Long-term morbidity from severe pneumonia in early childhood in The Gambia, West Africa: a follow-up study

OBJECTIVE: To assess long-term outcomes in severe early childhood pneumonia in The Gambia. DESIGN: Observational cohort study of children hospitalised with severe pneumonia between 1992 and 1 04 compared to age, sex, and neigh bourhood-marched controls on measures of current general and pulmonary health. RESULTS: Of 83 children successfully traced, 68 of the 69 alive at follow-up agreed to participate. Thirteen per Cent of cases and 4% of controls had lung disease clinically or on spirometry. Another 16 (13%) participants had abnormal spirometry but did not meet the American Thoracic Society technical criteria (formally 'inconclusive'). Odds ratios of lung disease among childhood pneumonia cases were 2.93 (95 %CI 0.69-12.48, P = 0.1468) with incon-clusives omitted; 2.53 (95 %CI 0.61-10.59, P = 0.2033) with inconclusives included as normal; and 2.83 (95%CI 1.09-7.36, P = 0.0334) with inconclusives included as lung disease. Among deceased cases, most deaths were reported within weeks of discharge, suggesting a possible connection between admission and subsequent death. CONCLUSION: These African data, while not conclusive, add to previous data suggesting a link between severe early, childhood pneumonia and later chronic lung disease. While larger-scale research is needed, increased awareness of possible long-term morbidity in children with severe pneumonia is warranted to limit its impact and optimise long-term health

Judged in a foreign language : A Chinese-Spanish court interpreting case study

Recent legislation in Spain has transposed Directive 2010/64/EU, which recognises interpretation as an essential tool for safeguarding fairness in criminal proceedings, in particular, for preventing any state of defencelessness. Previous research, however, has suggested important deficiencies in court interpreting in this country. This article analyses court interpreting from Chinese to Spanish, based on a case study of a recording of a criminal trial that took place in Barcelona in February 2015. The trial was transcribed verbatim and annotated in accordance with Cecilia Wadensjö's distinction between "talk as text" and "talk as activity." The analysis focuses on examples of errors of interpretation (non-translated speech acts, omissions, and additions), speech style and non-renditions. The results are compared with those of a corpus of 55 court proceedings in which the interpretation was from Spanish to English and from French to Romanian. The article concludes with a discussion of the factors-such as lack of specialised training, lack of deontological codes or general unawareness of the interpreter's role-that may have affected the quality of the interpretation in the trial analysed. The low proportion of interpretation during that court session (only 17.6% of the total duration) is perhaps the most striking result of the case stud

Longitudinal Numbers-Needed-To-Treat (NNT) for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis

<p>Abstract</p> <p>Background</p> <p>Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs.</p> <p>Methods</p> <p>This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation.</p> <p>Results</p> <p>For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks.</p> <p>Conclusions</p> <p>For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide additional, complementary information beyond population mean responses when assessing efficacy compared to placebo and amongst active therapies.</p

A perspective on two decades of policies and regulations influencing the protection and restoration of submerged aquatic vegetation in Chesapeake Bay, USA

Seagrasses along with many other species of freshwater rooted submerged macrophytes in Chesapeake Bay (collectively called SAV) underwent serious declines in population abundances in the 1970s and have not as yet rebounded to previous levels. Cooperative efforts by scientists, politicians, federal and state resource managers, and the general public have developed policies and plans to protect, preserve and enhance SAV populations of Chesapeake Bay. These include the Chesapeake Bay Agreements (1983, 1987, 1992, 1993, 2000), an SAV Management Policy and Implementation Plan for Chesapeake Bay and Tidal Tributaries (1989 and 1990), Chesapeake Bay Blue Crab Fishery Management Plan (1997), as well as federal and state guidelines for protecting SAV communities from direct human impacts such as dredge and fill operations. The foundation for many of these management efforts has been the recognition of the habitat value of SAV to many fish and shellfish, and the elucidation of linkages between water quality conditions and the continuing occurrence of SAV as established by minimal water quality habitat requirements for growth and survival. Because of these linkages, the distribution of SAV in the Bay and its tidal tributaries is being used as an initial measure of progress in the restoration of living resources and water quality. Restoration targets and goals have been established to link demonstrable improvements in water quality to increases in SAV abundance. The major challenge facing the Chesapeake Bay community will be to restore SAV habitat and ecosystem functions to historic levels. However, the recent success in the development of policies, plans, regulations and laws highlighting the importance of SAV communities in Chesapeake Bay and their protection and restoration, is an excellent example of effective communication linkages and adaptive management principles between scientists, resource managers, politicians and the public in the Chesapeake Bay region. Only through these interactions will SAV restoration become a reality

Pregabalin in fibromyalgia - responder analysis from individual patient data

<p>Abstract</p> <p>Background</p> <p>Population mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores.</p> <p>Methods</p> <p>We obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (≥ 0%), minimal improvement (≥ 15%), moderate improvement (≥ 30%), substantial improvement (≥ 50%), and extensive improvement (≥ 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo.</p> <p>Results</p> <p>Information from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for ≥ 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for ≥ 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response.</p> <p>Conclusions</p> <p>Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.</p

Maternal nutrition at conception modulates DNA methylation of human metastable epialleles.

In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles

Submucosal diclofenac for acute postoperative pain in third molar surgery: A randomized, controlled clinical trial

Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) for relief of inflammatory pain. A recent formulation combines this drug with hydroxypropyl-β-cyclodextrin (HPβCD) to improve its solubility and to enable subcutaneous administration. Previous studies confirmed the efficacy of this combination. This study’s aim was to evaluate the efficacy, safety, and local tolerability of diclofenac HPβCD administered as a local submucosal injection prior to lower third molar surgery. We conducted a prospective, randomized, double-blind, placebo-controlled, parallel-group phase II single-center study. Seventy-five patients requiring mandibular third molar surgery were randomized into 1 of 5 groups: 5 mg/1 mL diclofenac HPβCD, 12.5 mg/1 mL diclofenac HPβCD, 25 mg/1 mL diclofenac HPβCD, 50 mg/1 mL diclofenac HPβCD, or 1 mL placebo. The respective study drug was injected into the mucosal tissue surrounding the surgical site prior to surgery following achievement of local anesthesia. The primary outcome measure was the area under the curve (AUC) of cumulative pain scores from end of surgery to 6 h postsurgery. This demonstrated a global treatment effect between the active groups and placebo, hence confirming the study drug’s efficacy (P = 0.0126). Secondary outcome measures included the time until onset of pain and the time until patients required rescue medication, both showing statistical significance of the study drug compared to placebo (P < 0.0161 and P < 0.0001, respectively). The time until rescue medication ranged between 7.8 h (for 25 mg/1 mL diclofenac HPβCD) and 16 h (for 50 mg/1 mL diclofenac HPβCD). Interestingly, the 5-mg/1-mL solution appeared superior to the 12.5-mg/1-mL and 25-mg/1-mL solutions (time until rescue medication = 12.44 h). A total of 14% of patients experienced minor adverse drug reactions (ADRs), of which 2 cases demonstrated flap necrosis. These resolved without further intervention. The study results overall indicate efficacy, safety, and relative tolerability of diclofenac HPβCD used locally as a submucosal injection prior to third molar surgery (ClinicalTrials.gov NCT01706588)

Effectiveness of pharmacist home visits for individuals at risk of medication-related problems: A systematic review and meta-analysis of randomised controlled trials

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: Not applicable, as this research article reviewed the published literature. The data published may be found in the original manuscripts cited in the references list.Background: Medication mismanagement is a major cause of both hospital admission and nursing home placement of frail older adults. Medication reviews by community pharmacists aim to maximise therapeutic benefit but also minimise harm. Pharmacist-led medication reviews have been the focus of several systematic reviews, but none have focussed on the home setting. Review methods: To determine the effectiveness of pharmacist home visits for individuals at risk of medication-related problems we undertook a systematic review and meta-analysis of randomised controlled trials (RCTs). Thirteen databases were searched from inception to December 2018. Forward and backward citation of included studies was also performed. Articles were screened for inclusion independently by two reviewers. Randomised controlled studies of home visits by pharmacists for individuals at risk of medication-related problems were eligible for inclusion. Data extraction and quality appraisal were performed by one reviewer and checked by a second. Random-effects meta-analyses were performed where sufficient data allowed and narrative synthesis summarised all remaining data. Results: Twelve RCTs (reported in 15 articles), involving 3410 participants, were included in the review. The frequency, content and purpose of the home visit varied considerably. The data from eight trials were suitable for meta-analysis of the effects on hospital admissions and mortality, and from three trials for the effects on quality of life. Overall there was no evidence of reduction in hospital admissions (risk ratio (RR) of 1.01 (95%CI 0.86 to 1.20, I2 = 69.0%, p = 0.89; 8 studies, 2314 participants)), or mortality (RR of 1.01 (95%CI 0.81 to 1.26, I2 = 0%, p = 0.94; 8 studies, 2314 participants)). There was no consistent evidence of an effect on quality of life, medication adherence or knowledge. Conclusion: A systematic review of twelve RCTs assessing the impact of pharmacist home visits for individuals at risk of medication related problems found no evidence of effect on hospital admission or mortality rates, and limited evidence of effect on quality of life. Future studies should focus on using more robust methods to assess relevant outcomes.National Institute for Health Research (NIHR

2010 ACVIM Small Animal Consensus Statement on Leptospirosis: Diagnosis, Epidemiology, Treatment, and Prevention

This report offers a consensus opinion on the diagnosis, epidemiology, treatment, and prevention of leptospirosis in dogs, an important zoonosis. Clinical signs of leptospirosis in dogs relate to development of renal disease, hepatic disease, uveitis, and pulmonary hemorrhage. Disease may follow periods of high rainfall, and can occur in dogs roaming in proximity to water sources, farm animals, or wildlife, or dogs residing in suburban environments. Diagnosis is based on acute and convalescent phase antibody titers by the microscopic agglutination test (MAT), with or without use of polymerase chain reaction assays. There is considerable interlaboratory variation in MAT results, and the MAT does not accurately predict the infecting serogroup. The recommended treatment for optimal clearance of the organism from renal tubules is doxycycline, 5 mg/kg PO q12h, for 14 days. Annual vaccination can prevent leptospirosis caused by serovars included in the vaccine and is recommended for dogs at risk of infection