Unknown Outcomes Research Articles

The Role of l-arginine in prevention of testicular function toxicity induced by monosodium glutamate burden in Wistar rats

Background: Monosodium glutamate, MSG, is a widely consumed and inadvertently abused glutamate-based flavour enhancer that could impair male fertility. L-arginine, is a fatherhood amino acid that could improve male reproductive apparatus. Possibility of simultaneous consumption of MSG and l-arginine exists with unknown outcomes on testicular function. This study aimed to evaluate the role of l-arginine in prevention of testicular function toxicity induced by monosodium glutamate burden in Wistar rats. Methods: The study involved five rat groups (n = 5). Group 1 rats, normal control, received distilled water. Groups 2,3,4 and 5 rats, respectively received MSG (8000 mg/kg), l-arginine (60 mg/kg), MSG (8000 mg/kg) plus l-arginine (60 mg/kg) and MSG (8000 mg/kg) plus l-arginine (120 mg/kg). Exposure was by oral intubation for 28 consecutive days. Testicular function indicators studied included testosterone activity (in the rats' testes homogenate and serum), sperm quality (sperm count, sperm motility, sperm volume and sperm morphology) and testes histomorphology. Results: Results revealed significant (P<0.05) and marked diminution of testosterone activity (in the testes and serum), sperm quality and spermatogenic cells of the testes in the rats that received MSG compared to rats in normal control and other groups, notably group 5 that received MSG and high dose of l-arginine together. Conclusion: The study demonstrated that MSG burden caused testicular function toxicity in the rats, demonstrated by the altered testes histomorphology, diminished testosterone activity and compromised sperm quality. There was a significant reversal by l-arginine notably at 120 mg/kg of the testicular function toxicity caused by MSG burden in the rats via probable modulation of the compromised indicators as determined in the rats. Thus, l-arginine could play a significant role in the prevention of testicular function toxicity induced by MSG burden in rats.

533. OUTCOMES OF RADIOFREQUENCY ABLATION TO TREAT BARRETT’S OESOPHAGUS: AN IRISH MULTICENTRE STUDY

Abstract The standard two-step approach of endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) has shown to be both safe and effective in achieving complete eradication of intestinal metaplasia (CEIM). Despite confidence in the regimen, the long-term sustainability of CEIM has not been well-described, nor has the ideal number of RFA sessions and frequency and length of surveillance. This study used the RIBBON database in Ireland to analyse these factors. Analysis was performed on 398 eligible patients who underwent at least one session of RFA to treat BE from 2009 to 2021 in major centres across Ireland. Patients included had a minimum of 12 months follow-up (FU), with a total 1433.76 patient-years of FU analysed. CEIM was defined as histological and endoscopic absence of BE at post-RFA FU. Patient outcomes were categorised according to recurrence status at FU: sustained CEIM, primary recurrence, treatment failure and unknown outcomes. They were also grouped according to the extent of dysplasia using the Vienna Grading System. Of the 398 patients, 78.14% were male, the mean age at diagnosis was 61.55 years, mean length of Barrett’s segment was 5.36cm, and baseline dysplasia was 19.3% intramucosal carcinoma (IMC), 19% high-grade dysplasia (HGD), 23.3% low-grade dysplasia (LGD) and 37.1% non-dysplastic BE (NBDE). Of these patients, 321 (80.65%) achieved CEIM, at similar proportions. Of those, 67 (20.87%) experienced recurrence over 404.97 patient-years of FU. Further recurrence following subsequent treatment was rare (6 cases). The most common type of recurrence was NDBE (95.64%), and dysplastic recurrence was uncommon (4.36%). The mean time to recurrence was 647.21 days. The results of this study showed that CEIM was achieved by RFA in the majority of cases, with dysplastic recurrence occurring at a very low rate, equating to significantly reduced disease progression. There was a significant difference between the mean number of treatments for those who achieved sustained CEIM (4.15) and those who experienced recurrence (3.29). It is clear that some adjustments to the existing treatment and surveillance regimen could result in improvements in outcome.

Mortality, incidence and seasonality of canine and feline patients treated with tick antiserum in three far North Queensland veterinary clinics from 2000 to 2020.

Tick paralysis is a paralysis caused by bites from Ixodes holocyclus, affecting an estimated 10,000 companion animals in Australia annually. Despite tick antiserum being the cornerstone of treatment, there are no large-scale general practice studies that examine survival outcomes in tick antiserum-treated animals. In this retrospective study, clinical records from three far north Queensland general practice veterinary clinics were searched for tick antiserum-treated canine and feline patients were seen between 2000 and 2020. Patient records were assessed for survival outcomes,then logistic regression and Bayesian structural time-series model were used to assess trends in incidence and mortalityand the relationship between these and time of year, rainfall, and species. The study included 2019 dog and 953 cat records. When patients with unknown outcomes were removed, canine mortality was 11.8% (213/1799) and feline mortality was 5.3% (46/872). Dogs were found to have 2.41 odds of dying following treatment than cats. August and September had the highest mean number of monthly treatments, and rainfall in the previous 5-8months was positively correlated with the number of patients treated in each month. The odds of mortality did not vary significantly by month or season, and from 2015 onwards, there was a significant decrease in the proportion of dogs treated by the clinics. Overall, this study provides new information on tick antiserum treatment outcomes in general practice as well as new information on tick paralysis incidence in far north Queensland.

Australia needs to implement a national health strategy for doctors.

Australia needs to implement a national health strategy for doctors.

Urological Society of Australia and New Zealand (USANZ) and Australasian Chapter of Sexual Health Medicine (AChSHM) for the Royal Australasian College of Physicians (RACP) clinical guidelines on the management of erectile dysfunction.

These clinical practice recommendations by the Urological Society of Australia and New Zealand (USANZ) and the Australasian Chapter of Sexual Health Medicine (AChSHM) for the Royal Australasian College of Physicians (RACP) provide evidence-based clinical guidelines on the management of erectile dysfunction (ED) in Australia. A comprehensive clinical history and a tailored physical examination are essential (Level of evidence [LoE] 3; GRADE B). Laboratory testing should include fasting glucose, lipid profile and total testosterone level (LoE 3; GRADE A). Specialised diagnostic tests are recommended in selected cases and the patient should be counselled accordingly (LoE 4; GRADE B). Lifestyle changes and optimisation of existing medical conditions should accompany all ED treatment regimens (LoE 1; GRADE A). Oral phosphodiesterase type 5 inhibitor (PDE5i) is an effective first line medical therapy (LoE 1; GRADE A). Intracavernosal injections and vacuum erection devices are recommended as second line therapy (LoE 1; GRADE B). A penile prosthesis implant can be considered in men who are medically refractory or unable to tolerate the side effects of medical therapy (LoE 4; GRADE B). Pro-erectile regenerative therapy remains largely experimental (LoE 3; GRADE B). Modification of lifestyle behaviour, management of reversible risk factors and optimisation of existing medical conditions remain pivotal, and existing standard ED therapies are often effective and safe following cardiovascular risk stratification. Caution should be exercised on the use of regenerative technology in ED due to unknown long term outcomes.

Trends in Maternal Mortality in Tertiary Care Hospital, Peshawar Pakistan- A Follow up study

Objective: To describe the trends in maternal mortality in tertiary care hospitals in the last five years and compare the mortalities in the previous ten years. Methods: All pregnant women from January 2016 to December 2020 were analyzed. The primary outcome of this research was maternal mortality ratios. Various causes of maternal mortality were also evaluated. The correlation between maternal characteristics and maternal mortality was inspected using logistic regression models. Pregnancy outcomes of mothers who died versus mothers who survived were also evaluated. Results: One hundred seventy-three maternal deaths were noted in 49283 pregnant women in 2016-2020. The average maternal mortality ratio in 5 years period was 409 per 100,000 live births. It showed a decreasing curve over the five years, from 539/100,000 live births in 2016 to 295 in 2020. Five year clusters also demonstrated a falling trend, from 856/100,000 live births to 409. Hemorrhage (34.68%), hypertensive disorders of pregnancy (21.38%), suspected cases of thromboembolism (20.80%) were the leading causes of maternal mortality. Pregnancy outcomes in mothers who survived and who expired were evaluated. Almost 33% of maternal deaths had stillbirths as compared to 4.69% in alive mothers (RR 6.87); similarly, unknown outcomes (RR7.56) and ectopic pregnancies (RR 3.01) were more frequent in cases of maternal demise. Conclusion: Trends in maternal mortality show a decreasing curve. Hemorrhage remains the leading cause. Attainment of SDGs requires interventions both at primary and tertiary health care. Keywords: Maternal mortality and Maternal Mortality Ratio (MMR), trends, causes of maternal mortality.

Mortality From Combined Fractures of the Atlas (C1) and Axis (C2) in Adults.

Study designA retrospective case report of all upper cervical spine fractures diagnosed by CT imaging between 01/01/2013 and 31/12/2015 in NHS Greater Glasgow and Clyde, Scotland.ObjectiveTo compare the mortality following combined fractures of the atlas and axis to that of isolated fractures of either vertebra.BackgroundThe mortality from axis fractures is well documented in the literature. However, a combined fracture of the atlas and axis is seldom reported, leading to relatively unknown outcomes and mortality.MethodsA total of 171 patients with atlas and/or axis fractures. Thirty-three presented with concurrent lower cervical spine fractures and were excluded from further analysis. Kaplan-Meier curves were used to compare survivorship between 108 patients with isolated and 30 with combined fractures. Similar analysis adjusted for comorbidities, including dementia and previous fragility fractures.ResultsPatients were followed up for 47.3±10.3 months (SD). Patients with isolated atlas fractures were significantly younger than those with an axis or combined fracture. Nearly half (8/17) of combined fracture mortalities occurred within the first 120 days. The mortality at 120 days was 26.7% in the combined fractures group and 18.5% in the isolated fracture group. There was no significant difference in the 120-day and overall mortality between these injury patterns. Furthermore, cognitive impairment and previous fragility fractures bore no significant impact on mortality. Nevertheless, mortality in the combined fracture group with previous fragility fractures did trend to shorter survivorship.ConclusionsPatients with combined fractures are older and with the ever-increasing elderly population, the incidence of these injuries is expected to rise. While our data show that the 120-day mortality is proportionally higher in the combined fractures group, no long-term statistically significant difference is demonstrated. This evidence contests the notion that combined fractures of the atlas and axis have higher mortality than isolated injuries of either cervical vertebra.

Prioritizing farm management interventions to improve climate change adaptation and mitigation outcomes—a case study for banana plantations

Intervening into agricultural systems necessarily includes risks, uncertainties, and ultimately unknown outcomes. Decision analysis embraces uncertainty through an interdisciplinary approach that involves relevant stakeholders in evaluating complex decisions. We applied decision analysis approaches to prioritize 21 farm management interventions, which could be considered in certification schemes for banana production. We estimated their contribution to climate change adaptation and mitigation as well as ecological outcomes. We used a general model that estimated the impacts of each intervention on adaptation (benefits minus costs), mitigation (global warming potential), ecological parameters (e.g., biodiversity and water and soil quality), and farming aspects (e.g., yield, implementation costs and production risks). We used expert and documented knowledge and presented uncertainties in the form of 90% confidence intervals to feed the model and forecast the changes in system outcomes caused by each intervention compared to a baseline scenario without the measure. By iterating the model function 10,000 times, we obtained probability distributions for each of the outcomes and farm management interventions. Our results suggest that interventions associated with nutrient management (e.g., composting and nutrient management plan) positively affect climate change adaptation, mitigation, and ecological aspects. Measures with no direct yield benefits (e.g., plastic reduction) correlate negatively with adaptation but have positive impacts on ecology. Creating buffer zones and converting low-productivity farmland (incl. unused land) also have positive ecological and adaptation outcomes. Decision analysis can help in prioritizing farm management interventions, which may vary considerably in their relationship with the expected outcomes. Additional work may be required to elaborate a comprehensive assessment of the underlying aspects modulating the impacts of a given measure on the evaluated outcome. Our analysis provides insights on the most promising interventions for banana plantations and may help practitioners and researchers in focusing further studies.

Assessment of leopard translocations in South Africa

Translocations are commonly employed to mitigate human–carnivore conflict but rarely evaluated, resulting in conflicting reports of success, particularly for leopards (Panthera pardus). We evaluate the status of available leopard translocation data, the factors driving the intentional removal of leopards, and the potential causal factors associated with successful and failed translocation events. We obtained data on 60 leopard translocation events across five provinces in South Africa between 1994 and 2021. We considered a successful translocation outcome when (1) the animal was moved outside of its original home range, (2) the animal established a new home range away from the capture site, (3) no substantive livestock losses were linked to the translocated animal in the post-release monitoring period, and (4) the animal survived at least 6 months post-translocation. If mortality occurred due to factors that were equally likely to impact resident individuals and were unrelated to the translocation event (e.g., poaching), the event was not considered a failed effort. Most translocations were the result of human–carnivore conflict (HCC; 82%, n = 49), stressing the high prevalence of HCC and the importance of advocating preventative conflict mitigation efforts to conserve leopards. The leopards were moved distances from 2.5 to 196.3 km (63.3 ± 51.7km). Forty (67%) translocation events had unknown outcomes, indicating the limited data available on translocation outcomes. This also indicates the disparity in the objectives of translocations by various entities involved with translocations and suggests that monitoring be a prerequisite for future translocations. Twenty events offered reliable outcomes by means of post-event monitoring, with seven (12%) considered successful, with three (5%) as failures, and with four (7%) not moved beyond their original home ranges, while six (8%) ended in unrelated deaths. The failed events were attributed to inter/intra-specific competition, and one animal returned to its original home range after a translocation distance of 68 km. Translocation success was strongly explained by translocation distance. We found that damage-causing leopards were successfully translocated under specific conditions, and longer translocation distances increase success. Translocations are commonly employed but are still poorly monitored. We discuss basic standardized protocols to improve future leopard translocations (including pre- and post-monitoring) while advocating alternative non-lethal practices to reduce the prevalence of human–carnivore conflict.

Medical Malpractice Lawsuits Involving Trainees in Obstetrics and Gynecology in the USA.

Background: While the liability risks for obstetrics and gynecology (ob/gyn) physicians are widely recognized, little is known about how trainees have been involved in ob/gyn lawsuits. Objectives: To characterize involvement of trainees in malpractice lawsuits related to ob/gyn. Methods: The legal database Westlaw was utilized to collect ob/gyn-related malpractice lawsuits involving trainees reported from 1986 to 2020 in the USA. Outcome: Forty-six malpractice cases involving ob/gyn trainees were identified, including 34 cases related to obstetrics and 12 to gynecology. There were 11 cases alleging lack of informed consent, including 7 cases alleging lack of consent for trainee involvement. Of the 34 obstetrics cases, 27 related to procedural complications, 17 to treatment, 13 to diagnosis, and 4 to informed consent. Of these, 17 were decided in favor of the physician, 6 resulted in findings of negligence, 9 had unknown outcomes, and 3 ended in settlement. For the 6 cases ending in a finding of negligence, the mean award was $2,174,472 compared to $685,000 for those that were settled. Of the 12 gynecology cases, 8 related to procedural complications, 7 to informed consent, 3 to diagnosis, and 2 to treatment. Of these, 6 were decided in favor of the physician, 3 resulted in findings of negligence, and 3 had unknown outcomes. For the cases ending in a finding of negligence, the mean award was $465,000. Conclusions and Outlook: This review of malpractice cases highlights types of situations in which trainees are sued and reveals the importance of designing curriculum around faculty training and supervision regarding trainee involvement in patient care.

Safety, Tolerability, Pharmacokinetics and Initial Pharmacodynamics of a Subcommissural Organ-Spondin-Derived Peptide: A Randomized, Placebo-Controlled, Double-Blind, Single Ascending Dose First-in-Human Study.

IntroductionThis randomized, double-blind, placebo-controlled study in healthy volunteers assessed the safety, tolerability, and pharmacokinetics of single ascending doses of intravenously administered NX210—a linear peptide derived from subcommissural organ-spondin—and explored the effects on blood/urine biomarkers and cerebral activity.MethodsParticipants in five cohorts (n = 8 each) were randomized to receive a single intravenous dose of NX210 (n = 6 each) (0.4, 1.25, 2.5, 5, and 10 mg/kg) or placebo (n = 2 each); in total, 10 and 29 participants received placebo and NX210, respectively. Blood samples were collected for pharmacokinetics within 180 min post dosing. Plasma and urine were collected from participants (cohorts: 2.5, 5, and 10 mg/kg) for biomarker analysis and electroencephalography (EEG) recordings within 48 h post dosing. Safety/tolerability and pharmacokinetic data were assessed before ascending to the next dose.ResultsThe study included 39 participants. All dosages were safe and well tolerated. All treatment-emergent adverse events (n = 17) were of mild severity and resolved spontaneously (except one with unknown outcome). Twelve treatment-emergent adverse events (70.6%) were deemed drug related; seven of those (58.3%) concerned nervous system disorders (dizziness, headache, and somnolence). The pharmacokinetic analysis indicated a short half-life in plasma (6–20 min), high apparent volume of distribution (1870–4120 L), and rapid clearance (7440–16,400 L/h). In plasma, tryptophan and homocysteine showed dose-related increase and decrease, respectively. No drug dose effect was found for the glutamate or glutamine plasma biomarkers. Nevertheless, decreased blood glutamate and increased glutamine were observed in participants treated with NX210 versus placebo. EEG showed a statistically significant decrease in beta and gamma bands and a dose-dependent increasing trend in alpha bands. Pharmacodynamics effects were sustained for several hours (plasma) or 48 h (urine and EEG).ConclusionNX210 is safe and well tolerated and may exert beneficial effects on the central nervous system, particularly in terms of cognitive processing.

P-461 “15 years of cryopreservation of semen and testicular tissue samples and outcomes of fertility treatments – a single centre experience at Charité-Universitätsmedizin Berlin”

Abstract Study question To explore practices of cryopreservation among male cancer patients and describe outcomes of fertility treatments with samples collected before and after cancer treatment. Summary answer Only 9.1% of cancer patients used their samples for fertility treatment (ART). Patients underwent ART mostly within the first two years and following high-risk treatment. What is known already Fertility preservation has become an important issue, due to the potential gonadotoxicity of oncological therapies. Most cancer patients who undergo gonadotoxic treatment desire to have children. Yet, cancer patients may suffer impaired spermatogenesis in more than a third to over two thirds of cases following standard or high dose cancer treatments, respectively. Identifying risk factors of infertility is therefore fundamental for individual and risk adapted patient counseling. Current guidelines recommend fertility preservation, especially cryopreservation of sperm/testicular tissue, in cancer patients who require gonadotoxic treatment. Rates of utilisation of cryopreserved samples for fertility treatment are low (often <10%). Study design, size, duration In our retrospective study, we collected data from 506 cancer patients who cryopreserved semen/testicular tissue samples between 2004 and 2019 in our centre and for who oncological treatment data was available. Additionally, former patients who had used their previously cryopreserved samples were asked for informed consent to collect information on fertility treatment from the respective fertility centre in which they were treated. Participants/materials, setting, methods We collected oncologic and cryopreservation data from medical records, and fertility treatment data from external clinics. Patients were stratified according to age at diagnosis (<18 or ≥ 18 years old), diagnosis (brain, testicular or solid tumors in other locations or hematologic malignancy) and time-point of cryopreservation (before or after gonadotoxic treatment). We assessed the following fertility outcomes: fertilisation, pregnancy, miscarriage and live birth rate as well as perinatal outcomes (gestational age, weight and height at delivery). Main results and the role of chance The majority of the 506 cancer patients (including 10.5% adolescents) had suffered from a testicular or hematological malignancy. The number of patients that underwent cryopreservation annually in our centre had increased over time. On average, patients collected one sample (1.2±0.4, range:1-3). The majority of samples were collected before oncologic treatment (460/600, 76.7%) and were semen samples (554/601, 92.2%). The rate of cryopreserved tissue was higher in adolescents compared to adults. At the time-point of our study, only 46 patients (9.1%) had used their samples (15,2% tissue samples) for fertility treatment after a median of 18 months following cryopreservation (IQR:7.25±27.5). We received fertility cycle information on 21 patients. Eleven couples (55.0%) had only required one cycle to achieve a pregnancy (range:1-3 cycles, n = 38). Between 70-80% of couples, depending on the cancer diagnosis, achieved at least one pregnancy. Out of 16 patients who had successfully achieved a pregnancy, thirteen succeeded using cryopreserved sperm, one patient required to change from fresh to cryopreserved sperm in the third cycle and two patients used fresh sperm. Rate of pregnancy per e mbryo transfer (ET) was 51.4% (19/37), including eleven singletons, three twin pairs, four miscarriages (in two patients) and one pregnancy with unknown outcome. Limitations, reasons for caution Bias might be caused by the restrospective study design and the fact that recommendations for clinical practice have changed over time. We could not collect information on patients who would have been eligible but did not perform cryopreservation, whose partners conceived spontaneously or who used tissue samples for ART. Wider implications of the findings This study supports sperm and tissue cryopreservation as effective methods for fertility preservation. The rate of ART utilisation is still low, however results from ART cycles are reassuring, also when cryopreserved semen samples are used. Upcoming high-risk treatment is a predictor for ART utilisation, whereas follow-up time is not. Trial registration number Our study was approved by the ethics committee of Charité-Universitätsmedizin Berlin (EA4/158/19).

Risk Assessment of Whale Entanglement and Vessel Strike Injuries From Case Narratives and Classification Trees

Entanglements and vessel strikes impact large whales worldwide. Post-event health status is often unknown because whales are seen once or over short spans that conceal long-term health declines. Well-studied populations with high site fidelity verified by photo-ID offer opportunity to confirm deaths, health declines and recoveries. We used known outcome entanglements and vessel strikes of right whales (Eubalaena glacialis) and humpback whales (Megaptera novaeangliae) to model probabilities of deaths, health declines and recoveries with Random Forest (RF) classification trees. Variables included presence or absence of phrases from case narratives (‘deep laceration’, ‘cyamid’, ‘healing’, ‘superficial’) and a categorical variable for vessel size. Health status post-entanglement was correctly classified in 95.7% of right whale and 93.6% of humpback whale cases (expected by chance=50%). Health status post-vessel strike was correctly classified in 91.4% of right whale and 88.6% of humpback whale cases. Important variables included cyamid presence, emaciation, discolored skin, constricting entanglements, gear-free resightings, superficial or healing lacerations, and vessel size. Cross-validated RF models were applied to unknown outcome cases to estimate the probability of deaths, health declines and recoveries. Total serious injuries (probability of death or health decline > 0.50) assigned by RF were nearly equal to current injury assessment methods applied by biologists for known outcomes. However, RF consistently predicted higher serious injury totals for unknown outcomes, suggesting that current assessment methods may underestimate risk for cases lacking details or long-term observations. Advantages of the RF method include: 1) risk models are based on known outcomes; 2) unknown outcomes are assigned post-event health status probabilities; and 3) identification of important predictor variables improves data collection standards.

Advancing Nursing Science Through Site-Based Clinical Inquiry: Designing Problem Pyramids.

Advancing Nursing Science Through Site-Based Clinical Inquiry: Designing Problem Pyramids.

Severity of Disease and COVID-19 Complications During Hospital Stay: A Prospective Cohort Study.

COVID-19, with its high transmission and mortality rates and unknown outcomes, has become a major concern in the world. Among people with COVID-19, severe cases can quickly progress to serious complications, and even death. So, the present study aimed to examine the relationship between the severity of the disease and the outcome in patients afflicted by COVID-19 during hospitalization. A total of 653 patients with COVID-19 aged 18 years or older were included from Khorshid hospital in Isfahan, Iran and followed for a mean of 22.72 days (median 23.50; range 1-47). Severe COVID-19 was defined by respiration rate≥30 times/min, oxygen saturation level≤88% in the resting position, and pulse rate≥130/min. The primary outcome was mortality. The secondary outcomes included need for mechanical ventilation and intensive care unit (ICU) admission. During 4233 person-days of follow-up, 49 (7.5%) deaths, 27 (4.1%) invasive ventilation and 89 (13.6%) ICU admissions in hospital were reported. After adjustment for potential confounders, severity of the disease was positively associated with risk of mortality, invasive ventilation and ICU admissions (hazard ratio [HR]: 5.99; 95% CI: 2.85, 12.59; P<0.001, HR: 7.09; 95% CI: 3.24, 15.52; P<0.001 and HR: 4.88; 95% CI: 2.98, 7.98; P<0.001, respectively). In addition, greater age (HR=1.04; 95% CI=1.02-1.07; P=0.002), chronic kidney disease (HR=3.05; 95% CI=1.35, 6.90; P=0.008), blood urea nitrogen (BUN) (HR=1.04; 95% CI=1.03-1.05; P<0.001) and creatinine (HR=1.44; 95% CI=1.26-1.65; P<0.001) were probably significant risk factors for mortality in severe COVID-19 patients. More intensive therapy and special monitoring should be implemented for patients with older age, hypertension and kidney disease who are infected with COVID-19 to prevent rapid worsening.

Aortic Stenosis in the Low-Risk Patient: Overview of the Management Options and Possible Permutations.

Young and low-risk patients with aortic stenosis pose a clinical dilemma. The need for life-long anticoagulation with mechanical prostheses, the risk of early degeneration of stented and stentless bioprostheses, the unknown long-term outcomes of transcatheter valve implantation and the high surgical risk of a Ross procedure all have long-term implications namely with regards to re-operation strategy. Aortic valve intervention can take several forms: surgical valve replacement with a stented or stentless bioprosthesis or with a mechanical prosthesis, transcatheter aortic valve implantation (TAVI), and the Ross procedure.1 While the choice of strategy is often straightforward in the elderly and high-risk population, young and low-risk patients with aortic stenosis are challenging to the Heart Team, namely because of their longer life expectancy, and higher cumulative life-time risk of valve-related complications.1 Herein, we review the currently available options for first and subsequent interventions for managing aortic stenosis in low-risk patients.

Multidrug-Resistant Tuberculosis Treatment Outcome and Associated Factors at the University of Gondar Comprehensive Specialized Hospital: A Ten-Year Retrospective Study.

BackgroundMultidrug-resistant tuberculosis (MDR-TB) remains a public health crisis and a health security threat worldwide. Poor public health infrastructure, inefficient infection control and mismanagement of TB treatment are among the reasons for the continuous emergence and spread of drug-resistant TB (DR-TB). The final treatment outcome is the most direct measurement of TB control programs. Therefore, this study sought to determine the proportions and predictors of TB treatment outcomes among MDR/RR-TB treated patients.MethodsA 10-year, 2011 to 2021, hospital-based retrospective cohort study was conducted at the University of Gondar Comprehensive Specialized Hospital. The records of 408 MDR-TB patients, 389 with treatment outcome and 19 on treatment, were collected using a structured checklist.ResultsA total of 389 patients with a recorded MDR/RR-TB treatment outcome were included. The treatment success rate was 77.12%, with 58.35% cured and 18.76% treatment completed. The proportion of death rate, treatment default loss to follow-up, treatment failure, and unknown treatment outcome was 9.25%, 6.94%, 3.1%, and 3.6%, respectively. Regarding the patient category, the most successful treatment outcome (83.5%) came from patients diagnosed with relapse cases, followed by new cases (81.8%). An unsuccessful treatment outcome was significantly associated with patients aged >44 years (AOR, 3.3, 95% CI = 1.55–6.99).Conclusion and RecommendationsThis study indicated that nearly 23% of MDR/RR-TB patients had unsuccessful treatment outcomes and being older was significantly correlated with these outcomes. For better outcomes, it is recommended to strengthen combined treatment adherence interventions and evaluate treatment regimens and administration options. A prospective cohort study may be required to investigate the full range of potential causes of unfavorable outcomes.

Diagnosed with advanced prostate cancer: A population-based cohort from national oncology practices.

5087 Background: Clinical trials can provide access to novel systemic agents and possible improved survival for men diagnosed with regional and metastatic prostate cancer. Although clinical trials should be accessible to all patient populations, racial disparities to enrollment of clinical trials and its outcomes remain an important unknown outcome. Herein, we sought to elucidate the racial disparities in clinical trial enrollment and survival amongst advanced prostate cancer patients from a large community-based medical oncology consortium. Methods: Using CancerLinQ, we identified all patients who were diagnosed with regional (N1+) and/or metastatic (M1) prostate cancer from 2011 – 2021. Enrollment into a clinical trial and overall survival constituted the primary outcomes in this study. Multivariable logistic regression and Cox proportional hazard regression were used to identify covariates associated with each outcome. Results: Amongst the 160,888 patients with regional/metastatic prostate cancer, only 1.5% patients were enrolled in a clinical trial (n = 2,368). On multivariable analysis, patients with worse ECOG performance status were associated with lowers odds of clinical trial enrollment (p &lt; 0.001). Relative to white patients, African-American men (AAM) also had lower odds of clinical trial enrollment (OR: 0.67; p &lt; 0.001). For the entire cohort, clinical trial enrollment correlated with higher survival (HR: 1.19; p &lt; 001) and lower survival for AAM men (HR: 0.85; p &lt; 0.001) compared to white men after adjusting for other covariates. In the subgroup analysis of patients enrolled in clinical trials, AAM demonstrated similar survival to white patients (HR: 0.96, p = 0.95). Conclusions: Although African-American men with regional/metastatic prostate cancer face barriers to clinical trial enrollment, racial disparities in survival appear to resolve for patients who enroll in clinical trials. Increased attention is needed to address barriers to communication and access to clinical trials.

OP0129 REPORTED CONGENITAL MALFORMATIONS AFTER EXPOSURE TO NON-TNF-Α INHIBITORS: A RETROSPECTIVE COMPARATIVE STUDY IN EUDRAVIGILANCE DATABASE

BackgroundTumor necrosis factor-α inhibitors (TNFis) such as certolizumab pegol (CZP), are a subgroup of biologics, which have shown no increase in risk of congenital malformations (CMs) after use during pregnancy. (1) However, for the subgroup of non-TNFis, very scarce data is available.ObjectivesTo evaluate the number and nature of reported CMs after intrauterine exposure to non-TNFis compared to CZP, in Eudravigilance database.MethodsA retrospective comparative study in EudraVigilance database was conducted. Reports of all pregnancies exposed to non-TNFis and CZP, were extracted. Multiple versions of a unique case, pregnancies with unknown outcome, paternal exposures, CMs due to known genetic abnormalities, and cases exposed only via breast milk were excluded. Odd ratios for CMs were calculated for each non-TNFi, with CZP as reference group. Due to limitations of pharmacovigilance databases, such as possibility of under-reporting normal outcomes and information bias (2), in consultation with a clinical geneticist, CM patterns were compared between non-TNFi and CZP groups.ResultsIn total 851 non-TNFi and 1179 CZP exposed pregnancy reports were included. Numerical differences for CMs after exposure to non-TNFis were not statistically significant except for belimumab and vedolizumab (Table 1).Table 1.Reported number, crude and adjusted ORs [95%CIs] for major and minor CMs and TOPFAs after intrauterine exposure to non-TNFis compared to CZPMedicationReported CMs and TOPFAs, n/N (%)Crude ORs [95%CIs],Adjusted ORs (for maternal age) [95%CIs],Stratified ORs (teratogen unexposed cases only) [95%CIs] *Certolizumab pegol95/1179 (8.05)ReferenceReferenceReferenceAbatacept2/64 (3.12)0.36 [0.08, 1.52]0.35 [0.08, 1.47]0.69 [0.16, 2,96]Anakinra3/20 (15.00)2.01 [0.57, 6.99]2.81 [0.77, 10.20]3.39 [0.91, 12.63]Belimumab17/93 (18.27)2.55 [1.44, 4.49]2.63 [1.40, 4.93]2.65 [1.35, 5.20]Ixekizumab1/29 (3.44)0.40 (0.05, 3.02]0.39 [0.05, 2.96]0.42 [0.05, 3.16]Rituximab8/57 (14.03)1.86 [0.85, 4.04]2.47 [1.05, 5.80]2.55 [0.94, 6.95]Secukinumab4/128 (3.12)0.36 [0.13, 1.01]0.34 [0.10, 1.11]0.37 [0.11, 1.19]Tocilizumab10/124 (8.06)1.00 [0.50, 1.97]0.79 [0.37, 1.68]0.62 [0.22, 1.76]Ustekinumab19/215 (8.83)1.10 [0.66, 1.85]0.92 [0.51, 1.66]1.01 [0.56, 1.82]Vedolizumab23/113 (20.35)2.91 [1.76, 4.82]2.66 [1.53, 4.61]2.27 [1.24, 4.15]OR: odds ratio; CI: confidence interval; CM: congenital malformation; TOPFA: termination of pregnancy due to foetal anomaly anomaly.*After adjusting for maternal age, stratified ORs are presented for patients who had no reported teratogen exposure during pregnancy.Pattern of CMs were reviewed by a clinical geneticist. Except for vedolizumab, no specific CM patterns were observed. For vedolizumab four cases of corpus callosum agenesis (CCA) were reported (versus null in CZP and other investigated non-TNFis). Three of the CCA cases were associated with other neurological CMs such as a neural tube defect, microcephaly and polymicrogyria. This indicates that the reported CCAs may have been related to undiagnosed genetic alterations or were associated with underlying maternal disease, although a definite relationship cannot be ruled out.ConclusionExcept for vedolizumab, no special safety signal was identified regarding occurrence of CMs after exposure to non-TNFis. Based on available information, no firm conclusions can be made regarding observed CCA cases in vedolizumab group.

Living Kidney Donation Stories and Advice Shared Through a Digital Storytelling Library: A Qualitative Thematic Analysis

Rationale & ObjectiveDespite the development of numerous educational interventions, there has been limited change in actual living donor kidney transplant (LDKT) rates over time. New strategies, such as the inclusion of patient stories in patient education, show promise to inspire more people to donate kidneys. This study identified the challenges faced, coping strategies used, and advice shared by transplant donors and recipients.Study DesignQualitative thematic analysis.Setting & ParticipantsOne hundred eighteen storytellers across the United States and Canada, including 82 living donors and 36 kidney recipients of living donor transplants who shared their stories on the Living Donation Storytelling Project (explorelivingdonation.org), an online digital storytelling platform and library.Analytical ApproachA poststorytelling survey assessed participant demographics. Two coders conducted tool-assisted (Dedoose v.8.3.35) thematic analysis on narrative storytelling videos and transcripts.ResultsStorytellers were predominantly White (79/118, 66.95%), female (76/118, 64.41%), and non-Hispanic (109/118, 92.37%) with college/vocational education (50/118, 42.37%). Common themes were found related to living donation challenges for donors and recipients (eg, the fear of not being able to complete the LDKT process, of unsupportive family or rejected donation requests, and of unknown or adverse surgical outcomes and graft rejection) and recommended coping strategies (eg, seeking LDKT information, using prayer, and relying on a support network). Recipients provided advice that included being proactive and staying hopeful, whereas donors recommended seeking support, researching LDKT to comprehensively learn, and building a community of support.LimitationsLimited representation of diverse demographics.ConclusionsAlthough supplementary to traditional education about LDKT, digital storytelling provides a source of peer support that can enhance the experience of donors and recipients and encourage autonomy and self-management after transplant.