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1.
Acad Med ; 95(9): 1346-1349, 2020 09.
Article in English | MEDLINE | ID: mdl-32459675

ABSTRACT

The COVID-19 pandemic has brought unique challenges to the delivery of undergraduate medical education, particularly for current third-year medical students who are preparing to apply to residency. In mid-March, medical schools suspended all clinical rotations for the remainder of the 2019-2020 academic year. As such, third-year medical students may not be able to complete sufficient clinical experiences to make important career choices before they have to submit their residency applications. While the decision to suspend clinical rotations was necessary to protect students, specialty organizations and residency programs must mitigate the deficits in students' clinical education caused by the COVID-19 pandemic.In this Perspective, the authors identify potential challenges for third-year medical students and advocate for solutions to improve the residency application process for students and programs. First, they propose delaying the date that programs can access applicant data through the Electronic Residency Application Service, thereby affording students more time to complete clinical experiences, solidify their specialty decision, and strengthen their residency application. Second, the authors recommend a restriction on the number of visiting rotations that students are expected to complete to allow for a more equitable distribution of these important experiences. Third, they suggest that program directors from each specialty agree on a maximum number of applications per applicant (based on historical data) to curb an upsurge in applications that may stem from the unique circumstances created by COVID-19 without causing applicants undue stress. Lastly, the authors advocate that residency programs develop infrastructure to conduct video-based interviews and engage students through virtual networking events.Amidst the unique environment created by COVID-19, the authors urge governing bodies, specialty organizations, and residency programs to consider these recommendations to improve the efficiency and reduce the stress surrounding the 2021 Match.


Subject(s)
Coronavirus Infections/epidemiology , Education, Medical, Undergraduate , Internship and Residency , Pneumonia, Viral/epidemiology , School Admission Criteria , Schools, Medical/organization & administration , Betacoronavirus , COVID-19 , Humans , Pandemics , SARS-CoV-2 , Students, Medical
2.
Int Breastfeed J ; 13: 41, 2018.
Article in English | MEDLINE | ID: mdl-30202424

ABSTRACT

BACKGROUND: Implications of donor milk feedings on infant growth in resource limited settings remain uncertain. This knowledge gap includes the impact of donor milk availability on infant intake of mother's own milk. Therefore, this investigation aimed to measure intake and growth in infants receiving donor milk when born to women from resource limited backgrounds with high rates of human immunodeficiency virus (HIV). METHODS: A retrospective cohort study enrolled eligible infants admitted to a South African combined neonatal intensive and secondary high care unit, within a one year admission period during 2015, with signed consent for donor milk feedings. A certified milk bank provided donor milk. Daily nutritional intake during the first month was recorded. Details included proportional intake of donor milk, mother's own milk and infant formula. The primary outcome of infant growth velocity from day back to birth weight to discharge was calculated when length of stay was ≥14 days. Analyses primarily used T-tests; mixed effects models compared weekly calorie intake. RESULTS: One hundred five infants with donor milk consent were born at 30.9 ± 3.6 weeks of gestation, weighing 1389 ± 708 g. Forty percent of mothers had HIV. Infant growth velocity did not differ based on percent of feedings as donor milk (≥ 50%: 11.8 ± 4.9 g/kg/d; < 50%: 13.5 ± 5.3 g/kg/d; p = 0.3). Percent of feedings from donor milk was similar based on maternal HIV status (positive: 31 ± 25%; negative: 36 ± 29%; p = 0.4), as was percent of feedings as mother's milk (positive: 53 ± 35%; negative: 58 ± 30%; p = 0.4). Calorie intake increased markedly during the first two weeks and then plateaued (p < 0.0001). CONCLUSIONS: Donor milk feedings in higher proportions did not further impair growth of infants managed in a South African combined neonatal intensive and secondary high care unit with growth rates already below reference ranges. The provision of donor milk contributed to feedings being composed of primarily human milk during the first month. Increasing early calorie intake may improve infant growth in this center.

3.
J Pediatr Surg ; 53(4): 794-797, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28927975

ABSTRACT

BACKGROUND/PURPOSE: Arterial catheter complications are a common problem in a pediatric critical care setting, but reported complication rates and risk factors associated with peripheral arterial catheter complications vary. We conducted a retrospective cohort study to identify risk factors in a pediatric patient population. METHODS: We performed a detailed abstraction of provider notes in the electronic medical records of inpatients ≤18years of age who underwent arterial line placement between January 1, 2008 and January 1, 2013 at a university-affiliated standalone pediatric hospital. Inpatient records were assessed for complications associated with arterial catheterization and risk factors inherent to arterial catheter insertion. RESULTS: Two hundred twenty-eight children were identified, of whom 75 (33%) had a total of 106 arterial catheter complications. Complications included line malfunctions (59%, n=63), bleeding (16%, n=17), multiple complications (11%, n=12), infiltration (8%, n=9), and hematoma (4%, n=4). Line malfunction was reported in all patients with multiple complications. Independent predictors of complications associated with arterial catheterization were the presence of more than one provider during the insertion (p=0.007) and insertion attempts at multiple sites (p=0.036). CONCLUSIONS: Our analysis suggests the need for a prospective study to comprehensively assess provider-related risk factors associated with arterial catheter complications in children. LEVEL OF EVIDENCE: IV.


Subject(s)
Catheterization, Peripheral/adverse effects , Postoperative Complications/etiology , Adolescent , Catheterization, Peripheral/methods , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Retrospective Studies , Risk Factors
4.
Am J Trop Med Hyg ; 97(3): 774-776, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28722573

ABSTRACT

Intestinal infection caused by Cryptosporidium is a major contributor to diarrhea morbidity and mortality in young children around the world. Current treatments for children suffering from cryptosporidiosis are suboptimal. Lactoferrin is a glycoprotein found in breast milk. It has showed bacteriostatic and antimicrobial activity in the intestine. However, the effects of lactoferrin on the intestinal parasite Cryptosporidium have not been reported. In this study, we investigated the anticryptosporidial activity of human lactoferrin on different stages of Cryptosporidium. Physiologic concentrations of lactoferrin killed Cryptosporidium parvum sporozoites, but had no significant effect on oocysts viability or parasite intracellular development. Since sporozoites are essential for the infection process, our data reinforce the importance of breastfeeding and point to the potential of lactoferrin as a novel therapeutic agent for cryptosporidiosis.


Subject(s)
Cryptosporidium/drug effects , Lactoferrin/pharmacology , Sporozoites/drug effects , Humans , Lactoferrin/chemistry , Milk, Human/chemistry , Oocysts/drug effects
5.
J Infect Dis ; 215(8): 1275-1284, 2017 04 15.
Article in English | MEDLINE | ID: mdl-28329187

ABSTRACT

Bumped kinase inhibitors (BKIs) of Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) are leading candidates for treatment of cryptosporidiosis-associated diarrhea. Potential cardiotoxicity related to anti-human ether-à-go-go potassium channel (hERG) activity of the first-generation anti-Cryptosporidium BKIs triggered further testing for efficacy. A luminescence assay adapted for high-throughput screening was used to measure inhibitory activities of BKIs against C. parvum in vitro. Furthermore, neonatal and interferon γ knockout mouse models of C. parvum infection identified BKIs with in vivo activity. Additional iterative experiments for optimum dosing and selecting BKIs with minimum levels of hERG activity and frequencies of other safety liabilities included those that investigated mammalian cell cytotoxicity, C. parvum proliferation inhibition in vitro, anti-human Src inhibition, hERG activity, in vivo pharmacokinetic data, and efficacy in other mouse models. Findings of this study suggest that fecal concentrations greater than parasite inhibitory concentrations correlate best with effective therapy in the mouse model of cryptosporidiosis, but a more refined model for efficacy is needed.


Subject(s)
Antiprotozoal Agents/administration & dosage , Cryptosporidiosis/drug therapy , Cryptosporidium parvum/drug effects , Protein Kinase Inhibitors/administration & dosage , Administration, Oral , Animals , Diarrhea/drug therapy , Disease Models, Animal , Female , Mice , Mice, Knockout , Mice, SCID
6.
J Infect Dis ; 214(12): 1850-1855, 2016 Dec 15.
Article in English | MEDLINE | ID: mdl-27738055

ABSTRACT

Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium-dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side chains that typically block a hydrophobic pocket in protein kinases. We exploited this to develop bumped kinase inhibitors (BKIs) that selectively target CDPK1. We have shown that several BKIs of Cryptosporidium CDPK1 potently reduce enzymatic activity and decrease parasite numbers when tested in vitro. In the present work, we studied the anticryptosporidial activity of BKI-1517, a novel BKI. The half maximal effective concentration for Cryptosporidium parvum in HCT-8 cells was determined to be approximately 50 nM. Silencing experiments of CDPK1 suggest that BKI-1517 acts on CDPK1 as its primary target. In a mouse model of chronic infection, 5 of 6 SCID/beige mice (83.3%) were cured after treatment with a single daily dose of 120 mg/kg BKI-1517. No side effects were observed. These data support advancing BKI-1517 as a lead compound for drug development for cryptosporidiosis.


Subject(s)
Antiprotozoal Agents/administration & dosage , Cryptosporidiosis/drug therapy , Immunocompromised Host , Protein Kinase Inhibitors/administration & dosage , Animals , Antiprotozoal Agents/adverse effects , Antiprotozoal Agents/isolation & purification , Calcium-Binding Proteins/antagonists & inhibitors , Cryptosporidium parvum/drug effects , Disease Models, Animal , Mice, SCID , Parasitic Sensitivity Tests , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/isolation & purification , Treatment Outcome
7.
Curr Trop Med Rep ; 2(3): 181-187, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26568906

ABSTRACT

Cryptosporidiosis is increasingly recognized as an important global health concern. While initially reported in immunocompromised such as AIDS patients, cryptosporidiosis has now been documented as a major cause of childhood diarrhea and an important factor in childhood malnutrition. Currently, nitazoxanide is the only proven anti-parasitic treatment for Cryptosporidium infections. However, it is not effective in severely immunocompromised patients and there is limited data in infants. Immune reconstitution or decreased immunosuppression is critical to therapy in AIDS and transplant patients. This limitation of treatment options presents a major public health challenge given the important burden of disease. Repurposing of drugs developed for other indications and development of inhibitors for novel targets offer hope for improved therapies, but none have advanced to clinical studies.

8.
Am J Trop Med Hyg ; 93(5): 970-5, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26240156

ABSTRACT

Dogs are the principal reservoir hosts of zoonotic visceral leishmaniasis (VL) but current serological methods are not sensitive enough to detect all subclinically infected animals, which is crucial to VL control programs. Polymerase chain reaction (PCR) methods have greater sensitivity but require expensive equipment and trained personnel, impairing its implementation in endemic areas. We developed a diagnostic test that uses isothermal recombinase polymerase amplification (RPA) to detect Leishmania infantum. This method was coupled with lateral flow (LF) reading with the naked eye to be adapted as a point-of-care test. The L. infantum RPA-LF had an analytical sensitivity similar to real time-PCR, detecting DNA of 0.1 parasites spiked in dog blood, which was equivalent to 40 parasites/mL. There was no cross amplification with dog or human DNA or with Leishmania braziliensis, Leishmania amazonensis, or Trypanosoma cruzi. The test also amplified Leishmania donovani strains (N = 7). In a group of clinically normal dogs (N = 30), RPA-LF detected more subclinical infections than rK39 strip test, a standard serological method (50% versus 13.3% positivity, respectively; P = 0.005). Also, RPA-LF detected L. infantum in noninvasive mucosal samples of dogs with a sensitivity comparable to blood samples. This novel molecular test may have a positive impact in leishmaniasis control programs.


Subject(s)
DNA, Kinetoplast/isolation & purification , Dog Diseases/parasitology , Leishmania/isolation & purification , Leishmaniasis, Visceral/veterinary , Nucleic Acid Amplification Techniques/veterinary , Point-of-Care Systems , Animals , Antigens, Protozoan/isolation & purification , Argentina/epidemiology , DNA, Kinetoplast/genetics , Dog Diseases/diagnosis , Dog Diseases/epidemiology , Dogs , Leishmania/genetics , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/epidemiology , Nucleic Acid Amplification Techniques/methods , Protozoan Proteins/isolation & purification , Sensitivity and Specificity
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