Long-term management of generalised anxiety disorder with low-dose continuous infusions of flumazenil: A case series

Background: Generalised anxiety disorder (GAD) is a common anxiety disorder associated with social and occupational impairment. Recently, a theory was postulated that dysfunctional gamma aminobutyric acid type A receptors (GABAA) are implicated in anxiety symptomology, which could be corrected by flumazenil, an antagonist at the benzodiazepine binding site on the GABAA receptor. Method: Participants had a primary diagnosis of GAD and were treated initially with an eight-day continuous low-dose flumazenil infusion (total 32 mg at a rate of 4 mg/24 h). Some participants were re-treated with a further four- or eight-day infusion. Treatment response was measured as a 50 % reduction in anxiety or stress scores on the Depression Anxiety Stress Scale — 21 (DASS-21). Remission was measured as scores ≤ 3 or ≤ 7 on the anxiety and stress subscales of the DASS-21, respectively. Results: Eight cases are reported. All cases met the criteria for treatment response on the anxiety and stress subscale of the DASS-21. Remission was achieved in seven participants on the anxiety subscale and in five on the stress subscale. No changes in hepatic, renal, or haematological function were likely attributed to flumazenil. Conclusion: Data suggest that low-dose continuous flumazenil infusion manages GAD symptoms and is safe. Although these results are promising, future randomised control trials are required to confirm these results

The learning curve associated with the introduction of the subcutaneous implantable defibrillator

Aims: The subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced to overcome complications related to transvenous leads. Adoption of the S-ICD requires implanters to learn a new implantation technique. The aim of this study was to assess the learning curve for S-ICD implanters with respect to implant-related complications, procedure time, and inappropriate shocks (IASs). Methods and results: In a pooled cohort from two clinical S-ICD databases, the IDE Trial and the EFFORTLESS Registry, complications, IASs at 180 days follow-up and implant procedure duration were assessed. Patients were grouped in quartiles based on experience of the implanter and Kaplan-Meier estimates of complication and IAS rates were calculated. A total of 882 patients implanted in 61 centres by 107 implanters with a median of 4 implants (IQR 1,8) were analysed. There were a total of 59 patients with complications and 48 patients with IAS. The complication rate decreased significantly from 9.8% in Quartile 1 (least experience) to 5.4% in Quartile 4 (most experience) (P = 0.02) and non-significantly for IAS from 7.9 to 4.8% (P = 0.10). Multivariable analysis demonstrated a hazard ratio of 0.78 (P = 0.045) for complications and 1.01 (P = 0.958) for IAS. Dual-zone programming increased with experience of the individual implanter (P 13 implants). Conclusion: There is a short and significant learning curve associated with physicians adopting the S-ICD. Performance stab

The controversy of patellar resurfacing in total knee arthroplasty: Ibisne in medio tutissimus?

Early arthroplasty designs were associated with a high level of anterior knee pain as they failed to cater for the patello-femoral joint. Patellar resurfacing was heralded as the saviour safeguarding patient satisfaction and success but opinion on its necessity has since deeply divided the scientific community and has become synonymous to topics of religion or politics. Opponents of resurfacing contend that the native patella provides better patellar tracking, improved clinical function, and avoids implant-related complications, whilst proponents argue that patients have less pain, are overall more satisfied, and avert the need for secondary resurfacing. The question remains whether complications associated with patellar resurfacing including those arising from future component revision outweigh the somewhat increased incidence of anterior knee pain recorded in unresurfaced patients. The current scientific literature, which is often affected by methodological limitations and observer bias, remains confusing as it provides evidence in support of both sides of the argument, whilst blinded satisfaction studies comparing resurfaced and non-resurfaced knees generally reveal equivalent results. Even national arthroplasty register data show wide variations in the proportion of patellar resurfacing between countries that cannot be explained by cultural differences alone. Advocates who always resurface or never resurface indiscriminately expose the patella to a random choice. Selective resurfacing offers a compromise by providing a decision algorithm based on a propensity for improved clinical success, whilst avoiding potential complications associated with unnecessary resurfacing. Evidence regarding the validity of selection criteria, however, is missing, and the decision when to resurface is often based on intuitive reasoning. Our lack of understanding why, irrespective of pre-operative symptoms and patellar resurfacing, some patients may suffer pain following TKA and others may not have so far stifled our efforts to make the strategy of selective resurfacing succeed. We should hence devote our efforts in defining predictive criteria and indicators that will enable us to reliably identify those individuals who might benefit from a resurfacing procedure. Level of evidence V

Characterization of antimicrobial resistant Gram-negative bacteria that cause neonatal sepsis in seven low and middle-income countries

Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Grand challenges in entomology: Priorities for action in the coming decades

Entomology is key to understanding terrestrial and freshwater ecosystems at a time of unprecedented anthropogenic environmental change and offers substantial untapped potential to benefit humanity in a variety of ways, from improving agricultural practices to managing vector-borne diseases and inspiring technological advances. We identified high priority challenges for entomology using an inclusive, open, and democratic four-stage prioritisation approach, conducted among the membership and affiliates (hereafter ‘members’) of the UK-based Royal Entomological Society (RES). A list of 710 challenges was gathered from 189 RES members. Thematic analysis was used to group suggestions, followed by an online vote to determine initial priorities, which were subsequently ranked during an online workshop involving 37 participants. The outcome was a set of 61 priority challenges within four groupings of related themes: (i) ‘Fundamental Research’ (themes: Taxonomy, ‘Blue Skies’ [defined as research ideas without immediate practical application], Methods and Techniques); (ii) ‘Anthropogenic Impacts and Conservation’ (themes: Anthropogenic Impacts, Conservation Options); (iii) ‘Uses, Ecosystem Services and Disservices’ (themes: Ecosystem Benefits, Technology and Resources [use of insects as a resource, or as inspiration], Pests); (iv) ‘Collaboration, Engagement and Training’ (themes: Knowledge Access, Training and Collaboration, Societal Engagement). Priority challenges encompass research questions, funding objectives, new technologies, and priorities for outreach and engagement. Examples include training taxonomists, establishing a global network of insect monitoring sites, understanding the extent of insect declines, exploring roles of cultivated insects in food supply chains, and connecting professional with amateur entomologists. Responses to different challenges could be led by amateur and professional entomologists, at all career stages. Overall, the challenges provide a diverse array of options to inspire and initiate entomological activities and reveal the potential of entomology to contribute to addressing global challenges related to human health and well-being, and environmental change

Grand challenges in entomology: priorities for action in the coming decades

1. Entomology is key to understanding terrestrial and freshwater ecosystems at a time of unprecedented anthropogenic environmental change and offers substantial untapped potential to benefit humanity in a variety of ways, from improving agricultural practices to managing vector-borne diseases and inspiring technological advances. 2. We identified high priority challenges for entomology using an inclusive, open, and democratic four-stage prioritisation approach, conducted among the membership and affiliates (hereafter ‘members’) of the UK-based Royal Entomological Society (RES). 3. A list of 710 challenges was gathered from 189 RES members. Thematic analysis was used to group suggestions, followed by an online vote to determine initial priorities, which were subsequently ranked during an online workshop involving 37 participants. 4. The outcome was a set of 61 priority challenges within four groupings of related themes: (i) ‘Fundamental Research’ (themes: Taxonomy, ‘Blue Skies’ [defined as research ideas without immediate practical application], Methods and Techniques); (ii) ‘Anthropogenic Impacts and Conservation’ (themes: Anthropogenic Impacts, Conservation Options); (iii) ‘Uses, Ecosystem Services and Disservices’ (themes: Ecosystem Benefits, Technology and Resources [use of insects as a resource, or as inspiration], Pests); (iv) ‘Collaboration, Engagement and Training’ (themes: Knowledge Access, Training and Collaboration, Societal Engagement). 5. Priority challenges encompass research questions, funding objectives, new technologies, and priorities for outreach and engagement. Examples include training taxonomists, establishing a global network of insect monitoring sites, understanding the extent of insect declines, exploring roles of cultivated insects in food supply chains, and connecting professional with amateur entomologists. Responses to different challenges could be led by amateur and professional entomologists, at all career stages. 6. Overall, the challenges provide a diverse array of options to inspire and initiate entomological activities and reveal the potential of entomology to contribute to addressing global challenges related to human health and well-being, and environmental change

Grand challenges in entomology: priorities for action in the coming decades

Entomology is key to understanding terrestrial and freshwater ecosystems at a time of unprecedented anthropogenic environmental change and offers substantial untapped potential to benefit humanity in a variety of ways, from improving agricultural practices to managing vector-borne diseases and inspiring technological advances. We identified high priority challenges for entomology using an inclusive, open, and democratic four-stage prioritisation approach, conducted among the membership and affiliates (hereafter ‘members’) of the UK-based Royal Entomological Society (RES). A list of 710 challenges was gathered from 189 RES members. Thematic analysis was used to group suggestions, followed by an online vote to determine initial priorities, which were subsequently ranked during an online workshop involving 37 participants. The outcome was a set of 61 priority challenges within four groupings of related themes: (i) ‘Fundamental Research’ (themes: Taxonomy, ‘Blue Skies’ [defined as research ideas without immediate practical application], Methods and Techniques); (ii) ‘Anthropogenic Impacts and Conservation’ (themes: Anthropogenic Impacts, Conservation Options); (iii) ‘Uses, Ecosystem Services and Disservices’ (themes: Ecosystem Benefits, Technology and Resources [use of insects as a resource, or as inspiration], Pests); (iv) ‘Collaboration, Engagement and Training’ (themes: Knowledge Access, Training and Collaboration, Societal Engagement). Priority challenges encompass research questions, funding objectives, new technologies, and priorities for outreach and engagement. Examples include training taxonomists, establishing a global network of insect monitoring sites, understanding the extent of insect declines, exploring roles of cultivated insects in food supply chains, and connecting professional with amateur entomologists. Responses to different challenges could be led by amateur and professional entomologists, at all career stages. Overall, the challenges provide a diverse array of options to inspire and initiate entomological activities and reveal the potential of entomology to contribute to addressing global challenges related to human health and well-being, and environmental change

Grand challenges in entomology: Priorities for action in the coming decades

Entomology is key to understanding terrestrial and freshwater ecosystems at a time of unprecedented anthropogenic environmental change and offers substantial untapped potential to benefit humanity in a variety of ways, from improving agricultural practices to managing vector-borne diseases and inspiring technological advances. We identified high priority challenges for entomology using an inclusive, open, and democratic four-stage prioritisation approach, conducted among the membership and affiliates (hereafter ‘members’) of the UK-based Royal Entomological Society (RES). A list of 710 challenges was gathered from 189 RES members. Thematic analysis was used to group suggestions, followed by an online vote to determine initial priorities, which were subsequently ranked during an online workshop involving 37 participants. The outcome was a set of 61 priority challenges within four groupings of related themes: (i) ‘Fundamental Research’ (themes: Taxonomy, ‘Blue Skies’ [defined as research ideas without immediate practical application], Methods and Techniques); (ii) ‘Anthropogenic Impacts and Conservation’ (themes: Anthropogenic Impacts, Conservation Options); (iii) ‘Uses, Ecosystem Services and Disservices’ (themes: Ecosystem Benefits, Technology and Resources [use of insects as a resource, or as inspiration], Pests); (iv) ‘Collaboration, Engagement and Training’ (themes: Knowledge Access, Training and Collaboration, Societal Engagement). Priority challenges encompass research questions, funding objectives, new technologies, and priorities for outreach and engagement. Examples include training taxonomists, establishing a global network of insect monitoring sites, understanding the extent of insect declines, exploring roles of cultivated insects in food supply chains, and connecting professional with amateur entomologists. Responses to different challenges could be led by amateur and professional entomologists, at all career stages. Overall, the challenges provide a diverse array of options to inspire and initiate entomological activities and reveal the potential of entomology to contribute to addressing global challenges related to human health and well-being, and environmental change

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study

Background Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. Methods The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. Findings Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69–234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04–74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37–2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. Interpretation Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. Funding Bill & Melinda Gates Foundation