Association of Early Life Prescriptions for Antibiotics and Acid Suppressants with Childhood Psychotropic Prescriptions.

OBJECTIVE: To examine the association between antibiotic and acid suppressant prescriptions in the first 2 years of life and subsequent treatment for childhood psychiatric disorders. STUDY DESIGN: This was a retrospective cohort study of children born between October 2001 and September 2012 in the Military Health System enrolled in TRICARE past age 2 years and within 35 days of birth, with an initial hospital stay <7 days, and without psychotropic agents dispensed during the first 2 years of life. Exposure was defined as a filled prescription for an antibiotic or acid suppressant before age 2 years, and the outcome was defined as a filled prescription for a psychotropic agent after age 2 years. RESULTS: For the 804 920 patients (51% males and 49% female) composing the study population, the mean age at first psychotropic prescription was 6.8 years. A total of 24 176 children (3%) were prescribed a proton pump inhibitor (PPI), 79 243 (10%) were prescribed a histamine-2 receptor antagonist (H2RA), and 607 348 (76%) were prescribed an antibiotic during the first 2 years of life. The adjusted hazard ratio (aHR) of a psychotropic prescription was significantly increased in children prescribed any H2RA (1.79; 95% CI, 1.63-1.96), PPI (1.47; 95% CI, 1.26-1.71), or antibiotic (1.71; 95% CI, 1.59-1.84). The aHR of psychotropic prescriptions increased commensurately with each additional antibiotic class added and with each additional class of medication (H2RA, PPI, or antibiotics) prescribed. CONCLUSIONS: Children prescribed antibiotic and acid suppressants in the first 2 years of life have a significant increase in future prescriptions for psychotropics, with a dose-related effect observed. This association represents a potential risk of early exposure to antibiotics and acid suppressants.

Antibiotic and acid-suppression medications during early childhood are associated with obesity.

OBJECTIVE: Gut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity. DESIGN: We performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression. RESULTS: 333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed. CONCLUSIONS: Antibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

Association of prematurity with the development of infantile hypertrophic pyloric stenosis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) has several known risk factors. The association between prematurity and IHPS and the timeline of presentation are poorly defined. Our aim was to evaluate the associations between IHPS and prematurity. METHODS: We performed a retrospective cohort study of 1,074,236 children born between June 2001 and April 2012 in the US Military Health System. IHPS cases and gestational ages (GA) were identified using billing codes. Additional risk factors for IHPS were controlled for in a multivariable logistic regression model. RESULTS: The incidence of IHPS was 2.99 per 1,000 in preterm infants and 2.25 per 1,000 in full term (relative risk (RR) = 1.33, 95% confidence interval (CI) 1.16-1.54). The adjusted odds ratio for prematurity was 1.26 (95% CI 1.08-1.46). The median (interquartile range (IQR)) chronological age at presentation was 40 d (30-56) in preterm infants vs. 33 d (26-45) in full term (P < 0.001). Median postmenstrual age at presentation was 42 wk in preterm infants (40-42) vs. 45 wk (44-46) in full term (P < 0.001). CONCLUSION: Prematurity is associated with IHPS. Premature infants develop IHPS at a later chronological age, but earlier postmenstrual age, than term infants. Providers should have an increased concern for IHPS development in premature infants.

Maternal and Fetal Health Risks Among Female Military Aviation Officers.

INTRODUCTION: Military aviation poses unique occupational risks, including exposures to intermittent hypoxia, high gravitational force, and toxic materials, in addition to circadian disruption, cosmic radiation, and ergonomic stressors also present in commercial flight. We sought to investigate whether a military aviation officer's career is associated with adverse maternal or fetal health outcomes.METHODS: We conducted a retrospective cohort study of female aviation and nonaviation officers in the Military Health System from October 2002 to December 2019. Exposure was identified as assignment of an aviation occupation code. Maternal and fetal health outcomes were identified by International Classification of Diseases codes from medical records. Regression analysis was used to estimate adjusted relative risks (aRR).RESULTS: Included in the study were 25,929 active-duty female officers, with 46,323 recorded pregnancies and 32,853 recorded deliveries; 2131 pregnancies were diagnosed in aviation officers. Pregnant aviation officers had a decreased risk of composite adverse pregnancy outcomes [aRR 0.82 (0.73-0.92)], including gestational diabetes [aRR 0.69 (0.57-0.85)] and gestational hypertension [aRR 0.84 (0.71-0.99)]. Pregnant aviation officers had a decreased risk of depression prior to delivery [aRR 0.43 (0.35-0.53)] and hyperemesis gravidarum [aRR 0.74 (0.57-0.96)], but an increased risk of placental complications [aRR 1.15 (1.02-1.30)] and fetal growth restriction [aRR 1.36 (1.16-1.60)].DISCUSSION: Pregnant military aviation officers have an increased risk of placental complications and fetal growth restriction in spite of a lower risk of gestational diabetes and gestational hypertension. Further research is needed to determine how flight-related occupations impact pregnancy.Stark CM, Sorensen IS, Royall M, Dorr M, Brown J, Dobson N, Salzman S, Susi A, Hisle-Gorman E, Huggins BH, Nylund CM. Maternal and fetal health risks among female military aviation officers. Aerosp Med Hum Perform. 2024; 95(9):675-682.

New frontiers in neonatal red blood cell transfusion research.

Red blood cell (RBC) transfusions are common in neonates requiring intensive care. Recent studies have compared restricted versus liberal transfusion guidelines, but limitations exist on evaluations of outcomes in populations that never required a transfusion compared to those receiving any transfusion. Although there are well-established risks associated with RBC transfusions, new data has emerged that suggests additional clinically relevant associations, including adverse neurodevelopmental outcomes, donor sex differences, and inflammation or immunosuppression. Further research is needed to delineate the magnitude of these risks and to further improve the safety of transfusions. The goal of this review is to highlight underappreciated, yet clinically important risks associated with neonatal RBC transfusions and to introduce several areas in which neonates may uniquely benefit from alterations in practice.

Massive fetomaternal haemorrhage warranting novel use of tandem isovolumetric partial exchange transfusion and therapeutic hypothermia.

A newborn male infant was pale, hypotonic, and had respiratory distress after delivery. Venous cord blood gas revealed a severe metabolic acidosis. His initial examination was consistent with moderate encephalopathy and laboratory testing uncovered severe congenital anaemia (haematocrit 0.127 L/L). He met the clinical criteria for therapeutic hypothermia (TH) and required red blood cell transfusions, but due to the severity of his anaemia, an exchange transfusion was favoured to prevent transfusion-associated circulatory overload. There are no previous reports of these procedures completed in tandem, but the benefits were perceived to outweigh the risks. During the 72 hours of TH, the infant received an isovolumetric partial exchange transfusion and tolerated both treatments without any adverse clinical events.Kleihauer-Betke testing detected a massive chronic fetomaternal haemorrhage with 475 mL (164 mL/kg) of blood. A brain MRI completed prior to discharge was normal. At 6 months of age, he is growing and developing normally.

Chest Pain and Fever in a Healthcare Provider During the Global Coronavirus Pandemic.

The coronavirus disease 2019 (COVID-19) global pandemic has posed unique challenges to healthcare providers that work in austere environments. Military healthcare providers advise commanders on endemic disease risk, prevention, and management during field training exercises. Healthcare workers are at increased risk of exposure to infectious pathogens. We present a case of a military healthcare provider who presented with fever, cough, and fatigue during the COVID-19 global pandemic that was diagnosed with a primary pulmonary coccidioidal infection. Treatment after appropriate diagnosis consisted of supportive care. Respiratory and pain symptoms resolved by 2 months post-diagnosis. Although COVID-19 must be closely monitored in the field training environment, it is important to maintain a high index of suspicion of endemic infectious diseases as a potential etiology for respiratory illnesses.

Association of Inflammatory Bowel Disease and Urolithiasis in Hospitalized Pediatric Patients.

BACKGROUND: Urolithiasis is rare in pediatric patients. All patients with inflammatory bowel disease (IBD) have an increased risk of urolithiasis, but this risk is poorly quantified in children. The objective of this study is to evaluate the association of IBD with urolithiasis, assess surgical outcomes, and analyze the financial burden for children hospitalized with urolithiasis and comorbid IBD. METHODS: The triennial Healthcare Cost and Utilization Project Kids' Inpatient Database for years 1997 to 2012 was used to evaluate the association between urolithiasis and IBD in hospitalized, nonpregnant children ages 5 to 20 years old. Billing codes were used to define conditions. Logistic regression analysis quantified the association between IBD types and urolithiasis. Length of hospital stay, costs, procedures, and complications were compared between urolithiasis patients with and without IBD. RESULTS: Among 8,828,522 hospital admissions, we identified 36,771 admissions with a primary diagnosis of urolithiasis. Of these cases, 230 were associated with Crohn's disease (odds ratios, 1.99; 95% confidence interval, 1.74-2.27) and 102 with ulcerative colitis (odds ratio, 1.63; 95% confidence interval, 1.34-1.99). Urolithiasis patients with ulcerative colitis, but not Crohn's disease, had significantly increased length of stay and costs. Patients with either IBD had a decreased number of urologic procedures. CONCLUSIONS: The diagnosis of urolithiasis in pediatric patients is associated with IBD, and those with ulcerative colitis have longer hospital stays and greater costs. Patients with IBD have fewer urologic procedures associated with their urolithiasis diagnosis.

Primary renal magnesium wasting: an unusual clinical picture of exercise-induced symptoms.

Magnesium is one of the most abundant cations in the human body and plays a key role as a metabolic enzyme cofactor and regulatory ion for neurons and cardiomyocytes. Hypomagnesemia due to isolated primary renal magnesium wasting is a rare clinical condition typically associated with neurological hyperexcitability. Exercise-related gastrointestinal symptoms are caused by ischemic, mechanical, or neurohormonal changes. The role of hypomagnesemia in gastrointestinal symptoms is not well understood. We present a case of a 15-year-old male who presented with exercise-induced abdominal pain, nausea, and vomiting, who was found to have profound hypomagnesemia and inappropriately elevated fractional excretion of magnesium (FEMg). Testing for multiple intrinsic and extrinsic etiologies of renal magnesium wasting was inconclusive. He was diagnosed with primary renal magnesium wasting and his symptoms resolved acutely with intravenous magnesium sulfate and with long-term oral magnesium chloride. Primary renal magnesium wasting is a rare clinical entity that can cause extreme hypomagnesemia. It has not been associated previously with exercise-induced gastrointestinal symptoms. The effects of hypomagnesemia on the human gastrointestinal tract are not well established. This case offers unique insights into the importance of magnesium homeostasis in the gastrointestinal tract. Exercise-induced splanchnic hypoperfusion may contribute to gastrointestinal symptoms observed in this chronically hypomagnesemic patient.

20-HETE mediates ozone-induced, neutrophil-independent airway hyper-responsiveness in mice.

BACKGROUND: Ozone, a pollutant known to induce airway hyper-responsiveness (AHR), increases morbidity and mortality in patients with obstructive airway diseases and asthma. We postulate oxidized lipids mediate in vivo ozone-induced AHR in murine airways. METHODOLOGY/PRINCIPAL FINDINGS: Male BALB/c mice were exposed to ozone (3 or 6 ppm) or filtered air (controls) for 2 h. Precision cut lung slices (PCLS; 250 microm thickness) containing an intrapulmonary airway ( approximately 0.01 mm(2) lumen area) were prepared immediately after exposure or 16 h later. After 24 h, airways were contracted to carbachol (CCh). Log EC(50) and E(max) values were then calculated by measuring the airway lumen area with respect to baseline. In parallel studies, dexamethasone (2.5 mg/kg), or 1-aminobenzotriazol (ABT) (50 mg/kg) were given intraperitoneal injection to naïve mice 18 h prior to ozone exposure. Indomethacin (10 mg/kg) was administered 2 h prior. Cell counts, cytokine levels and liquid chromatography-mass spectrometry (LC-MS) for lipid analysis were assessed in bronchoalveolar lavage (BAL) fluid from ozone exposed and control mice. Ozone acutely induced AHR to CCh. Dexamethasone or indomethacin had little effect on the ozone-induced AHR; while, ABT, a cytochrome P450 inhibitor, markedly attenuated airway sensitivity. BAL fluid from ozone exposed animals, which did not contain an increase in neutrophils or interleukin (IL)-6 levels, increased airway sensitivity following in vitro incubation with a naïve PCLS. In parallel, significant increases in oxidized lipids were also identified using LC-MS with increases of 20-HETE that were decreased following ABT treatment. CONCLUSIONS/SIGNIFICANCE: These data show that ozone acutely induces AHR to CCh independent of inflammation and is insensitive to steroid treatment or cyclooxygenase (COX) inhibition. BAL fluid from ozone exposed mice mimicked the effects of in vivo ozone exposure that were associated with marked increases in oxidized lipids. 20-HETE plays a pivotal role in mediating acute ozone-induced AHR.