The impact of anthropogenic climate change on pediatric viral diseases.

The adverse effects of climate change on human health are unfolding in real time. Environmental fragmentation is amplifying spillover of viruses from wildlife to humans. Increasing temperatures are expanding mosquito and tick habitats, introducing vector-borne viruses into immunologically susceptible populations. More frequent flooding is spreading water-borne viral pathogens, while prolonged droughts reduce regional capacity to prevent and respond to disease outbreaks with adequate water, sanitation, and hygiene resources. Worsening air quality and altered transmission seasons due to an increasingly volatile climate may exacerbate the impacts of respiratory viruses. Furthermore, both extreme weather events and long-term climate variation are causing the destruction of health systems and large-scale migrations, reshaping health care delivery in the face of an evolving global burden of viral disease. Because of their immunological immaturity, differences in physiology (e.g., size), dependence on caregivers, and behavioral traits, children are particularly vulnerable to climate change. This investigation into the unique pediatric viral threats posed by an increasingly inhospitable world elucidates potential avenues of targeted programming and uncovers future research questions to effect equitable, actionable change. IMPACT: A review of the effects of climate change on viral threats to pediatric health, including zoonotic, vector-borne, water-borne, and respiratory viruses, as well as distal threats related to climate-induced migration and health systems. A unique focus on viruses offers a more in-depth look at the effect of climate change on vector competence, viral particle survival, co-morbidities, and host behavior. An examination of children as a particularly vulnerable population provokes programming tailored to their unique set of vulnerabilities and encourages reflection on equitable climate adaptation frameworks.

National trends in the endovascular and surgical treatment of idiopathic intracranial hypertension.

BACKGROUND: The pattern of surgical treatments for Idiopathic Intracranial Hypertension (IIH) in the United States is not well-studied, specifically the trend of utilizing endovascular venous stenting (EVS) as an emerging technique. METHODS: In this cross-sectional study, we aimed to explore the national trend of utilizing different procedures for the treatment of IIH including EVS, Optic Nerve Sheath Fenestration (ONSF), and CSF Shunting, with a focus on novel endovascular procedures. Moreover, we explored rates of 90-day readmission and length of hospital stay following different procedures, besides the effects of sociodemographic and clinical parameters on procedure choice. RESULTS: 36,437 IIH patients were identified from records between 2010 and 2018. Those in the EVS group were 29 years old on average, and 93.4 % were female. Large academic hospital setting was independently associated with higher EVS utilization, while other factors were not predictive of procedure choice. The proportion of EVS use in IIH hospitalizations increased significantly from 2010 to 2018 (P < 0.001), while there was a relative decline in the frequency of shunting procedures (P = 0.001), with ONSF utilization remaining stable (P = 0.39). The rate of 90-day readmission and length of hospital stay were considerably lower following EVS compared to other procedures (Ps < 0.001). CONCLUSION: This study presents novel population-level data on national trends in the frequency and outcome of EVS for IIH therapy. EVS was associated with shorter length of hospital stays and fewer readmission rates. In addition, a continuous increase in venous stenting compared to other procedures suggests an increasing role for endovascular therapies in IIH.

Contemporary Incidence and Burden of Cerebral Venous Sinus Thrombosis in Children of the United States.

BACKGROUND: The incidence of cerebral venous thrombosis (CVT) in children of the United States is unknown, and it is uncertain how the burden of CVT hospitalizations in children changed over the last decade. METHODS: We conducted a retrospective cohort study using the State Inpatient Database and Kid's inpatient database. All new CVT cases in children (0-19 years) in the New York 2006 to 2018 State Inpatient Database (n=705), and all cases of CVT in the entire US contained in the 2006 to 2019 Kid's inpatient database (weighted n=6115) were identified using validated International Classification of Diseases (ICDs) codes. Incident counts were combined with census data to compute incidence. Between-group differences in incidence were tested using 2-proportions Z-test, and Joinpoint regression was used to trend incidence over time. RESULTS: Across the study period, 48.2% of all incident CVT cases and 44.6% of all CVT admissions nationally were in girls. Of all incident cases, 27.2% were infants and 65.8% of these infants were neonates. Average incidence across the study period was (1.1/100 000/year, SE:0.04) but incidence in infants (6.4/100 000/year) was at least 5 times the incidence in other age groups (1-4 years: 0.7/100 000/year, 15-19 years: 1.2/100 000/year). Incidence and national burden of CVT admissions was higher in girls in adolescents 15 to 19 years, but overall burden was higher in boys in other age groups. Age- and sex-standardized CVT incidence increased by 3.8% annually (95% CI, 0.2%-7.6%), while the overall burden of admissions increased by 4.9% annually (95% CI, 3.6%-6.2%). CONCLUSIONS: CVT incidence in New York and national burden of CVT increased significantly over the last decade.

The effect of a locally tailored intervention on the uptake of preconception care in the Netherlands: a stepped-wedge cluster randomized trial (APROPOS-II study).

BACKGROUND: The preconception period provides a window of opportunity for interventions aiming to reduce unhealthy lifestyle behaviours and their negative effect on pregnancy outcomes. This study aimed to assess the effectiveness of a locally tailored preconception care (PCC) intervention in a hybrid-II effectiveness implementation design. METHODS: A stepped-wedge cluster randomized controlled trial was performed in four Dutch municipalities. The intervention contained a social marketing strategy aiming to improve the uptake (prospective parents) and the provision (healthcare providers) of PCC. Prospective parents participated by administering a questionnaire in early pregnancy recalling their preconceptional behaviours. Experiences of healthcare providers were also evaluated through questionnaires. The composite primary outcome was adherence to at least three out of four preconceptional lifestyle recommendations (early initiation of folic acid supplements, healthy nutrition, no smoking or alcohol use). Secondary outcomes were preconceptional lifestyle behaviour change, (online) reach of the intervention and improved knowledge among healthcare providers. RESULTS: A total of 850 women and 154 men participated in the control phase and 213 women and 39 men in the intervention phase. The composite primary outcome significantly improved among women participating in the municipality where the reach of the intervention was highest (Relative Risk (RR) 1.57 (95% Confidence Interval (CI) 1.11-2.22). Among women, vegetable intake had significantly improved in the intervention phase (RR 1.82 (95%CI 1.14-2.91)). The aimed online reach- and engagement rate of the intervention was achieved most of the time. Also, after the intervention, more healthcare providers were aware of PCC-risk factors (54.5% vs. 47.7%; p = 0.040) and more healthcare providers considered it easier to start a conversation about PCC (75.0% vs. 47.9%; p = 0.030). CONCLUSION: The intervention showed some tentative positive effects on lifestyle behaviours among prospective parents. Primarily on vegetable intake and the knowledge and competence of healthcare providers. The results of this study contribute to the evidence regarding successfully implementing PCC-interventions to optimize the health of prospective parents and future generations. TRIAL REGISTRATION: Dutch Trial Register: NL7784 (Registered 06/06/2019).

Cardiac arrest in spontaneous subarachnoid hemorrhage and associated outcomes.

OBJECTIVE: The authors sought to analyze a large, publicly available, nationwide hospital database to further elucidate the impact of cardiopulmonary arrest (CA) in association with subarachnoid hemorrhage (SAH) on short-term outcomes of mortality and discharge disposition. METHODS: This retrospective cohort study was conducted by analyzing de-identified data from the National (Nationwide) Inpatient Sample (NIS). The publicly available NIS database represents a 20% stratified sample of all discharges and is powered to estimate 95% of all inpatient care delivered across hospitals in the US. A total of 170,869 patients were identified as having been hospitalized due to nontraumatic SAH from 2008 to 2014. RESULTS: A total of 5415 patients (3.2%) were hospitalized with an admission diagnosis of CA in association with SAH. Independent risk factors for CA included a higher Charlson Comorbidity Index score, hospitalization in a small or nonteaching hospital, and a Medicaid or self-pay payor status. Compared with patients with SAH and not CA, patients with CA-SAH had a higher mean NIS Subarachnoid Severity Score (SSS) ± SD (1.67 ± 0.03 vs 1.13 ± 0.01, p < 0.0001) and a vastly higher mortality rate (82.1% vs 18.4%, p < 0.0001). In a multivariable model, age, NIS-SSS, and CA all remained significant independent predictors of mortality. Approximately 18% of patients with CA-SAH survived and were discharged to a rehabilitation facility or home with health services, outcomes that were most predicted by chronic disease processes and large teaching hospital status. CONCLUSIONS: In the largest study of its kind, CA at onset was found to complicate roughly 3% of spontaneous SAH cases and was associated with extremely high mortality. Despite this, survival can still be expected in approximately 18% of patients.

Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: A national sample analysis.

INTRODUCTION: The real-world evolution of management and outcomes of patients with unruptured brain arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs. initial conservative medical therapy. METHODS: We analyzed the National Inpatient Sample from 2009-2018, capturing 20% of all admissions in the U.S. Validated ICD-9 and -10 codes defined brain AVMs, comorbidities, and the use of interventional modalities. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018). RESULTS: Among the national projected 88,037 AVM admissions, 72,812 (82.7%) were unruptured AVMs and 15,225 (17.3%) were ruptured AVMs. Among uAVMs, 51.4% admitted pre-ARUBA and 48.6% in post-ARUBA period. The post-ARUBA patients were mildly older (median age 53.3 vs. 51.8 (p = 0.001) and had more comorbidities including hypertension, diabetes, obesity, renal impairment, and smoking. Before the first platform report of ARUBA (2009-2012), rates of use of interventional treatments during uAVM admissions trended up from 31.8% to 35.4%. Thereafter, they declined significantly to 26.4% in 2018 (p = 0.02). The decline was driven by a reduction in the frequency of endovascular treatment from 18.8% to 13.9% and inpatient stereotactic radiosurgery from 0.5% to 0.1%. No change occurred in the frequency of microsurgery or combined endovascular and surgical approaches. Adjusted multivariable model of uAVMs showed increased odds of discharge to a long-term inpatient facility or in-hospital death [OR 1.14 (1.02-1.28), p = 0.020] in post-ARUBA. A significantly increased proportion of ruptured AVMs from 17.0% to 23.3% was observed consistently in post-ARUBA. CONCLUSION: Nationwide practice in the management of unruptured AVMs changed substantially with the publication of the ARUBA trial in a durable and increasing manner. Fewer admissions with the interventional treatment of unruptured AVMs occurred, and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event. Further studies are needed to determine whether these trends can be considered to be ARUBA trial effect or are merely coincidental.

Outcomes among patients with primary angiitis of the CNS: A Nationwide United States analysis.

BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a relapsing-remitting disease with a heterogeneous course. Case series have delineated the long-term disease course but not acute outcomes or their determinants. The national United States hospital burden of PACNS has not been quantified. METHODS: Analysis of the United States Nationwide Readmissions Database (2016-2018) to characterize the frequency of PACNS hospitalizations, demographic features, inpatient mortality, and discharge outcomes. RESULTS: During the 3-year study period, unweighted 1843 (weighted 3409) patients with PACNS were admitted to the 1078 Healthcare Cost and Utilization Project HCUP participating hospitals; with weighting, this value indicates that 1136 patients were admitted each year to US hospitals, representing yearly 0.01 cases per 100 000 national hospitalizations. The majority of patients were hospitalized in metropolitan teaching hospitals (81.6%). The median age at admission was 54.9 (IQR: 44.0-66.5) years and 59.4% were women. Neurologic manifestations included ischemic stroke in 38.2%, transient ischemic attack in 20.2%, seizure disorder in 22.8%, and intracranial hemorrhage in 13.0%. Overall, 60.0% of patients were discharged home, 35.0% discharged to a rehabilitation facility or nursing home and 5.0% died before discharge. Patient features independently associated with the discharge to another facility or death included older age (odds ratio [OR], 1.03 [95% CI, [1.03-1.04]]), male sex (OR, 1.22 [1.04-1.43]), intraparenchymal hemorrhage (OR, 1.41 [1.08-1.84]), ischemic stroke (OR, 2.79 [2.38-3.28]), and seizure disorder (OR, 1.57 [1.31-1.89]). CONCLUSION: Our study showed PACNS is still a rare inflammatory disorder of the blood vessels of the central nervous system suggesting an annual hospitalization of 5.1 cases per 1,000,000 person-years in the more diverse and contemporary US population. Overall, 4 in 10 had unfavorable discharge outcome, being unable to be discharged home, and 1 in 20 died before discharge.

Trends in age and sex-specific prevalence of cancer and cancer subtypes in acute ischemic stroke from 2007-2019.

OBJECTIVE: To describe age and sex-specific prevalence of cancer in acute ischemic stroke (AIS) hospitalizations in the United States over the last decade. METHODS: We conducted a retrospective serial cross-sectional study using all primary AIS discharges (weighted n=5,748,358) with and without cancer in the 2007-2019 National Inpatient Sample. Admissions with primary central nervous system cancers were excluded. Joinpoint regression was used to compute the average annualized percentage change (AAPC) in cancer prevalence over time. RESULTS: Across the study period, 12.7% of AIS admissions had previous/active cancer, while 4.4% had active cancer. Of these, 18.8% were hematologic cancers, 47.2% were solid cancers without metastasis and 34.0% were metastatic cancers of any type. Age-adjusted active cancer prevalence differed by sex (males:4.8%; females:4.0%) and increased with age up to age 70-79 years (30-39 years 1.4%; 70-79 years:5.7%). Amongst cancer admissions, lung (18.7%) and prostate (17.8%) were the most common solid cancers in men, while lung (19.6%) and breast (13.7%) were the most prevalent in women. Active cancer prevalence increased over time (AAPC 1.7%, p<0.05) but the pace of increase was significantly faster in women (AAPC 2.8%) compared to men (AAPC 1.1%) (p-comparison =0.003). Fastest pace of increased prevalence was seen for genitourinary cancers in women and for gastrointestinal cancers in both sexes. Genitourinary cancers in men declined over time (AAPC -2.5%, p<0.05). Lung cancer prevalence increased in women (AAPC 1.8%, p<0.05) but remained constant in men. Prevalence of head/neck, skin/bone, gastrointestinal, hematological and metastatic cancers increased over time at similar pace in both sexes. CONCLUSION: Prevalence of cancer in AIS admissions increased in the US over the last decade but the pace of this increase was faster in women compared to men. Gastrointestinal cancers in both sexes and genitourinary cancers in women are increasing at the fastest pace. Additional studies are needed to determine whether this increase is from co-occurrence or causation of AIS by cancer.

Interventional compared with medical management of symptomatic carotid web: A systematic review.

BACKGROUND: Carotid web (CaW) is non-atheromatous, shelf-like intraluminal projection, generally affecting the posterolateral wall of the proximal internal carotid artery, and associated with embolic stroke, particularly in younger patients without traditional stroke risk factors. Treatment options for symptomatic CaWs include interventional therapy with carotid endarterectomy or carotid stenting versus medical therapy with antiplatelet or anticoagulants. As safety and efficacy of these approaches have been incompletely delineated in small-to-moderate case series, we performed a systematic review of outcomes with interventional and medical management. METHODS: Systematic literature search was conducted and data analyzed per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) from January 2000 to October 2021 using the search strategy: "Carotid web" OR "Carotid shelf" OR "Web vessels" OR "Intraluminal web". Patient-level demographics, stroke risk factors, technical procedure details, medical and interventional management strategies were abstracted across 15 series. All data were analyzed using descriptive statistics. RESULTS: Among a total of symptomatic 282 CaW patients across 14 series, age was 49.5 (44-55.7) years, 61.7% were women, and 76.6% were black. Traditional stroke risk factors were less frequent than the other stroke causes, including hypertension in 28.6%, hyperlipidemia 14.6%, DM 7.0%, and smoking 19.8%. Thrombus adherent to CaW was detected on initial imaging in 16.2%. Among 289 symptomatic CaWs across 15 series, interventional management was pursued in 151 (52.2%), carotid artery stenting in 87, and carotid endarterectomy in 64; medical management was pursued in 138 (47.8%), including antiplatelet therapy in 80.4% and anticoagulants in 11.6%. Interventional and medical patients were similar in baseline characteristics. The reported time from index stroke to carotid revascularization was median 14 days (IQR 9.5-44). In the interventional group, no periprocedural mortality was noted, major periprocedural complications occurred in 1/151 (0.5%), and no recurrent ischemic events were observed over follow-up range of 3-60 months. In the medical group, over a follow-up of 2-55 months, the recurrence cerebral ischemia rate was 26.8%. CONCLUSION: Cumulative evidence from multiple series suggests that carotid revascularization is a safe and effective option for preventing recurrent ischemic events in patients with symptomatic carotid webs.

[Will science follow the changing dynamics in the mental health care practice?] / De praktijk binnen de ggz is in ontwikkeling, volgt de wetenschap?

BACKGROUND: There is awareness that the current paradigm that serves as the foundation for the system of mental health care services, has unintended detrimental consequences. Pilot projects such as the Mental Health Ecosystem (GEM), introducing a non-linear, complex adaptive network system of care, aim to address this situation. However, GEM does not sufficiently match with the current paradigm of reductionism and determinism. AIM: To stimulate the dialogue about the question which mental health care paradigm may align with GEM and its commitment to co-creation, self-organization, and more freedom of choice for patients. METHOD: From a philosophy of science perspective, testing broadly whether the current scientific paradigm fits with recent developments and describing another scientific paradigm, the complexity sciences. As an example case, we describe the Ecosystem Mental Health. RESULTS: GEM aligns well with complexity science and approaches the mental health system as a complex adaptive system. The concepts of emergence and feedback loops are also useful for understanding the dynamics within GEM. CONCLUSION: Complexity science, as an alternative scientific paradigm, potentially offers entry points to explore a form of contextual care within a mental health ecosystem.

Ischemic Stroke in Patients With Pulmonary Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Pulmonary arteriovenous fistulas (PAVFs) are a treatable cause of acute ischemic stroke (AIS), not mentioned in current American Heart/Stroke Association guidelines. PAVFs are recognized as an important complication of hereditary hemorrhagic telangiectasia. METHODS: The prevalence of PAVF and hereditary hemorrhagic telangiectasia among patients admitted with AIS in the United States (2005-2014) was retrospectively studied, utilizing the Nationwide Inpatient Sample database. Clinical factors, morbidity, mortality, and management were compared in AIS patients with and without PAVF/hereditary hemorrhagic telangiectasia. RESULTS: Of 4 271 910 patients admitted with AIS, 822 (0.02%) were diagnosed with PAVF. Among them, 106 of 822 (12.9%) were diagnosed with hereditary hemorrhagic telangiectasia. The prevalence of PAVF per million AIS admissions rose from 197 in 2005 to 368 in 2014 (Ptrend, 0.026). Patients with PAVF were younger than AIS patients without PAVF (median age, 57.5 versus 72.5 years), had lower age-adjusted inpatient morbidity (defined as any discharge other than home; 39.6% versus 46.9%), and had lower in-hospital case fatality rates (1.8% versus 5.1%). Multivariate analyses identified the following as independent risk markers (odds ratio [95% CI]) for AIS in patients with PAVF: hypoxemia (8.4 [6.3-11.2]), pulmonary hemorrhage (7.9 [4.1-15.1]), pulmonary hypertension (4.3 [4.1-15.1]), patent foramen ovale (4.2 [3.5-5.1]), epistaxis (3.7 [2.1-6.8]), venous thrombosis (2.6 [1.9-3.6]), and iron deficiency anemia (2 [1.5-2.7]). Patients with and without PAVF received intravenous thrombolytics at a similar rate (5.9% versus 5.8%), but those with PAVF did not receive mechanical thrombectomy (0% versus 0.7%). CONCLUSIONS: Pulmonary arteriovenous fistula-related ischemic stroke represents an important younger demographic with a unique set of stroke risk markers, including treatable conditions such as causal PAVFs and iron deficiency anemia.

Outcomes Among Patients With Reversible Cerebral Vasoconstriction Syndrome: A Nationwide United States Analysis.

BACKGROUND AND PURPOSE: Reversible cerebral vasoconstriction syndrome (RCVS) is a well-established cause of stroke, but its demographics and outcomes have not been well delineated. METHODS: Analysis of the United States Nationwide Inpatient Sample database (2016-2017) to characterize the frequency of hospitalizations for RCVS, demographic features, inpatient mortality, and discharge outcomes. RESULTS: During the 2-year study period, 2020 patients with RCVS were admitted to Nationwide Inpatient Sample hospitals, representing 0.02 cases per 100 000 national hospitalizations. The mean age at admission was 47.6 years, with 85% under 65 years of age, and 75.5% women. Concomitant neurological diagnoses during hospitalization included ischemic stroke (17.1%), intracerebral hemorrhage (11.0%), subarachnoid hemorrhage (32.7%), seizure disorders (6.7%), and reversible brain edema (13.6%). Overall, 70% of patients were discharged home, 29.7% discharged to a rehabilitation facility or nursing home and 0.3% died before discharge. Patient features independently associated with the poor outcome of discharge to another facility or death were advanced age (odds ratio [OR], 1.04 [95% CI, 1.03-1.04]), being a woman (OR, 2.45 [1.82-3.34]), intracerebral hemorrhage (OR, 2.91 [1.96-4.31]), ischemic stroke (OR, 5.72 [4.32-7.58]), seizure disorders (OR, 2.61 [1.70-4.00]), reversible brain edema (OR, 6.26 [4.41-8.89]), atrial fibrillation (OR, 2.97 [1.83-4.81]), and chronic kidney disease (OR, 3.43 [2.19-5.36]). CONCLUSIONS: Projected to the entire US population, >1000 patients with RCVS are hospitalized each year, with the majority being middle-aged women, and about 300 required at least some rehabilitation or nursing home care after discharge. RCVS-related inpatient mortality is rare.

Disruption and recovery of testicular function during and after androgen abuse: the HAARLEM study.

STUDY QUESTION: What is the speed and extent by which endogenous testosterone production and spermatogenesis recover after androgen abuse? SUMMARY ANSWER: Testosterone concentrations normalized within 3 months after discontinuation of androgen abuse in most subjects but recovery of spermatogenesis took longer-approximately 1 year. WHAT IS KNOWN ALREADY: An estimated 4-6% of amateur strength athletes use androgens. Abuse of supraphysiological doses of androgens completely suppresses endogenous testosterone production and spermatogenesis. STUDY DESIGN, SIZE, DURATION: Prospective and observational cohort study in which 100 male amateur athletes participated for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects (≥18 years) were included if they had not used androgens for at least 3 months and intended to start an androgen cycle within 2 weeks. Clinic visits took place before (T0), at the end (T1), and 3 months after the end of the cycle (T2), and 1 year after start of the cycle (T3), and included a blood test for gonadotrophins and sex hormones, and semen analysis. MAIN RESULTS AND THE ROLE OF CHANCE: During androgen abuse, 77% of subjects had a total sperm count (TSC) below 40 million. Three months after the end of the cycle (T2), total (-1.9 nmol/l, CI -12.2 to 8.33, P = 0.71) and free (-38.6 pmol/l, CI -476 to 399, P = 0.86) testosterone concentrations were not different compared to baseline, whereas mean TSC was 61.7 million (CI 33.7 to 90.0; P < 0.01) lower than baseline. At the end of follow-up (T3), there was no statistically significant difference for total (-0.82 nmol/l, CI -11.5 to 9.86, P = 0.88) and free (-25.8 pmol/l, CI -480 to 428, P = 0.91) testosterone compared to baseline, but there was for TSC (-29.7 million, CI -59.1 to -0.39, P = 0.05). In nine (11%) subjects, however, testosterone concentrations were below normal at the end of follow-up (T3), and 25 (34%) subjects still had a TSC below 40 million. LIMITATIONS, REASONS FOR CAUTION: The follow-up period (after the cycle) was relatively short, especially considering the long recovery time of spermatogenesis after discontinuation of androgens. WIDER IMPLICATIONS OF THE FINDINGS: Endogenous testosterone production and spermatogenesis recover following androgen abuse in the vast majority of users. Nevertheless, not all users achieve a normalized testicular function. This may especially be the case for athletes with a high past exposure to androgens. STUDY FUNDING/COMPETING INTEREST(S): There is no conflict of interest. The study was funded by the Spaarne Gasthuis academy. TRIAL REGISTRATION NUMBER: N/A.

Novel GDF2 Gene Mutation Associated with Pulmonary Arteriovenous Malformation.

Pulmonary arteriovenous malformations (PAVMs) are pathologic low-resistance conduits between a pulmonary artery and vein. Over 80% PAVMs occur in patients with hereditary hemorrhagic telangiectasia (HHT) and result from mutations in the transforming growth factor-beta signaling pathway. Mutations in the Growth Differentiation Factor 2 (GDF2) gene have recently been described to result in a vascular-anomaly syndrome with phenotypic overlap with HHT. We report a 43-year-old woman with a PAVM related ischemic stroke who was subsequently found to have a novel GDF2 gene mutation. The patient underwent coil-embolization of the PAVM with stable clinical and radiographic follow-up. It is important to diagnose PAVMs as they are an important cause of stroke-in-young; and can be treated definitively, reducing risk of recurrent stroke and migraine.

Malignant Cerebral Ischemia in A COVID-19 Infected Patient: Case Review and Histopathological Findings.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for an unprecedented worldwide pandemic that has severely impacted the United States. As the pandemic continues, a growing body of evidence suggests that infected patients may develop significant coagulopathy with resultant thromboembolic complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. However, this data is limited and comes from recent small case series and observational studies on stroke types, mechanisms, and outcomes.1-14 Furthermore, evidence on the role of therapeutic anticoagulation in SARS-CoV-2 infected patients with elevated inflammatory markers, such as D-dimer, is also limited. We report the case of a middle-aged patient who presented with a large vessel ischemic stroke likely resulting from an underlying inflammatory response in the setting of known novel coronavirus infection (COVID-19). Histopathologic analysis of the patient's ischemic brain tissue revealed hypoxic neurons, significant edema from the underlying ischemic insult, fibrin thrombi in small vessels, and fibroid necrosis of the vascular wall without any signs of vasculature inflammation. Brain biopsy was negative for the presence of SARS-CoV-2 RNA (RT-PCR assay). Along with a growing body of literature, our case suggests that cerebrovascular thromboembolic events in COVID-19 infection may be related to acquired hypercoagulability and coagulation cascade activation due to the release of inflammatory markers and cytokines, rather than virus-induced vasculitis. Further studies to investigate the mechanism of cerebrovascular thromboembolic events and their prevention is warranted.

Thirty-Day Readmissions After Upper and Lower Gastrointestinal Hemorrhage: A National Perspective in the United States.

BACKGROUND: Upper gastrointestinal hemorrhage (UGIH) and lower gastrointestinal hemorrhage (LGIH) are 2 of the most common reasons for hospital admissions across the United States. The 30-day readmission after index admission poses a major burden on the health care infrastructure, and thus, it is important to assess the causes of 30-day readmission for patients with UGIH and LGIH. METHODS: The study cohort was derived from the 2013 National Readmission Database. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) Volume 3 diagnosis codes were utilized to identify UGIH and LGIH patients from this data set. Patients who were readmitted to the hospital within 30 days within the same calendar year were further analyzed. Categorical variables and continuous variables were assessed by the χ test and the student t test, respectively. The independent predictors of unplanned 30-day readmissions were recognized by multivariate logistic regression, adjusting for stratified cluster design of National Readmission Database. SAS 9.4 (SAS Institute Inc., Cary, NC) was used for data analysis. RESULTS: The number of index admissions identified from the National Readmission Data 2013 were 82,290 for UGIH and 133,114 for LGIH. All-cause 30-day readmission rate for UGIH versus LGIH was 14.6% (readmitted N=12,046; 56.64% age 65 y and above) versus 14.4% (readmitted N=19,128; 70.21% age 65 y and above and 49.61% men). Gastrointestinal causes were most common (33.9% vs. 39.6%), followed by cardiac (13.3% vs. 15.3%), infectious (10.4% vs. 9.1%), and respiratory causes (7.8% vs. 7.1%) for 30-day readmission for UGIH and LGIH. Significant predictors of increased 30-day readmission (odds ratio, 95% confidence interval, P-value) included metastatic disease (2.15, 1.75-2.64, P<0.001), discharge against medical advice (1.85, 1.55-2.22, P<0.001), and length of stay >3 days (1.50, 1.38-1.63, P<0.001). Predictors for 30-day readmission for LGIH included metastatic disease (1.75, 1.48-2.06, P<0.001), liver disease (1.59, 1.49-1.71, P<0.001), and drug abuse (1.38, 1.21-1.58, P<0.001). CONCLUSIONS: Most common reason for UGIH and LGIH readmission was related to gastrointestinal disease, followed by cardiac, infectious, and respiratory etiologies. By addressing these etiologies for readmission, it may be possible to reduce adverse outcomes.

Does Natural Mentoring Matter? A Multilevel Meta-analysis on the Association Between Natural Mentoring and Youth Outcomes.

In this meta-analytic review, we examined the relation between natural mentoring and youth outcomes in four domains: academic and vocational functioning, social-emotional development, physical health, and psychosocial problems. Natural mentoring relationships are thought to foster positive youth development and buffer against the risks associated with the tumultuous years of adolescence. Two separate meta-analyses were conducted on the presence of a natural mentor and the quality of the natural mentoring relationship, including thirty studies from 1992 to present. The findings indicated that the presence of a natural mentor was significantly associated with positive youth outcomes (r = .106). A larger effect size was found for the quality of the natural mentoring relationship in terms of relatedness, social support, and autonomy support (r = .208). The largest effect sizes were found for social-emotional development and academic and vocational functioning. Risk-status (e.g., teenage mothers, homeless youth, youth in foster care, and youth of alcoholic parents) did not moderate the relation between presence and quality of natural mentoring relationships and youth outcomes, which may indicate that natural mentors are generally beneficial for all youth regardless of risk-status. Implications for theory and practice concerning the quality of the natural mentoring relationship are discussed.

Heritability of tic disorders: a twin-family study.

BACKGROUND: Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. METHOD: In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. RESULTS: Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects. CONCLUSIONS: Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.

Partnered pharmacist charting on admission in the General Medical and Emergency Short-stay Unit - a cluster-randomised controlled trial in patients with complex medication regimens.

WHAT IS KNOWN AND OBJECTIVE: Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. METHODS: We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. RESULTS: Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm (P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat (NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1). WHAT IS NEW AND CONCLUSION: Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy.