise primary health care

Extending the reach of the Fire Effects Planning Framework by taking a critical approach to science delivery and application

The Fire Effects Planning Framework (FEPF), developed under JFSP project (99-1-3-16) “Wildland fuels management: evaluating and planning risks and benefits,” was formally completed in June 2004. FEPF is a logical framework that uses available data (e.g., local, LANDFIRE data) and existing software (e.g., GIS, Farsite, FlamMap, expert knowledge) to produce maps of probable fire effects during the pre-season or in advance of a fire front. The initial project included significant technology transfer activities. As that project concluded, however, we continued to receive requests for assistance from field managers (District, Forest and Regional Forest Service offices), international organizations (Interior West Fire Council), and national fire planning organizations (Fire Program Analysis). These requests sought more information about the tool, assistance with using it for hazardous fuels planning, and guidance for incorporating FEPF into regional training courses. To enable us to continue our outreach efforts, we initiated JFSP 05-4-1-20 “Extending the reach of the the Fire Effects Planning Framework by taking a critical approach to science delivery and application”. This funding allowed us to meet requests for assistance and participation while allowing us to identify and concentrate on the most valuable transfer mechanisms. Our goal was to observe how field managers think about and use the tool, learn who they think the primary audience is, and then revise our materials and activities accordingly. FEPF is the only analysis tool we know of that helps managers (land and fire) articulate probable ecologic effects of fire and integrate these into fire decision-making and assessment. The technology and data used by FEPF is widely available. The scientific basis for crosswalk determinations are grounded in best available science, transparent, and easily updated as new information becomes available. As the federal fire agencies move toward more comprehensive implementation of Appropriate Management Response, FEPF remains the only process that can quickly and consistently indicate areas and conditions where fire may be neutral, beneficial or harmful to natural resources of interest. Thus, it provides the only existing process to link emergency fire operations (from full suppression to wildland fire use) with land management plans, a requirement of federal oversight entities (e.g., OIG)

Effects Of Community-Based Exercise Training Among Older Individuals With Metabolic Disease, Cardiovascular Disease, Or Muscle Atrophy

Exercise training is associated with increased health benefits such as improved quality of life, mental health, and physical functioning. PURPOSE: The purpose of this study is to quantify the effects of structured aerobic and resistance exercise training on body composition, functional tests, and quality of life in older individuals in a community-based facility. We hypothesized that at least moderate participation in the program would decrease fat mass, improve outcomes on grip and timed movement tests, and increase quality of life. METHODS: Twenty subjects who were members from a community-based institute participated in the study (7M:13F; 69.10 ± 6.40 yrs [mean ± sd]; 166.88 ± 10.52 cm; 76.40 ± 16.42 kg) and had metabolic or cardiovascular disease, or muscle atrophy. Subjects were expected to participate in 3, 30-min sessions/week for 8 weeks. The program was 30 min aerobic conditioning of intervals and 6–7 full-body resistance exercises and basic stretches. We measured height (cm), weight (kg), fat mass (kg), lean mass (kg), grip strength (kg), timed-up-go (TUG, s), 10-meter walk forwards (s), 10-meter walk backwards (a novel movement) (s), 6-minute walk tests (m), the Health-Related Quality of Life (CDC HRQOL-4) survey, and 36-Item Short-Form Health (SF-36), before and after the completion of exercise training. We performed paired t-tests on testing variables and the 8 subsections of the SF-36 and one-sample t-tests on the delta of questions on the HRQOL-4. Alpha \u3c0.05. RESULTS: There were no significant differences in any of the SF-36 subsections or testing variables (p \u3e 0.05) except for increased right-hand grip strength (2.02 ± 4.35 kg, p = 0.05) and decreased time in the backwards 10-meter walk (0.52 ± 0.88 s, p = 0.02). Concerning the HRQOL-4, no members had fair to poor self-rated health before or after the program, more members experienced fewer but non-significant physically unhealthy days (delta = -3.61 ± 8.67 days, p = 0.10), and a similar number of mentally unhealthy days and days when poor mental/physical health kept them from usual activities (p \u3e 0.05). CONCLUSION: These preliminary findings suggest that there may be clinically meaningful improvements in strength and novel movement in these older individuals after an 8-week prescribed and training program in the community setting. Different measurements of quality of life in this population should be explored

Effect of case management on neonatal mortality due to sepsis and pneumonia

<p>Abstract</p> <p>Background</p> <p>Each year almost one million newborns die from infections, mostly in low-income countries. Timely case management would save many lives but the relative mortality effect of varying strategies is unknown. We have estimated the effect of providing oral, or injectable antibiotics at home or in first-level facilities, and of in-patient hospital care on neonatal mortality from pneumonia and sepsis for use in the Lives Saved Tool (LiST).</p> <p>Methods</p> <p>We conducted systematic searches of multiple databases to identify relevant studies with mortality data. Standardized abstraction tables were used and study quality assessed by adapted GRADE criteria. Meta-analyses were undertaken where appropriate. For interventions with biological plausibility but low quality evidence, a Delphi process was undertaken to estimate effectiveness.</p> <p>Results</p> <p>Searches of 2876 titles identified 7 studies. Among these, 4 evaluated oral antibiotics for neonatal pneumonia in non-randomised, concurrently controlled designs. Meta-analysis suggested reductions in all-cause neonatal mortality (RR 0.75 95% CI 0.64- 0.89; 4 studies) and neonatal pneumonia-specific mortality (RR 0.58 95% CI 0.41- 0.82; 3 studies). Two studies (1 RCT, 1 observational study), evaluated community-based neonatal care packages including injectable antibiotics and reported mortality reductions of 44% (RR= 0.56, 95% CI 0.41-0.77) and 34% (RR =0.66, 95% CI 0.47-0.93), but the interpretation of these results is complicated by co-interventions. A third, clinic-based, study reported a case-fatality ratio of 3.3% among neonates treated with injectable antibiotics as outpatients. No studies were identified evaluating injectable antibiotics alone for neonatal pneumonia. Delphi consensus (median from 20 respondents) effects on sepsis-specific mortality were 30% reduction for oral antibiotics, 65% for injectable antibiotics and 75% for injectable antibiotics on pneumonia-specific mortality. No trials were identified assessing effect of hospital management for neonatal infections and Delphi consensus suggested 80%, and 90% reductions for sepsis and pneumonia-specific mortality respectively.</p> <p>Conclusion</p> <p>Oral antibiotics administered in the community are effective for neonatal pneumonia mortality reduction based on a meta-analysis, but expert opinion suggests much higher impact from injectable antibiotics in the community or primary care level and even higher for facility-based care. Despite feasibility and low cost, these interventions are not widely available in many low income countries.</p> <p>Funding</p> <p>This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US.</p

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

Patterns of domestication in the Ethiopian oil-seed crop noug (Guizotia abyssinica)

Noug (Guizotia abyssinica) is a semidomesticated oil-seed crop, which is primarily cultivated in Ethiopia. Unlike its closest crop relative, sunflower, noug has small seeds, small flowering heads, many branches, many flowering heads, and indeterminate flowering, and it shatters in the field. Here, we conducted common garden studies and microsatellite analyses of genetic variation to test whether high levels of crop–wild gene flow and/or unfavorable phenotypic correlations have hindered noug domestication. With the exception of one population, analyses of microsatellite variation failed to detect substantial recent admixture between noug and its wild progenitor. Likewise, only very weak correlations were found between seed mass and the number or size of flowering heads. Thus, noug's ‘atypical’ domestication syndrome does not seem to be a consequence of recent introgression or unfavorable phenotypic correlations. Nonetheless, our data do reveal evidence of local adaptation of noug cultivars to different precipitation regimes, as well as high levels of phenotypic plasticity, which may permit reasonable yields under diverse environmental conditions. Why noug has not been fully domesticated remains a mystery, but perhaps early farmers selected for resilience to episodic drought or untended environments rather than larger seeds. Domestication may also have been slowed by noug's outcrossing mating syste

Anti-tumour necrosis factor therapy for Dupuytren's Disease: a randomised dose response proof of concept phase 2a clinical trial

Background Dupuytren's disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytren's disease with a TNF inhibitor. Methods Patients were randomised to receive adalimumab on one occasion in dose cohorts of 15 mg in 0.3 ml, 35 mg in 0.7 ml, or 40 mg in 0.4 ml, or an equivalent volume of placebo in a 3:1 ratio. Two weeks later the injected tissue was surgically excised and analysed. The primary outcome measure was levels of mRNA expression for α-smooth muscle actin (ACTA2). Secondary outcomes included levels of α-SMA and collagen proteins. The trial was registered with ClinicalTrial.gov (NCT03180957) and the EudraCT (2015-001780-40). Findings We recruited 28 patients, 8 assigned to the 15 mg, 12 to the 35 mg and 8 to the 40 mg adalimumab cohorts. There was no change in mRNA levels for ACTA2, COL1A1, COL3A1 and CDH11. Levels of α-SMA protein expression in patients treated with 40 mg adalimumab (1.09 ± 0.09 ng per μg of total protein) were significantly lower (p = 0.006) compared to placebo treated patients (1.51 ± 0.09 ng/μg). The levels of procollagen type I protein expression were also significantly lower (p < 0.019) in the sub group treated with 40 mg adalimumab (474 ± 84 pg/μg total protein) compared with placebo (817 ± 78 pg/μg). There were two serious adverse events, both considered unrelated to the study drug. Interpretation In this dose-ranging study, injection of 40 mg of adalimumab in 0.4 ml resulted in down regulation of the myofibroblast phenotype as evidenced by reduction in expression of α-SMA and type I procollagen proteins at 2 weeks. These data form the basis of an ongoing phase 2b clinical trial assessing the efficacy of intranodular injection of 40 mg adalimumab in 0.4 ml compared to an equivalent volume of placebo in patients with early stage Dupuytren's disease