A STUDY ON THE EFFECTIVENESS OF CLOMIPHENE CITRATE IN COMPARISON TO GNRH ANTAGONIST IN PREVENTING LH SURGE AMONG PATIENTS UNDERGOING OVULATION INDUCTION IN IVF-ICSI

Objective: To determine the efficacy of clomiphene citrate (CC) in preventing luteinizing hormone (LH) surge without adding gonadotropin releasing hormone (GnRH) antagonist or GnRH agonist in stimulated first fresh intracytoplasmic sperm injection cycle by evaluating the outcome of oocytes and embryo quality. Design: Retrospective cohort study. Settings: Fertility Clinic registry at Hospital University Kebangsaan Malaysia. Patients: A total of 235 fresh stimulated ICSI cycle for patients aged 18-40 years old using clomiphene citrate plus gonadotropin (n=117) and GnRH antagonist plus gonadotropin (n=118) were studied. Intervention: Comparing two different ovarian stimulation protocol. Main outcome measure(s): Social economical demographic, ovarian stimulation response and laboratory outcome. Fertilization rate as our primary outcome and our secondary outcome were oocyte retrieval rate, mature oocyte rate and top quality embryo rate. Result(s):There were no difference in the demographic and hormonal characteristic of the study groups. The primary outcome of fertilization rate has significant difference with p value of 0.003; 73.2% for CC group and 64.2% for GnRH antagonist group. The secondary outcome of OR rate (78.4 + 17.6 VS 80.3 + 13.4, p=0.368), mature oocyte rate (85.2 + 19.0 VS 81.7 + 16.7, p=0.130) and top quality embryo rate (79.1 + 24.2 VS 75.8 + 21.9, p=0.178) were comparable between both groups. There were significant difference between the endometrial thickness on the day of trigger and OHSS risk among both groups (8.5 + 0.95 VS 9.4 + 1.1, p<0.001 and 12.8% VS 44.1% respectively). Discussion: Minimal stimulation protocol with CC and gonadotropin may be the answer to many infertile couples in need of IVF and yet having financial situation deterring them in attempting IVF treatment. GnRH antagonist could be safely replaced by CC by extending to 10 days as this protocol gives better primary outcome and comparable secondary outcomes with less OHSS. CC is recognized to induce thinning of endometrial lining and thus, may impair embryo implantation. However, with advancement of the vitrification system and higher success rate in frozen-thaw embryo transfer worldwide provides an excellent solution for this issue

Predation on Multiple Prey Types Across a Disturbance Gradient in Tropical Montane Forests of Peninsular Malaysia

Predation plays a critical role in animal and plant survivorship, and can be highly sensitive to habitat loss and disturbance. Tropical montane forests in Southeast Asia are being modified rapidly by land-use change, and the consequences of this on predation likelihood are poorly understood. In Peninsular Malaysia, we conducted predation experiments at eight tropical montane forest sites along a disturbance gradient. We investigated whether (1) predation pressure in primary forests differs between different mountains; (2) predation probability is linked to habitat degradation; and (3) vegetation variables explain predation occurrence. At each forest site, we placed artificial nests with real and model quail eggs, dishes with real and artificial seeds of the cempedak (Artocarpus champeden), models resembling four-lined tree frogs (Polypedetes leucomystax) and models of the late instar caterpillar of the common Mormon (Papilio polytes) at points 100 m apart for three nights. Using Bayesian binomial simulations, we showed that predation likelihood in primary forests from different mountains can vary (e.g., probability of the difference in predation rate of artificial caterpillars between two primary forests was estimated at 82–100%). We also found that higher predation was not linked to habitat degradation for all artificial prey and seeds (e.g., comparing forests of varying degrees of disturbance from the same mountain, the probability that predation of an artificial caterpillar is lower at the primary forest was estimated at 2–20% only). Model selection and hierarchical partitioning showed that vegetation variables can explain predation occurrence, suggesting microhabitat characteristics may be influential. Conducting predation experiments by using artificial prey and seeds is useful for comparing predation likelihood at different sites, making ecological comparisons, and for informing conservation decisions. This novel approach of using multiple prey items also showed that predation for each can vary and thus caution against deploying a single prey type to draw broad inferences of predation in degraded systems

First Captive Born Sunda Pangolin (Manis javanica Demarest, 1822) in Malaysia

Sunda pangolin (Manis javanica Desmarest, 1822), also known as Malayan or Javan pangolin, is one of four species of pangolin available in Asia that includes Indian pangolin (Manis crassicaudata E. Geoffroy, 1803), Chinese pangolin (Manis pentadactyla Linnaeus, 1758), and Philippine pangolin (Manis culionensis de Elera, 1915). The remaining four species are from the African lineage, which are the white-bellied pangolin (Phataginus tricuspis Rafinesque, 1821), African black-bellied pangolin (Phataginus tetradactyla Linnaeus, 1766), Giant pangolin (Smutsia gigantean Illiger, 1815), and Temminck's pangolin (Smutsia temminckii Smuts, 1832). Figure 1 shows the species ranges of the pangolin species on the African and Asian continents

Using a crime prevention framework to evaluate tiger counter-poaching in a Southeast Asian rainforest

Tigers are a conservation-reliant species, as multiple populations face the risk of local extinction due to poaching arising from the continued demand for their body parts. Preventing tiger poaching poses a challenge for the rangers responsible for their protection, particularly in Southeast Asia, where the protected areas are typically large, mountainous tropical forests guarded by small teams of rangers. Improving counter-wildlife crime tactics is hindered without robust evaluations, and inefficient approaches are perpetuated. We evaluate an eight-year project aiming to recover a tiger population in Peninsular Malaysia. Three distinct poaching problems by Vietnamese, Thai and Cambodian groups, differing by organisation, target species and tactics, were prioritised, and ranger counter-poaching tactics were tailored to reduce these. Applying a framework developed to evaluate crime prevention known by the acronym EMMIE, here we: (1) examine evidence our intervention was Effective in reducing the poaching threat; (2) resolve the Mechanisms by which our intervention caused a reduction in harm from poaching and how intervention effectiveness is Moderated by the three poaching types; (3) define the elements necessary for Implementation and the Economic costs involved. We found poaching incursion frequency fell 40% from baseline years to treatment years across all poaching types while poaching incursion depth declined, with disrupted incursions on average, 2.6 km (Thai) and 9.1 km (Cambodian) closer to the forest edge. However, wire snares increased from baseline to treatment years as Vietnamese poachers increased the number of snares per incursion eightfold. No poaching incursions were observed during the Covid-19 pandemic. Tiger density remained below recovery potential (0.48/100km2 in 2014 to 0.53/100 km2 in 2021) but stabilised as key females survived and were detected breeding. Leopard, sun bear, muntjac and wild boar densities remained stable. Disarming active snares and seizing an increased proportion of snares before being deployed directly reduced the potential risk of mortality to medium-large mammals once a poaching incursion began. Attributing the decline in poaching attempts to our intervention is supported for Cambodian poachers via three plausible mechanisms: increased cost of reoffending by repatriated poaching team leaders; reduction of detailed knowledge sharing and imitation by peers; general deterrence at community level from increased awareness of the elevated risk of arrest and low likelihood of enjoying rewards. We found ranger performance enhancements at three critical stages of counter-poaching were instrumental in increasing arrest certainty, this was made possible by institutionalising a learn-and-adapt cycle underpinned by a dedicated site analyst. This study highlights how investing in problem analysis and going beyond simple assumptions of deterrence can greatly enhance the effectiveness and efficiency of small wildlife protection teams

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Predation on Multiple Prey Types Across a Disturbance Gradient in Tropical Montane Forests of Peninsular Malaysia

Predation plays a critical role in animal and plant survivorship, and can be highly sensitive to habitat loss and disturbance. Tropical montane forests in Southeast Asia are being modified rapidly by land-use change, and the consequences of this on predation likelihood are poorly understood. In Peninsular Malaysia, we conducted predation experiments at eight tropical montane forest sites along a disturbance gradient. We investigated whether (1) predation pressure in primary forests differs between different mountains; (2) predation probability is linked to habitat degradation; and (3) vegetation variables explain predation occurrence. At each forest site, we placed artificial nests with real and model quail eggs, dishes with real and artificial seeds of the cempedak (Artocarpus champeden), models resembling four-lined tree frogs (Polypedetes leucomystax) and models of the late instar caterpillar of the common Mormon (Papilio polytes) at points 100 m apart for three nights. Using Bayesian binomial simulations, we showed that predation likelihood in primary forests from different mountains can vary (e.g., probability of the difference in predation rate of artificial caterpillars between two primary forests was estimated at 82–100%). We also found that higher predation was not linked to habitat degradation for all artificial prey and seeds (e.g., comparing forests of varying degrees of disturbance from the same mountain, the probability that predation of an artificial caterpillar is lower at the primary forest was estimated at 2–20% only). Model selection and hierarchical partitioning showed that vegetation variables can explain predation occurrence, suggesting microhabitat characteristics may be influential. Conducting predation experiments by using artificial prey and seeds is useful for comparing predation likelihood at different sites, making ecological comparisons, and for informing conservation decisions. This novel approach of using multiple prey items also showed that predation for each can vary and thus caution against deploying a single prey type to draw broad inferences of predation in degraded systems