Small Study Research Articles

Human and animal brucellosis and risk factors for human infection in Ethiopia: a systematic review and meta-analysis (2015–2024)

Background and objectiveBrucellosis is a neglected zoonotic disease caused by Brucella species. Unlike most developed nations, the problem of brucellosis in Ethiopia remains a public and animal health concern. This study was conducted to determine the magnitude of brucellosis in animals (mainly cattle, sheep, goats, dogs and camels) and humans, and to identify the risk factors for human brucellosis.MethodologyThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to conduct this systematic review and meta-analysis, which was performed from May 2024 to July 2024. Academic databases such as PubMed, ScienceDirect, Scopus, PubMed Central, Web of Science, and Google Scholar were searched to identify articles focusing on brucellosis in humans and animals in Ethiopia. Data extraction was performed according to predefined inclusion and exclusion criteria. The included articles were appraised using the appraisal tool for cross-sectional studies to assess study quality. Publication bias and small study effects were examined using funnel plot observation and Egger’s test, respectively. Statistical analysis was conducted using R software version 4.4.1.ResultsThirty-nine articles published between 2015 and 2024 were included in the final analysis from a total of 1,427 identified articles. The overall pooled seroprevalence of brucellosis was 5.0% (95% CI: 3.0, 6.0). The seroprevalence of brucellosis was higher in humans at 6.9% (95% CI: 4.9, 8.8) and lower in cattle at 3.5% (95% CI: 2.2, 4.7). There was high heterogeneity in the reports of brucellosis seroprevalence between studies (τ² = 0.0038, H² = 255.9, I² = 99.61%, Q-test = 1954.99, df = 56, p ≤ 0.001). Laboratory tests and study location were identified as factors contributing to potential sources of variation in the pooled seroprevalence. Drinking raw milk from aborted animals, touching aborted materials or fetuses, and occupation were among the risk factors for human brucellosis. No publication bias or small study effects were detected.ConclusionThe findings indicate that brucellosis continues to pose a significant zoonotic threat, particularly to humans, where the seroprevalence is notably higher than in animals. These results highlight the need for targeted public health interventions and greater awareness to reduce the incidence of brucellosis, especially among high-risk populations.

Effect of early essential newborn care on breastfeeding and outcomes of mothers/newborns post-cesarean section: a randomized controlled trial in China

BackgroundThe implementation of early essential newborn care (EENC) is important to maternal and neonatal health. However, few studies have conducted a complete procedure of EENC in cesarean section. This study aimed to systematically evaluate the effects of EENC during and after cesarean section.MethodsA randomized controlled trial was conducted at a tertiary hospital in Wuhan, China. Full-term pregnant women who had no comorbidities and underwent elective cesarean section were recruited and received EENC intervention or routine health care. The Infant Breastfeeding Assessment Tool (IBFAT), the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF), a questionnaire of the breastfeeding behavior, the Maternal Postnatal Attachment Scale (MPAS) and the Edinburgh Postnatal Depression Scale (EPDS) were used to collect data. The correlation between EENC implementation and breastfeeding, maternal-infant attachment, postpartum depression, and other maternal and neonatal outcomes was analyzed.ResultsMother-newborn pairs (N = 157) were enrolled in this study, 78 in the EENC group and 79 in the control group. A total of 155 (98.8%) were followed up at 14 days, 144 (91.7%) at 42 days, and 123 (78.3%) at 3 months. For the primary outcomes, generalized linear mixed model analysis showed that implementing EENC during cesarean section was beneficial for initiating breastfeeding (OR = 0.021), shortening the breastfeeding initiation time (β = − 45.321), improving the IBFAT scores (β = 2.740), and enhancing breastfeeding self-efficacy (β = 4.880). These effects were not influenced by time interaction. However, no difference was observed in the rate of exclusive breastfeeding between these two groups (P > 0.05). Implementing EENC during cesarean section significantly improved maternal-infant attachment (β = 9.668). Moreover, univariate analysis showed benefits of EENC in improving postpartum depression (P < 0.001) and decreasing maternal perinatal blood loss (P < 0.05).ConclusionsAccording to our small sample study, there is a trend of improvement in breastfeeding related behavior and maternal infant attachment in women who received EENC during cesarean deliveries. The effects of EENC on exclusive breastfeeding should be further explored in the future.Trial registration: Chinese Clinical Trial Register at www.chictr.org.cn, ChiCTR2300074760, retrospectively registration. Registration Date: August 15, 2023.

Meta-analysis: the prophylactic use of tranexamic acid to reduce blood loss during caesarean delivery.

The 2022 national guideline on The Prevention and Management of Primary Postpartum Haemorrhage (PPH) recommended consideration of prophylactic tranexamic acid (TXA) for women who are at high PPH risk undergoing caesarean section (CS). This meta-analysis reviews the basis for this recommendation. PubMed, OVID Medline, EMBASE, Science Citation Index, Scopus, CENTRAL, and ClinicalTrials.gov were searched (from inception to January 2024) for randomised controlled trials comparing prophylactic intravenous TXA with placebo or no treatment in women undergoing CS who received a uterotonic. Our main outcome was PPH > 1L. Secondary outcomes included estimated mean blood loss, blood transfusion, drop in haemoglobin, the need for additional uterotonics, or surgical intervention. Adverse effects of TXA were also assessed. Sixty-one studies including 25,098 women were identified, and 12,446 received prophylactic TXA. Patients who received prophylactic TXA had significantly reduced likelihood of PPH > 1L (RR, 0.47; 95% CI, 0.38 to 0.59), reduced estimated mean blood loss (MD 185.86 ml, 95% CI 159.14-212.59), and reduced drop in Hb (MD 0.84g/dl, 95% CI 0.72, 0.95). There was a significant reduction in need for additional uterotonics (RR 0.47, 95% CI 0.39-0.57) or surgical intervention (RR 0.54, 95% CI 0.30-0.95). The reduced risk of PPH > 1L was greatest in patients at higher risk of bleeding. The greatest risk reduction was seen in smaller studies and in studies undertaken in developing economies. Prophylactic TXA administration is effective at reducing the incidence of PPH > 1L at CS. The clinical benefit of universal prophylaxis is questionable; women who are high risk of PPH are more likely to derive benefit.

A retrospective cohort study of monthly rifampicin, ofloxacin and minocycline in the management of leprosy at the Hospital for Tropical Diseases, London, United Kingdom.

The World Health Organization (WHO) recommends rifampicin, dapsone and clofazimine multi-drug therapy (MDT) for the treatment of leprosy. Severe adverse effects include dapsone hypersensitivity syndrome, skin pigmentation, haemolytic anaemia, and hepatitis. At the Hospital for Tropical Diseases (HTD), London, United Kingdom monthly rifampicin, ofloxacin and minocycline (mROM) is used as first line treatment for leprosy. To determine the clinical outcomes and experiences of individuals treated with mROM. A retrospective study of individuals with leprosy who were prescribed mROM at HTD was conducted. Demographic and clinical data were collected on outcomes including relapses, leprosy reactions, bacterial index (BI) and adverse effects. Individuals were interviewed using a semi-structured questionnaire to understand their experiences of mROM. 29 individuals were identified and 20 interviewed. 26 (89.7%) individuals completed monthly mROM. 9 (31%) had switched from WHO MDT to mROM (five of whom (55.6%) were interviewed). BI reduced significantly following mROM treatment (p = 0.04). 17 individuals (58.6%) experienced a leprosy reaction. One of the 29 (3.4%) relapsed. The relapse rate was 9.5/1000 person years. 49 reports of adverse effects were either mild or moderate. The most frequent adverse effect (14/49) reported was orange discolouration of urine. No adverse effect required hospitalisation or discontinuation of mROM. Most individuals reported that skin lesions improved by the time they had completed mROM. In this small study in a non-endemic setting mROM was safe, effective and acceptable. mROM therapy is associated with improvement in skin lesions, decline in bacterial index and acceptable adverse effects. Larger, prospective, randomised studies are needed to determine whether relapse rates with mROM are equivalent or better than WHO MDT and to provide robust data on the seemingly better adverse effect profile of mROM.

Effectiveness of spinal cord stimulation in diabetic patients with chronic limb-threatening ischemia: small cohort study

BackgroundChronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease (PAD). Patients with diabetes mellitus (DM) have a faster progression of PAD and a fourfold increased risk of CLTI compared to patients without DM. Epidural spinal cord stimulation (SCS) has been used as a method to improve microcirculation, relieve ischemic pain and reduce the number of amputations in patients with PAD. This is a retrospective small cohort analysis of patients with diabetes and the long-term treatment effect of spinal cord stimulation.MethodsAs the main outcome of the study, we evaluated the survival and amputation of 13 diabetic patients with chronic lower-limb ischemia who were not eligible for surgical or interventional therapy. Secondary outcomes included ankle-brachial index (ABI), ischemic pain intensity, quality of life, use of analgesic medications and skin wound outcomes analyzed during long-term follow-up.ResultsBetween January 2010 and January 2017, 13 patients underwent SCS implantation in our vascular center. At 1-year follow-up, the limb salvage rate was 92.3% (12 of 13 patients), and limb ulcers healed in 75% of patients (6/8). No patient died during the one-year follow-up. A total of 4 of patients (31%) experienced major amputation during long-term follow-up, all of them were Fontaine stage IV. Pain intensity and quality of life improved significantly at 6-month follow-up (p &amp;lt; 0.05). ABI measurements were unaffected by SCS treatment. There were no complications related to the procedure or device.ConclusionsSCS is a promising treatment option for diabetic patients unsuitable for endovascular or surgical revascularization. The method improves limb survival in diabetic patients with critical limb ischemia, provides significant pain control, and improves patients' quality of life. However, more studies are needed to clarify the indications for SCS and clarify its effects on the vascular system.

Diagnostic Performance of Integrated 18F FDG PETMR in the Diagnosis of Recurrent Foot Infection—Comparison with 18F FDG PETCT and Conventional 99mTc MDP Bone Scan

Abstract Introduction Ulcerated foot is a forerunner for amputations among diabetics. Early detection of foot complications is imperative for guiding management; more so in recurrent foot infections. Purpose The objective of this study was first, to determine the diagnostic performance of integrated Fluorodeoxyglucose (FDG) Positron emission tomography (PET) magnetic resonance (MR) in suspected soft tissue infections (STIs)/osteomyelitis (OM) in patients presenting with recurrent foot infections. Second, to compare regional [18F] fluoro-2-deoxy-2-d-glucose (18F FDG) PET Computed tomography (CT) and conventional three-phase 99mTc methylene diphosphonate (MDP) bone scan (BS) in this group of patients along with integrated PETMR. Materials and Methods A total of 21 adult patients with suspected recurrent foot infections were prospectively enrolled from March 2020 until September 2023 in our tertiary care center. All patients were primarily referred for a regional PETMR (foot) study. We instituted a protocol to combine three-phase 99mTc MDP BS followed by PET imaging the next day (PETMR followed by PETCT). Images were correlated with patients' foot symptoms and clinical examination. Results Diagnostic performance of 18F FDG PETMR was superior compared with other two imaging modalities for STIs and OM. Using 18F FDG PETCT, sensitivity, specificity, and accuracy for diagnosing soft tissue (ST) foot infections was 91, 71, and 79%, respectively, while for PET MR, it was 99.4, 100, and 98.6% versus 74.4, 31.2, and 62% for BS. Conclusion Our study recommends the use of integrated 18F FDG PETMR for podiatry-related problems, as it provides excellent ST demarcation and information on associated bone involvement, if any. It helps in accurately differentiating OM versus Charcot's foot; more so in surgically intervened or previously debrided foot when compared with the other two modalities. 18F FDG PETMR clearly demarcates the depth and extent of surgery one must perform to get a reprieve from occult pockets of infection so as to attain a disease-free status. Given the paucity of evidence for integrated PETMR usage in foot-related indications, our small sample study highlights its superiority for clearly delineating and diagnosing various foot pathologies, infections, especially in the clinical setting of postsurgery/debrided foot.

Longitudinal Trends in the Incidence of Hyperactive Delirium and Its Causes of Change After Surgery for Degenerative Lumbar Disease: A Population-Based Study of 7250 Surgical Patients Over 11 Years.

Delirium is one of the common complications in elderly patients after spinal surgery. Severe delirium can lead to a series of adverse consequences such as drainage tube removal, wound rupture, patient falls, and severe adverse effects. The current research on POD is mostly small sample studies. This study aimed to investigate longitudinal changes in the incidence of hyper-postoperative delirium in patients with lumbar degenerative disease at our institution over the past 11 years and to identify the potential causes of these changes. This is a retrospective cohort study included 7250 patients who underwent surgical treatment for lumbar degenerative diseases at a single center from 2011 to 2021. These patients were diagnosed with delirium through the Confusion Assessment Method and then diagnosed with high activity delirium through the Richmond Agitation-Sedation Scale, totaling 130 cases. According to the incidence rate of hyper-postoperative delirium within 11 years, the trend test is divided into three groups: S1 upward trend (2011-2014), S2 downward trend (2015-2016) and S3 upward trend (2016-2021). The study collected variables from patients before, during, and after surgery, including gender, age, laboratory tests, anesthesia risk score, New York Heart Association cardiac function grading, number of surgical segments, surgical time, estimated intraoperative blood loss, anesthesia medication, and supplementary analgesic medication in the ward within 3 days after surgery. Kruskal Wallis one-way ANOVA test, Kruskal-Wallis H test, or chi-square test are used to evaluate inter group differences. p < 0.05 is considered statistically significant. The pooled incidence of hyper-postoperative delirium over the past 11 years was 1.79% (130/7250). The average age of 7250 patients was 54.5 ± 13 years, with a male/female ratio close to 1:1. We statistically analyzed the relevant influencing factors before, during, and after surgery of S1 and S3 in the incidence rate increase group and found no statistical difference between the two groups. Our research results show that the incidence of high activity delirium is correlated with age, number of surgical segments, surgical duration, use of dexmedetomidine, remifentanil, and benzodiazepines, with p < 0.05. The reduced use of dexmedetomidine, increased use of benzodiazepines, and prolonged surgical time are the reasons for the increased incidence of hyper-postoperative delirium. The joint management of orthopedic surgeons and anesthesiologists during the perioperative period is of great significance in reducing the incidence of hyper-postoperative delirium in patients undergoing lumbar spine surgery.

Bloodletting at the ear apex for acute stroke: A systematic review and meta-analysis of randomized controlled trials.

Stroke is a major cause of death and disability worldwide. Despite innovative developments in acute stroke treatment techniques in modern society, many stroke survivors still experience complications, leading to a demand for complementary and alternative medicines, including traditional medicine. Bloodletting at the ear apex (BLEA) is a nonpharmacological intervention used for various diseases, including acute stroke, in traditional medicine in East Asian countries, including China and Korea. This study aimed to evaluate the clinical efficacy of BLEA for acute stroke recovery. We searched PubMed, Embase, CENTRAL, AMED, CNKI, KoreaMed, ScienceOn, and OASIS databases for randomized controlled trials (RCTs) evaluating the effect of BLEA on acute stroke recovery. We systematically reviewed the literature published in academic journals up to September 8, 2024 and synthesized the data extracted from the final selected literature. The results of the meta-analysis are presented as mean differences (MDs) with 95% confidence intervals (CIs). The Cochrane Risk of Bias 2 tool and GRADE methodology were used for quality assessment. Six RCTs with 530 participants were included in this meta-analysis. In patients with acute stroke receiving conventional Western medical treatment, the addition of BLEA significantly improved neurological deficits assessed by the National Institute of Stroke Scale (MD, -2.83; 95% CIs, -4.48 to -1.17), consciousness impairment measured by the Glasgow Coma Scale (MD, 2.75. 95% CIs, 1.72 to 3.78), and motor function assessed by the Fugl-Meyer Assessment (MD, 5.31. 95% CIs, 3.04 to 7.58). It also significantly reduced the length of hospital stay (MD, -7.39; 95% CIs. -8.85 to -5.93). BLEA may be a promising intervention that provides additional benefits to patients with acute stroke receiving standard western medical care. However, the supporting evidence comes from a few small studies with a high risk of bias and low reporting quality. Future studies with appropriate population sizes and more rigorous methodology are warranted.

A simple statistical framework for small sample studies.

Most studies in psychology, neuroscience, and life science research make inferences about how strong an effect is on average in the population. Yet, many research questions could instead be answered by testing for the universality of the phenomenon under investigation. By using reliable experimental designs that maximize both sensitivity and specificity of individual experiments, each participant or subject can be treated as an independent replication. This approach is common in certain subfields. To date, there is however no formal approach for calculating the evidential value of such small sample studies and to define a priori evidence thresholds that must be met to draw meaningful conclusions. Here we present such a framework, based on the ratio of binomial probabilities between a model assuming the universality of the phenomenon versus the null hypothesis that any incidence of the effect is sporadic. We demonstrate the benefits of this approach, which permits strong conclusions from samples as small as two to five participants and the flexibility of sequential testing. This approach will enable researchers to preregister experimental designs based on small samples and thus enhance the utility and credibility of such studies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Group Aural Rehabilitation: A Scoping Review

Purpose: The purpose of this study was to synthesize published literature on group aural rehabilitation (AR) for older adults with hearing loss and update the research guidance since Hawkins (2005). Method: The scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Scoping Review extension and included five databases. Articles were selected for evaluation if they had been published since 2005, were primary research about group AR for older adults, and were in the English language. Evaluation criteria and data extraction were based on the study design, participant demographics, intervention, and outcome. Results: Three randomized controlled trials (Hickson et al., 2007; Preminger &amp; Yoo, 2010; Preminger &amp; Ziegler, 2008) met all criteria and were selected for further review. Common exclusion reasons included small sample sizes and study designs that were low on the hierarchy of evidence. Conclusion: A few published articles for group AR indicate effectiveness, but the area is in need of additional research that includes high-quality study designs, including consideration of effect sizes, reporting of participant demographics, variables specific to the intervention, and outcomes. Supplemental Material: https://doi.org/10.23641/asha.27122271

The Assessment of Knowledge About Cervical Cancer, HPV Vaccinations, and Screening Programs Among Women as an Element of Cervical Cancer Prevention in Poland

Introduction: Cervical cancer is the fourth most commonly diagnosed malignant tumor in women and the fourth leading cause of cancer-related deaths among this population. Since it is asymptomatic in its early stages, preventive screening plays a crucial role in rapid diagnosis. Such screenings are conducted in many countries worldwide, although their popularity varies. Given that nearly all cases of cervical cancer are linked to high-risk human papillomavirus (hrHPV) infection, vaccination against this virus could lead to a significant reduction in cancer incidence. It should be noted that the level of vaccination coverage against hrHPV varies significantly between countries, ranging from a few percent to over 90%. Globally, the vaccination coverage of the target population is estimated at only a few percent. Methods: This study was conducted using a proprietary, anonymous online questionnaire comprising 24 questions addressing various aspects of cervical cancer prevention. The newly designed questionnaire comprised 19 primary questions and 5 metric questions. The collected data were subjected to descriptive and statistical analysis. Results: The majority of respondents reported regularly participating in cervical cytology screening and gynecological visits. Non-participation in these screenings was primarily reported by younger respondents, not all of whom had indications for undergoing such examinations. Only 14% of the women surveyed had been vaccinated against hrHPV. However, it should be noted that, as the surveyed women were not covered by the relatively recently introduced vaccination program, they received their vaccinations through local programs conducted by certain cities or through private healthcare services. The respondents’ primary sources of information on cervical cancer are the internet and medical personnel. Conclusions: The level of knowledge among the women surveyed regarding cervical cancer prevention was satisfactory, though improvement is needed in some areas. Despite relatively good awareness of HPV’s role in cervical cancer development, the popularity of HPV vaccination remains unsatisfactory. The results should be interpreted with caution due to the small study group.

Evaluating the use of glucagon‐like peptide‐1 receptor agonists in a matched cohort of kidney and liver transplant recipients

AbstractBackgroundDiabetes mellitus (DM) and obesity are common among solid organ transplant recipients, but are associated with an increased risk of graft failure.AimAlthough glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are effective for managing both conditions in the general population, there is limited evidence regarding their use among transplant recipients.MethodThe effect of GLP‐1 RAs on post‐transplant glucose control (defined as haemoglobin A1c [HbA1c]) among 37 liver and kidney transplant patients was compared to a control cohort. Secondary outcomes included change in total daily insulin requirements and oral DM agents, estimated glomerular filtration rate (eGFR), weight, and body mass index (BMI). Adverse events attributed to GLP‐1 RAs, hypoglycaemia, incidence of pancreatitis, biopsy‐proven acute rejection, graft loss, and death were assessed. Ethical approval was granted by the Henry Ford Health Institutional Review Board (Reference no: 15959) and the study conforms with the US Federal Policy for the Protection of Human Subjects.ResultsWe observed that patients receiving GLP‐1 RAs had a median reduction in HbA1c of 0.5% and reduction in insulin and oral anti‐DM agents compared to the control group without GLP‐1 RAs. There were statistically significant reductions in both weight and BMI in the GLP‐1 RA group. Our observed incidence of adverse events was similar to previous literature. Unlike other smaller studies, a decline in eGFR was observed in the GLP‐1 RA group. There were no differences in incidence of biopsy‐proven acute rejection, graft loss, or death.ConclusionWhen compared to patients without GLP‐1 RA therapy, GLP‐1 RAs modestly reduced HbA1c and insulin requirements and statistically reduced weight/BMI review at 6 months. GLP‐1 RAs, even if initiated early post‐transplant, were seemingly safe and effective. Larger, prospective studies are warranted to evaluate the safety and efficacy of GLP‐1 RAs in this population.

Circulating prolactin levels and the effect of dopaminergic agonists in systemic lupus erythematosus: a systematic review and meta-analysis

This systematic review of clinical studies investigated whether circulating PRL levels differed between subjects with systemic lupus erythematosus (SLE) and healthy controls, the correlation between circulating PRL and SLE activity, and the effect of dopaminergic agonists as adjuvant therapy for SLE. We searched PubMed, Scopus, Web of Science, Cochrane, Embase, and Google Scholar for case-control and cross-sectional studies investigating circulating PRL levels in subjects with SLE and/or its correlation with disease activity, and clinical trials examining the effect of dopaminergic agonists on SLE activity assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Forty-five studies addressing circulating PRL levels in SLE met our inclusion criteria. SLE was associated with an increased odds of hyperprolactinemia (OR 11.69, 95%CI 5.64–24.22) and circulating PRL levels were significantly higher in subjects with SLE than in controls (standardized mean difference of 1.62, 95%CI 1.14–2.09). Circulating PRL was positively correlated with SLE activity assessed by the SLEDAI (correlation coefficient 0.38, 95% CI 0.26–0.48). Two randomized clinical trials with bromocriptine and three prospective open-label trials with quinagolide reported that treatment with dopaminergic agonists was associated with reduced frequency of disease flares and decreased SLEDAI score. Circulating PRL levels were higher in subjects with SLE than in healthy controls and were significantly associated with disease activity. In addition, treatment with the dopaminergic agonists bromocriptine and quinagolide reduced SLE disease activity in small studies and may be a beneficial adjuvant therapy for the disease if larger trials confirm these findings. This review was registered in PROSPERO (CRD42021237156).

Survival Outcomes in Patients Undergoing Pelvic Exenteration for Pelvic Mucosal Melanomas: Retrospective Single Institution Australian Study.

Pelvic mucosal melanomas, including anorectal and urogenital melanomas, are rare and aggressive with a median overall survival of up to 20 months. Pelvic mucosal melanomas behave differently to its cutaneous counterparts and presents late with locoregional disease, making pelvic exenteration its only curative surgical option. This study aimed to evaluate the survival outcomes post pelvic exenteration in pelvic mucosal melanomas at Royal Prince Alfred Hospital. Retrospective case series from a prospectively collected pelvic exenteration database from October 1994 to November 2023. Royal Prince Alfred Hospital (quaternary institution), Camperdown, New South Wales, Australia. Seven patients undergoing pelvic exenteration for pelvic mucosal melanoma. Overall survival, disease-free survival, and complication rates. Of the seven patients, most were female (n = 5, 71.4%) and had a median age of 65 years (range, 36-79). Five patients (71.4%) underwent pelvic exenteration for primary pelvic mucosal melanoma; 3 of which were anorectal and 2 vaginal melanomas. Two patients (28.6%) had recurrent anorectal melanoma and received neoadjuvant radiotherapy following an initial wide local excision. Three patients (42.9%) required total pelvic exenteration, while 2 required a central pelvic exenteration (28.6%). The remaining procedures were a central and lateral pelvic exenteration; along with anterior, central and lateral pelvic exenteration. Median length of hospital stay was 19.7 days. Five patients had postoperative complications with one major complication (Clavien-Dindo IIIa). At the study's completion, there were 4 mortalities. Mean survival was 23.6 months (range, 2-100) with a recurrence rate of 83%. Median time to recurrence was 3 months, despite 6 patients (85.7%) having R0 resections. Distant recurrence, i.e. to bone, lung and liver was most common. Small study cohort due to rarity of disease, limiting generalizability. Pelvic exenteration for pelvic mucosal melanoma appears to help control local disease as recurrence is most commonly distant or regional. See Video Abstract.

Clinical Diagnosis of Acute Noma: Essential Infection Markers and Clinical Presentations.

In clinical settings, understanding the markers and clinical signs of infection is critical for timely diagnosis and treatment. However, a point-of-care diagnostic test is lacking for noma, a debilitating orofacial infectious disease. This retrospective study reviewed electronic medical records (EMRs) and paper medical records (PMRs) of noma patients from Facing Africa (235 EMRs), Yekatit 12 Hospital (68 PMRs), and Project Harar (33 PMRs) in Ethiopia to identify essential infection markers and clinical presentations of acute noma. The review identified seven acute noma patients aged 4-9 years. The patients presented with facial edema, pain, anorexia, ecchymosis, excessive salivation, and drooling, as well as specific symptoms such as visual disturbances, high fever, foul odor, halitosis, and local tenderness. Laboratory findings included elevated white blood cell counts (13,500-14,500 cells/mcL), C-reactive protein levels (107-148 mg/L), and erythrocyte sedimentation rates (65-90 mm/hour). At >85 ng/mL, procalcitonin levels were particularly high. Accurate diagnosis of noma requires a comprehensive approach that includes thorough clinical examination, appropriate disease stage classification, medical history review, and laboratory testing. The study highlights the critical infection markers and clinical presentations associated with acute noma that may aid in early diagnosis of the disease. Further research with a much larger number of participants is needed. However, given the difficulty in identifying acute noma cases due to the rapid progression and very high mortality of the disease and the challenge of accessing acute noma cases owing to various socioeconomic barriers, the results of this small study are still relevant.

Impact of endometriosis on oocyte quality in women undergoing assisted reproduction.

Endometriosis is a chronic gynecological condition which can lead to infertility in women during reproductive age. Endometriosis influences the assisted reproductive technology (ART) outcomes by its impact on oocyte and embryo quality, oocyte numbers and subsequently the embryo numbers and endometrial receptivity. There has been clinical dilemma as to whether it is predominantly the oocyte, or the endometrium which affects the pregnancy outcomes in women with endometriosis. In this review we provide an overview of the effect of endometriosis on the oocyte molecular mechanism, the overall effect of endometriosis and its various stages as well as the effect of endometrioma on the oocyte quality in autologous study models. We have also provided a review of the donor oocyte models to study the effect of endometriosis on the endometrium. While initial small donor oocyte-based model studies suggested a possible major detrimental impact of oocyte quality on ART outcomes in women with endometriosis, the more recent studies have found minimal or no impact of oocyte quality on treatment outcomes. There is growing evidence to suggest an important contributory role of reduced oocyte yield on ART success in women with endometriosis. There is a need to explore whether oocyte yield and not the oocyte quality or endometrial receptivity, is the main reason for lower success in women with endometriosis following ART.

Beliefs and behaviors regarding abortion counseling among U.S. clinicians caring for adolescents.

To determine clinician factors associated with discussing abortion during pregnancy options counseling among adolescents. We recruited and surveyed a convenience sample of U.S. clinicians who care for pregnant adolescent patients (N=146). Clinicians were recruited at a national conference, through listservs, and via a physician mailing list. We used chi-square tests to analyze differences in our primary outcomes (routinely discussing abortion, routinely providing abortion referrals, and not routinely advising patients seeking abortion against termination) by clinician demographics, beliefs, and practice settings. Fifty-seven percent of clinicians reported routinely discussing abortion with adolescent patients, 58% routinely referred for abortion, and 76% did not routinely advise against termination. Female gender, pediatric specialty, and practicing in an academic setting were associated with routinely referring for abortion and not routinely counseling against abortion (p<0.05). Additionally, state abortion laws at the time of the survey were associated with abortion discussion and referrals. Having "a personal objection to abortion" or "belief that abortion will harm patients" were negatively associated with each outcome (p <0.05). Clinician demographics and personal beliefs were associated with differences among counseling. Although this was a small exploratory study, our findings highlight important clinician-level barriers to adolescents' access to abortion counseling and care.

Epinephrine Versus Dopamine in Children, What Is the Current Evidence and What Do We Need? A Systematic Review and Meta-analysis

INTRODUCTION Pediatric patients often receive vasoactive agents following cardiothoracic surgery or when in shock. The use of vasoactive agents varies between different settings and has largely changed because of anecdotal observations or small observational studies. Although vasoactive agents are frequently used, there are limited studies in pediatric populations comparing them to one another. The purpose of this systematic review is to quantify the comparative effects of epinephrine and dopamine while identifying gaps in knowledge. METHODS A systematic review of published manuscripts was completed to identify full-text manuscripts in English using PubMed, Embase, and Cochrane databases. Studies were included if they included clinical data using dopamine and epinephrine in different patients and included data for the same end points for patients receiving epinephrine or dopamine. RESULTS A total of 5 studies with 397 patients were included. Of the included patients, 187 received epinephrine and 210 received dopamine. The mean age for all the patients was 45 months. When all patient data were pooled, a significantly lower mortality was associated with epinephrine compared with dopamine (risk ratio, 0.74; 95% CI, 0.55–0.99). When only neonatal data were pooled, epinephrine was associated with a significantly higher average heart rate (10 bpm; 95% CI, 2.0–18.7) and a significantly lower average mean arterial blood pressure (−2.5 mm Hg; 95% CI, −4.6 to −0.4). CONCLUSION Limited data are available comparing dopamine to epinephrine in pediatric patients. The ­available data demonstrate an apparent mortality benefit associated with the use of epinephrine.

Preclinical safety and efficacy of the recombinant CR1 drug product CSL040 in rats and cynomolgus monkeys.

CSL040 is a soluble, recombinant fragment of the complement receptor 1 (CR1) extracellular domain that acts as an inhibitor of all three pathways of the complement system. Systemic toxicity, toxicokinetics (TK), and pharmacodynamics (PD) of CSL040 were assessed in two-week intravenous (IV) bolus studies in Han Wistar rats and cynomolgus monkeys. Recovery from any effects was evaluated during a four-week recovery period. Daily repeat-dose administration for 2 weeks at doses of up to 500 mg/kg CSL040 IV was well tolerated in rats and cynomolgus monkeys, leading to a no observed adverse effect level (NOAEL) of 500 mg/kg for both species. Safety pharmacology parameters such as electrophysiology of the heart, blood pressure, heart rate, and respiratory rate measurements, and general toxicological readouts were considered unaffected by CSL040 treatment. Anti-drug antibodies (ADAs) were observed in all cynomolgus monkeys and in some rats at the highest dose of CSL040, but with no effect on pharmacokinetics (PK), supportive of adequate exposure levels as required for a safety assessment. All three complement pathways were inhibited dose-dependently by CSL040. Additionally, no effect on cytokine levels by CSL040 was detected in vitro using a cytokine release assay. These non-clinical studies with CSL040 demonstrated PD activity consistent with its mode of action, adequate PK properties, and a safety profile supporting a phase 1 clinical strategy. A small follow-up study comparing the PK/PD effects of CSL040 following IV and subcutaneous (SC) administration also suggested that the latter route of administration might be a viable alternative to IV administration.

Small break LOCA studies for different layouts of passive safety systems in the IRIS reactor

IRIS (International Reactor Innovative and Secure) is an integral, medium power, light water reactor with advanced safety features. In the first decade of the 21st century, 22 institutions under the leadership of Westinghouse Electric Corporation were involved in its development. The University of Zagreb, along with the Polytechnic of Milan, was in charge of performing safety analyses. A detailed plant model is developed using the RELAP5 code for the analyses of thermal–hydraulic processes in the reactor vessel, the GOTHIC code for the analysis of the processes in the containment and, in addition, the ASYST code for the calculation of a severe accident. Some of the previous small break loss-of-coolant accident analyzes at the existing pipelines are repeated to test the improved plant model. However, the focus of the paper is on the new set of analyzes of hypothetical breaks along the reactor vessel with the aim of determining whether the passive safety systems can ensure successful core cooling. For this purpose, two models are developed with different configurations of the emergency heat removal system and the safety systems inside the containment that inject water into the reactor vessel. The results show the complex and rather ambiguous dependence of the reactor coolant system thermal–hydraulic behaviour on the selected boundary conditions. The scenarios analyzed vary from design basis events to severe accidents. The capabilities of specific safety systems in mitigating the consequences of an accident are determined, depending on the position and size of the break on the reactor vessel wall.