Objective

To investigate patterns of care for testicular torsion and influence of hospital transfers on testicular outcomes. Hospital transfer may be a source of treatment delay in a condition where delays increase likelihood of orchiectomy.

Methods

We used a retrospective cohort of Californian males with ICD-9/CPT-defined torsion from inpatient, emergency department (ED), and ambulatory surgery center (ASC) data. Logistic regression assessed predictors of orchiectomy.

Results

Predictors of orchiectomy were ages <1 year (OR 19.2, 95% CI 6.3-58.9), 1-9 years (OR 2.7, 95% CI 1.4-5.2), and ≥40 years (OR 6.6, 95% CI 3.1-13.9) (vs. masked age). Treatment at mid-volume (vs. high-volume) facilities was associated with lower odds of orchiectomy (OR 0.5, 95% CI 0.3-0.7). Rural location, non-private insurance, and hospital transfer were associated with orchiectomy on univariate but not multivariate analysis. During 2008-2010, 2794 subjects experienced torsion (average incidence 5.08 per 100,000 males yearly). Encounters occurred in ASCs (55%), inpatient facilities (36%), and EDs (9%). 60% of subjects were privately insured, 2% experienced hospital transfer, and 31% underwent orchiectomy.

Conclusion

Our census found that most cases of testicular torsion were treated in outpatient settings. Hospital transfer was not associated with orchiectomy.

Objective

To characterize urine test use in ambulatory, antibiotic-treated pediatric urinary tract infection (UTI).

Methods

We studied children <18 years who had an outpatient UTI and a temporally associated antibiotic prescription from 2002 through 2007 by using a large claims database, Innovus i3. We evaluated urine-testing trends and performed multivariable logistic regression to assess for factors associated with urine culture use.

Results

Of 40 603 treated UTI episodes in 28 678 children, urinalysis was performed in 76%, and urine culture in 57%; 32% of children <2 years had no urinalysis or culture performed for an antibiotic-treated UTI episode. Urine culture use decreased during the study period from 60% to 54% (P < .001). We observed variation in urine culture use with age (<2 years: odds ratio [OR] 1.0, 95% confidence interval [CI] 0.9-1.1; 2-5 years: OR 1.3, 95% CI 1.2-1.4; 6-12 years: OR 1.3, 95% CI 1.2-1.4, compared with 13-17 years); gender (boys: OR 0.8, 95% CI 0.8-0.9); and specialty (pediatrics: OR 2.6, 95% CI 2.5-2.8; emergency medicine, OR 1.2, 95% CI 1.1-1.3; urology: OR 0.5, 95% CI 0.4-0.6, compared with family/internal medicine). Recent antibiotic exposure (OR 1.1, 95% CI 1.1-1.2) and empirical broad-spectrum prescription (OR 1.2, 95% CI 1.1-1.2) were associated with urine culture use, whereas previous UTI and urologic anomalies were not.

Conclusions

Providers often do not obtain urine tests when prescribing antibiotics for outpatient pediatric UTI. Variation in urine culture use was observed based on age, gender, and physician specialty. Additional research is necessary to determine the implications of empirical antibiotic prescription for pediatric UTI without confirmatory urine testing.

Objective

To investigate whether orchiopexies are occurring later than recommended by American Academy of Pediatrics 1996 guidelines (around age 1). Adherence to guidelines is poorly studied.

Methods

The main cohort consisted of 4103 boys insured from birth (Innovus i3, insurance claims database). The complementary cohort consisted of 17 010 insured and noninsured boys (Pediatric Health Information System, PHIS). The inclusion criteria was age ≤ 5 years at time of International Classification of Disease, 9th revision-defined cryptorchidism diagnosis. The primary outcome was timely surgery (orchiopexy by age 18 months).

Results

In Innovus, 87% of boys who underwent an orchiopexy had a timely orchiopexy. Of those who did not undergo surgery (n = 2738), 90% had at least 1 subsequent well-care visit. Those who underwent timely surgery were referred to a surgeon at a younger age compared with those who underwent late surgery (4.1 vs 16.1 months, P < .00005). Predictors of timely surgery were number of well-care visits (odds ratio 1.5, 95% confidence interval 1.3-1.7), continuity of primary care (odds ratio 1.9, 95% confidence interval 1.3-2.7), and use of laparoscopy (odds ratio 4.5, 95% confidence interval 1.4-14.9). Family/internal medicine as referring provider was predictive of delayed surgery (odds ratio 0.5, 95% confidence interval 0.3-0.8). In the Pediatric Health Information System, 61% of those with private insurance had timely surgery compared with 54% of those without private insurance (P < .0001).

Conclusion

We found an unexpectedly high adherence to guidelines in our continuously insured since birth Innovus population. Primary care continuity and well-care visits were associated with timely surgery. Further studies can confirm these findings in nonprivately insured patients with the ultimate goal of instituting quality improvement initiatives.

Chloroquine and hydroxychloroquine are quinoline derivatives used to treat malaria. To date, these medications are not approved for the treatment of viral infections, and there are no well-controlled, prospective, randomized clinical studies or evidence to support their use in patients with coronavirus disease 2019 (COVID-19). Nevertheless, chloroquine and hydroxychloroquine are being studied alone or in combination with other agents to assess their effectiveness in the treatment or prophylaxis for COVID-19. The effective use of any medication involves an understanding of its pharmacokinetics, safety, and mechanism of action. This work provides basic clinical pharmacology information relevant for planning and initiating COVID-19 clinical studies with chloroquine or hydroxychloroquine, summarizes safety data from healthy volunteer studies, and summarizes safety data from phase II and phase II/III clinical studies in patients with uncomplicated malaria, including a phase II/III study in pediatric patients following administration of azithromycin and chloroquine in combination. In addition, this work presents data describing the proposed mechanisms of action against the severe acute respiratory distress syndrome coronavirus-2 and summarizes clinical efficacy to date.

Background

Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001.

Objectives

We conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months.

Methods

Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (ΣDMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype.

Results

There was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (β = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (β = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (β per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics.

Conclusions

Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure.

Citation

Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. 2016. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environ Health Perspect 124:822-830; http://dx.doi.org/10.1289/ehp.1409474.

Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.