Serological cross-sectional survey of equine infectious anemia in Saudi Arabia.

The equine infectious anaemia virus (EIAV) is one of the most serious equine diseases worldwide. There is scarce information on the epizootiology of equine infectious anaemia (EIA) in Saudi Arabia. Given the importance of the equine industry in Saudi Arabia, this cross- -sectional study aims to provide information about the prevalence of EIAV based on serological surveillance of the equine population in the country. A total of 4728 sera samples were collected (4523 horses and 205 donkeys) between December 2017 and November 2019. All samples were tested using commercially available EIAV ELISA. All tested samples showed negative results for EIAV antibodies with a 95% confidence interval. The results provided evidence that Saudi Arabia's equine populations (horses and donkeys) are currently free of EIAV. The results also suggest the need for continuous monitoring of EIAV and strict regulation when importing horses from other countries.

Predictors of Long-Term Response With Pazopanib in Patients With Advanced Renal-Cell Carcinoma.

BACKGROUND: Pazopanib is among the current standards of care for first-line treatment of patients with unresectable advanced renal-cell carcinoma (aRCC) or metastatic renal-cell carcinoma. This real-world study aimed to characterize those with long-term response to pazopanib in the treatment of aRCC in a community oncology setting, and to identify predictors of long-term response. PATIENTS AND METHODS: aRCC patients treated with first-line pazopanib were classified as having long-term or non-long-term response (progression-free survival [PFS] of ≥ 18 or < 18 months, respectively). Baseline patient demographics and clinical characteristics were evaluated and compared between the 2 groups. Differences in PFS and overall survival were also evaluated. RESULTS: A total of 153 eligible patients were identified, of which 33 (21.6%) and 120 (78.4%) patients were identified as having disease with long-term and non-long-term response, respectively. The median PFS for those with long-term response was 27.2 months (95% confidence interval [CI], 23.0-35.2) versus 6.9 months (95% CI, 5.0-8.6) for those with non-long-term response. Median overall survival was not reached (NR) for those with long-term response (95% CI, NR to 39.1) compared to 15.3 months (95% CI, 12.3-21.6) for those with non-long-term response. Baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 (vs. ECOG PS of 1 and ≥ 2) and history of nephrectomy were identified as significant predictors of long-term response to pazopanib. CONCLUSION: In aRCC patients treated with first-line pazopanib, 22% had a long-term response. Significant predictors of long-term response included an ECOG PS of 0 and a history of nephrectomy.

Epidemiological study of Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia, April-May 2015.

A cross-sectional study was conducted in five regions in Saudi Arabia to investigate the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels (Camelus dromedarius) during April and May2015. Serum and nasal swab samples were tested for MERS-CoV antibodies andribonucleic acid (RNA) using a recombinant enzyme-linked immunosorbent assay (rELISA) and real-time reverse-transcription polymerase chain reaction (rRT-PCR), respectively. The overall MERS-CoV antibody seroprevalence was 80.5%, whereas the overall viral RNA prevalence was 2.4%. The associations of risk factors with each prevalence were quantified using univariate and multivariate analyses. The multivariate models identified region, age, grazing system, exposure to wild animals and dung removal as factors significantly associated with seroprevalence (p ??0.05). A higher seroprevalence was more likely to occur in camels from the Riyadh, Eastern, Northern and Makkah regions than those from the Jazan region; camels ??4 and 1-3 years of age (marginally significant) than calves < 1 year; and camels raised in zero grazing and semi-open grazing systems than those raised in an open grazing system. However, the presence of wild animals and daily dung removal were negatively associated with seroprevalence. On the other hand, region and sex were significantly associated with MERS-CoV RNA prevalence(p ??0.05). A higher viral RNA prevalence was more likely to occur in camels from the Riyadh region and Eastern region (marginally significant) than in those from the Makkah region, and in male camels than female camels. In conclusion, the risk factors identified in this study can be considered to be predictors of MERS-CoV infection in camels and should be taken into account when developing an efficient and cost-effective control strategy.

Une étude transversale a été réalisée au cours des mois d'avril et de mai 2015 dans cinq régions d'Arabie saoudite afin d'élucider l'épidémiologie de l'infection par le coronavirus responsable du syndrome respiratoire du Moyen-Orient(MERS­CoV) chez les dromadaires (Camelus dromedarius). Des échantillons de sérum et des écouvillons nasaux prélevés de dromadaires ont été analysés afin de détecter la présence d'anticorps dirigés contre le MERS-CoV ou d'ARN de ce même virus, en utilisant respectivement une épreuve immuno-enzymatique recombinante (ELISAr) et une amplification en chaîne par polymérase couplée à une transcription inverse (PCR­RT) en temps réel. La prévalence sérologique globale des anticorps dirigés contre le MERS-CoV s'élevait à 80,5 %, tandis que la prévalence globale de l'ARN viral était de 2,4 %. Les corrélations entre les facteurs de risque et les prévalences obtenues ont été quantifiées au moyen d'analyses à une seule et à plusieurs variables. Les modèles à plusieurs variables ont fait apparaître une association significative (p ??0,05) entre la prévalence sérologique et les facteurs suivants : la région, l'âge des animaux, le système pastoral pratiqué, l'exposition à la faune sauvage et l'élimination du fumier. La probabilité d'une forte prévalence sérologique était plus élevée chez les dromadaires provenant des régions de Riyad, de l'Est, du Nord et de la Mecque que chez ceux de la région de Jizan ; chez les dromadaires âgés de plus de quatre ans, ou âgés d'un à trois ans (différence marginalement significative) plutôt que chez les jeunes de moins d'un an ; et enfin chez les dromadaires nourris en stabulation (zéro pâturage) ou en pâturage semi-ouvert plutôt que chez ceux nourris dans des systèmes de pâturage ouvert. En revanche, une corrélation négative a été constatée entre la prévalence sérologique d'une part et la présence d'animaux sauvages et/ou l'élimination quotidienne du fumier, d'autre part. En ce qui concerne la détection virale, une corrélation significative (p ??0,05) a été constatée entre la région et le sexe des animaux et la prévalence de l'ARN du MERS-CoV. La probabilité d'une prévalence plus élevée de l'ARN viral était plus prononcée chez les dromadaires des régions de Riyad et de l'Est (différence marginalement significative) que chez ceux de la région de La Mecque, et chez les mâles que chez les chamelles. En conclusion, les facteurs de risque identifiés dans cette étude peuvent servir d'annonciateurs de l'infection par le MERS-CoV chez les dromadaires et devraient être pris en compte pour élaborer une stratégie efficace et rentable de lutte contre cette maladie.

Los autores describen un estudio transversal efectuado en abril y mayo de 2015 en cinco regiones de Arabia Saudí con objeto de investigar la epidemiologia de la infección de dromedarios (Camelus dromedarius) por el coronavirus del síndrome respiratorio de Oriente Medio (MERS­CoV). A tal efecto se analizaron muestras de suero y exudado nasal para detectar en ellas anticuerpos contra el MERS­CoV y ácido ribonucleico (ARN) del virus, empleando para ello, respectivamente, una técnica de ensayo inmunoenzimático recombinante (ELISAr) y una de reacción en cadena de la polimerasa acoplada a transcripción inversa en tiempo real (rRT­PCR, por sus siglas en inglés). Se calculó que la seroprevalencia global de anticuerpos contra el virus era del 80,5% y que la prevalencia global de ARN vírico era del 2,4%. Utilizando análisis multifactoriales y de una sola variable se cuantificó también la correlación de cada una de esas prevalencias con una serie de factores de riesgo. Con los modelos multifactoriales se observó que la región, la edad, el régimen de pastoreo, la exposición a animales salvajes y la retirada de estiércol eran factores que presentaban una asociación significativa con la seroprevalencia (p ??0,05): era más probable encontrar niveles elevados de seroprevalencia en dromedarios de las regiones de Riad y La Meca y las regiones oriental y septentrional del país que en los de la región de Jizán; en los de 4 o más años y entre 1 y 3 años de edad (correlación ligeramente significativa) que en las crías menores de 1 año; y en los animales estabulados o criados en sistemas de pasto semiabierto que en los criados con regímenes de pasto al aire libre. La presencia de animales salvajes y la retirada cotidiana del estiércol, por su parte, presentaban una correlación negativa con la seroprevalencia. Por otro lado, los factores asociados significativamente con la prevalencia de ARN vírico (p ??0,05) eran la región y el sexo: había mayor probabilidad de encontrar niveles elevados de prevalencia de ARN vírico en dromedarios de la región de Riad y la región oriental (correlación ligeramente significativa) que en los de la región de La Meca, y en machos más que en hembras. En conclusión, los factores de riesgo detectados con este estudio pueden ser considerados predictivos de la infección de dromedarios por el MERS­CoV y deben ser tenidos en cuenta para elaborar una estrategia de lucha que ofrezca a la vez eficacia y rentabilidad.

Outbreak investigation and molecular diagnosis of Lumpy skin disease among livestock in Saudi Arabia 2016.

Lumpy skin disease (LSD) is a highly infectious disease of cattle caused by a virus of the Capripoxvirus genus in the family Poxviridae. The disease is a major concern for the dairy industry in Saudi Arabia. In this study, an outbreak of LSD in cattle herds was detected in Saudi Arabia in 2016. LSD outbreak was investigated in five regions of Saudi Arabia: Al-Hassa, Al-Sharqia, Al-Qassim, Riyadh and Al-Taif during the period from April to July 2016. Tissues from skin nodules were collected to characterize the virus by a real-time polymerase chain reaction (rt-PCR). During this period, 64,109 cattle were examined and morbidity, mortality and case fatality rates were 6%, 0.99% and 16.6%, respectively. The analysis showed 3,852 infected cases and 641 deaths. highest number of infected animals was reported in Al-Hassa (2,825), followed by Al-Qassim (547), Riyadh (471), Al-Sharqia (6) and Al-Taif (3). The highest morbidity rates were observed in Al-Qassim (6.8%), Al-Hassa (6.2%), Riyadh (5.5%) and Al-Taif (0.96%), while the lowest morbidity rates were recorded in Al-Sharqia (0.27%). The highest mortality rates were also observed in Al-Qassim (2.3%), followed by Al-Hassa (0.97%), Riyadh (0.19%) and lowest in Al-Sharqia and Taif (0%). LSD virus was detected in all samples (n = 191) by real-time PCR analysis. The disease has been observed in the cattle regardless of previous vaccination using the locally Romanian-pox vaccine; therefore, vaccination programme and vaccine efficacy should be assessed under field conditions.

Does Teriparatide Improve Femoral Neck Fracture Healing: Results From A Randomized Placebo-controlled Trial.

BACKGROUND: There is a medical need for therapies that improve hip fracture healing. Teriparatide (Forteo(®)/ Forsteo(®), recombinant human parathyroid hormone) is a bone anabolic drug that is approved for treatment of osteoporosis and glucocorticoid-induced osteoporosis in men and postmenopausal women at high fracture risk. Preclinical and preliminary clinical data also suggest that teriparatide may enhance bone healing. QUESTIONS/PURPOSES: We wished to test the hypotheses that treatment with teriparatide versus placebo would improve femoral neck fracture healing after internal fixation as measured by (1) frequency of revision surgery, (2) radiographic fracture healing, and (3) other outcomes including pain control, gait speed, and safety. METHODS: We initiated two separate, but identically designed, clinical trials to meet FDA requirements to provide substantial evidence to support approval of a new indication. The two prospective, randomized double-blind, placebo-controlled Phase III studies were designed to evaluate the effect of subcutaneous teriparatide (20 µg/day) for 6 months versus placebo on fracture healing at 24 months. The trials were conducted concurrently with a planned enrollment of 1220 patients per trial. However, enrollment was stopped owing to very slow patient accrual, and an a priori decision was made to pool the results of those studies for statistical analyses before study completion; pooling was specified in both protocols. Randomization was stratified by fixation (sliding hip screw or multiple cancellous screws) and fracture type (displaced or nondisplaced). An independent Central Adjudication Committee reviewed revision surgical procedures and radiographs. A total of 159 patients were randomized in the two trials (81 placebo, 78 teriparatide). The combined program had very low power to detect the originally expected treatment effect but had approximately 80% power to detect a larger difference of 12% between treatment groups for risk of revision surgery. RESULTS: The proportion of patients undergoing revision surgery at 12 months was 14% (11 of 81) in the placebo group versus 17% (13 of 78) in the teriparatide group. Central Adjudication Committee review excluded two of these patients treated with placebo from the primary analysis. After exclusions, the proportion of patients who did not undergo revision surgery at 12 months (primary endpoint) was not different between the study and placebo groups, at 88% in the placebo group (90% CI, 0.79-0.93) versus 84% in the teriparatide group (90% CI, 0.75-0.90; p = 0.743). There also were no differences between groups in the proportion of patients achieving radiographic fracture healing at 12 months (75% [61 of 81] placebo versus 73% [57 of 78] teriparatide; odds ratio, 0.89; 90% CI, 0.46-1.72; p = 0.692) or in measures of pain control (such as pain during ambulation, 92% [55 of 62] placebo versus 91% [52 of 57] teriparatide; odds ratio, 0.91; 90% CI, 0.25-3.37; p = 0.681). The frequency of patients reporting adverse events was 49% [40 of 81] in the placebo group versus 45% [35 of 78] in the teriparatide group (p = 0.634) during the 6-month treatment period. CONCLUSIONS: The small sample size limited this study's power to detect potential differences, and the results are exploratory. With the patients available, teriparatide did not decrease the risk of revision surgery, improve radiographic signs of fracture healing, or decrease pain compared with the placebo. The adverse event data observed were consistent with the teriparatide safety profile. Functional and health outcome data from the studies may help improve our understanding of patients recovering from femoral neck fractures. Further large controlled studies are required to determine the effect of teriparatide on fracture healing. LEVEL OF EVIDENCE: Level II, prospective study.

Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial.

BACKGROUND: Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) and improves physical performance in older individuals who have had recent falls and low muscle strength and power. METHODS: In this proof-of-concept, randomised, placebo-controlled, double-blind, parallel, multicentre, phase 2 study, we recruited patients aged 75 years or older who had fallen in the past year from 21 investigator sites across Argentina, Australia, France, Germany, Sweden, and the USA. Eligible patients had low performance on hand grip strength and chair rise tests, tested with the procedure described by Guralnik and colleagues. Participants were stratified by country, age, hand grip strength, and performance on the chair rise test, and were randomly assigned (1:1) by a computer-generated random sequence to receive subcutaneous injections of placebo or 315 mg LY at weeks 0 (randomisation visit), 4, 8, 12, 16, and 20, followed by 16 weeks observation. The primary outcome was change in aLBM from baseline to 24 weeks. We measured physical performance as secondary outcomes (four-step stair climbing time, usual gait speed, and time to rise five times from a chair without arms, or with arms for participants unable to do it without arms) and exploratory outcomes (12-step stair climbing test, 6-min walking distance, fast gait speed, hand grip strength, and isometric leg extension strength). Efficacy analyses included all randomly assigned patients who received at least one dose and had a baseline and at least one subsequent measure. The primary analysis and all other tests of treatment effect (except physical performance tests) were done at a two-sided alpha level of 0·05. Tests of treatment effect on physical performance tests were done at a pre-specified two-sided alpha level of 0·1. This trial is registered with ClinicalTrials.gov, number NCT01604408. FINDINGS: Between June 19, 2012, and Dec 12, 2013, we screened 365 patients. 99 were randomly assigned to receive placebo and 102 to receive LY. Treatment was completed in 85 (86%) of patients given placebo and in 82 (80%) given LY. At 24 weeks, the least-squares mean change in aLBM was -0·123 kg (95% CI -0·287 to 0·040) in the placebo group and 0·303 kg (0·135 to 0·470) in the LY group, a difference of 0·43 kg (95% CI 0·192 to 0·660; p<0·0001). Stair climbing time (four-step and 12-step tests), chair rise with arms, and fast gait speed improved significantly from baseline to week 24 with differences between LY and placebo of respectively -0·46 s (p=0·093), -1·28 s (p=0·011), -4·15 s (p=0·054), and 0·05 m/s (p=0·088). No effect was detected for other performance-based measures. Injection site reactions were recorded in nine (9%) patients given placebo and in 31 (30%) patients given LY (p<0·0001), and were generally mild, and led to treatment discontinuation in two patients given LY. INTERPRETATION: Our findings show LY treatment increases lean mass and might improve functional measures of muscle power. Although additional studies are needed to confirm these results, our data suggest LY should be tested for its potential ability to reduce the risk of falls or physical dependency in older weak fallers. FUNDING: Eli Lilly and Company.