Overcoming Operational Challenges to Ebola Case Investigation in Sierra Leone.

The Ebola virus disease (EVD) epidemic that hit West Africa in 2013 was the worst outbreak of EVD in recorded history. While much has been published regarding the international and national-level EVD responses, there is a dearth of literature on district-level coordination and operational structures, successes, and failures. This article seeks to understand how the EVD response unfolded at the district level, namely the challenges to operationalizing EVD surveillance over the course of the outbreak in Port Loko and Kambia districts of Sierra Leone. We present here GOAL Global's understanding of the fundamental challenges to case investigation operations during the EVD response, including environmental and infrastructural, sociocultural, and political and organizational challenges, with insight complemented by a survey of 42 case investigators. Major challenges included deficiencies in transportation and communication resources, low morale and fatigue among case investigators, mismanagement of data, mistrust among communities, and leadership challenges. Without addressing these operational challenges, technical surveillance solutions are difficult to implement and hold limited relevance, due to the poor quality and quantity of data being collected. The low prioritization of operational needs came at a high cost. To mediate this, GOAL addressed these operational challenges by acquiring critical transportation and communication resources to facilitate case investigation, including vehicles, boats, fuel, drivers, phones, and closed user groups; addressing fatigue and low morale by hiring more case investigators, making timely payments, arranging for time off, and providing meals and personal protective equipment; improving data tracking efforts through standard operating procedures, training, and mentorship to build higher-quality case histories and make it easier to access information; strengthening trust in communities by ensuring familiarity and consistency of case investigators; and improving operational leadership challenges through meetings and regular coordination, establishing an active surveillance strategy in Port Loko, and conducting an after-action review. Resolving or addressing these challenges was of primary importance, and requisite for the implementation of technical epidemiological complements to EVD case investigation

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance: Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions. Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016. Surveillance for new evidence in targeted publications was conducted through July 1, 2017. Study Selection: English-language randomized clinical trials reporting health outcomes. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures: Beneficial or harmful changes in risks for various chronic conditions. Results: Eighteen trials (n = 40 058; range, 142-16 608; mean age, 53-79 years) were included. Women using estrogen-only therapy compared with placebo had significantly lower risks, per 10 000 person-years, for diabetes (-19 cases [95% CI, -34 to -3]) and fractures (-53 cases [95% CI, -69 to -39]). Risks were statistically significantly increased, per 10 000 person-years, for gallbladder disease (30 more cases [95% CI, 16 to 48]), stroke (11 more cases [95% CI, 2 to 23]), venous thromboembolism (11 more cases [95% CI, 3 to 22]), and urinary incontinence (1261 more cases [95% CI, 880 to 1689]). Women using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 person-years, for colorectal cancer (-6 cases [95% CI, -9 to -1]), diabetes (-14 cases [95% CI, -24 to -3), and fractures (-44 cases [95% CI, -71 to -13). Risks, per 10 000 person-years, were significantly increased for invasive breast cancer (9 more cases [95% CI, 1 to 19]), probable dementia (22 more cases [95% CI, 4 to 53]), gallbladder disease (21 more cases [95% CI, 10 to 34]), stroke (9 more cases [95% CI, 2 to 19]), urinary incontinence (876 more cases [95% CI, 606 to 1168]), and venous thromboembolism (21 more cases [95% CI, 12 to 33]). Conclusions and Relevance: Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms. The available evidence regarding benefits and harms of early initiation of hormone therapy is inconclusive

Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Five to ten percent of individuals with latent tuberculosis infection (LTBI) progress to active tuberculosis (TB) disease. Identifying and treating LTBI is a key component of the strategy for reducing the burden of TB disease. To review the evidence about targeted screening and treatment for LTBI among adults in primary care settings to support the US Preventive Services Task Force in updating its 1996 recommendation. MEDLINE, Cochrane Library, and trial registries, searched through August 3, 2015; references from pertinent articles; and experts. Literature surveillance was conducted through May 31, 2016. English-language studies of LTBI screening, LTBI treatment with recommended pharmacotherapy, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of individuals for whom LTBI screening and treatment is part of public health surveillance or disease management were excluded. Two investigators independently reviewed abstracts and full-text articles. When at least 3 similar studies were available, random-effects meta-analysis was used to generate pooled estimates of outcomes. Sensitivity, specificity, reliability, active TB disease, mortality, hepatotoxicity, and other harms. The review included 72 studies (n = 51 711). No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at both 5-mm and 10-mm induration thresholds were 0.79 (5-mm: 95% CI, 0.69-0.89 [8 studies, n = 803]; 10 mm: 95% CI, 0.71-0.87 [11 studies; n = 988]), and those for IGRAs ranged from 0.77 to 0.90 (57 studies; n = 4378). Pooled estimates for specificity of the TST at the 10-mm and 15-mm thresholds and for IGRAs ranged from 0.95 to 0.99 (34 studies; n = 23 853). A randomized clinical trial (RCT) of 24 weeks of isoniazid in individuals with pulmonary fibrotic lesions and LTBI (n = 27 830) found a reduction in absolute risk of active TB at 5 years from 1.4% to 0.5% (relative risk [RR], 0.35 [95% CI, 0.24-0.52]) and an increase in absolute risk for hepatoxicity from 0.1% to 0.5% (RR, 4.59 [95% CI, 2.03-10.39]) for 24 weeks of daily isoniazid compared with placebo. An RCT (n = 6886) found that 3 months of once-weekly rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing active TB. The risk difference for hepatoxicity comparing isoniazid with rifampin ranged from 3% to 7%, with a pooled RR of 3.29 (95% CI, 1.72-6.28 [3 RCTs; n = 1327]). No studies evaluated the benefits and harms of screening compared with no screening. Both the TST and IGRAs are moderately sensitive and highly specific within countries with low TB burden. Treatment reduced the risk of active TB among the populations included in this review. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin

Book Reviews

Book reviews of: Grant at Vicksburg: The General and the Siege. By Michael B. Ballard. Carbondale: Southern Illinois University Press, 2013. Illustrations, maps, notes, index. Pp. xiii, 232. $32.95 cloth,$32.95 e-book. ISBN: 9780809332403. A Voice That Could Stir an Army: Fannie Lou Hamer and the Rhetoric of the Black Freedom Movement. By Maegan Parker Brooks (Jackson: University Press of Mississippi, 2014. Index, bibliography. Pp. 314. $60 cloth,$60 e-book. ISBN 978- 1-628646-004-9.) A New Southern Woman: T he Correspondence of Eliza Lucy Irion Neilson, 1871-1883. Edited by Giselle Roberts. (Columbia: University of South Carolina Press, 2013. Acknowledgements, illustrations, notes, index. Pp. viii, 306. $49.95 cloth. ISBN: 9781611171037.) Pageants, Parlors, and Pretty Women: Race and Beauty in the Twentieth-Century South. By Blain Roberts. (Chapel Hill: University of North Carolina Press, 2014). Acknowledgments, illustrations, notes, bibliography, index. Pp. ix, 363.$39.95 hardcover, $29.99 e-book. ISBN: 978-1-4696-1420-5.) Black Freedom, White Resistance, and Red Menace: Civil Rights and Anticommunism in the Jim Crow South. By Yasuhiro Katagiri. (Baton Rouge: Louisiana State University Press, 2014. Acknowledgements, illustrations, notes, index. Pp.xi, 392.$47.50 hardcover. ISBN 9780807153130.) Natchez Country: Indians, Colonists, and the Landscapes of Race in French Louisiana. By George Edward Milne. (Athens: The University of Georgia Press, 2015. List of figures, acknowledgments, notes, bibliography, index. Pp. xi, 293. $84.95 cloth,$26.95 paper. ISBN: 9780820347509.) In Remembrance of Emmett Till: Regional Stories and Media Responses to the Black Freedom Struggle. By Darryl Mace. (Lexington: University Press of Kentucky, 2014. Preface, introduction, illustrations, acknowledgements, notes, bibliography, index. Pp. xi, 212. $40 cloth. ISBN: 978- 0-8131-4536-5.) The Edible South: The Power of Food and the Making of an American Region. By Marcie Cohen Ferris. (Chapel Hill: The University of North Carolina Press, 2014. 496 pp., 7x10, 50 halftones, notes, bibl., index.$35 cloth, $34.99 e-book. ISBN: 978- 1-4696-1768-8.) Down to the Crossroads: Civil Rights, Black Power, and the Meredith March Against Fear. By Aram Goudsouzian. (New York: Farrar, Straus and Giroux, 2014. Map, notes, acknowledgements, index. Pp. ix, 351.$30 cloth, $18 paper. ISBN: 0374192200.) After Slavery: Race, Labor, and Citizenship in the Reconstruction South. Edited by Bruce Baker and Brian Kelly. Afterword by Eric Foner. (Gainesville: University Press of Florida, 2013. Acknowledgments, images, maps, notes, bibliography, index. Pp. vii, 279.$74.95 cloth. $24.95 paper. ISBN 978- 0-8130-4477-4.) George Ohr: Sophisticate and Rube. By Ellen J. Lippert. (Jackson: University Press of Mississippi, 2013. Acknowledgements, illustrations, notes, bibliography, index, Pp. x, 163.$40 cloth. ISBN: 9781617039010.

Remote Focusing for 2-photon Microscopy to Follow Action Potential Propagation Transmurally in Acute Rabbit Cardiac Slices

In the heart, action potentials travel through the tissue to orchestrate muscle contraction and make the organ an efficient pump. Scar tissues caused by myocardial infarction impairs electrical conduction. In the rabbit heart, action potentials propagate from the endocardium to the epicardium with a conduction velocity of 30 cm/s. Therefore, a rapid vertical scan is necessary to observe this transmural cardiac conduction at cellular resolution. Here we present an implementation of a versatile remote focusing module, compatible with retrofitting to commercial two-photon microscopes and capable of 0.3 kHz rate axial scanning over the range of 100 μm in cardiac tissue without disturbing the sample or the sample objective. We discuss the necessary optimization to compensate for pulse broadening, power losses and optical aberrations. We demonstrate fast imaging of cardiac cell structure in functionally viable rabbit ventricular slice model. We will apply this system to resolve cardiac electrical signal propagation transmurally in healthy and infarcted hearts

Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.

Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead to network hyperexcitability. Here, we introduce a human Na+-activated K+ (KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, find motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increases KNa currents in cortical excitatory and inhibitory neurons, there is an increase in the KNa current across subthreshold voltages only in inhibitory neurons, particularly in those with non-fast-spiking properties, resulting in inhibitory-neuron-specific impairments in excitability and action potential (AP) generation. We further observe evidence of synaptic rewiring, including increases in homotypic synaptic connectivity, accompanied by network hyperexcitability and hypersynchronicity. These findings support inhibitory-neuron-specific mechanisms in mediating the epileptogenic effects of KCNT1 channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention

Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis

Study question What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults?Methods This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT.Summary answer and limitations Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, −0.38, −2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings.What this study adds Second generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences.Funding, competing interests, data sharing This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/

Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial.

OBJECTIVE To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. DESIGN Cluster randomised controlled trial. SETTING 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. PARTICIPANTS 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). INTERVENTION Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. MAIN OUTCOME MEASURE Primary outcome was first drug related hospital admission within 12 months. RESULTS 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). CONCLUSIONS Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. TRIAL REGISTRATION ClinicalTrials.gov NCT02986425

Brief intervention to reduce risky drinking in pregnancy: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Risky drinking in pregnancy by UK women is likely to result in many alcohol-exposed pregnancies. Studies from the USA suggest that brief intervention has promise for alcohol risk reduction in antenatal care. However, further research is needed to establish whether this evidence from the USA is applicable to the UK. This pilot study aims to investigate whether pregnant women can be recruited and retained in a randomized controlled trial of brief intervention aimed at reducing risky drinking in women receiving antenatal care.</p> <p>Methods</p> <p>The trial will rehearse the parallel-group, non-blinded design and procedures of a subsequent definitive trial. Over 8 months, women aged 18 years and over (target number 2,742) attending their booking appointment with a community midwife (n = 31) in north-east England will be screened for alcohol consumption using the consumption questions of the Alcohol Use Disorders Identification Test (AUDIT-C). Those screening positive, without a history of substance use or alcohol dependence, with no pregnancy complication, and able to give informed consent, will be invited to participate in the trial (target number 120). Midwives will be randomized in a 1:1 ratio to deliver either treatment as usual (control) or structured brief advice and referral for a 20-minute motivational interviewing session with an alcohol health worker (intervention). As well as demographic and health information, baseline measures will include two 7-day time line follow-back questionnaires and the EuroQoL EQ-5D-3 L questionnaire. Measures will be repeated in telephone follow-ups in the third trimester and at 6 months post-partum, when a questionnaire on use of National Health Service and social care resources will also be completed. Information on pregnancy outcomes and stillbirths will be accessed from central health service records before the follow-ups. Primary outcomes will be rates of eligibility, recruitment, intervention delivery, and retention in the study population, to inform power calculations for a definitive trial. The health-economics component will establish how cost-effectiveness will be assessed, and examine which data on health service resource use should be collected in a main trial. Participants’ views on instruments and procedures will be sought to confirm their acceptability.</p> <p>Discussion</p> <p>The study will produce a full trial protocol with robust sample-size calculations to extend evidence on effectiveness of screening and brief intervention.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN43218782</p