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Therapeutic drug monitoring using saliva as matrix: an opportunity for linezolid, but challenge for moxifloxacin

The World Health Organization (WHO) has listed moxifloxacin and linezolid among the preferred "group A" drugs in the treatment of multidrug-resistant (MDR)-tuberculosis (TB) [1]. Therapeutic drug monitoring (TDM) could potentially optimise MDR-TB therapy, since moxifloxacin and linezolid show large pharmacokinetic variability [1–4]. TDM of moxifloxacin focuses on identifying patients with low drug exposure who are at risk of treatment failure and acquired fluoroquinolone resistance [5, 6]. Alternatively, TDM of linezolid strives to reduce toxicity while ensuring an adequate drug exposure because of its narrow therapeutic index [1, 3, 7].




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Forced oscillation technique for optimising PEEP in ventilated extremely preterm infants

Ventilatory settings are critical in mechanically ventilated extremely preterm newborn infants due to the risk of ventilation-induced lung injury (VILI) and the subsequent development of bronchopulmonary dysplasia (BPD) [1]. Positive end-expiratory pressure (PEEP) settings usually rely on blood gases, oxygen requirement, lung auscultation, evaluation of chest radiograph and assessment of the pressure/volume curves provided by ventilators. Studies of optimal PEEP settings in the surfactant-treated preterm infant in need of mechanical ventilation are limited and evidence-based clinical guidelines are sparse [2, 3]. A bedside method identifying the PEEP value that comprises maximal lung volume recruitment and minimising tissue overdistension could improve real-time optimisation of PEEP and potentially minimise the risk of VILI and BPD [4, 5].




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Eosinophils, basophils and type 2 immune microenvironments in COPD-affected lung tissue

Although elevated blood or sputum eosinophils are present in many patients with COPD, uncertainties remain regarding the anatomical distribution pattern of lung-infiltrating eosinophils. Basophils have remained virtually unexplored in COPD. This study mapped tissue-infiltrating eosinophils, basophils and eosinophil-promoting immune mechanisms in COPD-affected lungs.

Surgical lung tissue and biopsies from major anatomical compartments were obtained from COPD patients with severity grades Global Initiative for Chronic Obstructive Lung Disease stages I–IV; never-smokers/smokers served as controls. Automated immunohistochemistry and in situ hybridisation identified immune cells, the type 2 immunity marker GATA3 and eotaxins (CCL11, CCL24).

Eosinophils and basophils were present in all anatomical compartments of COPD-affected lungs and increased significantly in very severe COPD. The eosinophilia was strikingly patchy, and focal eosinophil-rich microenvironments were spatially linked with GATA3+ cells, including type 2 helper T-cell lymphocytes and type 2 innate lymphoid cells. A similarly localised and interleukin-33/ST2-dependent eosinophilia was demonstrated in influenza-infected mice. Both mice and patients displayed spatially confined eotaxin signatures with CCL11+ fibroblasts and CCL24+ macrophages.

In addition to identifying tissue basophilia as a novel feature of advanced COPD, the identification of spatially confined eosinophil-rich type 2 microenvironments represents a novel type of heterogeneity in the immunopathology of COPD that is likely to have implications for personalised treatment.




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Immediate reactions with glatiramer acetate: Diagnosis of allergy and desensitization protocols

Purpose of review

Diverse adverse events have been associated with administration of glatiramer acetate (GA), mainly local reactions at the injection site. Other, less frequent generalized reactions include isolated postinjection reactions and anaphylaxis, which may lead to discontinuation of GA.

Recent findings

Close collaboration between the allergy and neurology departments is needed to study adverse reactions to GA. The allergy study should include a detailed history and skin prick and intradermal tests with GA and, if possible, determination of specific IgE levels. Furthermore, the implication of other drugs should be ruled out.

Summary

An accurate diagnosis of reactions to GA is essential if we are to confirm or rule out allergy to GA. When an allergy diagnosis is confirmed or firmly suspected based on clinical evidence, desensitization protocols are increasingly seen as safe methods for reintroduction of GA.




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Apraxia of speech involves lesions of dorsal arcuate fasciculus and insula in patients with aphasia

Objective

To determine the contributions of apraxia of speech (AOS) and anomia to conversational dysfluency.

Methods

In this observational study of 52 patients with chronic aphasia, 47 with concomitant AOS, fluency was quantified using correct information units per minute (CIUs/min) from propositional speech tasks. Videos of patients performing conversational, how-to and picture-description tasks, word and sentence repetition, and diadochokinetic tasks were used to diagnose AOS using the Apraxia of Speech Rating Scale (ASRS). Anomia was quantified by patients' scores on the 30 even-numbered items from the Boston Naming Test (BNT).

Results

Together, ASRS and BNT scores accounted for 51.4% of the total variance in CIUs/min; the ASRS score accounted for the majority of that variance. The BNT score was associated with lesions in the left superior temporal gyrus, left inferior frontal gyrus, and large parts of the insula. The global ASRS score was associated with lesions in the left dorsal arcuate fasciculus (AF), pre- and post-central gyri, and both banks of the central sulcus of the insula. The ASRS score for the primary distinguishing features of AOS (no overlap with features of aphasia) was associated with less AF and more insular involvement. Only ~27% of this apraxia-specific lesion overlapped with lesions associated with the BNT score. Lesions associated with AOS had minimal overlap with the frontal aslant tract (FAT) (<1%) or the extreme capsule fiber tract (1.4%). Finally, ASRS scores correlated significantly with damage to the insula but not to the AF, extreme capsule, or FAT.

Conclusions

Results are consistent with previous findings identifying lesions of the insula and AF in patients with AOS, damage to both of which may create dysfluency in patients with aphasia.




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Levodopa-induced dyskinesia in dementia with Lewy bodies and Parkinson disease with dementia

Objective

To investigate the frequency of levodopa-induced dyskinesia in dementia with Lewy bodies (DLBs) and Parkinson disease with dementia (PDD) and compare these frequencies with patients with incident Parkinson disease (PD) through a population-based cohort study.

Methods

We identified all patients with DLB, PDD, and PD without dementia in a 1991–2010 population-based parkinsonism-incident cohort, in Olmsted County, Minnesota. We abstracted information about levodopa-induced dyskinesia. We compared patients with DLB and PDD with dyskinesia with patients with PD from the same cohort.

Results

Levodopa use and dyskinesia data were available for 141/143 (98.6%) patients with a diagnosis of either DLB or PDD; 87 (61.7%), treated with levodopa. Dyskinesia was documented in 12.6% (8 DLB and 3 PDD) of levodopa-treated patients. Among these patients, median parkinsonism diagnosis age was 74 years (range: 64–80 years); 63.6%, male. The median interval from levodopa initiation to dyskinesia onset was 2 years (range: 3 months–4 years); the median daily levodopa dosage was 600 mg (range: 50–1,600 mg). Dyskinesia severity led to levodopa adjustments in 5 patients, and all improved. Patients with dyskinesia were diagnosed with parkinsonism at a significantly younger age compared with patients without dyskinesia (p < 0.001). Levodopa dosage was unrelated to increased risk of dyskinesias among DLB and PDD. In contrast, 30.1% of levodopa-treated patients with PD developed dyskinesia. In age-, sex-, and levodopa dosage–adjusted models, Patients with DLB and PDD each had lower odds of developing dyskinesia than patients with PD (odds ratio = 0.42, 95% CI 0.21–0.88; p = 0.02).

Conclusions

The dyskinesia risk for levodopa-treated patients with DLB or PDD was substantially less than for levodopa-treated patients with PD.




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Neurology consults in emergency departments: Opportunities to streamline care

Objective

To use the variations in neurology consultations requested by emergency department (ED) physicians to identify opportunities to implement multidisciplinary interventions in an effort to reduce ED overcrowding.

Methods

We retrospectively analyzed ED visits across 3 urban hospitals to determine the top 10 most common chief complaints leading to neurology consultation. For each complaint, we evaluated the likelihood of consultation, admission rate, admitting services, and provider-to-provider variability of consultation.

Results

Of 145,331 ED encounters analyzed, 3,087 (2.2%) involved a neurology consult, most commonly with chief complaints of acute-onset neurologic deficit, subacute neurologic deficit, or altered mental status. ED providers varied most in their consultation for acute-onset neurologic deficit, dizziness, and headache. Neurology consultation was associated with a 2.3-hour-longer length of stay (LOS) (95% CI: 1.6–3.1). Headache in particular has an average of 6.7-hour-longer ED LOS associated with consultation, followed by weakness or extremity weakness (4.4 hours) and numbness (4.1 hours). The largest estimated cumulative difference (number of patients with the specific consultation multiplied by estimated difference in LOS) belongs to headache, altered mental status, and seizures.

Conclusion

A systematic approach to identify variability in neurology consultation utilization and its effect on ED LOS helps pinpoint the conditions most likely to benefit from protocolized pathways.




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Worldwide survey of neurologists on approach to autoimmune encephalitis

Objective

To explore practice differences in the diagnosis and management of autoimmune encephalitis (AE), which is complicated by issues with sensitivity/specificity of antibody testing, nonspecific MRI/EEG/CSF findings, and competing differential diagnoses.

Methods

We used a worldwide electronic survey with practice-related demographic questions and clinical questions about 2 cases: (1) a 20-year-old woman with a neuropsychiatric presentation strongly suspicious of AE and (2) a 40-year-old man with new temporal lobe seizures and cognitive impairment. Responses among different groups were compared using multivariable logistic regression.

Results

We received 1,333 responses from 94 countries; 12.0% identified as neuroimmunologists. Case 1: those treating >5 AE cases per year were more likely to send antibodies in both serum and CSF (adjusted odds ratio [aOR] vs 0 per year: 3.29, 95% CI 1.31–8.28, p = 0.011), pursue empiric immunotherapy (aOR: 2.42, 95% CI 1.33–4.40, p = 0.004), and continue immunotherapy despite no response and negative antibodies at 2 weeks (aOR: 1.65, 95% CI 1.02–2.69, p = 0.043). Case 2: neuroimmunologists were more likely to send antibodies in both serum and CSF (aOR: 1.80, 95% CI 1.12–2.90, p = 0.015). Those seeing >5 AE cases per year (aOR: 1.86, 95% CI 1.22–2.86, p = 0.004) were more likely to start immunotherapy without waiting for antibody results.

Conclusions

Our results highlight the heterogeneous management of AE. Neuroimmunologists and those treating more AE cases generally take a more proactive approach to testing and immunotherapy than peers. Results highlight the need for higher-quality cohorts and trials to guide empiric immunotherapy, and evidence-based guidelines aimed at both experts and nonexperts. Because the average AE patient is unlikely to be first seen by a neuroimmunologist, ensuring greater uniformity in our approach to suspected cases is essential to ensure that patients are appropriately managed.




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Factors associated with 30-day readmission for patients hospitalized for seizures

Background

We sought to determine the cumulative incidence of readmissions after a seizure-related hospitalization and identify risk factors and readmission diagnoses.

Methods

We performed a retrospective cohort study of adult patients hospitalized with a primary discharge diagnosis of seizure (International Classification of Diseases, Ninth Edition, Clinical Modification codes 345.xx and 780.3x) using the State Inpatient Databases across 11 states from 2009 to 2012. Hospital and community characteristics were obtained from the American Hospital Association and Robert Wood Johnson Foundation. We performed logistic regressions to explore effects of patient, hospital, and community factors on readmissions within 30 days of discharge.

Results

Of 98,712 patients, 13,929 (14%) were readmitted within 30 days. Reasons for readmission included epilepsy/convulsions (30% of readmitted patients), mood disorders (5%), schizophrenia (4%), and septicemia (4%). The strongest predictors of readmission were diagnoses of CNS tumor (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.9–2.4) or psychosis (OR 1.8, 95% CI 1.7–1.8), urgent index admission (OR 2.0, 95% CI 1.8–2.2), transfer to nonacute facilities (OR 1.7, 95% CI 1.6–1.8), long length of stay (OR 1.7, 95% CI 1.6–1.8), and for-profit hospitals (OR 1.7, 95% CI 1.6–1.8). Our main model's c-statistic was 0.66. Predictors of readmission for status epilepticus included index admission for status epilepticus (OR 3.5, 95% CI 2.6–4.7), low hospital epilepsy volume (OR 0.4, 95% CI 0.3–0.7), and rural hospitals (OR 4.8, 95% CI 2.1–10.9).

Conclusion

Readmission is common after hospitalization for seizures. Prevention strategies should focus on recurrent seizures, the most common readmission diagnosis. Many factors were associated with readmission, although readmissions remain challenging to predict.




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Cerebral venous thrombosis: Associations between disease severity and cardiac markers

Background

Plasma cardiac troponin (cTn) elevation occurs in acute ischemic stroke and intracranial hemorrhage and can suggest a poor prognosis. Because acute cerebral venous thrombosis (CVT) might lead to venous stasis, which could result in cardiac stress, it is important to evaluate whether cTn elevation occurs in patients with CVT.

Methods

Inpatients at Johns Hopkins Hospital from 2005 to 2015 meeting the following criteria were included: CVT (ICD-9 codes with radiologic confirmation) and available admission electrocardiogram (ECG) and cTn level. In regression models, presence of ECG abnormalities and cTn elevation (>0.06 ng/mL) were evaluated as dependent variables in separate models, with location and severity of CVT involvement as independent variables, adjusted for age, sex, and hypertension.

Results

Of 81 patients with CVST, 53 (66%) met the inclusion criteria. Participants were, on average, aged 42 years, white (71%), and female (66%). The left transverse sinus was most commonly thrombosed (47%), with 66% having >2 veins thrombosed. Twenty-two (41%) had cTn elevation. Odds of cTn elevation increased per each additional vein thrombosed (adjusted OR 2.79, 95% CI [1.08–7.23]). Of those with deep venous involvement, 37.5% had cTn elevation compared with 4.4% without deep clots (p = 0.02). Venous infarction (n = 15) was associated with a higher mean cTn (0.14 vs 0.02 ng/mL, p = 0.009) and was predictive of a higher cTn in adjusted models (β = 0.15, 95% CI [0.06–0.25]).

Conclusions

In this single-center cohort study, markers of CVT severity were associated with increased odds of cTn elevation; further investigation is needed to elucidate causality and significance.




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Risk of stroke after emergency department visits for neurologic complaints

Objective

To assess the risk of subsequent stroke among older patients discharged from an emergency department (ED) without a diagnosis of TIA or stroke.

Methods

Using electronic health record data from a large urban, university hospital and a community-based hospital, we analyzed patients aged 60–89 years discharged to home from the ED without an International Statistical Classification of Diseases and Related Health Problems, 9th or 10th Revision diagnosis of TIA or stroke. Based on the presence/absence of a head CT and the presence/absence of a chief complaint suggestive of TIA or stroke ("symptoms") during the index ED visit, we created 4 mutually exclusive groups (group 1, reference: head CT no, symptoms no; group 2: head CT no, symptoms yes; group 3: head CT yes, symptoms no; and group 4: head CT yes, symptoms yes). We calculated rates of stroke in the 30, 90, and 365 days after the index visit and used multivariable logistic regression to estimate odds ratios (ORs) for subsequent stroke.

Results

Among 35,622 patients (mean age 70 years, 59% women, and 16% African American), unadjusted rates of stroke in 365 days were as follows: group 4: 2.5%; group 3: 1.1%; group 2: 0.69%; and group 1: 0.54%. The adjusted OR for stroke was 3.30 (95% confidence interval [CI], 1.61–6.76) in group 4, 1.56 (95% CI, 1.16–2.09) in group 3, and 0.61 (95% CI, 0.22–1.67) in group 2.

Conclusions

Among patients discharged from the ED without a diagnosis of TIA or stroke, the occurrence of a head CT and/or specific neurologic symptoms established a clinically meaningful risk gradient for subsequent stroke.




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Machine learning as a diagnostic decision aid for patients with transient loss of consciousness

Background

Transient loss of consciousness (TLOC) is a common reason for presentation to primary/emergency care; over 90% are because of epilepsy, syncope, or psychogenic non-epileptic seizures (PNES). Misdiagnoses are common, and there are currently no validated decision rules to aid diagnosis and management. We seek to explore the utility of machine-learning techniques to develop a short diagnostic instrument by extracting features with optimal discriminatory values from responses to detailed questionnaires about TLOC manifestations and comorbidities (86 questions to patients, 31 to TLOC witnesses).

Methods

Multi-center retrospective self- and witness-report questionnaire study in secondary care settings. Feature selection was performed by an iterative algorithm based on random forest analysis. Data were randomly divided in a 2:1 ratio into training and validation sets (163:86 for all data; 208:92 for analysis excluding witness reports).

Results

Three hundred patients with proven diagnoses (100 each: epilepsy, syncope and PNES) were recruited from epilepsy and syncope services. Two hundred forty-nine completed patient and witness questionnaires: 86 epilepsy (64 female), 84 PNES (61 female), and 79 syncope (59 female). Responses to 36 questions optimally predicted diagnoses. A classifier trained on these features classified 74/86 (86.0% [95% confidence interval 76.9%–92.6%]) of patients correctly in validation (100 [86.7%–100%] syncope, 85.7 [67.3%–96.0%] epilepsy, 75.0 [56.6%–88.5%] PNES). Excluding witness reports, 34 features provided optimal prediction (classifier accuracy of 72/92 [78.3 (68.4%–86.2%)] in validation, 83.8 [68.0%–93.8%] syncope, 81.5 [61.9%–93.7%] epilepsy, 67.9 [47.7%–84.1%] PNES).

Conclusions

A tool based on patient symptoms/comorbidities and witness reports separates well between syncope and other common causes of TLOC. It can help to differentiate epilepsy and PNES. Validated decision rules may improve diagnostic processes and reduce misdiagnosis rates.

Classification of evidence

This study provides Class III evidence that for patients with TLOC, patient and witness questionnaires discriminate between syncope, epilepsy and PNES.




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Author response: Functional neurologic disorders: Bringing the informal and hidden curriculum to light

Dr. Sethi raises an excellent point about the term functional neurologic disorder (FND) in his comment on the editorial.1 It seems clear that reticence to use the term functional creates the ambiguity he mentions. Medically unexplained symptoms, categorized in the international classification of diseases as undifferentiated somatoform disorders, are a diagnosis that many providers are loathed to give. Whether that is because of concern about missing a diagnosis is not clear. Having evaluated and treated more than 400 of these individuals in the FND clinic at the University of Colorado, I can attest to the fact that patients arrive confused about their diagnosis. Multiple incorrect diagnoses, as Dr. Sethi points out, pack the medical histories of patients with FND, leading doctors and patients astray. I believe that the commentary by Perez et al.2 gives us the best chance for a way forward, by teaching a new generation of residents and fellows how to approach patients in a nonjudgmental and open-minded fashion. It took 30 years to add Functional Neurologic Disorder to the Diagnostic and Statistical Manual, and it is still parenthetical to the term Conversion.3 Stripping the diagnosis of FND of its stigma and empowering care providers to rule in functional disorders is an actionable step which should be taken.




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Reader response: Functional neurologic disorders: Bringing the informal and hidden curriculum to light

I read with interest the editorial by Strom1 about functional neurologic disorders (FNDs). As a treating physician, I have struggled with the multiple diagnostic labels attached to these patients by physicians of different medical specialties during the course of their clinical disease presentation. A neurologist may assign a patient who presents with chronic fatigue the diagnostic labels of narcolepsy, idiopathic hypersomnia, or chronic Lyme disease. A rheumatologist may assign the label of collagen vascular disease, and a psychiatrist may diagnose depression. This diagnostic ambiguity is troublesome for patients and clinicians alike. I contend that even the term FND needs to be revisited. A patient should be broadly labeled as having a functional disorder and only after characterization sublabeled and referred to an appropriate specialty physician.




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Author response: Symptom burden among individuals with Parkinson disease: A national survey

We appreciate the readers' comments on the prevalence and impact of apathy on quality of life among individuals with Parkinson disease. In constructing our survey instrument, we discussed the inclusion of apathy as a symptom. However, we ultimately opted against inclusion because of concerns about the specificity of terminology in our online survey. Patients and care partners may not be familiar with the term "apathy,"and near-synonyms such as "reduced motivation" have substantial overlap with other nonmotor features. Still, as the readers point out, apathy is extremely common and under-recognized. Similar to many of the nonmotor symptoms identified in our study,1 we agree that clinicians should be screening for apathy among those with Parkinson disease.




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Reader response: Symptom burden among individuals with Parkinson disease: A national survey

We read with great interest the study by Tarolli et al.,1 which explored the burden of disease in Parkinson disease (PD) by evaluating the prevalence of nonmotor symptoms and their association with quality of life. The authors selected nonmotor symptoms based on literature review, expert opinions, and patient interviews. We note that apathy, which has major consequences for patients and carers, was not included as a relevant nonmotor symptom in their study. We performed a subcohort analysis of 60 patients from a study of pain in PD in 110 outpatients (PaCoMo-study, registered trial number: NL6311402917 [toetsingonline.nl]). We retrospectively reviewed the medical records to check whether the clinician identified apathy in these patients in the previous year, which was the case in 15% of the patients (n = 9). Blind to those results, patients were examined with the Apathy Scale (AS).2 In total, 63.3% (n = 38) of the patients scored positive on the AS. Only 18.4% of the patients who scored positive on the AS were also classified or mentioned with apathy in the medical records by clinicians.




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Serial 18F-FDG PET/CT findings in a patient with neurocutaneous melanosis

With high sensitivity in detecting acute brain events such as seizures, FDG PET can be used as an important tool for neurocutaneous melanosis disease monitoring.




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Unusual and important cause of acute neck pain: Longus colli calcific tendinitis

Early recognition of longus colli calcific tendinitis can prevent unnecessary interventions including antibiotics and surgical procedures.




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Optimizing Resources in Childrens Surgical Care: An Update on the American College of Surgeons' Verification Program

Surgical procedures are performed in the United States in a wide variety of clinical settings and with variation in clinical outcomes. In May 2012, the Task Force for Children’s Surgical Care, an ad hoc multidisciplinary group comprising physicians representing specialties relevant to pediatric perioperative care, was convened to generate recommendations to optimize the delivery of children’s surgical care. This group generated a white paper detailing the consensus opinions of the involved experts. Following these initial recommendations, the American College of Surgeons (ACS), Children’s Hospital Association, and Task Force for Children’s Surgical Care, with input from all related perioperative specialties, developed and published specific and detailed resource and quality standards designed to improve children’s surgical care (https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification). In 2015, with the endorsement of the American Academy of Pediatrics (https://pediatrics.aappublications.org/content/135/6/e1538), the ACS established a pilot verification program. In January 2017, after completion of the pilot program, the ACS Children’s Surgery Verification Quality Improvement Program was officially launched. Verified sites are listed on the program Web site at https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification/centers, and more than 150 are interested in verification. This report provides an update on the ACS Children’s Surgery Verification Quality Improvement Program as it continues to evolve.




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Shellhaas RA, Burns JW, Barks JDE, Fauziya Hassan F, Chervin RD. Maternal Voice and Infant Sleep in the Neonatal Intensive Care Unit. Pediatrics. 2019;144(3):e30190288




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Initial Resuscitation Algorithm for Children




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Nickel Allergic Contact Dermatitis: Identification, Treatment, and Prevention

Nickel is a ubiquitous metal added to jewelry and metallic substances for its hardening properties and because it is inexpensive. Estimates suggest that at least 1.1 million children in the United States are sensitized to nickel. Nickel allergic contact dermatitis (Ni-ACD) is the most common cutaneous delayed-type hypersensitivity reaction worldwide. The incidence among children tested has almost quadrupled over the past 3 decades. The associated morbidities include itch, discomfort, school absence, and reduced quality of life. In adulthood, individuals with Ni-ACD may have severe disabling hand eczema. The increasing rate of Ni-ACD in children has been postulated to result from early and frequent exposure to metals with high amounts of nickel release (eg, as occurs with ear piercing or with products used daily in childhood such as toys, belt buckles, and electronics).

To reduce exposure to metal sources with high nickel release by prolonged and direct contact with human skin, Denmark and the European Union legislated a directive several decades ago with the goal of reducing high nickel release and the incidence of Ni-ACD. Since then, there has been a global reduction in incidence of Ni-ACD in population-based studies of adults and studies of children and young adults being tested for allergic contact dermatitis. These data point to nickel exposure as a trigger for elicitation of Ni-ACD and, further, provide evidence that legislation can have a favorable effect on the economic and medical health of a population.

This policy statement reviews the epidemiology, history, and appearances of Ni-ACD. Examples of sources of high nickel release are discussed to highlight how difficult it is to avoid this metal in modern daily lives. Treatments are outlined, and avoidance strategies are presented. Long-term epidemiological interventions are addressed. Advocacy for smarter nickel use is reviewed. The American Academy of Pediatrics supports US legislation that advances safety standards (as modeled by the European Union) that protect children from early and prolonged skin exposure to high–nickel-releasing items. Our final aim for this article is to aid the pediatric community in developing nickel-avoidance strategies on both individual and global levels.




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Emerging Issues in Male Adolescent Sexual and Reproductive Health Care

Pediatricians are encouraged to address male adolescent sexual and reproductive health on a regular basis, including taking a sexual history, discussing healthy sexuality, performing an appropriate physical examination, providing patient-centered and age-appropriate anticipatory guidance, and administering appropriate vaccinations. These services can be provided to male adolescent patients in a confidential and culturally appropriate manner, can promote healthy sexual relationships and responsibility, can and involve parents in age-appropriate discussions about sexual health.




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Children With Intellectual and Developmental Disabilities as Organ Transplantation Recipients

The demand for transplantable solid organs far exceeds the supply of deceased donor organs. Patient selection criteria are determined by individual transplant programs; given the scarcity of solid organs for transplant, allocation to those most likely to benefit takes into consideration both medical and psychosocial factors. Children with intellectual and developmental disabilities have historically been excluded as potential recipients of organ transplants. When a transplant is likely to provide significant health benefits, denying a transplant to otherwise eligible children with disabilities may constitute illegal and unjustified discrimination. Children with intellectual and developmental disabilities should not be excluded from the potential pool of recipients and should be referred for evaluation as recipients of solid organ transplants.




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Ames SG, Davis BS, Marin JR, L. Fink EL, Olson LM, Gausche-Hill M, Kahn JM. Emergency Department Pediatric Readiness and Mortality in Critically Ill Children. Pediatrics. 2019;144(3):e20190568




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Early and Often: The Need for Comprehensive Discussion of Treatment-Induced Cancer Late Effects




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Ahmed A, Fend PI, Gaensbauer JT, Reves RR, Khurana R, Salcedo K, Punnoose R, Katz DJ, for the TUBERCULOSIS EPIDEMIOLOGIC STUDIES CONSORTIUM. Interferon-{gamma} Release Assays in Children <15 Years of Age. Pediatrics. 2020:145(1):e20191930




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Family Values Means Covering Families: Parents Need to Focus on Parenting, Not Access to Care




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Adolescent Sexual Health Interventions: Innovation, Efficacy, Cost, and the Urgent Need to Scale




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Exploring Early Childhood Factors as an Avenue to Address Chronic Peer Victimization




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Every Child Counts: The Importance of the 2020 Census for Pediatric Health Equity




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Optimizing Human Papillomavirus Immunization: The Role of Centralized Reminder and Recall Systems




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Providing the Evidence for Managing Depression in Pregnancy




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Trends in Outpatient Procedural Sedation: 2007-2018

BACKGROUND:

Pediatric subspecialists routinely provide procedural sedation outside the operating room. No large study has reported trends in outpatient pediatric procedural sedation. Our purpose in this study was to identify significant trends in outpatient procedural sedation using the Pediatric Sedation Research Consortium.

METHODS:

Prospectively collected data from 2007 to 2018 were used for trending procedural sedation. Patient characteristics, medications, type of providers, serious adverse events, and interventions were reported. The Cochran–Armitage test for trend was used to explore the association between the year and a given characteristic.

RESULTS:

A total of 432 842 sedation encounters were identified and divided into 3 4-year epochs (2007–2011, 2011–2014, and 2014–2018). There was a significant decrease in infants <3 months of age receiving procedural sedation (odds ratio = 0.97; 95% confidence interval, 0.96–0.98). A large increase was noticed in pediatric hospitalists providing procedural sedation (0.6%–9.5%; P < .001); there was a decreasing trend in sedation by other providers who were not in emergency medicine, critical care, or anesthesiology (13.9%–3.9%; P < .001). There was an increasing trend in the use of dexmedetomidine (6.3%–9.3%; P < .001) and a decreasing trend in the use of chloral hydrate (6.3%–0.01%; P < .001) and pentobarbital (7.3%–0.5%; P < .001). Serious adverse events showed a nonsignificant increase overall (1.35%–1.75%).

CONCLUSIONS:

We report an increase in pediatric hospitalists providing sedation and a significant decrease in the use of chloral hydrate and pentobarbital by providers. Further studies are required to see if sedation services decrease costs and optimize resource use.




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Parental Considerations Regarding Cure and Late Effects for Children With Cancer

BACKGROUND:

More than 80% of children with cancer become long-term survivors, yet most survivors experience late effects of treatment. Little is known about how parents and physicians consider late-effects risks against a potential survival benefit when making treatment decisions.

METHODS:

We used a discrete choice experiment to assess the importance of late effects on treatment decision-making and acceptable trade-offs between late-effects risks and survival benefit. We surveyed 95 parents of children with cancer and 41 physicians at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center to assess preferences for 5 late effects of treatment: neurocognitive impairment, infertility, cardiac toxicity, second malignancies, and impaired growth and development.

RESULTS:

Each late effect had a statistically significant association with treatment choice, as did survival benefit (P < .001). Avoidance of severe cognitive impairment was the most important treatment consideration to parents and physicians. Parents also valued cure and decreased risk of second malignancies; physician decision-making was driven by avoidance of second malignancies and infertility. Both parents and physicians accepted a high risk of infertility (parents, a 137% increased risk; physicians, an 80% increased risk) in exchange for a 10% greater chance of cure.

CONCLUSIONS:

Avoidance of severe neurocognitive impairment was the predominant driver of parent and physician treatment preferences, even over an increased chance of cure. This highlights the importance of exploring parental late-effects priorities when discussing treatment options.




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Racial and Ethnic Differences in Emergency Department Pain Management of Children With Fractures

OBJECTIVES:

To test the hypotheses that minority children with long-bone fractures are less likely to (1) receive analgesics, (2) receive opioid analgesics, and (3) achieve pain reduction.

METHODS:

We performed a 3-year retrospective cross-sectional study of children <18 years old with long-bone fractures using the Pediatric Emergency Care Applied Research Network Registry (7 emergency departments). We performed bivariable and multivariable logistic regression to measure the association between patient race and ethnicity and (1) any analgesic, (2) opioid analgesic, (3) ≥2-point pain score reduction, and (4) optimal pain reduction (ie, to mild or no pain).

RESULTS:

In 21 069 visits with moderate-to-severe pain, 86.1% received an analgesic and 45.4% received opioids. Of 8533 patients with reassessment of pain, 89.2% experienced ≥2-point reduction in pain score and 62.2% experienced optimal pain reduction. In multivariable analyses, minority children, compared with non-Hispanic (NH) white children, were more likely to receive any analgesics (NH African American: adjusted odds ratio [aOR] 1.72 [95% confidence interval 1.51–1.95]; Hispanic: 1.32 [1.16–1.51]) and achieve ≥2-point reduction in pain (NH African American: 1.42 [1.14–1.76]; Hispanic: 1.38 [1.04–1.83]) but were less likely to receive opioids (NH African American: aOR 0.86 [0.77–0.95]; Hispanic: aOR 0.86 [0.76–0.96]) or achieve optimal pain reduction (NH African American: aOR 0.78 [0.67–0.90]; Hispanic: aOR 0.80 [0.67–0.95]).

CONCLUSIONS:

There are differences in process and outcome measures by race and ethnicity in the emergency department management of pain among children with long-bone fractures. Although minority children are more likely to receive analgesics and achieve ≥2-point reduction in pain, they are less likely to receive opioids and achieve optimal pain reduction.




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Asking for Identification and Retail Tobacco Sales to Minors

BACKGROUND AND OBJECTIVES:

A previous single-county study found that retail stores usually asked young-looking tobacco customers to show proof-of-age identification, but a large proportion of illegal tobacco sales to minors occurred after the customers had shown identification proving they were too young to purchase tobacco. We sought to investigate these findings on a larger scale.

METHODS:

We obtained state reports for federal fiscal years 2017 and 2018 from a federal agency that tracks tobacco sales to supervised minors conducting compliance checks in retail stores. We used descriptive and multivariable logistic regression methods to determine (1) how often stores in 17 states requested identifications, (2) what proportion of violations occurred after identification requests, and (3) if violation rates differed when minors were required versus forbidden to carry identification.

RESULTS:

Stores asked minors for identification in 79.6% (95% confidence interval: 79.3%–80.8%) of compliance checks (N = 17 276). Violations after identification requests constituted 22.8% (95% confidence interval: 20.0%–25.6%; interstate range, 1.7%–66.2%) of all violations and were nearly 3 times as likely when minors were required to carry identification in compliance checks. Violations were 42% more likely when minors asked for a vaping product versus cigarettes.

CONCLUSIONS:

Stores that sell tobacco to underage customers are more likely to be detected and penalized when youth inspectors carry identification during undercover tobacco sales compliance checks. The new age-21 tobacco sales requirement presents an opportunity to require identifications be carried and address other long-standing weaknesses in compliance-check protocols to help combat the current adolescent vaping epidemic.




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Teenage Use of Smartphone Applications for Menstrual Cycle Tracking




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Enhancing CPR During Transition From Prehospital to Emergency Department: A QI Initiative

BACKGROUND AND OBJECTIVES:

High-quality cardiopulmonary resuscitation (CPR) increases the likelihood of survival of pediatric out-of-hospital cardiac arrest (OHCA). Maintenance of high-quality CPR during transition of care between prehospital and pediatric emergency department (PED) providers is challenging. Our objective for this initiative was to minimize pauses in compressions, in alignment with American Heart Association recommendations, for patients with OHCA during the handoffs from prehospital to PED providers. We aimed to decrease interruptions in compressions during the first 2 minutes of PED care from 17 seconds (baseline data) to 10 seconds over 12 months. Our secondary aims were to decrease the length of the longest pause in compressions to <10 seconds and eliminate encounters in which time to defibrillator pad placement was >120 seconds.

METHODS:

Our multidisciplinary team outlined our theory for improvement and designed interventions aimed at key drivers. Interventions included specific roles and responsibilities, CPR handoff choreography, and empowerment of frontline providers. Data were abstracted from video recordings of patients with OHCA receiving manual CPR on arrival.

RESULTS:

We analyzed 33 encounters between March 2018 and July 2019. We decreased total interruptions from 17 to 12 seconds during the first 2 minutes and decreased the time of the longest single pause from 14 to 7 seconds. We saw a decrease in variability of time to defibrillator pad placement.

CONCLUSIONS:

Implementation of a quality improvement initiative involving CPR transition choreography resulted in decreased interruptions in compressions and decreased variability of time to defibrillator pad placement.




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A Triadic Intervention for Adolescent Sexual Health: A Randomized Clinical Trial

OBJECTIVES:

In this study, we evaluate the efficacy of Families Talking Together (FTT), a triadic intervention to reduce adolescent sexual risk behavior.

METHODS:

Adolescents aged 11 to 14 and their female caregivers were recruited from a pediatric clinic; 900 families were enrolled; 84 declined. Families were randomly assigned to FTT or 1 of 2 control conditions. The FTT triadic intervention consisted of a 45-minute face-to-face session for mothers, health care provider endorsement of intervention content, printed materials for families, and a booster call for mothers. The primary outcomes were ever having had vaginal intercourse, sexual debut within the past 12 months, and condom use at last sexual intercourse. Assessments occurred at baseline, 3 months post baseline, and 12 months post baseline.

RESULTS:

Of enrolled families, 73.4% identified as Hispanic, 20.4% as African American, and 6.2% as mixed race. Mean maternal age was 38.8 years, and mean adolescent grade was seventh grade. At the 12-month follow-up, 5.2% of adolescents in the experimental group reported having had sexual intercourse, compared with 18% of adolescents in the control groups (P < .05). In the experimental group, 4.7% of adolescents reported sexual debut within the past 12 months, compared with 14.7% of adolescents in the control group (P < .05). In the experimental group, 74.2% of sexually active adolescents indicated using a condom at last sexual intercourse, compared with 49.1% of adolescents in the control group (P < .05).

CONCLUSIONS:

This research suggests that the FTT triadic intervention is efficacious in delaying sexual debut and reducing sexual risk behavior among adolescents.




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Bereaved Parents, Hope, and Realism




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Rates and Stability of Mental Health Disorders in Children Born Very Preterm at 7 and 13 Years

OBJECTIVES:

Children born very preterm (VPT) are at an increased risk of developing mental health (MH) disorders. Our aim for this study was to assess rates of MH disorders in children born VPT and term at 13 years of age and stability of MH disorders between ages 7 and 13 years by using a diagnostic measure.

METHODS:

Participants were from the Victorian Infant Brain Study longitudinal cohort and included 125 children born VPT (<30 weeks’ gestational age and/or <1250 g) and 49 children born term (≥37 weeks’ gestational age) and their families. Participants were followed-up at both 7 and 13 years, and the Development and Well-Being Assessment was administered to assess for MH disorders.

RESULTS:

Compared with term peers, 13-year-olds born VPT were more likely to meet criteria for any MH disorder (odds ratio 5.9; 95% confidence interval 1.71–20.03). Anxiety was the most common disorder in both groups (VPT = 14%; term = 4%), whereas attention-deficit/hyperactivity disorder carried the greatest differential elevated risk (odds ratio 5.6; 95% confidence interval 0.71–43.80). Overall rates of MH disorders remained stable between 7 and 13 years, although at an individual level, many participants shifted in or out of diagnostic categories over time.

CONCLUSIONS:

Children born VPT show higher rates of MH disorders than their term peers, with changing trajectories over time. Findings highlight the importance of early identification and ongoing assessment to support those with MH disorders in this population.




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Effect of State Immunization Information System Centralized Reminder and Recall on HPV Vaccination Rates

BACKGROUND:

Although autodialer centralized reminder and recall (C-R/R) from state immunization information systems (IISs) has been shown to raise childhood vaccination rates, its impact on human papillomavirus (HPV) vaccination rates is unclear.

METHODS:

In a 4-arm pragmatic randomized controlled trial across 2 states, we randomly selected practices representative of the specialty (pediatrics, family medicine, and health center) where children received care. Within each practice, patients 11 to 17.9 years old who had not completed their HPV vaccine series (NY: N = 30 616 in 123 practices; CO: N = 31 502 in 80 practices) were randomly assigned to receive 0, 1, 2, or 3 IIS C-R/R autodialer messages per vaccine dose. We assessed HPV vaccine receipt via the IIS, calculated intervention costs, and compared HPV vaccine series initiation and completion rates across study arms.

RESULTS:

In New York, HPV vaccine initiation rates ranged from 37.0% to 37.4%, and completion rates were between 29.1% and 30.1%, with no significant differences across study arms. In Colorado, HPV vaccine initiation rates ranged from 31.2% to 33.5% and were slightly higher for 1 reminder compared with none, but vaccine completion rates, ranging from 27.0% to 27.8%, were similar. On adjusted analyses in Colorado, vaccine initiation rates were slightly higher for 1 and 3 C-R/R messages (adjusted risk ratios 1.07 and 1.04, respectively); completion rates were slightly higher for 1 and 3 C-R/R messages (adjusted risk ratios 1.02 and 1.03, respectively).

CONCLUSIONS:

IIS-based C-R/R for HPV vaccination did not improve HPV vaccination rates in New York and increased vaccination rates slightly in Colorado.




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Systemic Sclerosis Sine Scleroderma With Pulmonary Arterial Hypertension in a 3-Year-Old Girl

Systemic sclerosis sine scleroderma (ssSSc) is a rare variant of systemic sclerosis, with only one pediatric case reported in the medical literature to date. Pulmonary arterial hypertension as the presenting feature of ssSSc is extremely rare, even in adults, and so far has never been reported in children. We report, for the first time, a case of pediatric ssSSc in a 3-year-old girl, who presented with interstitial lung disease and pulmonary hypertension. The patient was prescribed early aggressive pulmonary vasodilators combined with anti-inflammatory medications. The clinical response was good, and her current condition at 12 years of age is remarkable, considering the high mortality rates reported in adults. We underscore the importance of early aggressive treatment in future cases of similar presentation.




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Teenager With Abdominal Pain and Decreased Appetite

A 16-year-old girl presented to her primary care physician with a one-month history of decreased appetite and abdominal pain. She had normal bowel movements and no vomiting, but her periumbilical pain limited her ability to finish most meals. She had gradual weight loss over the previous 2 years, and during the previous 4 years, she intermittently received counseling for depression after the loss of her mother. Her initial physical examination and laboratory evaluation were unremarkable. She was referred to a nutritionist, adolescent medicine, and pediatric gastroenterology. Her presentation evolved over time, which ultimately led to a definitive diagnosis.




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Network Implementation of Guideline for Early Detection Decreases Age at Cerebral Palsy Diagnosis

BACKGROUND AND OBJECTIVES:

Early diagnosis of cerebral palsy (CP) is critical in obtaining evidence-based interventions when plasticity is greatest. In 2017, international guidelines for early detection of CP were published on the basis of a systematic review of evidence. Our study aim was to reduce the age at CP diagnosis throughout a network of 5 diverse US high-risk infant follow-up programs through consistent implementation of these guidelines.

METHODS:

The study leveraged plan-do-study-act and Lean methodologies. The primary outcome was age at CP diagnosis. Data were acquired during the corresponding 9-month baseline and quarterly throughout study. Balancing measures were clinic no-show rates and parent perception of the diagnosis visit. Clinic teams conducted strengths, weaknesses, opportunities, and threats analyses, process flow evaluations, standardized assessments training, and parent questionnaires. Performance of a 3- to 4-month clinic visit was a critical process step because it included a Hammersmith Infant Neurologic Examination, a General Movements Assessment, and standardized assessments of motor function.

RESULTS:

The age at CP diagnosis decreased from a weighted average of 19.5 (95% confidence interval 16.2 to 22.8) to 9.5 months (95% confidence interval 4.5 to 14.6), with P = .008; 3- to 4-month visits per site increased from the median (interquartile range) 14 (5.2–73.7) to 54 (34.5–152.0), with P < .001; and no-show rates were not different. Parent questionnaires revealed positive provider perception with improvement opportunities for information content and understandability.

CONCLUSIONS:

Large-scale implementation of international guidelines for early detection of CP is feasible in diverse high-risk infant follow-up clinics. The initiative was received positively by families and without adversely affecting clinic operational flow. Additional parent support and education are necessary.




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Apparent Cause Analysis: A Safety Tool

Causal analysis is a core function of safety programs. Although established protocols exist for conducting root cause analysis for serious safety events, there is limited guidance for apparent cause analysis (ACA) in health care. At our institution, through a novel facilitated ACA approach, we aim to improve safety culture and provide a clear approach to address precursor safety events and near-miss safety events. We define facilitated ACA as limited investigation (scope and duration) of a safety event that resulted in little to no harm. These investigations require fewer resources and focus on preventive strategies. Our facilitated ACA model, with an operational algorithm and structured process, was developed and implemented at our tertiary-care, freestanding, urban pediatric hospital in 2018. Sixty-four ACAs were completed, and 83% were identified with the algorithm. Process measures, including time from event reporting to ACA launch (median 3 days; interquartile range 2–6 days), are tracked. Patient safety consultants averaged 5 hours to complete a facilitated ACA. A median of 3 disciplines or departments participated in each facilitated ACA. Through an iterative process, we implemented a structured process for facilitated ACA, and the model’s strength includes (1) right event, (2) right team, (3) right analysis, and (4) right action plans. This novel facilitated ACA model may support organizational cause analysis and improve safety culture with higher-reliability processes.




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Preparing Residents for Children With Complex Medical Needs




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E-cigarette Product Characteristics and Subsequent Frequency of Cigarette Smoking

BACKGROUND:

There is a dearth of evidence regarding the association of use of electronic cigarettes (e-cigarettes) with certain product characteristics and adolescent and young adult risk of unhealthy tobacco use patterns (eg, frequency of combustible cigarette smoking), which is needed to inform the regulation of e-cigarettes.

METHODS:

Data were collected via an online survey of participants in the Southern California Children’s Health Study from 2015 to 2016 (baseline) and 2016 to 2017 (follow-up) (N = 1312). We evaluated the association of binary categories of 3 nonmutually exclusive characteristics of the e-cigarette used most frequently with the number of cigarettes smoked in the past 30 days at 1-year follow-up. Product characteristics included device (vape pen and/or modifiable electronic cigarette [mod]), use of nicotine in electronic liquid (e-liquid; yes or no), and use for dripping (directly dripping e-liquid onto the device; yes or no).

RESULTS:

Relative to never e-cigarette users, past-30-day e-cigarette use was associated with greater frequency of past-30-day cigarette smoking at follow-up. Among baseline past-30-day e-cigarette users, participants who used mods (versus vape pens) smoked >6 times as many cigarettes at follow-up (mean: 20.8 vs 1.3 cigarettes; rate ratio = 6.33; 95% confidence interval: 1.64–24.5) after adjustment for sociodemographic characteristics, baseline frequency of cigarette smoking, and number of days of e-cigarette use. After adjustment for device, neither nicotine e-liquid nor dripping were associated with frequency of cigarette smoking.

CONCLUSIONS:

Baseline mod users (versus vape pen users) smoked more cigarettes in the past 30 days at follow-up. Regulation of e-cigarette device type warrants consideration as a strategy to reduce cigarette smoking among adolescents and young adults who vape.




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In Utero Antidepressants and Neurodevelopmental Outcomes in Kindergarteners

OBJECTIVES:

To determine if in utero selective serotonin reuptake inhibitor (SSRI) or selective serotonin norepinephrine inhibitor (SNRI) exposure is associated with developmental vulnerability in kindergarten among children whose mothers were diagnosed with prenatal mood or anxiety disorder.

METHODS:

Linkable administrative data were used to create a population-based cohort of 266 479 mother-child dyads of children born in Manitoba, Canada, between 1996 and 2014, with follow-up through 2015. The sample was restricted to mothers who had a mood or anxiety disorder diagnosis between 90 days before conception (N = 13 818). Exposed women had ≥2 SSRI or SNRI dispensations during pregnancy (n = 2055); unexposed mothers did not have a dispensation of an SSRI or SNRI during pregnancy (n = 10 017). The Early Development Instrument (EDI) was used to assess developmental health in kindergarten children. The EDI is a 104-component kindergarten teacher-administered questionnaire, encompassing 5 developmental domains.

RESULTS:

Of the 3048 children included in the study who met inclusion criteria and had an EDI, 21.43% of children in the exposed group were assessed as vulnerable on 2 or more domains versus 16.16% of children in the unexposed group (adjusted odds ratio = 1.43; 95% confidence interval 1.08–1.90). Children in the exposed group also had a significant risk of being vulnerable in language and/or cognition (adjusted odds ratio = 1.40; 95% confidence interval 1.03–1.90).

CONCLUSIONS:

Exposure to SSRIs or SNRIs during pregnancy was associated with an increased risk of developmental vulnerability and an increased risk of deficits in language and/or cognition. Replication of results is necessary before clinical implications can be reached.