Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 255
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Age Ageing ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043116

RESUMO

BACKGROUND: medication-related problems occur frequently when older patients are discharged from hospital. Interventions to support medication use have been developed; however, their effectiveness in older populations are unknown. This review evaluates interventions that support successful transitions of care through enhanced medication continuity. METHODS: a database search for randomised controlled trials was conducted. Selection criteria included mean participant age of 65 years and older, intervention delivered during hospital stay or following recent discharge and including activities that support medication continuity. Primary outcome of interest was hospital readmission. Secondary outcomes related to the safe use of medication and quality of life. Outcomes were pooled by random-effects meta-analysis where possible. RESULTS: twenty-four studies (total participants = 17,664) describing activities delivered at multiple time points were included. Interventions that bridged the transition for up to 90 days were more likely to support successful transitions. The meta-analysis, stratified by intervention component, demonstrated that self-management activities (RR 0.81 [0.74, 0.89]), telephone follow-up (RR 0.84 [0.73, 0.97]) and medication reconciliation (RR 0.88 [0.81, 0.96]) were statistically associated with reduced hospital readmissions. CONCLUSION: our results suggest that interventions that best support older patients' medication continuity are those that bridge transitions; these also have the greatest impact on reducing hospital readmission. Interventions that included self-management, telephone follow-up and medication reconciliation activities were most likely to be effective; however, further research needs to identify how to meaningfully engage with patients and caregivers to best support post-discharge medication continuity. Limitations included high subjectivity of intervention coding, study heterogeneity and resource restrictions.

2.
Neuron ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31924446

RESUMO

Recent interest in astrocyte activation states has raised the fundamental question of how these cells, normally essential for synapse and neuronal maintenance, become pathogenic. Here, we show that activation of the unfolded protein response (UPR), specifically phosphorylated protein kinase R-like endoplasmic reticulum (ER) kinase (PERK-P) signaling-a pathway that is widely dysregulated in neurodegenerative diseases-generates a distinct reactivity state in astrocytes that alters the astrocytic secretome, leading to loss of synaptogenic function in vitro. Further, we establish that the same PERK-P-dependent astrocyte reactivity state is harmful to neurons in vivo in mice with prion neurodegeneration. Critically, targeting this signaling exclusively in astrocytes during prion disease is alone sufficient to prevent neuronal loss and significantly prolongs survival. Thus, the astrocyte reactivity state resulting from UPR over-activation is a distinct pathogenic mechanism that can by itself be effectively targeted for neuroprotection.

3.
Anat Sci Int ; 95(1): 67-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31338726

RESUMO

Circumscapular pain is a frequent complaint in clinical practice. The dorsal scapular and long thoracic nerves course through the neck, where they may become entrapped between or within adjacent scalene muscles. Additionally, a high frequency of brachial plexus "piercing" variants have recently been documented, and it is unclear how they influence branching patterns distally along the brachial plexus. In the project reported here we strived to identify and quantify variations in dorsal scapular nerve and long thoracic nerve secondary to brachial plexus piercing variation. Ninety brachial plexuses from human cadavers (45 female/45 male) were evaluated to identify nerve branching patterns, specifically piercing versus non-piercing variants in the brachial plexus roots and nerves. Anatomical entrapment of the dorsal scapular nerve and long thoracic nerve was found in high frequencies (60.8% and 44.6%, respectively). Anomalous brachial plexus piercing variants were associated with higher frequencies of distal nerve branches also coursing through the scalene musculature, and there was a statistically significant correlation between brachial plexus and long thoracic nerve piercings (p = 0.027). Anatomical entrapment of nerves within scalene musculature is common and may be causative factors for idiopathic circumscapular pain, dorsalgia, and dysfunction of scapulohumeral rhythm. This study revealed a link between anatomical arrangement of the brachial plexus and occurrence of long thoracic nerve entrapment, which may lead to a series of cascading neurologic effects in which affected individuals may suffer from increased incidence of thoracic outlet syndrome and long thoracic nerve entrapment resulting in additional symptoms of interscapular pain and compromised shoulder mobility.

4.
Patient Saf Surg ; 13: 38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827615

RESUMO

Background: Early drain removal after pancreatic resection is encouraged for individuals with low postoperative day 1 drain amylase levels (POD1 DA) to mitigate associated morbidity. Although various protocols for drain management have been published, there is a need to assess the implementation of a standardized protocol. Methods: The Ottawa pancreatic drain algorithm (OPDA), based on POD1 DA and effluent volume, was developed and implemented at our institution. A retrospective cohort analysis was conducted of all patients undergoing pancreatic resection January 1, 2016-October 30, 2017, excluding November and December 2016 (one month before and after OPDA implementation). Results: 42 patients pre-implementation and 53 patients post-implementation were included in the analysis. The median day of drain removal was significantly reduced after implementation of the OPDA (8 vs. 5 days; p = 0.01). Early drain removal appeared safe with no difference in reoperation or readmission rate after protocol implementation (p = 0.39; p = 0.76). On subgroup analysis, median length of stay was significantly shorter following OPDA implementation for patients who underwent DP and did not develop a postoperative pancreatic fistula (POPF) (6 vs 10 days, p = 0.03). Although the incidence of both surgical site infection and POPF were reduced following the intervention, neither reached statistical significance (38.1 to 28.3%, p = 0.31; and 38.1 to 28.3%, p = 0.31 respectively). Conclusions: Implementing the OPDA was associated with earlier drain removal and decreased length of stay in patients undergoing distal pancreatectomy who did not develop POPF, without increased morbidity. Standardizing drain removal may help facilitate early drain removal after pancreatic resection at other institutions.

5.
J Multidiscip Healthc ; 12: 935-945, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819468

RESUMO

Purpose: The study aims were: (i) to convert the Research and Development Culture Index (a validated rating instrument for assessing the strength of organizational Research and Development culture) into electronic format (eR&DCI), and (ii) to test the format and assess the feasibility of administering it to the multidisciplinary (allied health professionals, doctors and nurses) workforce in a National Health Service Hospital (NHS) in the United Kingdom (UK) by trialing it with the workforce of the tertiary Children's Hospital within the organization. Population and methods: The eR&DCI was emailed to all professional staff (n=907) in the Children's Hospital. Data were analyzed using IBM SPSS Statistics 22. Results: The eR&DCI was completed by 155 respondents (doctors n=38 (24.52%), nurses n=79 (50.96%) and allied health professionals (AHPs) n=38 (24.52%)). The response rate varied by professional group: responses were received from 79 out of 700 nurses (11%); 38 out of 132 doctors (29%) and 38 out of 76 AHPs (50%). Index scores demonstrated a positive research culture within the multidisciplinary workforce. Survey responses demonstrated differences between the professions related to research training and engagement in formal research activities. Conclusion: This is the first study to assess the feasibility of assessing the strength of an organization's multidisciplinary workforce research and development (R&D) culture by surveying that workforce using the eR&DCI. We converted the index to "Online Surveys" and successfully administered it to the entire multidisciplinary workforce in the Children's Hospital. We met our criteria for feasibility: ability to administer the survey and a response rate comparable with similar studies. Uptake could have been increased by also offering the option of the paper-based index for self-administration. Results of the survey are informing delivery of the research strategy in the Children's Hospital. This methodology has potential application in other healthcare contexts.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31845993

RESUMO

OBJECTIVES: A prediction model developed by Passman et al. stratifies patients' risk of postoperative atrial fibrillation (POAF) after major non-cardiac thoracic surgery using 3 simple factors (sex, age and preoperative resting heart rate). The model has neither undergone external validation nor proven to be relevant in current thoracic surgery practice. METHODS: A retrospective single-centre analysis of all patients who underwent major non-cardiac thoracic surgery (2008-2017) with prospective documentation of incidence and severity of POAF was used for external validation of Passman's derivation sample (published in 2005 with 856 patients). The model calibration was assessed by evaluating the incidence of POAF and patients' risk scores (0-6). RESULTS: A total of 2054 patients were included. Among them, POAF occurred in 164 (7.9%), compared to 147 (17.2%) in Passman's study. Differences in our sample compared to Passman's sample included mean heart rate (75.7 vs 73.7 bpm, P < 0.001), proportion of patients with hypertension (46.1 vs 29.4%, P < 0.001), proportion of extensive lung resections, particularly pneumonectomy (6.1 vs 21%, P < 0.001) and proportion of minimally invasive surgeries (56.6% vs 0%). The model demonstrated a positive correlation between risk scores and POAF incidence (risk score 1.2% vs 6.16%). CONCLUSIONS: The POAF model demonstrated good calibration in our population, despite a lower overall incidence of POAF compared to the derivation study. POAF rates were higher among patients with a higher risk score and undergoing procedures with greater intrathoracic dissection. This tool may be useful in identifying patients who are at risk of POAF when undergoing major thoracic surgery and may, therefore, benefit from targeted prophylactic therapy.

7.
Front Immunol ; 10: 2623, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781116

RESUMO

Type 1 diabetes (T1D) is a chronic autoimmune disease that results from destruction of pancreatic ß-cells. T1D subjects were recently shown to harbor distinct intestinal microbiome profiles. Based on these findings, the role of gut bacteria in T1D is being intensively investigated. The mechanism connecting intestinal microbial homeostasis with the development of T1D is unknown. Specific gut bacteria such as Bacteroides dorei (BD) and Ruminococcus gnavus (RG) show markedly increased abundance prior to the development of autoimmunity. One hypothesis is that these bacteria might traverse the damaged gut barrier, and their constituents elicit a response from human islets that causes metabolic abnormalities and inflammation. We have tested this hypothesis by exposing human islets to BD and RG in vitro, after which RNA-Seq analysis was performed. The bacteria altered expression of many islet genes. The commonly upregulated genes by these bacteria were cytokines, chemokines and enzymes, suggesting a significant effect of gut bacteria on islet antimicrobial and biosynthetic pathways. Additionally, each bacteria displayed a unique set of differentially expressed genes (DEGs). Ingenuity pathway analysis of DEGs revealed that top activated pathways and diseases included TREM1 signaling and inflammatory response, illustrating the ability of bacteria to induce islet inflammation. The increased levels of selected factors were confirmed using immunoblotting and ELISA methods. Our data demonstrate that islets produce a complex anti-bacterial response. The response includes both symbiotic and pathogenic aspects. Both oxidative damage and leukocyte recruitment factors were prominent, which could induce beta cell damage and subsequent autoimmunity.

8.
JAMA Ophthalmol ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31697304

RESUMO

Importance: Lower bevacizumab dosages are being used for type 1 retinopathy of prematurity, but there are limited data on long-term ocular outcomes with lower doses. Objective: To evaluate ocular outcomes at 12 months' corrected age for eyes that received a dose of 0.625 mg, 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg of bevacizumab for type 1 retinopathy of prematurity. Design, Setting, and Participants: This prospective cohort study used a masked, multicenter, phase 1 dose de-escalation study design and was conducted from April 2016 to October 2017. Study eyes were treated with a dose of 0.25, 0.125, 0.063, or 0.031 mg of bevacizumab; fellow eyes were treated with a dosage 1 level higher than the study eye. Additional treatment after 4 weeks was at investigator discretion. Data analysis occurred from November 2018 to March 2019. Interventions: Intravitreous bevacizumab injections of 0.625 mg to 0.031 mg. Main Outcomes and Measures: Visual fixation, amblyopia, alignment, nystagmus, cycloplegic refraction, and ocular examinations were assessed at 12 months' corrected age as preplanned secondary outcomes. The primary outcome 4 weeks after treatment and secondary outcomes after 6 months' corrected age have been previously reported. Results: Forty-six of 61 infants (75%) had a 12-month follow-up examination (46 study eyes and 43 fellow eyes; median [interquartile range] birth weight, 650 [590-760] g). Of 87 eyes with a cycloplegic refraction, 12 (14% [95% CI, 7%-27%]) had myopia of more than -5.00 D spherical equivalent; 2 (2%; [95% CI, 0%-8%]) had hyperopia greater than 5.00 D spherical equivalent; and 5 infants (11% [95% CI, 4%-24%]) had anisometropia greater than 1.50 D spherical equivalent. Abnormalities of the cornea, lens, or anterior segment were reported in 1 eye (1% [95% CI, 0%-6%]), 3 eyes (3% [95% CI, 1%-10%]), and 3 eyes (3% [95% CI, 1%-10%]), respectively. Optic nerve atrophy was identified in 11 eyes (13% [95% CI, 6%-26%]), and 1 eye (1% [95% CI, 0%-6%]) had total retinal detachment. Strabismus was reported in 13 infants (30% [95% CI, 17%-45%]), manifest nystagmus in 7 infants (15% [95% CI, 6%-29%]), and amblyopia in 3 infants (7% [95% CI, 1%-18%]). Overall, 98% of infants had central fixation in each eye (44 of 45 eyes). Conclusions and Relevance: In this study of low-dose bevacizumab, the secondary outcomes of high myopia, strabismus, retinal detachment, nystagmus, and other ocular abnormalities at 1 year were consistent with rates reported in other studies with higher dosages. Trial Registration: ClinicalTrials.gov identifier: NCT02390531.

9.
PeerJ ; 7: e7823, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592354

RESUMO

Background: Variation within the submandibular triangle, including variant paths of facial neurovasculature, could increase risk of neurovascular derangement during submandibular gland (SMG) dysfunction, enlargement, interventions, or removal. Methods: Frequency of anatomical variants enveloped within or piercing the SMG, including facial artery, vein, or branches of CN VII, were assessed in 70 cadaveric submandibular glands (39M/31F). Results: Eighteen of 70 SMGs (25.7%) were pierced by at least one aberrant neurovasculature structure: Facial artery most frequently (n = 13), followed by facial vein (n = 2), inferior labial artery and vein (n = 1), and CN VII cervical branch (n = 1). This study demonstrated the high variability of neurovasculature within submandibular parenchyma. These aberrant neurovascular structures, especially facial artery, are in danger of compromise during surgical and other medical procedures on the SMG. To avoid potential neurovascular compromise, ultrasonographic or other imaging is recommended prior to procedures involving the SMG.

10.
Psychol Sci ; 30(11): 1625-1637, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566081

RESUMO

Societal inequality has been found to harm the mental and physical health of its members and undermine overall social cohesion. Here, we tested the hypothesis that economic inequality is associated with a wish for a strong leader in a study involving 28 countries from five continents (Study 1, N = 6,112), a study involving an Australian community sample (Study 2, N = 515), and two experiments (Study 3a, N = 96; Study 3b, N = 296). We found correlational (Studies 1 and 2) and experimental (Studies 3a and 3b) evidence for our prediction that higher inequality enhances the wish for a strong leader. We also found that this relationship is mediated by perceptions of anomie, except in the case of objective inequality in Study 1. This suggests that societal inequality enhances the perception that society is breaking down (anomie) and that a strong leader is needed to restore order (even when that leader is willing to challenge democratic values).

11.
BMJ Open ; 9(9): e031319, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530619

RESUMO

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common cause of major morbidity following pancreatic resection. Intra-abdominal drains are frequently positioned adjacent to the pancreatic anastomosis or transection margin at the time of surgery to aid in detection and management of CR-POPF. Drains can either evacuate fluid by passive gravity (PG) or be attached to a closed suction (CS) system using negative pressure. There is controversy as to whether one of these two systems is superior. The objective of this review is to identify and compare the incidence of adverse events (AEs) and resource utilisation associated with PG and CS drainage following pancreatic resections. METHODS AND ANALYSIS: MEDLINE, EMBASE, CINAHL and Cochrane Central Registry of Controlled Trials will be searched from inception to April 2019, to identify interventional and observational studies comparing PG and CS drains following pancreatic resection. The primary outcome is POPF as defined by the International Study Group for Pancreatic Fistula in 2017. Secondary outcomes include postoperative AE, resource utilisation (length of stay, return to emergency department, readmission and reintervention), time to drain removal and quality of life. Study selection, data extraction and risk of bias assessment will be performed independently, by two reviewers. A meta-analysis will be conducted if deemed statistically appropriate. Subgroup analysis by study design will be performed. Study heterogeneity will be calculated with the χ2 test and reported as I2 statistics. Statistical analyses will be conducted and displayed using RevMan V.5.3 ETHICS AND DISSEMINATION: Ethics approval is not required. The results of this study will be submitted to relevant conferences for presentation and peer-reviewed journals for publication. PROSPERO REGISTRATION NUMBER: CRD42019123647.

12.
Stroke ; 50(10): 2790-2798, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31495328

RESUMO

Background and Purpose- Endovascular thrombectomy is highly effective in acute ischemic stroke patients with an anterior circulation large vessel occlusion (LVO), decreasing morbidity and mortality. Accurate and prompt identification of LVOs is imperative because these patients have large volumes of tissue that are at risk of infarction without timely reperfusion, and the treatment window is limited to 24 hours. We assessed the accuracy and speed of a commercially available fully automated LVO-detection tool in a cohort of patients presenting to a regional hospital with suspected stroke. Methods- Consecutive patients who underwent multimodal computed tomography with thin-slice computed tomography angiography between January 1, 2017 and December 31, 2018 for suspected acute ischemic stroke within 24 hours of onset were retrospectively identified. The multimodal computed tomographies were assessed by 2 neuroradiologists in consensus for the presence of an intracranial anterior circulation LVO or M2-segment middle cerebral artery occlusion (the reference standard). The patients' computed tomography angiographies were then processed using an automated LVO-detection algorithm (RAPID CTA). Receiver-operating characteristic analysis was used to determine sensitivity, specificity, and negative predictive value of the algorithm for detection of (1) an LVO and (2) either an LVO or M2-segment middle cerebral artery occlusion. Results- CTAs from 477 patients were analyzed (271 men and 206 women; median age, 71; IQR, 60-80). Median processing time was 158 seconds (IQR, 150-167 seconds). Seventy-eight patients had an anterior circulation LVO, and 28 had an isolated M2-segment middle cerebral artery occlusion. The sensitivity, negative predictive value, and specificity were 0.94, 0.98, and 0.76, respectively for detection of an intracranial LVO and 0.92, 0.97, and 0.81, respectively for detection of either an intracranial LVO or M2-segment middle cerebral artery occlusion. Conclusions- The fully automated algorithm had very high sensitivity and negative predictive value for LVO detection with fast processing times, suggesting that it can be used in the emergent setting as a screening tool to alert radiologists and expedite formal diagnosis.

13.
J Soc Work End Life Palliat Care ; 15(2-3): 85-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385743

RESUMO

Since 2002, the Department of Veterans Affairs (VA) has provided a unique training opportunity in palliative care at six VA medical centers. The VA Interprofessional Fellowship in Palliative Care has trained chaplains, nurses, pharmacists, physicians, psychologists, and social workers to provide clinical palliative care and to develop as leaders in the profession. This article describes the program's origin, mission, outcomes, and lessons learned.

14.
Int J Clin Pharm ; 41(5): 1239-1246, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392581

RESUMO

Background The patient transition from a hospital to a post-discharge healthcare setting has potential to disrupt continuity of medication management and increase the risk of harm. "Connect with Pharmacy" is a new electronic web-based transfer of care initiative employed by Leeds Teaching Hospitals NHS Trust. This allows the sharing of discharge information between the hospital and a patient's chosen community pharmacy. Objective We investigated whether the timely sharing of discharge information with community pharmacies via "Connect with Pharmacy" reduced hospital readmission rates in older patients. Method To evaluate intervention efficacy, hospital admission data was retrospectively collected. For primary analysis, admission rates were tracked 6-months prior (baseline) and 6-months post-intervention. Secondary measures included effect on total length of stay if readmitted, emergency department attendance and duration, and impact of polypharmacy. Main outcome measure The rate of non-elective hospital readmissions, 6-months post-intervention. Results In the sample (n = 627 patients; Mean age = 81 years), emergency readmission rates following the intervention (M = 1.1, 95% CI [0.98, 1.22]) reduced by 16.16% relative to baseline (M = 1.31, 95% CI [1.21, 1.42]) (W = 54,725; p < 0.001). There was no reduction in total length of stay. Subsidiary analysis revealed a post-intervention reduction in number of days spent in hospital lasting more than three days (χ2 = 13.37, df = 1, p < 0 .001). There were no statistically reliable differences in the remaining secondary measures. Conclusion The results showed a reduction in readmissions and potential post-intervention length of stay, indicating there may be further benefits for our older patients' experiences and hospital flow.

15.
Dev Psychopathol ; : 1-11, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31298177

RESUMO

While child self-regulation is shaped by the environment (e.g., the parents' caregiving behaviors), children also play an active role in influencing the care they receive, indicating that children's individual differences should be integrated in models relating early care to children's development. We assessed 409 children's observed temperamental behavioral inhibition (BI), effortful control (EC), and the primary caregiver's parenting at child ages 3 and 5. Parents reported on child behavior problems at child ages 3, 5, and 8. Mediation analyses were conducted to examine relations between child temperament and parenting in predicting child problems. BI at age 3 was positively associated with structured parenting at age 5, which was negatively related to child internalizing and attention-academic problems at age 8. In contrast, parenting at child age 3 did not predict child BI or EC at age 5, nor did age 3 EC predict parenting at age 5. Findings indicate that child behavior may shape the development of caregiving and, in turn, long-term child adjustment, suggesting that studies of caregiving and child outcomes should consider the role of child temperament toward developing more informative models of child-environment interplay.

16.
Pharmacy (Basel) ; 7(3)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349584

RESUMO

There is concern internationally that many older people are using an inappropriate number of medicines, and that complex combinations of medicines may cause more harm than good. This article discusses how person-centred medicines optimisation for older people can be conducted in clinical practice, including the process of deprescribing. The evidence supports that if clinicians actively include people in decision making, it leads to better outcomes. We share techniques, frameworks, and tools that can be used to deprescribe safely whilst placing the person's views, values, and beliefs about their medicines at the heart of any deprescribing discussions. This includes the person-centred approach to deprescribing (seven steps), which incorporates the identification of the person's priorities and the clinician's priorities in relation to treatment with medication and promotes shared decision making, agreed goals, good communication, and follow up. The authors believe that delivering deprescribing consultations in this manner is effective, as the person is integral to the deprescribing decision-making process, and we illustrate how this approach can be applied in real-life case studies.

17.
JAMA Psychiatry ; 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31268507

RESUMO

Importance: Genome-wide association studies (GWASs) in European populations have identified more than 100 schizophrenia-associated loci. A schizophrenia GWAS in a unique Indian population offers novel findings. Objective: To discover and functionally evaluate genetic loci for schizophrenia in a GWAS of a unique Indian population. Design, Setting, and Participants: This GWAS included a sample of affected individuals, family members, and unrelated cases and controls. Three thousand ninety-two individuals were recruited and diagnostically ascertained via medical records, hospitals, clinics, and clinical networks in Chennai and surrounding regions. Affected participants fulfilled DSM-IV diagnostic criteria for schizophrenia. Unrelated control participants had no personal or family history of psychotic disorder. Recruitment, genotyping, and analysis occurred in consecutive phases beginning January 1, 2001. Recruitment was completed on February 28, 2018, and genotyping and analysis are ongoing. Main Outcomes and Measures: Associations of single-nucleotide polymorphisms and gene expression with schizophrenia. Results: The study population included 1321 participants with schizophrenia, 885 family controls, and 886 unrelated controls. Among participants with schizophrenia, mean (SD) age was 39.1 (11.4) years, and 52.7% were male. This sample demonstrated uniform ethnicity, a degree of inbreeding, and negligible rates of substance abuse. A novel genome-wide significant association was observed between schizophrenia and a chromosome 8q24.3 locus (rs10866912, allele A; odds ratio [OR], 1.27 [95% CI, 1.17-1.38]; P = 4.35 × 10-8) that attracted support in the schizophrenia Psychiatric Genomics Consortium 2 data (rs10866912, allele A; OR, 1.04 [95% CI, 1.02-1.06]; P = 7.56 × 10-4). This locus has undergone natural selection, with the risk allele A declining in frequency from India (approximately 72%) to Europe (approximately 43%). rs10866912 directly modifies the abundance of the nicotinate phosphoribosyltransferase gene (NAPRT1) transcript in brain cortex (normalized effect size, 0.79; 95% CI, 0.6-1.0; P = 5.8 × 10-13). NAPRT1 encodes a key enzyme for niacin metabolism. In Indian lymphoblastoid cell lines, (risk) allele A of rs10866912 was associated with NAPRT1 downregulation (AA: 0.74, n = 21; CC: 1.56, n = 17; P = .004). Preliminary zebrafish data further suggest that partial loss of function of NAPRT1 leads to abnormal brain development. Conclusions and Relevance: Bioinformatic analyses and cellular and zebrafish gene expression studies implicate NAPRT1 as a novel susceptibility gene. Given this gene's role in niacin metabolism and the evidence for niacin deficiency provoking schizophrenialike symptoms in neuropsychiatric diseases such as pellagra and Hartnup disease, these results suggest that the rs10866912 genotype and niacin status may have implications for schizophrenia susceptibility and treatment.

18.
Neurosurgery ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31350851

RESUMO

BACKGROUND: The natural history and management of dural ectasia in Neurofibromatosis 1 (NF1) is still largely unknown. Dural ectasias are one of the common clinical manifestations of NF1; however, the treatment options for dural ectasias remain unstudied. OBJECTIVE: To investigate the natural history, diagnosis, management, and outcome of the largest case series of patients with NF1-associated dural ectasia to date. METHODS: Records from our NF1 clinic were reviewed to identify NF1 patients with computed tomography or magnetic resonance imaging evidence of dural ectasia(s) to determine their clinical course. Demographics, symptoms, radiographic and histopathologic findings, treatment, and clinical course were assessed. RESULTS: Thirty-four of 37 patients were managed without surgery. Of the 18 initially asymptomatic patients, 5 (27.8%) progressed to symptoms attributable to a dural ectasia (onset of 2.7% per patient-year). Three patients required surgical intervention because of extraspinal mass effect. All 3 initially improved but had symptom recurrence within 2 yr. Reoperation involved shunt placement for cerebrospinal fluid (CSF) diversion. On imaging review, 26 (76.5%) of the nonsurgical patients harbored an associated nearby plexiform neurofibroma. Pathology of one surgical case revealed dural infiltration by diffuse neurofibroma. CONCLUSION: Using the largest NF1-associated dural ectasia group to date, we report the first symptom-onset rate for nonsurgical patients. In the few cases requiring surgery for decompression, primary resection, and patching of ectasias failed, subsequently requiring CSF shunting. We demonstrate imaging evidence of nearby plexiform neurofibroma in a majority of cases, which, when combined with histopathology, provides a novel explanation for the formation of dural ectasias.

19.
J Allergy Clin Immunol ; 143(6): 2271-2278, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31178019

RESUMO

BACKGROUND: Caregivers of children with primary immunodeficiency disorders (PIDs) experience significant psychological distress during their child's hematopoietic cell transplantation (HCT) process. OBJECTIVES: This study aims to understand caregiver challenges and identify areas for health care system-level improvements to enhance caregiver well-being. METHODS: In this mixed-methods study caregivers of children with PIDs were contacted in August to November 2017 through online and electronic mailing lists of rare disease consortiums and foundations. Caregivers were invited to participate in an online survey assessing sociodemographic variables, the child's medical characteristics, psychosocial support use, and the World Health Organization-5 Well-Being Index. Open-ended questions about health care system improvements were included. Descriptive statistics and linear multivariate regression analyses were conducted. A modified content analysis method was used to code responses and identify emergent themes. RESULTS: Among the 80 caregiver respondents, caregivers had a median age of 34 years (range, 23-62 years) and were predominantly female, white, and married with male children given a diagnosis of severe combined immune deficiency. In the adjusted regression model lower caregiver well-being was significantly associated with lower household income and medical complications. Challenges during HCT include maintaining relationships with partners and the child's healthy sibling or siblings, managing self-care, and coping with feelings of uncertainty. Caregivers suggested several organizational-level solutions to enhance psychosocial support, including respite services, online connections to other PID caregivers, and bedside mental health services. CONCLUSIONS: Certain high-risk subpopulations of caregivers might need more targeted psychosocial support to reduce the long-term effect of the HCT experience on their well-being. Caregivers suggested several organizational-level solutions for provision of this support.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA