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Presents several letters to the editor. Information on breast-conserving surgery; Characteristics of cerebral amyloid angiopathy; Complications in the laparoscopic hepatectomy for hepatecellular carcinoma.

The article tackles a report regarding the preparations made to a cloth for finishing. It mentions the characteristics a cotton should possess for it to have the best quality even with minimum labor. Faults that hinder the spinner to achieve the best quality of cotton such as cotton, mechanical and chemical faults were also pointed out. Cotton faults are found in the raw material that affect the color and quality of the product. Manufacturers commit most of the mechanical faults including uneven weaving and floats among others. Chemical faults are those caused by the chemicals being used in the production and dyeing of cloth. Recommendations to counter these faults were also laid in the article.

Background: The Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™) and afoxolaner + milbemycin (NexGard Spectra®) was evaluated against an artificial infestation of I. holocyclus. Methods: Twenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days − 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal® (control group), Simparica Trio™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means. Results: Against an existing infestation, efficacy of both Simparica Trio™ and NexGard Spectra® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study. Conclusions: Single doses of Simparica Trio™ and NexGard Spectra® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days. [ABSTRACT FROM AUTHOR]

Background: Haemaphysalis longicornis is the major tick affecting dogs in most of the East Asia/Pacific region and has recently been detected in a number of areas of the USA. This tick is a vector for a number of pathogens of dogs, other mammals and humans. In this study, the efficacy of a single oral administration of sarolaner (Simparica®, Zoetis) at the minimum label dosage (2 mg/kg) was evaluated against an existing infestation of H. longicornis and subsequent weekly reinfestations for 5 weeks after treatment. Methods: Sixteen dogs were ranked on pretreatment tick counts and randomly allocated to treatment on Day 0 with sarolaner at 2 mg/kg or a placebo. The dogs were infested with H. longicornis nymphs on Days − 2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 hours after treatment and subsequent re-infestations based on live tick counts relative to placebo-treated dogs. Results: There were no adverse reactions to treatment. A single dose of sarolaner provided 100% efficacy on Days 2, 7, 14 and 21; and ≥ 97.4% efficacy on Days 28 and 35. Considering only attached, live ticks, efficacy was 100% for the entire 35 days of the study. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (11.62 ≤ t(df) ≤ 59.99, where 13.0 ≤ df ≤ 14.1, P < 0.0001). Conclusions: In this study, a single oral administration of sarolaner at 2 mg/kg provided 100% efficacy against an existing infestation of H. longicornis nymphs and ≥ 97.4% efficacy (100% against attached ticks) against weekly reinfestation for at least 35 days after treatment. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of a new spot-on formulation of selamectin plus sarolaner were evaluated for the treatment and control of natural flea infestations on cats in two non-randomised, multi-centre clinical trials conducted in 8 different locations in Queensland, Australia. Methods: One hundred and four cats from 65 different households were enrolled across the two studies. Demographic characteristics of cats in the two studies were similar. The new spot-on formulation of selamectin and sarolaner was administered topically once a month for 3 consecutive months at a minimum dosage of 6 mg/kg selamectin (dose range 6–12 mg/kg) plus 1 mg/kg sarolaner (dose range 1–2 mg/kg). Cats were dosed on Days 0 (pre-treatment), 30 and 60 and physical examinations and flea counts were conducted on Days 0, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0. Results: In Study A, at enrolment, primary cats had flea counts ranging from 6 to 107 (arithmetic mean 21.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 98.0%, 100% and 100% on Days 30, 60 and 90, respectively. In Study B, at enrolment, primary cats had flea counts ranging from 6 to 22 (arithmetic mean 10.0). The selamectin and sarolaner spot-on formulation resulted in arithmetic mean efficacy of 99.7%, 100% and 100% on Days 30, 60 and 90, respectively. Conclusions: The new spot-on formulation of selamectin plus sarolaner topically administered at monthly intervals at the minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was safe and highly effective against natural infestations of fleas under a range of geographical conditions, representative of both tropical and subtropical regions of Australia. [ABSTRACT FROM AUTHOR]

The authors discuss research on determinants of childhood mortality, published within the issue. They report that reduction of childhood mortality rate in sub-Saharan Africa and southern Asia remains slow. In addition to national income, the factors associated with childhood mortality include access to sanitation, political instability, and HIV prevalence. The public health-related challenges that need to be addressed by policymakers are also noted.

A rapid reduction in under-five mortality has put Bangladesh on-track to reach Millennium Development Goal 4. Little research, however, has been conducted into neonatal reductions and sub-national rates in the country, with considerable disparities potentially masked by national reductions. The aim of this paper is to estimate national and sub-national rates of neonatal mortality to compute relative and absolute inequalities between sub-national groups and draw comparisons with rates of under-five mortality. Mortality rates for under-five children and neonates were estimated directly for 1980-1981 to 2010-2011 using data from six waves of the Demographic and Health Survey. Rates were stratified by levels of rural/urban location, household wealth and maternal education. Absolute and relative inequalities within these groups were measured by rate differences and ratios, and where possible, slope and relative indices of inequality. National mortality was shown to have decreased dramatically although at differential rates for under-fives and neonates. Across all equity markers, a general pattern of declining absolute but constant relative inequalities was found. For mortality rates stratified by education and wealth mixed evidence suggests that relative inequalities may have also fallen. Although disparities remain, Bangladesh has achieved a rare combination of substantive reductions in mortality levels without increases in relative inequalities. A coalescence of substantial increases in coverage and equitable distribution of key child and neonatal interventions with widespread health sectoral and policy changes over the last 30 years may in part explain this exceptional pattern. [ABSTRACT FROM AUTHOR]

As a part of the Millennium Development Goals, India seeks to substantially reduce its burden of childhood mortality. The success or failure of this goal may depend on outcomes within India's most populous state, Uttar Pradesh. This study examines the level of disparities in under-five and neonatal mortality across a range of equity markers within the state. Estimates of under-five and neonatal mortality rates were computed using five datasets, from three available sources: sample registration system, summary birth histories in surveys, and complete birth histories. Disparities were evaluated via comparisons of mortality rates by rural-urban location, ethnicity, wealth, and districts. While Uttar Pradesh has experienced declines in both rates of under-five (162-108 per 1,000 live births) and neonatal (76-49 per 1,000 live births) mortality, the rate of decline has been slow (averaging 2 % per annum). Mortality trends in rural and urban areas are showing signs of convergence, largely due to the much slower rate of change in urban areas. While the gap between rich and poor households has decreased in both urban and rural areas, trends suggest that differences in mortality will remain. Caste-related disparities remain high and show no signs of diminishing. Of concern are also the signs of stagnation in mortality amongst groups with greater ability to access services, such as the urban middle class. Notwithstanding the slow but steady reduction of absolute levels of childhood mortality within Uttar Pradesh, the distribution of the mortality by sub-state populations remains unequal. Future progress may require significant investment in quality of care provided to all sections of the community. [ABSTRACT FROM AUTHOR]

Abstract: The point prevalence of Tardive Dyskinesia (TD) in schizophrenia outpatients (n =6981) participating in a study of health outcomes was 8.9%. Duration of diagnosis, age, and prior use of typical antipsychotics were diagnostic indicators of TD in this population, with male sex further increasing risk. This study provides new data in a non-Western population with a unique regional geography comparison. [Copyright &y& Elsevier]

The efficacy of a single oral dose of a novel isoxazoline, sarolaner (Simparica™, Zoetis), for the treatment and control of flea infestations on dogs was confirmed in five laboratory studies. The studies were conducted using adult purpose-bred Beagles and/or mixed breed dogs. All animals were individually identified and housed, and were allocated randomly to treatment with either placebo or sarolaner (eight to 10 per group) based on pretreatment parasite counts. Three studies used cat flea ( Ctenocephalides felis felis ) strains recently isolated from the field from the US, EU, or Australia; in the fourth study a laboratory strain (KS1) with documented tolerance to a number of insecticides such as fipronil, imidacloprid, and permethrin was used. In the fifth study, dogs were infested with dog fleas, Ctenocephalides canis . Dogs were treated orally on Day 0 with a placebo or a sarolaner tablet providing a minimum dose of 2 mg/kg. Dogs were infested with approximately 100 unfed, adult fleas prior to treatment and at weekly intervals post-treatment. Comb counts were conducted to determine the numbers of viable fleas at 24 h after treatment and after each subsequent infestation. Efficacy against C. felis and C. canis was 99.8–100% from treatment through Day 35. In all five studies, elimination of existing infestations was achieved within 24 h after dosing, with only a single live C. felis found on one dog on Day 1. Similarly, control of flea challenges was achieved within 24 h after infestation throughout the 35 day study periods, with only single live C. felis found on two dogs on Day 28 in one study, and on a single dog on Day 35 in another study. There were no adverse reactions to treatment with sarolaner. These studies confirmed that a single oral dose of sarolaner at 2 mg/kg provided highly effective treatment of existing C. felis infestations and persistent control of C. felis on dogs for 35 days after treatment. Efficacy equivalent to that seen with C. felis was confirmed against C. canis and a known insecticide-tolerant strain of C. felis . [ABSTRACT FROM AUTHOR]

Background Few previous studies have examined non-wealth-based inequalities in child mortality within developing countries. This study estimates changes in under-5-year-olds and neonatal mortality in Nepal across a range of subnational levels, which allows us to assess the degree of equity in Nepal’s progress towards Millennium Development Goal 4.Methods Direct estimates of under-5-year-olds and neonatal death rates were generated for 1990–2005using three Demographic and Health Surveys and two Living Standards Surveys by the following levels:national, rural/urban location, ecological region,development region, ethnicity and wealth. Absolute and relative inequalities were measured by rate differences and rate ratios, respectively. Additionally, wealth-related inequality was calculated using slope and relative indexes of inequality and concentration indices.Results Estimates suggest that while most rates of under-5-year-olds and neonatal mortality have declined across the different equity markers, leading to a downward trend in absolute inequalities, relative inequalities appear to have remained stable over time.The decline in absolute inequalities is strongest for under-5-year-olds’ mortality, with no statisticallysignificant trend in either relative or absolute inequalities found for neonatal mortality. A possible increase in inequalities, at least in relative terms, was found across development regions, where death rates remain high in the mid-western region.Conclusions By 2015, our estimates suggest that more than 65% of deaths of under-5-year-olds will occur in the neonatal period, with stable trends in neonatal mortality inequalities. These findings along with the fact that health outcomes for neonates are more highly dependent on health systems, suggest further equitable reductions in under-5-year-olds mortality will require broad health-system strengthening, with a focus on the improvement of healthcare services provided for mothers and newborns. Other inequities suggest continued special attention for vulnerable subpopulations is warranted, particularly to overcome social exclusion and financial barriers to care in urban areas. [ABSTRACT FROM AUTHOR]

Intensive farming practices and heavy reliance on anthelmintics have contributed significantly to the problem of macrocyclic lactone (ML) resistance in New Zealand. Farmers now have few options for effectively controlling cattle gastrointestinal nematodes (GINs) and regularly experience sub-optimal efficacy against economically important species. We present a novel fixed-dose combination injectable (FDCI) that simultaneously delivers 0.2 mg/kg doramectin and 6 mg/kg levamisole hydrochloride (HCl) to target a broad spectrum of cattle GINs in a single dose, providing an additional solution to endoparasite control in an environment of anthelmintic resistance. A dose confirmation study was conducted using naturally acquired infections of GINs in beef cattle in New Zealand. Cattle with GIN infections confirmed by fecal egg count (FEC) were randomly allocated (n = 12 per group) to the control (saline-treated), FDCI-treated or doramectin-treated group. On Day 0, cattle were weighed and administered a single subcutaneous injection of saline or endectocide. Rectal fecal samples were collected from each animal on Day 7 for individual duplicate fecal egg count (FEC) analysis, and coprocultures were conducted on pooled fecal samples within each treatment group. All animals were euthanized and necropsied for worm recovery on Days 14 through 16. Treatment efficacy was calculated based on reduction in FECs and worm burdens. All enrolled cattle were positive for GINs based on Day -5 FECs, with geometric mean (GM) FECs ranging from 337 to 521 eggs per gram (EPG). All saline-treated cattle remained positive for GIN infections for the study duration (Day 7 GM FEC = 427 EPG). Necropsy and worm recoveries revealed the presence of doramectin-resistant Cooperia oncophora, C. surnabada and Trichostrongylus longispicularis, as evidenced by ≤ 72.3 % efficacy of doramectin against these species. The new FDCI was ≥ 99.8 % effective against all GIN species, including ML-resistant C. oncophora, C. surnabada and T. longispicularis, providing broad-spectrum efficacy and eliminating economically important cattle GINs, including ML-resistant populations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Andrew A. DeRosa reports a relationship with Zoetis Inc that includes: employment. Raj Packianathan reports a relationship with Zoetis Australia Pty Limited that includes: employment. Andrew Hodge reports a relationship with Zoetis Australia Pty Limited that includes: employment. Jacqueline Wright reports a relationship with Zoetis Australia Pty Limited that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Australian producers have long used macrocyclic lactones (MLs) to successfully control cattle gastrointestinal nematodes (GINs) and consequently improve production parameters. However, the trajectory of ML resistance development in cattle GINs is following that of small ruminant nematode populations, highlighting a need for novel treatment options to provide efficacy in the current environment and interrupt the long-term establishment of ML-resistant GIN populations in Australian cattle. Here, we describe three field studies conducted in Australia to evaluate the efficacy of a single administration of a novel fixed-dose combination injectable (FDCI) endectocide against naturally acquired infections of cattle GINs. The FDCI is administered subcutaneously to deliver 0.2 mg/kg doramectin and 6 mg/kg levamisole hydrochloride (HCl). Study sites consisted of three farms in New South Wales (n = 2) and Victoria (n = 1). At each site, cattle were randomly allocated into one of three treatment groups: (1) untreated control (saline), (2) FDCI (0.2 mg/kg doramectin, 6 mg/kg levamisole HCl) or (3) positive control (0.2 mg/kg ivermectin). All treatments were administered on Day 0. Fecal samples were collected prior to treatment on Days -1 (Study 3) or 0 (Studies 1 and 2) and again on Day 14 (post-treatment) to evaluate efficacy via fecal egg count (FEC) and for coproculture. Adequacy of infection was confirmed at all three study sites, with Day 14 geometric mean (GM) FECs for saline-treated cattle ranging from 32.5 eggs per gram (EPG) to 623.7 EPG. FECs for FDCI-treated cattle were significantly reduced compared to saline-treated cattle (p ≤ 0.0001) on Day 14, with GM-based efficacy ≥ 99.7% at all three study sites. In contrast, ivermectin was 97.4% effective against cattle GINs in Study 1 but was only 47.2% and 39.8% effective at study site 2 and 3, respectively. Genus-specific efficacies suggest the presence of ivermectin-resistant Cooperia spp. (Study 1), Haemonchus spp. (Study 2) and Ostertagia spp. (Study 3) populations in the naturally infected cattle used in these studies. The post-treatment FEC and genus-specific efficacy estimations indicate the doramectin + levamisole HCl FDCI was highly efficacious against cattle GINs even in the face of ivermectin LOE at study sites 2 and 3. The efficacy of the new FDCI against both ML-susceptible and ML-resistant economically important cattle GINs in Australia affirms it is a valuable treatment option for producers operating in an environment of ML loss of efficacy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew A. DeRosa reports a relationship with Zoetis Inc that includes: employment. Raj Packianathan reports a relationship with Zoetis Australia Pty Limited that includes: employment. Andrew Hodge reports a relationship with Zoetis Australia Pty Limited that includes: employment. Jacqueline Wright reports a relationship with Zoetis Australia Pty Limited that includes: employment. Michael Pearce reports a relationship with Zoetis Australia Pty Limited that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

We describe a new fixed-dose combination injectable (FDCI) formulated with doramectin and levamisole hydrochloride (HCl) to target broad and overlapping spectra of gastrointestinal nematodes (GINs) through two distinct modes of action. Here, we demonstrate the superior efficacy of the FDCI against mixed populations of cattle GINs in two dose confirmation studies conducted in Australia using artificially induced adult (Study 1) and immature (Study 2) GIN infections. Artificial infections consisted of Cooperia spp., Haemonchus placei, Ostertagia ostertagi, and Trichostrongylus axei. In both studies, cattle were inoculated with third-stage larvae and infections were confirmed by fecal egg count (FEC). Treatment groups in both studies were as follows: (1) negative control (saline, 0.9% sodium chloride), (2) positive control injectable endectocide (Study 1-0.2 mg/kg ivermectin; Study 2-0.2 mg/kg doramectin), (3) positive control injectable anthelmintic (7.5 mg/kg levamisole HCl), and (4) FDCI (0.2 mg/kg doramectin + 6.0 mg/kg levamisole HCl). Cattle were treated either 28 days (Study 1) or 6 days (Study 2) post-infection. On Days 14-16 (Study 1) or Days 20-21 (Study 2) post-treatment, cattle were euthanized and necropsied for the recovery, identification, and enumeration of worms. Treatment efficacy was calculated as reduction in worm burdens of treated cattle compared to saline-treated cattle, and treatments were considered effective if the geometric mean worm burden in the treatment group was reduced by ≥ 95% compared to the negative control group. In both studies, saline-treated cattle remained positive for GIN infections for the study duration. Ivermectin was less than 95% effective against Cooperia spp. (80.2%) and H. placei (24.8%) in Study 1, and levamisole HCl was less than 95% effective against Ostertagia spp. (47.1%) in Study 2. In contrast, the novel FDCI was 100% effective in treating adult and immature life stages of all cattle GINs included in the artificial infections, with no worms recovered at necropsy from doramectin + levamisole HCl-treated cattle. These data show a single administration of the FDCI provides broad-spectrum treatment of economically important cattle GINs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew A. DeRosa reports a relationship with Zoetis Inc that includes: employment. Raj Packianathan reports a relationship with Zoetis Australia Pty Limited that includes: employment. Andrew Hodge reports a relationship with Zoetis Australia Pty Limited that includes: employment. Jacqueline Wright reports a relationship with Zoetis Australia Pty Limited that includes: employment. Andrew Pearce reports a relationship with Zoetis Australia Pty Limited that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic placed the UK healthcare system under unprecedented pressure, and recovery will require whole-system investment in innovative, flexible and pragmatic solutions. Positioned at the heart of the healthcare system, ambulance services have been tasked with addressing avoidable hospital conveyance and reducing unnecessary emergency department and hospital attendances through the delivery of care closer to home. Having begun to implement models of care intended to increase 'see and treat' opportunities through greater numbers of senior clinical decision makers, emphasis has now been placed upon the use of remote clinical diagnostic tools and near-patient or point-of-care testing (POCT) to aid clinical decision making. In terms of POCT of blood samples obtained from patients in the pre-hospital setting, there is a paucity of evidence beyond its utility for measuring lactate and troponin in acute presentations such as sepsis, trauma and myocardial infarction, although potential exists for the analysis of a much wider panel of analytes beyond these isolated biomarkers. In addition, there is a relative dearth of evidence in respect of the practicalities of using POCT analysers in the pre-hospital setting. This single-site feasibility study aims to understand whether it is practical to use POCT for the analysis of patients' blood samples in the urgent and emergency care pre-hospital setting, through descriptive data of POCT application and through qualitative focus group interviews of advanced practitioners (specialist paramedics) to inform the feasibility and design of a larger study. The primary outcome measure is focus group data measuring the experiences and perceived self-reported impact by specialist paramedics. Secondary outcome measures are number and type of cartridges used, number of successful and unsuccessful attempts in using the POCT analyser, length of time on scene, specialist paramedic recruitment and retention, number of patients who receive POCT, descriptive data of safe conveyance, patient demographics and presentations where POCT is applied and data quality. The study results will inform the design of a main trial if indicated., Competing Interests: RP is a previous editorial board member of the BPJ., (© 2023 The Author(s).)

There has been a reemergence of research into the use of substances such as LSD, MDMA, and psilocybin for the treatment of psychiatric disorders. This increase in consideration toward the medicinal use of these compounds has been termed the "Psychedelic Renaissance." This article specifically explores the background of psilocybin, a psychoactive compound that is naturally derived from certain species of fungi. Pubmed was searched by one doctoral-level researcher using specific Boolean operator terms. The results were filtered by title and abstract and 76 articles were screened and analyzed in full detail. Oral psilocybin is showing itself to be clinically efficacious by producing statistically significant reductions in depression and anxiety symptoms over time versus control in multiple clinical trials. It has also been shown to reduce cigarettes per day and drinks per day in patients with substance use disorders. Thus far, there have been no significant adverse clinical events from psilocybin and there also have been no verifiable recorded deaths reported. Larger studies need to be performed before the drug can potentially become approved for use in the general population.

Introduction: Ambulance services play a key role in the recognition and care of patients nearing their end of life, yet are expected to recognise and manage these complex presentations often with limited education. Paramedics operate across large geographical areas, meaning education delivery is challenging. Yorkshire Ambulance Service implemented Project Extension for Community Healthcare Outcomes (ECHO), which is the creation of virtual communities of practice to address this problem and increase access to specialist supervision, education and sharing of practice. We undertook a service evaluation of the programme and interviewed paramedics about their experiences with ECHO., Methods: Semi-structured interviews were conducted with eight ambulance clinicians who took part in the end-of-life care (EoLC) ECHO programme. Thematic analysis and coding was undertaken to identify and develop the emerging themes., Results: This study identified three key themes: programme structure, factors influencing engagement and professional impact. The provision of a virtual community of practice through Project ECHO was a unique and highly valued experience, which was accessible and allowed for networking, peer support and sharing of practice. The concept of a ripple effect was reported in disseminating learning across the wider team., Conclusion: The development of virtual communities of practice as a novel educational intervention has the potential to transform clinical supervision and ongoing education for ambulance clinicians who are often isolated by the nature of ambulance services that cover large regions., Competing Interests: None declared., (© 2022 The Author(s).)

Introduction: One-fifth of emergency department presentations by ambulance are due to acute-on-chronic breathlessness. We explored the feasibility of an evaluation-phase, cluster randomised controlled trial (cRCT) of the effectiveness and cost-effectiveness of a paramedic-administered, non-pharmacological breathlessness intervention for people with acute-on-chronic breathlessness at ambulance call-out (BREATHE) regarding breathlessness intensity and conveyance to hospital., Methods: This mixed-methods, feasibility cRCT (ISRCTN80330546) randomised paramedics to usual care or intervention plus usual care. Retrospective patient consent to use call-out data (primary end-point) and prospective patient/carer consent for follow-up was sought. Potential primary outcomes included breathlessness intensity (numerical rating scale) and conveyance. Follow-up included: interviews with patients/carers and questionnaires at 14 days, 1 and 6 months; paramedic focus groups and surveys., Results: Recruitment was during COVID-19, with high demands on paramedics and fewer call-outs by eligible patients. We enrolled 29 paramedics; nine withdrew. Randomisation/trial procedures were acceptable. Paramedics recruited 13 patients, not meeting recruitment target (n=36); eight patients and three carers were followed-up. Data quality was good but insufficient for future sample size estimation. The intervention did not extend call-out time, was delivered with fidelity and was acceptable to patients, carers and paramedics. There were no repeat call-outs within 48 h. All trained paramedics strongly recommended BREATHE as a highly relevant, simple intervention., Conclusion: Patient recruitment to target was not feasible during the pandemic. Training and intervention were acceptable and delivered with fidelity. Results include valuable information on recruitment, consent, attrition and data collection that will inform the design and delivery of a definitive trial., Competing Interests: Conflict of interest: A. Hutchinson reports grants from NIHR during the conduct of the study. Conflict of interest: V. Allgar reports grants from NIHR during the conduct of the study. Conflict of interest: J. Cohen reports grants from NIHR during the conduct of the study. Conflict of interest: D.C. Currow reports the following. Helsinn Pharmaceuticals: advisory board member; Mayne Pharma: paid consultant and received payment for intellectual property. Conflict of interest: S. Griffin reports grants from NIHR during the conduct of the study. Conflict of interest: S. Hart reports grants from NIHR during the conduct of the study; and personal fees from Trevi Therapeutics, and personal fees and nonfinancial support from Chiesi and Boehringer Ingelheim, outside the submitted work. He is an associate editor of this journal. Conflict of interest: K. Hird reports grants from NIHR, during the conduct of the study. Conflict of interest: A. Hodge reports grants from NIHR during the conduct of the study. Conflict of interest: S. Mason reports grants from NIHR during the conduct of the study. Conflict of interest: M. Northgraves reports grants from NIHR during the conduct of the study. Conflict of interest: J. Reeve reports grants from NIHR outside the submitted work. Conflict of interest: F. Swan reports grants from NIHR during the conduct of the study. Conflict of interest: M.J. Johnson reports grants from NIHR during the conduct of the study., (Copyright ©The authors 2022.)

Canine parvovirus type 2 (CPV-2) remains one of the most significant viral pathogens in dogs in Australia and worldwide despite the availability of safe and effective CPV vaccines. At least three different variants of CPV-2 have emerged and spread all around the world, namely CPV-2a, CPV-2b, and CPV-2c. The ability of the current vaccines containing either original CPV-2 type or CPV-2b variant to cross protect the heterologous variants has been well demonstrated in laboratory studies, despite some concerns regarding the vaccine efficacy against the emerging variants. Vanguard ® , a series of multivalent vaccines, has been in the market for a considerable period of time and demonstrated to provide efficacy against all three types of CPV variants CPV-2a, CPV-2b, and CPV-2c. The purpose of this study was to evaluate the ability of the recently registered Vanguard C4 vaccine to induce cross-neutralizing antibodies against the Australian isolates of CPV-2a, CPV-2b, and CPV-2c variants. Blood samples collected from dogs vaccinated with Vanguard C4 were analyzed by virus neutralizing assays developed for each of three CPV variants. The results of the study demonstrated that Vanguard vaccine induced cross-neutralizing antibodies against the Australian isolates of CPV-2a, CPV-2b, and CPV-2c, thus offering cross protection against all three Australian CPV variants.

Introduction: NHS ambulance service non-conveyance rates in the United Kingdom are around 30%, despite an increase in non-emergency cases and a national policy of integrating urgent and emergency care to provide patients with the 'right care, in the right place, at the right time'. Emergency department overcrowding is a significant issue for patients, resulting in poorer quality of care, increased healthcare costs and potentially, increased mortality. It also contributes to increased ambulance turnaround times. Yorkshire Ambulance Service NHS Trust (YAS) introduced a specialist paramedic (SP) to improve the management of lower acuity cases, but non-conveyance rates in this group have not been as high as expected.In 2018, Health Education England funded a pilot scheme to rotate paramedics into a range of healthcare settings and in YAS, 10 SPs undertook a 10-week placement in a GP practice. This study aimed to evaluate whether a primary care placement appropriately increased the level and trend of non-conveyance decisions made by SPs following a 10-week GP placement, in a cost-effective manner., Methods: We conducted a controlled interrupted time series analysis using data from incidents between 1 June 2017 and 31 December 2019, to study appropriate non-conveyance rates before and after a GP placement. A costing analysis, examining the average cost per appropriate non-conveyance achieved for patients receiving care from intervention group SPs pre- and post-placement, was also conducted., Results: A total of 7349 incidents attended by intervention group SPs were eligible for inclusion. Following removal of cases with missing data, 5537 (75.3%) cases remained. Post-placement, the intervention group demonstrated an increase in appropriate non-conveyance rate of 35.0% (95% CI 23.8%-46.2%), and a reduction in the trend of appropriate non-conveyance of -1.2% (95% CI -2.8%-0.5%), relative to the control group.Post-placement, the cost per appropriate non-conveyance for intervention group SPs was a mean of £509.41 (95% bootstrapped CI £454.92-£564.26) versus £1257.81 (95% bootstrapped CI £1233.42-£1283.95) for the same group in the pre-placement phase., Conclusion: In this single UK NHS ambulance service study, we found a clinically important and statistically significant increase in appropriate non-conveyance rates by SPs who had completed a 10-week GP placement. This improvement persisted for the 12-month period following the placement and demonstrated cost savings compared to usual care., (© 2022 The Author(s).)

Chronic breathlessness, persistent and disabling despite optimal treatment of underlying causes, is a prevalent and frightening symptom and is associated with many emergency presentations and admission to hospital. Breathlessness management techniques used by paramedics may reduce the need for conveyance to hospital. The Breathlessness RElief AT HomE study (BREATHE) aims to explore the feasibility of conducting a definitive cluster randomised controlled trial (cRCT) for people with acute-on-chronic breathlessness who have called an ambulance, to evaluate the effectiveness and cost-effectiveness of a paramedic-administered non-pharmacological breathlessness intervention. The trial is a mixed-methods feasibility cRCT. Eight paramedics will be randomised 1:1 to deliver either the BREATHE intervention in addition to usual care or usual care alone at call-outs for acute-on-chronic breathlessness. Sixty participants will be recruited to provide access to routine data relating to the index call-out with optional follow-up questionnaires at 14 days, 1 month and 6 months. An in-depth interview will be conducted with a subgroup. Feasibility outcomes relating to recruitment, data quality (especially candidate primary outcomes), and intervention acceptability and fidelity will be collected as well as providing data to estimate a sample size for a definitive trial. Yorkshire and The Humber-Sheffield Research Ethics Committee approved the trial protocol (19/YH/0314). The study results will inform progression to, or not, and design of a main trial according to predetermined stop-go criteria. Findings will be disseminated to relevant stakeholders and submitted for publication in a peer-reviewed journal., Competing Interests: Conflict of interest: M. Northgraves has nothing to disclose. Conflict of interest: J. Cohen reports grants from the NIHR during the conduct of the study. Conflict of interest: V. Allgar has nothing to disclose. Conflict of interest: D. Currow reports he is an unpaid advisory board member for Helsinn Pharmaceuticals. He is a paid consultant and receives payment for intellectual property with Mayne Pharma and is a consultant with Specialised Therapeutics Australia Pty. Ltd. Conflict of interest: S. Hart reports personal fees and nonfinancial support from Chiesi UK; and grants, personal fees and nonfinancial support from Boehringer Ingelheim, all outside the submitted work. Conflict of interest: K. Hird has nothing to disclose. Conflict of interest: A. Hodge has nothing to disclose. Conflict of interest: M. Johnson has nothing to disclose. Conflict of interest: S. Mason has nothing to disclose. Conflict of interest: F. Swan has nothing to disclose. Conflict of interest: A. Hutchinson has nothing to disclose., (Copyright ©The authors 2021.)

Background: Anecdotal experience demonstrates the existence of patients with superiorly located carotid stenosis, neoplasms, or aneurysms where the mandible obstructs effective surgical access using standard techniques. As carotid pathology extends anatomically beyond the limits of standard operative technique, additional exposure becomes paramount to safely and effectively address the lesion. Double mandibular osteotomy (DMO) is one of several techniques to obtain additional exposure to high-carotid pathology; however, there is no large series to address the outcomes of patients undergoing this procedure., Methods: A retrospective case series was performed for all patients undergoing surgery for carotid pathology from 2011-2019 that could not be approached with standard cervical incision. The primary predictor variable was high-anatomic carotid pathology necessitating DMO. The primary outcome variable was early and late complications sustained by patients., Results: Fifteen patients met study criteria and underwent 16 DMOs to access high-carotid pathology including carotid stenosis (n = 8 patients), carotid aneurysm (n = 2 patients), and carotid body tumor (n = 8 patients). Two patients had dual ipsilateral pathology with one patient having both carotid artery stenosis and aneurysm, and the other patient diagnosed with carotid artery stenosis and carotid body tumor. One patient had bilateral carotid artery stenosis, each requiring high anatomic exposure for treatment. Early complications occurred in 8 patients. Five patients experienced significant dysphagia requiring enteral feeding, and 2 patients developed malocclusion directly related to the double mandibular osteotomy. One patient experienced contralateral cortical watershed infarcts. Late complications included one patient developing osteomyelitis of the mandible, and this patient also developed distal mandibular segment screw exposure. The comparison of the outcome groups for categorical predictor variables using Fisher's exact test detected no statistically significant differences for gender, hypertension, hyperlipidemia, type 2 diabetes, chronic obstructive pulmonary disease, tobacco use, chronic kidney disease, or cerebrovascular disease. For the continuous variable comparisons, independent-samples t-tests detected no difference between the complication groups for age, operative time, or years of follow-up. No significant differences were found between the groups for body mass index or intraoperative blood loss., Conclusions: The double mandibular osteotomy provides excellent exposure and surgical access to the distal internal carotid artery for repair of vascular pathology with acceptable outcomes and long-term complications compared with previously reported techniques. Because of the early complications realized with the DMO, we recommend the procedure for symptomatic patients with a high risk of failing medical therapy alone and not appropriate for endovascular treatment as well as those patients with tumors requiring surgical intervention., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™) and afoxolaner + milbemycin (NexGard Spectra ® ) was evaluated against an artificial infestation of I. holocyclus., Methods: Twenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days - 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal ® (control group), Simparica Trio™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra ® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means., Results: Against an existing infestation, efficacy of both Simparica Trio™ and NexGard Spectra ® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio™ and NexGard Spectra ® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio™ and NexGard Spectra ® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study., Conclusions: Single doses of Simparica Trio™ and NexGard Spectra ® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days.

Background: Haemaphysalis longicornis is the major tick affecting dogs in most of the East Asia/Pacific region and has recently been detected in a number of areas of the USA. This tick is a vector for a number of pathogens of dogs, other mammals and humans. In this study, the efficacy of a single oral administration of sarolaner (Simparica ® , Zoetis) at the minimum label dosage (2 mg/kg) was evaluated against an existing infestation of H. longicornis and subsequent weekly reinfestations for 5 weeks after treatment., Methods: Sixteen dogs were ranked on pretreatment tick counts and randomly allocated to treatment on Day 0 with sarolaner at 2 mg/kg or a placebo. The dogs were infested with H. longicornis nymphs on Days - 2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 hours after treatment and subsequent re-infestations based on live tick counts relative to placebo-treated dogs., Results: There were no adverse reactions to treatment. A single dose of sarolaner provided 100% efficacy on Days 2, 7, 14 and 21; and ≥ 97.4% efficacy on Days 28 and 35. Considering only attached, live ticks, efficacy was 100% for the entire 35 days of the study. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (11.62 ≤ t (df)  ≤ 59.99, where 13.0 ≤ df ≤ 14.1, P < 0.0001)., Conclusions: In this study, a single oral administration of sarolaner at 2 mg/kg provided 100% efficacy against an existing infestation of H. longicornis nymphs and ≥ 97.4% efficacy (100% against attached ticks) against weekly reinfestation for at least 35 days after treatment.

Background: The efficacy and safety of a novel isoxazoline compound, sarolaner (Simparica ® , Zoetis) and spinosad (Comfortis ® , Elanco) as a positive control were evaluated for the treatment and control of natural flea infestations on dogs in two randomised, blinded, multi-centric clinical trials conducted in 11 veterinary clinics in northeastern and southeastern states of Australia., Methods: A total of 162 client-owned dogs (80 in northern study and 82 in southern study) from 105 households were enrolled. Each household was randomly allocated to receive either sarolaner (Simparica ® , Zoetis) or spinosad (Comfortis ® , Elanco). Dogs were dosed on Days 0, 30 and 60 and physical examinations and flea counts were conducted on Days 0, 14, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0., Results: In the northern study, at enrolment, primary dogs had flea counts ranging from 5 to 772. At the first efficacy assessment on Day 14, sarolaner resulted in 99.3% mean reduction in live flea counts relative to Day 0, compared to 94.6% in the spinosad group. On Day 30, the sarolaner-treated group had mean efficacy of 99.2% compared to 95.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.8%. In the southern study, at enrolment, primary dogs had flea counts ranging from 5 to 156. Both sarolaner and spinosad resulted in ≥ 96.7% mean reduction in live flea counts on Day 14. On Day 30, the sarolaner-treated group had mean efficacy of 99.5% compared to 89.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.6%. No treatment-related adverse events were observed in either study., Conclusions: A single monthly dose of sarolaner (Simparica ® ) administered orally at 2-4 mg/kg for three consecutive months was well tolerated and provided excellent efficacy against natural infestations of fleas under a range of Australian field conditions including different climatic and housing conditions. Similar efficacy was observed with spinosad (Comfortis ® ) after the second and third monthly treatments.

Background: The Australian paralysis tick, Ixodes holocyclus, causes paralysis predominantly in dogs and cats in the Eastern coastal regions of Australia. Rapid onset of effect of a parasiticide is critical to minimize the deleterious effects of these tick infestations, especially tick paralysis caused by the salivary neurotoxin. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica ® ), against I. holocyclus on dogs was evaluated and compared with afoxolaner (NexGard ® ) for 5 weeks after a single oral dose., Methods: Twenty-four (24) dogs were randomly allocated to treatment with either placebo, sarolaner (label dose of 2 to 4 mg/kg as per dosing table), or afoxolaner (label dose of 2.7 to 6.9 mg/kg) based on pre-treatment body weights. Following artificial infestation on Day -1, dogs were examined and live ticks counted at 8, 12, 24 and 48 h after treatment on Day 0, and at 12, 24 and 48 h after subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs based on geometric means., Results: At 8 and 12 h time points on Day 0, sarolaner-treated dogs had significantly lower geometric mean tick counts compared to the dogs treated with afoxolaner (P ≤ 0.0303). Efficacy of sarolaner against an existing infestation was 86.2 and 96.9% compared with that of afoxolaner which had efficacy of 21.3 and 85.0% at 8 and 12 h time points, respectively. Against subsequent weekly re-infestations at 12 h time points, treatment with sarolaner resulted in significantly lower geometric mean tick counts than afoxolaner-treated dogs on all days (P ≤ 0.0077) with the efficacy ranging from 60.2 to 92.2%, compared to 5.8 to 61.0% in the afoxolaner-treated dogs. Against subsequent weekly re-infestations at the 24 h time points on Days 22 and 36, efficacy of sarolaner was significantly higher at 99.2 and 97.9%, respectively, compared with afoxolaner which had efficacy of 92.4 and 91.9% (P ≤ 0.0356). At the 48 h time points following each of the five weekly re-infestations, the mean efficacy results of sarolaner and afoxolaner treated dogs were similar on most occasions. There were no adverse reactions to treatments., Conclusions: In this controlled laboratory evaluation, a single dose of sarolaner had a significantly faster speed of kill against an existing infestation of I. holocyclus, than afoxolaner at 8 and 12 h post-treatment. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and following weekly re-infestations over 35 days suggests this treatment will provide highly effective, rapid and reliable control of ticks over the entire treatment interval, thereby minimizing the risk of tick paralysis in dogs.

Growing evidence suggests that early life investments in health are associated with improved human capital and economic outcomes. Various recent global studies have simulated the expected economic returns from alternative packages of interventions in reproductive, maternal, newborn and child health (RMNCH). However, very little is known about the comparability of estimates of the economic returns of RMNCH interventions across studies in low and middle income countries. Our study aims to fill this gap. We performed a comprehensive scoping review of the recent literature (2000-2013) on the economic returns (i.e. benefit-cost ratios) of RMNCH-related interventions, conducted in low and middle income countries. A total of 36 studies were identified. They were read in full and information was abstracted on both the estimates of benefit-cost ratios, the methodological approach and assumptions used. The estimated economic returns fluctuated considerably across settings as the associated costs of disease patterns, social behaviours and health systems varied. Yet, greater sources of variation stemmed from differences in methodology. The observed methodological inconsistencies limit the accuracy and comparability of the estimated returns across various contexts. The reviewed studies suggest that the benefit-cost ratios are favourable in the majority of cases, providing further support to a growing body of economic literature that suggests investments early in life, such as those interventions related to RMNCH, are good investments. Beyond advocacy purposes, for the reviewed literature to be used by policymakers to inform their decisions on investments, a consistent methodological approach should be adopted., (© The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Many priority countries in the countdown to the millennium development goals deadline are lagging in progress towards maternal and child health (MCH) targets. Papua New Guinea (PNG) is one such country beset by challenges of geographical inaccessibility, inequity and health system weakness. Several countries, however, have made progress through focused initiatives which align with the burden of disease and overcome specific inequities. This study identifies the potential impact on maternal and child mortality through increased coverage of prioritised interventions within the PNG health system., Methods: The burden of disease and health system environment of PNG was documented to inform prioritised MCH interventions at community, outreach, and clinical levels. Potential reductions in maternal and child mortality through increased intervention coverage to close the geographical equity gap were estimated with the lives saved tool., Results: A set community-level interventions, with highest feasibility, would yield significant reductions in newborn and child mortality. Adding the outreach group delivers gains for maternal mortality, particularly through family planning. The clinical services group of interventions demands greater investment but are essential to reach MCH targets. Cumulatively, the increased coverage is estimated to reduce the rates of under-five mortality by 19 %, neonatal mortality by 26 %, maternal mortality ratio by 10 % and maternal mortality by 33 %., Conclusions: Modest investments in health systems focused on disadvantaged populations can accelerate progress in maternal and child survival even in fragile health systems like PNG. The critical approach may be to target interventions and implementation appropriately to the sensitive context of lagging countries.

While established that geographical inaccessibility is a key barrier to the utilisation of health services, it remains unknown whether disparities are driven only by limited access to these services, or are also attributable to health behaviour. Significant disparities exist in health outcomes and the coverage of many critical health services between the mountains region of Nepal and the rest of the country, yet the principal factors driving these regional disparities are not well understood. Using national representative data from the 2011 Nepal Demographic and Health Survey, we examine the extent to which observable factors explain the overall differences in the utilisation of maternal health services. We apply nonlinear Blinder-Oaxaca-type decomposition methods to quantify the effect that differences in measurable characteristics have on the regional coverage gap in facility-based delivery. The mean coverage of facility-based deliveries was 18.6 and 36.3 % in the mountains region and the rest of Nepal, respectively. Between 54.8 and 74.1 % of the regional coverage gap was explained by differences in observed characteristics. Factors influencing health behaviours (proxied by mothers' education, TV viewership and tobacco use, and household wealth) and subjective distance to the health facility were the major factors, contributing between 52.9 and 62.5 % of the disparity. Mothers' birth history was also noteworthy. Policies simultaneously addressing access and health behaviours appear necessary to achieve greater coverage and better health outcomes for women and children in isolated areas.

Results from worm egg counts (WECs) of cattle from across Australia over an 11 year period have been analysed to provide contemporary data on WEC and worm genus distribution in Australian cattle. A sampling kit consisted of ten sample containers. Faecal samples were collected into each sampling kit from groups of cattle and WEC and larval cultures were conducted using standard procedures. A submission form was completed for each kit with data requested including date of sampling, property address, age, average estimated weight and production type of cattle, last drench used and date of drenching. Regional analysis was done by postcode region and postcode regions were grouped into bioclimatic regions. A total of 5069 submissions were received from 2002 to the end of 2012 representing over 50,000 individual faecal samples. Seventy-seven percent of cattle sampled were no more than 2 years of age with the remainder representing a range of age groups. Samples were collected from all of the significant cattle producing regions of Australia. There was a tendency for higher geometric mean WEC in cattle in northern Australia and in high rainfall areas along the east coast of Australia. Geometric mean WEC for bioclimatic regions varied seasonally with a peak in autumn in regions with summer dominant rainfall, but little seasonal variation in regions with winter dominant rainfall patterns. Worm genera cultured varied throughout Australia with Cooperia spp. being most prevalent across the country, followed by Haemonchus spp. and Oesophagostomum spp. in summer rainfall dominant regions and Ostertagia spp. and Trichostrongylus spp. in winter rainfall regions. In the coastal, tablelands, and temperate rangelands regions of NSW, Haemonchus spp. were as prevalent as Cooperia spp. during autumn months and levels of Haemonchus spp. found in south-western Western Australia were higher than previously documented. These data provide an up-to-date summary of internal parasites in Australian cattle. Regional differences in WEC between northern and southern Australia are evident and should be further explored. These data suggest that there has been a move to Cooperia spp. being the predominant worm genus in Australian cattle, with increasing levels of Haemonchus spp. being evident in southern temperate regions of Australia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Significant disparities in reproductive, maternal, newborn, and child health (RMNCH) outcomes and intervention coverage exist between the Mountains and other ecoregions of Nepal. Delivery of essential health services to remote mountainous areas is challenging and access is a known barrier to utilization. However, the contribution of demand-side barriers is poorly understood. Consequently, policies and programs cannot strategically target constraints to increase coverage. This systematic review identifies demand-side barriers to utilization of RMNCH services in the Mountain districts of Nepal. Research was drawn from MEDLINE, Web of Science, Scopus, Google Scholar, Eldis, and unpublished literature. Beyond inaccessibility, utilization is undermined by costs of care-seeking, traditional attitudes and practices, low status of women, limited health knowledge, dissatisfaction with service quality, and low and inequitable care by community health workers. The intensity and repercussions of these barriers are of greater magnitude in the Mountains where delayed care-seeking combines with long distances for critical health consequences.

The objective of the present studies was to evaluate the efficacy of a combined formulation (Startect(®) Dual Active Oral Solution for Sheep, Pfizer Animal Health) of derquantel (DQL) and abamectin (ABA) for the treatment of: (1) sheep experimentally infected with a moxidectin (MOX)-resistant isolate of Teladorsagia circumcincta, and (2) multi-drug resistant gastrointestinal nematode parasites under UK field conditions. In the first study, a total of 40 animals were allocated into 4 treatment groups, and were either left untreated or treated with DQL+ABA, MOX or ABA. Faecal samples were collected on days 1-5 and on day 7 after treatment to examine the reduction in faecal egg excretion and to evaluate the egg viability. On day 14 post treatment all animals were euthanised for abomasal worm counts. There was a 100% reduction in geometric mean worm counts for the DQL+ABA treated animals compared to the untreated control animals (P<0.0001), whereas the percentage reduction in worm counts for the MOX- (P>0.05) and ABA-treated (P=0.0004) animals was 12.4% and 71.8%, respectively. The data from the egg hatch assay (EHA) indicated that in the MOX-treated and the ABA-treated animals, the majority of the eggs hatched after treatment. In the field study, performed on four farms, animals were allocated into 6 groups of 11-15 animals each in order to conduct a faecal egg count reduction test (FECRT), based on arithmetic mean egg counts. One group of animals remained untreated, whereas the other animals were treated with DQL+ABA, MOX, fenbendazole (FBZ), levamisole (LV) or ivermectin (IVM). On each of the farms the reduction in egg excretion after treatment with FBZ, LV or IVM was below 95.0%, indicating anthelmintic resistance. The efficacy of DQL+ABA ranged from 99.1 to 100%, yielding significantly lower egg counts compared to the untreated control group (P ≤ 0.003). For MOX the egg counts were significantly (P ≤ 0.003) lower compared to the untreated group at each farm, with reductions varying from 98.2 to 100%. The post-treatment copro-cultures for larva identification indicated that T. circumcincta was the most abundant worm species after treatment (52-99% of the larvae). The results of these studies confirm the high efficacy of the DQL+ABA combination formulation against anthelmintic resistant nematodes in the UK., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(®)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal and respiratory nematode parasites of sheep, as follows: ≥ 98.9% efficacy against Haemonchus contortus (adult and L4); Teladorsagia circumcincta (adult, L4 and hypobiotic L4); Teladorsagia trifurcata (L4); Trichostrongylus axei (adult and L4); Trichostrongylus colubriformis (adult and L4); Trichostrongylus falculatus (adult); Trichostrongylus rugatus (adult); Trichostrongylus vitrinus (adult and L4); Cooperia curticei (adult and L4); Cooperia oncophora (adult and L4); Nematodirus spathiger (adult); Nematodirus battus (adult); Nematodirus spp. (hypobiotic L4); Strongyloides papillosus (adult); Strongyloides spp. (L4); Chabertia ovina (adult); Oesophagostomum venulosum (adult); Dictyocaulus filaria (adult); and Protostrongylus rufescens (adult); ≥ 97.0% efficacy against Trichuris ovis (adult); and ≥ 95.9% efficacy against T. trifurcata (adult). Derquantel-abamectin is a highly effective combination anthelmintic, which will provide an important new tool for controlling helminths of sheep when used in conjunction with sustainable drenching practices., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective and Design: Tumor necrosis factor alpha (TNF-α) has been implicated in the pathogenesis of cardiovascular disease and sepsis-associated cardiac dysfunction. Although initially described solely as a lipopolysaccharide (LPS)-induced macrophage product, evidence exists that cardiac myocytes themselves produce substantial amounts of TNF-α in response to ischemia as well as LPS. The use of phosphodiesterase inhibitors has been shown to decrease LPS-induced TNF-α elaboration. The aim of the present study was to determine the effect of diazepam (Type IV phosphodiesterase inhibitor) on (1) myocardial function and (2) coronary vascular flow after LPS-induced endotoxic shock in an isolated rat heart model., Materials and Methods: Endotoxemia was induced by intraperitoneal LPS administration in adult male Wistar rats. Hearts were isolated after 6 h and perfused in a working mode with oxygenated Krebs-Henseleit buffer at 37°C. Diazepam was mixed with Krebs-Henseleit buffer and administered (3.0 μg/ml) for 20 min., Results: LPS-treated hearts showed depressed cardiac function and reduced coronary flow. Myocardial functional parameters (LVDP, +dP/dt, -dP/dt, RPP) and coronary flow (ml/min) were significantly (p < 0.01) improved by diazepam administration., Conclusions: These findings suggest that diazepam can salvage myocardial function and undo coronary vascular constriction in the endotoxemic rat heart. These findings are clinically relevant to the treatment of cardiovascular depression caused by endotoxic shock.

Background and Aims of the Study: Implanted non-crosslinked tissues suffer rapid degeneration, shrinkage and absorption, whereas standard crosslinked tissues cause local cytotoxicity and calcification. Both approaches diminish implant capacity for long-term function. The study aim was to examine the tissue-engineered characteristics (cytotoxicity, calcification potential, biocompatibility) of bovine pericardium, crosslinked with a low concentration of glutaraldehyde (GA) followed by ADAPT anti-mineralization, following prolonged implantation in a subcutaneous rat model., Methods: Bovine pericardium was decellularized with Triton X-100, deoxycholate, IgePal CA-630, and nucleases. The resulting matrices were allocated to: group I (control, n=10), crosslinked in 0.2% polymeric GA; and group II (treatment, n=10), crosslinked in 0.05% monomeric GA + ADAPT. Cytotoxicity was determined by in vitro cell seeding with human fibroblasts, and quantified using an Alamar Blue assay. The matrices were then implanted in a subcutaneous rat model and retrieved after extended implantation times (26 and 52 weeks). This was followed by further histology, immunohistochemical staining, and measurement of calcium deposition., Results: Complete acellularity and biostability were significantly (p < 0.01) achieved in group II. Inflammatory responses were reduced and beneficial host cell infiltration with neocapillary formation was limited to group II. Fibroblast infiltration was significantly increased from six to 12 months' implantation time. Only group II tested positive for Factor VIII and vimentin. After 52 weeks, extractable calcium levels were significantly (p < 0.001) reduced in group II (2.56 +/- 0.22 microg Ca/mg tissue) compared to group I (136.02 +/- 0.39 microg Ca/mg tissue)., Conclusion: Acellular bovine pericardium, when crosslinked with a low concentration of GA and treated with ADAPT, retains and improves its integrity with a low immunoreactivity over a prolonged period. Host cell infiltration is also optimized over time. The maintenance of reduced calcification levels in group II suggests that such a biomaterial might have an advanced long-term in vivo potential.

Background and Aim of the Study: Matrix preparation remains controversial due to incomplete cell removal, inflammatory responses, reabsorption and thrombocyte activation. Previously, crosslinked matrices have been considered unsatisfactory due to cytotoxicity. In the present study, the biostability, biocompatibility and calcification potential of a decellularized matrix crosslinked with a low concentration of monomeric glutaraldehyde (GA) and treated with the ADAPT anti-calcification process were examined., Methods: Bovine pericardium was decellularized with Triton X-100, deoxycholate, IgePal CA-630 and ribonuclease. The resulting matrices were allocated to either group I (control, n = 5), crosslinked in 0.2% polymeric GA + ADAPT, or to group II (treatment, n = 5), crosslinked in 0.05% monomeric GA + ADAPT. The physical properties, enzymatic degradation, histology and immunohistochemical staining of the tissues were monitored. The matrices were also implanted in the jugular vein of juvenile sheep for 200 days., Results: Complete acellularity was achieved. Biostability was significantly (p <0.01) enhanced in group II, but inflammatory responses were limited in both groups. Host fibroblasts infiltrated the periphery in group I and the entire matrix in group II. The luminal surfaces were free from thrombotic depositions and covered with endothelial cells. Both groups tested positive for Factor VIII, smooth muscle alpha-actin and vimentin. Tissue extractable calcium levels were low (group I = 1.02 +/- 0.39, group II = 0.86 +/- 0.22 microg Ca/mg tissue)., Conclusion: Low-concentration GA-crosslinked matrices proved to be stable. The immunoreactivity of both groups was low, with host cell infiltration, migration and trans-differentiation being optimized in those grafts crosslinked with an ultra-low monomeric GA concentration. Calcification levels were close to zero in both groups. Enhanced crosslinking and effective anti-calcification produce a biomaterial with advanced in-vivo tissue-engineering properties.