Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial.

RATIONALE & OBJECTIVE: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease. STUDY DESIGN: Phase 3, open-label, single-arm trial. SETTING & PARTICIPANTS: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age <12 months), and POx ≥20 µmol/L at screening, including patients with or without systemic oxalosis. INTERVENTION: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing. OUTCOME: Primary end point: percent change in POx from baseline to month 6 (cohort A; not receiving hemodialysis at enrollment) and percent change in predialysis POx from baseline to month 6 (cohort B; receiving hemodialysis at enrollment). Pharmacodynamic secondary end points: percent change in POx area under the curve between dialysis sessions (cohort B only); absolute change in POx; percent and absolute change in spot urinary oxalate-creatinine ratio; and 24-hour urinary oxalate adjusted for body surface area. RESULTS: All patients (N = 21; 43% female; 76% White) completed the 6-month primary analysis period. Median age at consent was 8 (range, 0-59) years. For the primary end point, least-squares mean reductions in POx were 33.3% (95% CI, -15.2% to 81.8%) in cohort A (n = 6) and 42.4% (95% CI, 34.2%-50.7%) in cohort B (n = 15). Improvements were also observed in all pharmacodynamic secondary end points. Most adverse events were mild or moderate. No patient discontinued treatment or withdrew from the study. The most commonly reported lumasiran-related adverse events were injection-site reactions, all of which were mild and transient. LIMITATIONS: Single-arm study without placebo control. CONCLUSIONS: Lumasiran resulted in substantial reductions in POx with acceptable safety in patients with PH1 who have advanced kidney disease, supporting its efficacy and safety in this patient population. FUNDING: Alnylam Pharmaceuticals. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT04152200 and at EudraCT with study number 2019-001346-17. PLAIN-LANGUAGE SUMMARY: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive hepatic oxalate production that frequently causes kidney failure. Lumasiran is an RNA interference therapeutic that is administered subcutaneously for the treatment of PH1. Lumasiran has been shown to reduce oxalate levels in the urine and plasma of patients with PH1 who have relatively preserved kidney function. In the ILLUMINATE-C study, the efficacy and safety of lumasiran were evaluated in patients with PH1 and advanced kidney disease, including a cohort of patients undergoing hemodialysis. During the 6-month primary analysis period, lumasiran resulted in substantial reductions in plasma oxalate with acceptable safety in patients with PH1 complicated by advanced kidney disease.

Inguinal hernia repair among Jordanian infants; A cohort study from a university based tertiary center.

BACKGROUND: Inguinal hernia is the most common surgical procedure performed in infants. Still, there is major debate about the optimal timing of performing this procedure. The goal of this review is to determine the incidence of inguinal hernia among our infant population in Jordan, review the current practice regarding the timing of repair, and identify the risk of incarceration and postoperative apnea. METHODS: A retrospective cohort study of chart review of infants admitted with inguinal hernia in the period 2012-2016. Data collected about demographics, timing of diagnosis, timing of repair, exploration of contralateral side, incarceration, and postoperative apnea. RESULTS: A total of 272 infants were diagnosed with inguinal hernia. The overall incidence was 1.9%, compared with 11% among premature babies <32-week gestation. Half were term, and 23% less than 32-week gestation. Male to female ratio was 5 : 1. Of the 172 babies admitted to the neonatal ICU, only 19 cases (11%) were diagnosed during their NICU stay, and one case got repaired emergently. All cases were repaired by open herniorrhaphy. The median postconceptional age at time of repair was 49 weeks (IQR 45-55), and the median interval between diagnosis and repair was 8 days (IQR 1-17). Incarceration affected 9% and the main risk factor was >7-day delay in repair. Only one case developed apnea and required intubation postoperatively. CONCLUSIONS: Our approach of elective inguinal hernia repair seems to be safe without increasing risk of complications like incarceration or postoperative apnea if performed within seven days following diagnosis.

Predictive utility of prior positive urine culture of extended- spectrum ß -lactamase producing strains.

Rising incidence of extended- spectrum beta-lactamase (ESBL) induced urinary tract infections (UTIs) is an increasing concern worldwide. Thus, it is of paramount importance to investigate novel approaches that can facilitate the identification and guide empiric antibiotic therapy in such episodes. The study aimed to evaluate the usability of antecedent ESBL-positive urine culture to predict the pathogenic identity of future ones. Moreover, the study evaluated the accuracy of selected empiric therapy in index episodes. This was a retrospective study that included 693 cases with paired UTI episodes, linked to two separate hospital admissions within 12 month-period, and a conditional previous ESBL positive episode. Pertinent information was obtained by reviewing patients' medical records and computerized laboratory results. Multivariate analysis showed that shorter interval between index and previous episodes was significantly associated with increased chance of ESBL-positive results in current culture (OR = 0.912, 95CI% = 0.863-0.963, p = 0.001). Additionally, cases with ESBL-positive results in current culture were more likely to have underlying urological/surgical condition (OR = 1.416, 95CI% = 1.018-1.969, p = 0.039). Investigations of the accuracy of current empirical therapy revealed that male patients were less accurately treated compared to female patients (OR = 0.528, 95CI% = 0.289-0.963, p = 0.037). Furthermore, surgical patients were treated less accurately compared to those treated in internal ward (OR = 0.451, 95CI% = 0.234-0.870, p = 0.018). Selecting an agent concordant with previous microbiologic data significantly increased the accuracy of ESBL-UTIs therapy (p<0.001). A quick survey of the previous ESBL urine culture results can guide practitioners in the selection of empiric therapy for the pending current culture and thus improve treatment accuracy.

Determinants of antenatal care attendance among women residing in highly disadvantaged communities in northern Jordan: a cross-sectional study.

BACKGROUND: One of the major reproductive health challenges among disadvantaged populations is to provide pregnant women with the necessary antenatal care (ANC). In this study, we suggest applying an integrated conceptual framework aimed at ascertaining the extent to which attendance at ANC clinics may be attributed to individual determinants or to the quality of the care received. METHODS: Using a cross-sectional design, data were collected from a sample of 831 women residing in nine sub-districts in three northern governorates of Jordan and designated according to national categorization as persistent poverty pockets. All of the sampled women were recruited from public maternal and child health centers and interviewed using a structured pre-tested survey. This tool covered certain predictors, ranging from the user's attributes, including predisposing, enabling, and need factors, to the essential components of the experience of care. These components assessed the quality of ANC in terms of five elements: woman-provider relations, technical management, information exchange, continuity of care, and appropriate constellation of services. Adequate ANC content was assessed in relation to the frequency of antenatal visits and the time of each visit. RESULTS: The results of multivariate logistic regression analyses show that the use of ANC facilities is affected by various factors related to the quality of service delivery. These include receiving information and education on ANC during clinic visits (OR = 9.1; 95% CI = 4.9-16.9), providing pregnant women with opportunities for dialogue and health talks (OR = 7.2; 95% CI = 4.1-12.8), having scheduled follow-up appointments (OR = 6.5; 95% CI = 3.5-12.0), and offering dignified and respectful care (OR = 5.7; 95% CI = 2.5-13.1). At the individual level, our findings have identified a woman's education level (OR = 1.2; 95% CI = 1.1-1.3), desire for the pregnancy (OR = 1.7; 95% CI = 1.1-2.7), and living in a district served by an ANC clinic (OR = 4.3; 95% CI = 2.3-8.1) as determinants affecting ANC utilization. CONCLUSION: Taking women's experiences of ANC as a key metric for reporting the quality of the care is more likely to lead to increased utilization of ANC services by women in highly disadvantaged communities. Our findings suggest that the degree to which women feel that they are respected, informed, and engaged in their care has potential favorable implications for ANC.

A Case of Compartment Syndrome in the Scrotum and Inguinal Area Complicating Idiopathic Nephrotic Syndrome of Childhood.

Idiopathic nephrotic syndrome (INS) is a kidney disease characterized by massive proteinuria. Protein loss leads to decreased oncotic pressure shifting the fluids into the interstitial space causing edema, complications such as infections and thromboembolism occur. We report a 7-year-old, diagnosed with NS presenting with a relapse. He developed ascites and scrotal edema followed by severe scrotal pain and redness, progressing rapidly to ecchymosis in the inguinal areas not in continuity with the scrotum. Ultrasound with color Doppler was inconclusive, scrotal exploration was done along with skin incision in the inguinal areas and scrotum, which appeared to relieve the condition rapidly.

Evaluation of the safety and efficacy of metoprolol infusion for children and adolescents with hypertensive crises: a retrospective case series.

BACKGROUND: Acute severe hypertension occurs infrequently in pediatric patients and, consequently, data on the efficacy and safety of most antihypertensive agents, as well as the adverse events associated with these agents, are very limited in this population. In this case series, we evaluated the use of metoprolol infusion in children with hypertensive emergencies. METHODS: The study population comprised children younger than 18 years who had been admitted to the pediatric intensive care unit at King Abdullah University Hospital with blood pressure above the 99th percentile for age, height, and sex and who were symptomatic at the time of presentation. Metoprolol was given as an infusion at a dose of 1-5 mcg/kg/min. The rate of decrease in blood pressure, side effects from the medication, and outcome were assessed. RESULTS: Thirteen patients ranging in age from 2 months to 16 years were included in this study. The initial mean blood pressure was 23-75 mmHg above the 99th percentile for age, height, and sex. Metoprolol was initiated at a dose of 0.5 mcg/kg/min and titrated according to the target blood pressure to a maximum of 5 mcg/kg/min. Mean blood pressure fell by an average of 12.3, 20.4, and 27.1% at 1, 8, and 24 h, respectively, which is consistent with findings on the use of other intravenous medications reported in published studies. The heart rate did not decrease below the normal range for age. There were no significant side effects of the metoprolol infusion. All patients were discharged home with no neurological sequelae secondary to their hypertension. CONCLUSION: An infusion of metoprolol for a hypertensive emergency is a safe and effective treatment for pediatric patients.

Advanced Uropathy in a Child With Underactive Bladder: Unusual Presentation, Treatment, and Long-term Follow Up.

Underactive bladder in children is characterized by low voiding frequency; straining, hypotonic high capacity bladder, and significant residual urine. The usual presentation is recurrent urinary tract infections. Accurate evidence-based diagnosis and treatment is crucial. Subjective and objective improvement and regain of normal voiding can be achieved in response to bladder rehabilitation program and correction of serious complications.

Body size in children with chronic kidney disease after gastrostomy tube feeding.

Outcome body size of gastrostomy tube (g-tube)-fed children with chronic kidney disease (CKD) was investigated. CKD patients, stages 2-5, who had a g-tube inserted and removed between 1985 and 2007 were retrospectively reviewed (n=20) for anthropometrics, lab values, and steroid use from insertion to latest date. CKD patients never having had a g-tube placed (n=82) acted as the comparison population with similar data collection at start and end of the latest 5-year period. Body mass index (BMI)-for-age, weight (Wt)-for-age, and height (Ht)-for-age z scores were calculated and compared between groups. Median age at insertion and duration of g-tube treatment was 1.7 years (range 0.9-15.6), and 2.9 years (range 0.9-11.8), respectively. There was a significant increase in Wt- (p<0.01), and BMI-for-age (p<0.03) z score, but not for Ht-for-age between insertion and removal for subjects. There were no significant differences in Ht-, Wt-, or BMI-for-age z scores, from removal to 5 years post-removal. In the comparison population, there were no significant differences in Ht-, Wt-, or BMI-for-age z scores over the 5-year period. Approximately 36% of the non-tube-fed comparison population and 50% of the tube-fed subjects were overweight or obese at the most recent evaluation. In both subjects and the comparison group, overweight and obesity is associated with transplant status and steroid use. G-tube feeding is an effective method for achieving catch-up weight and moderate height gain in pediatric CKD patients, and does not apparently predispose patients to obesity after removal; however, overweight and obesity may pose problems to children with CKD whether or not they are tube fed.

Familial focal segmental glomerulosclerosis and retinitis pigmentosa: a new association.

The association of retinitis pigmentosa with renal disease is rare and occurs mainly in two conditions: medullary cystic disease and Bardet-Biedl syndrome; here we describe a case of retinitis pigmentosa with familial focal segmental glomerulosclerosis, which to the best of our knowledge has never been reported previously.