Determination of prevalence of subclinical mastitis, characterization of intra-mammary infection-causing bacteria, and antibiotic susceptibility in dairy camels in Jigjiga City, Somali region, Ethiopia.

Background: Subclinical mastitis in camels, an inflammation of the udder without visible signs, can reduce milk quality and raise bacteria levels. Regular monitoring of camel milk is crucial for consumer safety. Methods: A cross sectional study was conducted in Jigjiga city, Ethiopia to investigate the prevalence and characteristics of subclinical mastitis in she-camels. The study included 244 lactating she-camels from three privately-owned camel dairy farms, and a questionnaire survey was conducted with 60 camel owners. Results: The overall prevalence of subclinical mastitis in she-camels was 10.6% (26/244), with no significant difference among the studied dairy farms. Risk factors that influenced the result of California Mastitis Test (CMT) included age and udder and leg hygiene. The study revealed that S. aureus was the most prevalent bacterium among the isolated bacteria, with a prevalence rate of 34.5%. This was followed by S. agalactiae, S. dysgalactiae, and Pasteurella multocida, with prevalence rates of 29.8, 19.4, and 16.2%, respectively. Among the isolated bacteria, 84.5% were sensitive to Erythromycin, 60% to Streptomycin, 44.7% to Oxytetracycline, and 36.7% to Tetracycline. Interviews with camel owners revealed that 66.7% used mixed herd grazing methods and reported feed shortage. Treatment practices for sick camels included modern veterinary drugs, traditional medicines, or a combination of both. The owners of camel dairy farms did not maintain proper hygiene practices during milking, such as not using soap when washing hands. Conclusion: Addressing camel mastitis necessitates access to alternative drugs, comprehensive herder training, and enhanced management practices.

Participatory and Conventional Investigation of Tick Infestation in Camels and Cattle of Somali Pastoral Areas, Eastern Ethiopia.

Ticks are a common parasite that affect many animals by causing slowed growth, reduced milk output, and financial losses for industries that depend on animal hides and skins. From June to December 2017, participatory and conventional investigations on tick infestation in camels and cattle were conducted in Kebribayah and Afdem districts of Ethiopia's Somali Regional State. The aim of this study was to determine the prevalence and density of ticks in these animals and establish strategic control measures to enhance livestock productivity and livelihoods in pastoral areas. The current study found that the prevalence of tick infestation in Kebribayah and Afdem districts was 83.3% and 86.8%, respectively. Rhipicephalus pulchellus (48.9%) was identified as the most common tick species in camels and cattle, followed by Amblyomma gemma (26.3%), Hyalomma truncatum (11.6%), Amblyomma lepidum (6.7%), and Amblyomma variegatum (6.5%). Among the variables considered, age and body condition score were significant risk factors (p < 0.001). Tick density varied depending on the recorded months and seasons (p < 0.001), with the highest mean tick density occurring in November (32.69 ± 21.750) and during the wet season (28.56 ± 19.750). Livestock owners in Kebribayah and Afdem ranked topical acaricide application as the most effective tick control method, followed by ivermectin injections, with the traditional hand removal method being the least effective. These rankings were consistent across both districts, and there was moderate agreement among livestock keepers from both regions regarding the best method. Afdem livestock keepers had slightly weak agreement on high tick burden in spring (W = 0.475, p = 0.127), and Kebribayah livestock keepers showed slightly strong agreement in tick burden across seasons (W = 0.700, p = 0.038), with spring having a significantly higher burden than winter. Consequently, participatory appraisal indicated that ticks were important and prevalent ectoparasites in the study area. Finally, strategic tick control appropriate for specific management and production environments should be implemented biannually in wet seasons.

Assessment of the Impact of Mandated Postmarketing Pediatric-Focused Safety Reviews on Safety-Related Regulatory Actions 2013-2019.

The US Food and Drug Administration's (FDA's) routine postmarketing drug safety monitoring may lead to safety-related labeling changes for identified risks. Additionally, the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA) require the FDA to conduct postmarket pediatric-focused safety reviews of adverse events. The purpose of these pediatric reviews is to identify risks associated with drug or biological products 18 months after the FDA approves a pediatric labeling change pursuant to studies conducted under the BPCA or PREA. These reviews are presented to the FDA Pediatric Advisory Committee (PAC) or publicly posted on FDA's website. The aim of this study was to evaluate the impact of pediatric reviews prompted by BPCA/PREA from October 1, 2013, to September 30, 2019. The impact was quantified by the number of new safety signals identified and the subsequent safety-related labeling changes resulting from pediatric reviews relative to safety-related labeling changes triggered by other data sources. Among 163 products with at least one pediatric review completed, a new safety signal that resulted in a safety-related labeling change was found for 5 of these products (representing 3 active ingredients); none described risks specific to the pediatric population. Between October 2013 and September 2021, there were 585 safety-related labeling changes implemented for products with at least one completed pediatric review. Less than 1% of 585 safety-related labeling changes were the result of a mandated pediatric review. Our study suggests that mandated pediatric reviews conducted 18 months after a pediatric labeling change provided minimal value over other postmarket safety surveillance activities.

A cohort study to assess risk of cutaneous small vessel vasculitis among users of different oral anticoagulants.

PURPOSE: Cutaneous small vessel vasculitis (CSVV) was identified as a safety signal among patients treated with direct oral anticoagulants (DOAC). This study aimed to determine if CSVV risk differed among patients with atrial fibrillation (Afib) who newly initiated warfarin or a DOAC. METHODS: We identified enrollees aged ≥21 years diagnosed with Afib who newly initiated rivaroxaban, dabigatran, apixaban, and warfarin in the Sentinel Distributed Database from October 19, 2010 to February 29, 2020. We selected and followed patients who did not have evidence of the following in the 183 days prior to initiating treatment: CSVV diagnosis, dispensing of other study drugs, select autoimmune diseases or autoimmune medications, cancer diagnoses or chemotherapeutic treatment, kidney dialysis or transplant, alternative anticoagulation indications, or an institutional (nursing home, hospice, hospital) stay on the treatment initiation date (index date) until CSVV outcome or pre-specified censoring. We conducted 1:1 propensity score matching in six comparisons. RESULTS: CSVV incidence rates for DOACs and warfarin ranged from 3.3 to 5.6 per 10 000-person years in our matched Afib population. The adjusted CSVV hazard ratio (HR) and 95% confidence interval (CI) was 0.94 (0.64, 1.39) for rivaroxaban versus warfarin; 1.17 (0.67, 2.06) for dabigatran vs. warfarin; 0.85 (0.62, 1.16) for apixaban vs. warfarin; 0.86 (0.49, 1.50) for rivaroxaban vs. dabigatran; 0.99 (0.68, 1.45) for rivaroxaban versus apixaban; and 1.70 (0.90, 3.21) for dabigatran versus apixaban. CONCLUSION: We did not find significant evidence of differential CSVV risk in pair-wise comparisons of DOACs and warfarin.

Acute Hyperkinetic Movement Disorders as a Multifactorial Pharmacodynamic Drug Interaction Between Methylphenidate and Risperidone in Children and Adolescents.

PURPOSE/BACKGROUND: Acute hyperkinetic movement disorders have been reported with the concomitant use of attention-deficit/hyperactivity disorder (ADHD) stimulants and antipsychotics in children and adolescents. We analyzed postmarketing reports of suspected acute hyperkinetic movement disorder associated with concomitant use of ADHD stimulants and antipsychotics. METHODS/PROCEDURES: We searched for postmarketing reports of acute hyperkinetic movement disorders associated with concomitant use of ADHD stimulants-antipsychotics in the US Food and Drug Administration Adverse Event Reporting System through December 6, 2019. PubMed and EMBASE were also searched for acute hyperkinetic movement reports with the concomitant use of ADHD stimulants-antipsychotics through January 13, 2020. FINDINGS/RESULTS: We identified 36 cases resulting in acute hyperkinetic movement disorder associated with the concomitant use of ADHD stimulants-antipsychotics, 19 of which were also identified in the medical literature. From an ADHD stimulant perspective, methylphenidate products accounted for the largest number of cases (n = 23 [64%]), followed by amphetamine products (n = 9 [25%]) and atomoxetine (n = 4 [11%]). From an antipsychotic perspective, all 36 cases were reported with second-generation antipsychotics, particularly risperidone (n = 20 [56%]). Most of the cases were reported in boys (n = 31 [86%]) aged 6 to 12 years (n = 27 [75%]). Approximately 53% of the cases reported a time to onset within 24 hours of the drug change. Acute dystonic reactions (n = 27 [75%]) were the most frequently reported movement disorder. IMPLICATIONS/CONCLUSIONS: As outlined in changes to the US prescribing information for all methylphenidate and risperidone products, health care professionals should be aware that changes to this combination may be associated with a pharmacodynamic drug-drug interaction resulting in acute hyperkinetic movement disorder.

Complementary Use of U.S. FDA's Adverse Event Reporting System and Sentinel System to Characterize Direct Oral Anticoagulants-Associated Cutaneous Small Vessel Vasculitis.

BACKGROUND: Cutaneous small vessel vasculitis (CSVV) has been reported after exposure to direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban. OBJECTIVE: We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to describe clinical characteristics associated with CSVV among DOAC-exposed patients. Furthermore, we characterized this signal in the Sentinel System to relate the clinical data from the individual FAERS cases to population-based electronic healthcare data. METHODS: We queried FAERS for all cases of CSVV associated with DOACs from U.S. approval date of each DOAC through March 16, 2018. Within the Sentinel System, we identified incident CSVV cases using ICD-9 and ICD-10 diagnosis codes among adults aged ≥ 30 years who received a DOAC in the prior 90 days between January 1, 2010, and June 30, 2018. We excluded patients with evidence of select autoimmune diagnoses in the 183 days prior to their CSVV diagnoses and reported patient characteristics in the 183-day period prior to CSVV diagnoses. RESULTS: In FAERS, we identified 50 cases of CSVV reported with rivaroxaban (n=26), apixaban (n=14), dabigatran (n=9), and edoxaban (n=1). Approximately 50% of the cases reported time to onset within 10 days after DOAC exposure. When specified, the predominant type of CSVV reported was leukocytoclastic vasculitis (n=31), followed by Henoch-Schonlein purpura (n=4). Hospitalization occurred in most of the cases (n=37). Switching of the offending agent after the development of CSVV was reported (n=26). Three rivaroxaban (n=3) cases and one dabigatran case (n=1) reported positive rechallenge. In the Sentinel system, we identified 3659 CSVV cases with prior DOAC exposure, with 85% of events occurring within 10 days. CONCLUSIONS: The assessment of FAERS cases, combined with the temporal clustering of the Sentinel System cases suggest a possible causal relationship of DOACs and CSVV. Future efforts should characterize the risk of CSVV among the various DOAC users.

Health Status and Health Care Needs of Drought-Related Migrants in the Horn of Africa-A Qualitative Investigation.

Somalia, Kenya and Ethiopia, situated in the Horn of Africa, are highly vulnerable to climate change, which manifests itself through increasing temperatures, erratic rains and prolonged droughts. Millions of people have to flee from droughts or floods either as cross-border refugees or as internally displaced persons (IDPs). The aim of this study was to identify knowledge status and gaps regarding public health consequences of large-scale displacement in these countries. After a scoping review, we conducted qualitative in-depth interviews during 2018 with 39 stakeholders from different disciplines and agencies in these three countries. A validation workshop was held with a selection of 13 interviewees and four project partners. Malnutrition and a lack of vaccination of displaced people are well-known challenges, while mental health problems and gender-based violence (GBV) are less visible to stakeholders. In particular, the needs of IDPs are not well understood. The treatment of mental health and GBV is insufficient, and IDPs have inadequate access to essential health services in refugee camps. Needs assessment and program evaluations with a patients' perspective are either lacking or inadequate in most situations. The Horn of Africa is facing chronic food insecurity, poor population health and mass displacement. IDPs are an underserved group, and mental health services are lacking. A development approach is necessary that moves beyond emergency responses to the building of long-term resilience, the provision of livelihood support and protection to reduce displacement by droughts.

Evaluation of the Inter and Intra-Observer Reliability of the AO Classification of Intertrochanteric Fractures and the Device Choice (DHS, PFNA, and DCS) of Fixations.

BACKGROUND: ArbeitsgemeinschaftfürOsteosynthesefragen (AO) classification is the most frequently used tool to classify intertrochanteric fractures. However, there is limited evidence regarding its reliability. Therefore, this study was designed to evaluate inter-observer and intra-observer reliability of the AO-2018 intertrochanteric fracture classification. METHOD: A retrospective study was conducted in Imam Khomeini Hospital Complex, on radiography of patients who came with intertrochanteric fractures from March 21, 2018, to March 19, 2019. Four orthopedic trauma surgeons assessed 96 anteroposterior pelvic radiographs of intertrochanteric fractures and classified using an AO intertrochanteric fracture classification of 2018. The reading and review of radiography were performed in 2 separate occasions in a 1-month interval. The inter-observer and intra-observer reliability was assessed using kappa statistics. RESULT: The level of both mean inter-observer (K =0.322; 95%CI: 0.321-0.323) and intra-observer agreement (K =0.317; 95%CI: 0.314-0.320) in AO intertrochanteric fracture classification subgrouping were not satisfactory. The inter-observer (K =0.61; 95%CI: 0.608-0.611) and intra-observers' (K=0.560; 95%CI: 0.544-0.566) reliability in AO main groupings showed moderate agreement. CONCLUSION: The AO classification does not show adequate and acceptable inter-observer and intra-observer reliability and reproducibility. Therefore, it will be hard to base on the AO classification for treatment protocols.

Concomitant use of buprenorphine for medication-assisted treatment of opioid use disorder and benzodiazepines: Using the prescription behavior surveillance system.

BACKGROUND: Despite clinical guidelines discouraging the practice, it is well-documented that the concomitant use of benzodiazepines and opioid analgesics occurs regularly. Information on concomitant use of buprenorphine for medication-assisted treatment (MAT) of opioid use disorder (OUD) and benzodiazepines, however, is limited. Thus, we aimed to describe real-world drug dispensing patterns for the concomitant use of buprenorphine products approved for MAT and benzodiazepines. METHODS: We examined concomitant use of buprenorphine for MAT and benzodiazepines using the 2013 Prescription Behavior Surveillance System data from eight states. For prescription-level analysis, we estimated the proportion of concomitant buprenorphine and benzodiazepine prescriptions and the proportions of concomitant prescriptions prescribed by the same provider (co-prescribing) and dispensed by the same pharmacy (co-dispensing) for each state. For patient-level analysis, we calculated the proportion of patients with ≥1 buprenorphine therapy episode overlapping with a benzodiazepine episode, i.e., concomitant users, and the proportion of concomitant users who experienced co-prescribing or co-dispensing. RESULTS: In 2013, 1,925,072 prescriptions of buprenorphine products for MAT were dispensed to 190,907 patients in eight states. Approximately 1 in 8 buprenorphine prescriptions was used concomitantly with ≥1 benzodiazepine prescription(s). Co-prescribing proportions ranged from 22.2 to 64.6% across states, while co-dispensing proportions ranged from 54.7 to 91.0%. Approximately 17.7% of patients had >1 buprenorphine episode overlapping a benzodiazepine episode for ≥7 cumulative days' supply. Among these patients, 33.1-65.2% experienced co-prescribing, and 65.1-93.3% experienced co-dispensing. CONCLUSIONS: The concomitant use of buprenorphine for MAT and benzodiazepines occurs frequently, with variations by state in co-prescribing and co-dispensing.

Enrollment and Retention in 34 United States Pregnancy Registries Contrasted with the Manufacturer's Capture of Spontaneous Reports for Exposed Pregnancies.

INTRODUCTION: Pregnancy registries and spontaneous reports are essential pharmacovigilance tools to evaluate drug safety during pregnancy. OBJECTIVES: The aim of this study was to evaluate postmarket capture of exposed pregnancies. METHODS: Pregnancy registries for drugs and biologics were identified in a systematic review. Through a standardized questionnaire, manufacturers provided information on (1) pregnancy registry enrollment and retention, and (2) worldwide receipt of spontaneous reports for exposed pregnancies. A validated algorithm for live-birth pregnancies allowed calculation of exposure rates per 100,000 live births using claims data. RESULTS: Among 34 products with a pregnancy registry, median (interquartile range) registry enrollment was 36 pregnancies (5-258) and median spontaneous report capture was 450 pregnancies (89-1192). Products used in >20/100,000 live births had a median registry enrollment of 490 pregnancies and median capture of 1061 spontaneously reported exposed pregnancies. Lower median registry enrollment and spontaneous report capture was observed for products used in 0.5-20/100,000 live births (36 from registries, 541 spontaneous reports) and <0.5/100,000 live births (3 from registries, 41 spontaneous reports). Among 24 registries enrolling ≥10 pregnancies, median capture of pregnancy outcomes (e.g. live birth, spontaneous abortion) was 83.9%. For 19 registries enrolling ≥10 infants, the median proportion of infants achieving protocol-specified follow-up was 89.9% for up to 4 weeks post-birth, 75.0% for 1-5 months, and 57.1% for ≥6 months. CONCLUSIONS: Relatively higher product utilization among pregnant women predicted greater pregnancy registry enrollment. For products rarely used during pregnancy, registry enrollment was low and differences in registry enrollment compared with worldwide spontaneous report receipt were most pronounced. Products with very low utilization levels during pregnancy may require a combination of worldwide pharmacovigilance, pregnancy registries, and additional study methods to achieve adequate surveillance.