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1.
BMC Med ; 21(1): 319, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620865

RESUMO

BACKGROUND: Many countries have introduced reforms with the aim of primary care transformation (PCT). Common objectives include meeting service delivery challenges associated with ageing populations and health inequalities. To date, there has been little research comparing PCT internationally. Our aim was to examine PCT and new models of primary care by conducting a systematic scoping review of international literature in order to describe major policy changes including key 'components', impacts of new models of care, and barriers and facilitators to PCT implementation. METHODS: We undertook a systematic scoping review of international literature on PCT in OECD countries and China (published protocol: https://osf.io/2afym ). Ovid [MEDLINE/Embase/Global Health], CINAHL Plus, and Global Index Medicus were searched (01/01/10 to 28/08/21). Two reviewers independently screened the titles and abstracts with data extraction by a single reviewer. A narrative synthesis of findings followed. RESULTS: A total of 107 studies from 15 countries were included. The most frequently employed component of PCT was the expansion of multidisciplinary teams (MDT) (46% of studies). The most frequently measured outcome was GP views (27%), with < 20% measuring patient views or satisfaction. Only three studies evaluated the effects of PCT on ageing populations and 34 (32%) on health inequalities with ambiguous results. For the latter, PCT involving increased primary care access showed positive impacts whilst no benefits were reported for other components. Analysis of 41 studies citing barriers or facilitators to PCT implementation identified leadership, change, resources, and targets as key themes. CONCLUSIONS: Countries identified in this review have used a range of approaches to PCT with marked heterogeneity in methods of evaluation and mixed findings on impacts. Only a minority of studies described the impacts of PCT on ageing populations, health inequalities, or from the patient perspective. The facilitators and barriers identified may be useful in planning and evaluating future developments in PCT.


Assuntos
Grupos Minoritários , Organização para a Cooperação e Desenvolvimento Econômico , Humanos , China/epidemiologia , Envelhecimento , Atenção Primária à Saúde
2.
Am J Emerg Med ; 52: 64-68, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34871845

RESUMO

OBJECTIVE: Delays in care for patients with acute cardiac complaints are associated with increased morbidity and mortality. The objective of this study was to quantify rural and urban differences in prehospital time intervals for patients with cardiac complaints. METHODS: The ESO Data Collaborative dataset consisting of records from 1332 EMS agencies was queried for 9-1-1 encounters with acute cardiac problems among adults (age ≥ 18) from 1/1/2013-6/1/2018. Location was classified as rural or urban using the 2010 United States Census. The primary outcome was total prehospital time. Generalized estimating equations evaluated differences in the average times between rural and urban encounters while controlling for age, sex, race, transport mode, loaded mileage, and patient stability. RESULTS: Among 428,054 encounters, the median age was 62 (IQR 50-75) years with 50.7% female, 75.3% white, and 10.3% rural. The median total prehospital, response, scene, and transport times were 37.0 (IQR 29.0-48.0), 6.0 (IQR 4.0-9.0), 16.0 (IQR 12.0-21.0), and 13.0 (IQR 8.0-21.0) minutes. Rural patients had an average total prehospital time that was 16.76 min (95%CI 15.15-18.38) longer than urban patients. After adjusting for covariates, average total time was 5.08 (95%CI 4.37-5.78) minutes longer for rural patients. Average response and transport time were 4.36 (95%CI 3.83-4.89) and 0.62 (95%CI 0.33-0.90) minutes longer for rural patients. Scene time was similar in rural and urban patients (0.09 min, 95%CI -0.15-0.33). CONCLUSION: Rural patients with acute cardiac complaints experienced longer prehospital time than urban patients, even after accounting for other key variables, such as loaded mileage.


Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , População Rural/estatística & dados numéricos , Tempo para o Tratamento , Doença Aguda/terapia , Idoso , Doenças Cardiovasculares/terapia , Estudos Transversais , Serviços Médicos de Emergência/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia
3.
Wilderness Environ Med ; 32(3): 271-277, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34183233

RESUMO

INTRODUCTION: Every year drowning is responsible for 7% of injury-related deaths worldwide, making it the third leading cause of unintentional injury-related death. However, in the United States, little is known regarding the prehospital presentation and management of these patients. The purpose of this study was to describe the drowning population in the United States, with a focus on prehospital time intervals, transport, and cardiac arrest frequency. METHODS: A retrospective cross-sectional study was performed querying records from emergency medical services encounters across the United States over 30 mo (January 2016 to July 2018) using the ESO (Austin, TX) national emergency medical services data registry. Patients with a dispatch or chief complaint of drowning were included. Descriptive statistics, binomial proportion tests, and general linear and logistic regression models were used. RESULTS: There were 1859 encounters that met the study criteria. Median age was 18 y (n=1855, LQ-UQ 4-46). Pediatric patients accounted for 50% (n=919, 95% CI 47-52). Cardiac arrest occurred in 29% (n=537, 95% CI 27-31), and return of spontaneous circulation occurred in 37% (n=186, 95% CI 32-41). Times were 8±5, 19±17, and 15±10 min (mean±SD) for arrival, on-scene, and transport times, respectively. CONCLUSIONS: This national prehospital drowning study demonstrated that despite an 18% fatality rate in drowning encounters, patients were more likely to have return of spontaneous circulation when compared to the overall prehospital national average, with rates higher in pediatric patients. Future studies with outcomes data should focus on identifying factors that improve cardiopulmonary resuscitation success rates.


Assuntos
Reanimação Cardiopulmonar , Afogamento , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Adolescente , Criança , Estudos Transversais , Afogamento/epidemiologia , Humanos , Estudos Retrospectivos , Estados Unidos/epidemiologia
4.
Ann Emerg Med ; 75(5): 559-567, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31983499

RESUMO

STUDY OBJECTIVE: Out-of-hospital naloxone has been championed as a lifesaving solution during the opioid epidemic. However, the long-term outcomes of out-of-hospital naloxone recipients are unknown. The objectives of this study are to describe the 1-year mortality of presumed opioid overdose victims identified by receiving out-of-hospital naloxone and to determine which patient factors are associated with subsequent mortality. METHODS: This was a regional retrospective cohort study of out-of-hospital records from 7 North Carolina counties from January 1, 2015 to February 28, 2017. Patients who received out-of-hospital naloxone were included. Out-of-hospital providers subjectively assessed patients for improvement after administering naloxone. Naloxone recipients were cross-referenced with the North Carolina death index to examine mortality at days 0, 1, 30, and 365. Naloxone recipient mortality was compared with the age-adjusted, at-large population's mortality rate in 2017. Generalized estimating equations and Cox proportional hazards models were used to assess for mortality-associated factors. RESULTS: Of 3,085 out-of-hospital naloxone encounters, 72.7% of patients (n=2,244) improved, whereas 27.3% (n=841) had no improvement with naloxone. At day 365, 12.0% (n=269) of the improved subgroup, 22.6% (n=190) of the no improvement subgroup, and 14.9% (n=459) of the whole population were dead. Naloxone recipients who improved were 13.2 times (95% confidence interval 13.0 to 13.3) more likely to be dead at 1 year than a member of the general populace after age adjusting of the at-large population to match this study population. Older age and being black were associated with 1-year mortality, whereas sex and multiple overdoses were not. CONCLUSION: Opioid overdose identified by receiving out-of-hospital naloxone with clinical improvement carries a 13-fold increase in mortality compared to the general population. This suggests that this is a high-risk population that deserves attention from public health officials, policymakers, and health care providers in regard to the development of long-term solutions.


Assuntos
Analgésicos Opioides/intoxicação , Overdose de Drogas/tratamento farmacológico , Serviços Médicos de Emergência , Mortalidade/tendências , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Overdose de Drogas/mortalidade , Feminino , Humanos , Lactente , Recém-Nascido , Cuidados para Prolongar a Vida/métodos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
5.
Childs Nerv Syst ; 36(8): 1773-1776, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32215714

RESUMO

INTRODUCTION: OssDsign have developed a new type of cranioplasty plate, consisting of calcium phosphate reinforced with titanium. Currently, there is little known about the cosmetic outcomes and infection rate when OssDsign cranioplasty plates are implanted into paediatric patients. METHODS: A retrospective case series was performed to include all paediatric patients who received an OssDsign cranioplasty at a single centre, Sheffield Children's Hospital. The cosmetic outcomes were subjectively reported by the parents of the children. RESULTS: We identified seven paediatric patients where OssDsign cranioplasty was performed. This included two bifrontal and five hemicranioplasties. However, there was failure to implant an OssDsign hemicranioplasty in one patient where a titanium plate was subsequently used. The median duration of follow-up was 15 months. The infection rate was zero. The parents of the patients who successfully received OssDsign cranioplasties were pleased with the cosmetic outcomes. There were cosmetic complaints from the parents of the one patient who received a titanium plate. CONCLUSION: Our early experience with OssDsign cranioplasty in paediatric patients indicates that it may potentially be associated with a low rate of infection and good cosmetic outcomes.


Assuntos
Craniectomia Descompressiva , Procedimentos de Cirurgia Plástica , Criança , Humanos , Complicações Pós-Operatórias , Estudos Retrospectivos , Crânio/cirurgia
6.
Childs Nerv Syst ; 36(9): 2013-2019, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152667

RESUMO

INTRODUCTION: Ventriculoperitoneal shunt insertion during the neonatal period and early infancy is associated with a high rate of shunt failure when compared to the adult population. Furthermore, the function of flow-regulated valves and differential pressure valves may be different in neonatal hydrocephalus. METHODS: A retrospective case series of all primary shunt procedures carried out during or immediately following the neonatal period, from August 2011 to February 2018 at Sheffield Children's Hospital. The total sample size was 55. This included 34 patients with adjustable valves (Miethke ProGav) and 21 with flow-regulated valves (Orbis-Sigma); however, only 53 had adequate follow-up. RESULTS: The overall 1 year shunt survival was 34% (18/53), and there was no significant difference depending on which shunt valve was implanted. The primary shunt infection rate was 11% (6/53) with S. aureus being the most common causative organism. During the first year of life, clinical signs of shunt overdrainage were seen more frequently in patients with adjustable valves than in those with flow-regulated valves (59% [19/32] versus 24% [5/21], p = 0.02). Furthermore, 2 patients in the adjustable valve group developed sagittal craniosynostosis secondary to shunt overdrainage. CONCLUSION: Shunt failure is high when inserted during or immediately following the neonatal period. Overdrainage may be less common in patients with flow-regulated valves. However, if overdrainage is observed, adjusting the setting of a differential pressure valve can effectively treat the overdrainage without the need for invasive shunt revision surgery.


Assuntos
Hidrocefalia , Staphylococcus aureus , Adulto , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Criança , Seguimentos , Humanos , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Estudos Retrospectivos , Resultado do Tratamento , Derivação Ventriculoperitoneal/efeitos adversos
7.
Mol Psychiatry ; 23(2): 316-322, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28289280

RESUMO

Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia), cognition (Measurement and Treatment Research to Improve Cognition in Schizophrenia composite) and three complementary magnetic resonance imaging measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared with placebo, l-methylfolate increased plasma methylfolate levels (d=1.00, P=0.0009) and improved PANSS Total (d=0.61, P=0.03) as well as PANSS Negative and General Psychopathology subscales. Although PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving l-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity and increased cortical thickness. In conclusion, l-methylfolate supplementation was associated with salutary physiological changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials. ClinicalTrials.gov, NCT01091506.


Assuntos
Esquizofrenia/tratamento farmacológico , Tetra-Hidrofolatos/farmacologia , Adulto , Antipsicóticos/uso terapêutico , Cognição/efeitos dos fármacos , Método Duplo-Cego , Feminino , Ácido Fólico/metabolismo , Ácido Fólico/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Tetra-Hidrofolatos/uso terapêutico , Resultado do Tratamento
8.
J Antimicrob Chemother ; 73(9): 2405-2410, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29939267

RESUMO

Background: 'Last-line' antimicrobial usage has promoted the emergence of MDR bacteria. Production of Klebsiella pneumoniae carbapenemases (KPCs) is increasingly common and leads to resistance to most antimicrobials. However, ceftazidime/avibactam demonstrates activity against KPC-producing strains. Ceftazidime/avibactam in the empirical setting remains unknown. Methods: Strains underwent genetic analysis evaluating blaKPC presence/production and MICs were determined. Four strains were assessed in an in vitro, one-compartment pharmacokinetic (PK)/pharmacodynamic (PD) model for 96 h. The following bolus dosing exposures were tested: 2.5 g of ceftazidime/avibactam every 8 h, 2 g of meropenem every 8 h, 1.25 mg/kg polymyxin B every 12 h, amikacin 'once-daily dosing' (peak of 70-80 mg/L), tigecycline at 200 mg ×1 dose followed by 100 mg every 12 h, and a drug-free growth control. Results: Thirty blaKPC-producing strains were evaluated; 97% of strains were ceftazidime/avibactam susceptible with MIC50/MIC90 values of 0.38/1.5 mg/L (range 0.032-16 mg/L). Two K. pneumoniae strains, one Klebsiella oxytoca strain and one Citrobacter freundii strain underwent further analysis in PK/PD models. Ceftazidime/avibactam displayed potent activity with a reduction of 4.23 ±âŸ0.42 cfu/mL from the initial inoculum at 96 h. Against susceptible isolates, amikacin displayed similar activity compared with ceftazidime/avibactam at 96 h, although this was not demonstrated against all strains. Polymyxin B produced comparable activity to ceftazidime/avibactam against two strains. Neither meropenem nor tigecycline produced effective killing and were comparable to the drug-free growth control at 96 h. Conclusions: blaKPC-producing organisms demonstrated susceptibility to ceftazidime/avibactam and bactericidal activity was observed in the PK/PD model. Based on these data, ceftazidime/avibactam is a valuable agent for treating KPC-producing organisms and should be considered for treatment of infections caused by these pathogens.


Assuntos
Antibacterianos/administração & dosagem , Compostos Azabicíclicos/administração & dosagem , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Ceftazidima/administração & dosagem , Infecções por Enterobacteriaceae/tratamento farmacológico , Inibidores de beta-Lactamases/administração & dosagem , beta-Lactamases/genética , Amicacina/administração & dosagem , Amicacina/farmacocinética , Amicacina/farmacologia , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacocinética , Compostos Azabicíclicos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Ceftazidima/farmacocinética , Ceftazidima/farmacologia , Combinação de Medicamentos , Meropeném/administração & dosagem , Meropeném/farmacocinética , Meropeném/farmacologia , Modelos Teóricos , Polimixina B/administração & dosagem , Polimixina B/farmacocinética , Polimixina B/farmacologia , Resultado do Tratamento , Inibidores de beta-Lactamases/farmacocinética , Inibidores de beta-Lactamases/farmacologia
9.
Psychol Med ; 48(7): 1139-1147, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28889814

RESUMO

BACKGROUND: Distinguishing temporal patterns of depressive symptoms during pregnancy and after childbirth has important clinical implications for diagnosis, treatment, and maternal and child outcomes. The primary aim of the present study was to distinguish patterns of chronically elevated levels of depressive symptoms v. trajectories that are either elevated during pregnancy but then remit after childbirth, v. patterns that increase after childbirth. METHODS: The report uses latent growth mixture modeling in a large, population-based cohort (N = 12 121) to investigate temporal patterns of depressive symptoms. We examined theoretically relevant sociodemographic factors, exposure to adversity, and offspring gender as predictors. RESULTS: Four distinct trajectories emerged, including resilient (74.3%), improving (9.2%), emergent (4.0%), and chronic (11.5%). Lower maternal and paternal education distinguished chronic from resilient depressive trajectories, whereas higher maternal and partner education, and female offspring gender, distinguished the emergent trajectory from the chronic trajectory. Younger maternal age distinguished the improving group from the resilient group. Exposure to medical, interpersonal, financial, and housing adversity predicted membership in the chronic, emergent, and improving trajectories compared with the resilient trajectory. Finally, exposure to medical, interpersonal, and financial adversity was associated with the chronic v. improving group, and inversely related to the emergent class relative to the improving group. CONCLUSIONS: There are distinct temporal patterns of depressive symptoms during pregnancy, after childbirth, and beyond. Most women show stable low levels of depressive symptoms, while emergent and chronic depression patterns are separable with distinct correlates, most notably maternal age, education levels, adversity exposure, and child gender.


Assuntos
Depressão Pós-Parto/diagnóstico , Depressão/diagnóstico , Adulto , Diagnóstico Diferencial , Escolaridade , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Idade Materna , Gravidez , Escalas de Graduação Psiquiátrica , Resiliência Psicológica , Índice de Gravidade de Doença , Fatores Sexuais , Estresse Psicológico , Fatores de Tempo , Adulto Jovem
10.
Eur J Nucl Med Mol Imaging ; 44(2): 296-307, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27699720

RESUMO

PURPOSE: To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates (Papio hamadryas) using PET-CT. METHODS: In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography-tandem mass spectrometry. [18F]PBR102 and [18F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [18F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed. RESULTS: Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K1 was similar for baseline and blocking studies for both radiotracers; VT was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain. CONCLUSIONS: [18F]PBR102 and [18F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [18F]PBR102 in rodents; the impact in primates was less pronounced. Both [18F]PBR102 and [18F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands.


Assuntos
Encéfalo/metabolismo , Imidazóis/farmacocinética , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Piridinas/farmacocinética , Receptores de GABA/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Marcação por Isótopo/métodos , Ligantes , Masculino , Taxa de Depuração Metabólica , Especificidade de Órgãos , Papio , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Especificidade da Espécie , Distribuição Tecidual
11.
Acta Psychiatr Scand ; 136(5): 465-472, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28851055

RESUMO

OBJECTIVE: This study examined the effect of adjunctive telmisartan on psychopathology and cognition in olanzapine- or clozapine-treated patients with schizophrenia. METHOD: In a 12-week randomized, double-blind, placebo-controlled study, patients diagnosed with schizophrenia or schizoaffective disorder received either telmisartan (80 mg once per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS), and a neuropsychological battery was used to assess cognitive performance. Assessments for psychopathology and cognition were conducted at baseline and week 12. RESULTS: Fifty-four subjects were randomized, and 43 completed the study (22 in the telmisartan group, 21 in the placebo group). After 12-weeks of treatment, the telmisartan group had a significant decrease in PANSS total score compared withthe placebo group (mean ± SD: - 4.1 ± 8.1 vs. 0.4 ± 7.5, P = 0.038, SCohen's d = 0.57). There were no significant differences between the two groups in change from baseline to week 12 in PANSS subscale scores, SANS total score, or any cognitive measures (P > 0.100). CONCLUSION: The present study suggests that adjunctive treatment with telmisartan may improve schizophrenia symptoms. Future trials with larger sample sizes and longer treatment durations are warranted.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antipsicóticos/farmacologia , Benzimidazóis/farmacologia , Benzoatos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Antipsicóticos/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Benzodiazepinas/administração & dosagem , Benzodiazepinas/farmacologia , Clozapina/administração & dosagem , Clozapina/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Telmisartan
13.
Pediatr Surg Int ; 33(8): 855-859, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28601901

RESUMO

AIM OF THE STUDY: Hirschsprung's disease (HSCR) is known to occur in families. The reported overall incidence of familial cases is 7.6%, with a higher incidence of 15-21% in total colonic aganglionosis and 50% in the rare total intestinal aganglionosis. HSCR is extremely rare in twins. The aim of this study was to systematically analyse the patterns of HSCR in twins published in the literature. METHODS: Electronic databases Pubmed and Medline were screened for relevant articles using the keywords "Hirschsprung's disease", "aganglionosis", "twins", "monozygotic", and "dizygotic". Examining reference lists identified further relevant papers. MAIN RESULTS: Twelve studies with a total of 18 twin pairs were included in this analysis. 67% twins were discordant. HSCR was found in 24 out of 36 twin subjects (67%), of which 83% affected were male. Rectosigmoid type was reported in 71% of patients, long-segment disease in 21, and 8% presented with a total aganglionosis. Three twin pairs had at least one family member affected with HSCR. CONCLUSION: HSCR was found in two-thirds of twin subjects with a male predominance. Rectosigmoid aganglionosis was the most common variant. Disease discordance was identified, where environmental insults were postulated to be predisposing factors to disease expression. Future studies investigating the disease-associated mutations in the already identified HSCR genes should provide insights into the genetic basis of HSCR in twins.


Assuntos
Doenças em Gêmeos/epidemiologia , Doença de Hirschsprung/epidemiologia , Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/genética , Feminino , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Humanos , Incidência , Masculino , Gêmeos/genética
14.
Am J Epidemiol ; 183(5): 381-6, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26928219

RESUMO

Surveillance systems in public health practice have increased in number and sophistication with advances in data collection, analysis, and communication. When the Communicable Disease Center (now the Centers for Disease Control and Prevention) was founded some 70 years ago, surveillance referred to the close observation of individuals with suspected smallpox, plague, or cholera. Alexander Langmuir, head of the Epidemiology Branch, redefined surveillance as the epidemiology-based critical factor in infectious disease control. I joined Langmuir as assistant chief in 1955 and was appointed chief of the Surveillance Section in 1961. In this paper, I describe Langmuir's redefinition of surveillance. Langmuir asserted that its proper use in public health meant the systematic reporting of infectious diseases, the analysis and epidemiologic interpretation of data, and both prompt and widespread dissemination of results. I outline the Communicable Disease Center's first surveillance systems for malaria, poliomyelitis, and influenza. I also discuss the role of surveillance in the global smallpox eradication program, emphasizing that the establishment of systematic reporting systems and prompt action based on results were critical factors of the program.


Assuntos
Monitoramento Epidemiológico , Saúde Pública/história , Centers for Disease Control and Prevention, U.S./história , Notificação de Doenças/história , História do Século XX , História do Século XXI , Humanos , Saúde Pública/métodos , Estados Unidos
15.
Child Care Health Dev ; 42(4): 464-72, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27103590

RESUMO

BACKGROUND: Recent evidence suggests that fostering strategies to enable youth with chronic health conditions to work towards gradual self-management of their health is key in successful transition to adult healthcare. To date, there is limited research on self-management promotion for youth. The purpose of this study is to explore self-management from the perspectives of youth, parents and healthcare providers in transition to adult healthcare. METHODS: Part of a larger longitudinal transition (TRACE-2009-2013) study, interpretive phenomenology was used to explore the meaning of the lived experiences and perceptions of youth, parents, and healthcare providers about transition to adult healthcare. Purposeful sampling was utilized to select youth with a range of chronic health conditions from the TRACE cohort (spanning 20 diagnoses including developmental disabilities and chronic conditions), their parents and healthcare providers. RESULTS: The emerging three themes were: increasing independence of youth; parents as safety nets and healthcare providers as enablers and collaborators. The findings indicate that the experiences of transitioning youth, parents and service providers are interconnected and interdependent. CONCLUSIONS: Results support a dynamic and developmentally appropriate approach when working with transitioning youth and parents in practice. As youth depend on parents and healthcare providers for support in taking charge of their own health, parents and healthcare providers must work together to enable youth for self-management. At a policy level, adequate funding, institutional support and accreditation incentives are recommended to allow for designated time for healthcare providers to foster self-management skills in transitioning youth and parents.


Assuntos
Doença Crônica/reabilitação , Pessoas com Deficiência/reabilitação , Pessoal de Saúde/organização & administração , Pais/psicologia , Autocuidado/psicologia , Transição para Assistência do Adulto , Adaptação Psicológica , Adolescente , Canadá , Doença Crônica/psicologia , Pessoas com Deficiência/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Formulação de Políticas , Pesquisa Qualitativa , Qualidade da Assistência à Saúde , Apoio Social , Transição para Assistência do Adulto/organização & administração , Transição para Assistência do Adulto/normas , Adulto Jovem
16.
Br J Neurosurg ; 30(4): 461-3, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26488339

RESUMO

We report a case of intractable proctalgia on a background of lower back and bilateral leg pain secondary to spinal canal stenosis and spondylolisthesis. A complete resolution was observed following spinal surgery. This case highlights consideration of a spinal aetiology when intractable proctalgia is associated with back and leg pain.


Assuntos
Descompressão Cirúrgica , Procedimentos Neurocirúrgicos , Dor/etiologia , Estenose Espinal/cirurgia , Idoso , Dorso , Descompressão Cirúrgica/métodos , Feminino , Humanos , Perna (Membro) , Fusão Vertebral/métodos , Estenose Espinal/complicações , Resultado do Tratamento
17.
Br J Cancer ; 113(10): 1502-11, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26575822

RESUMO

BACKGROUND: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. METHODS: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold>3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. RESULTS: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). CONCLUSIONS: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression.


Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/cirurgia , Progressão da Doença , Regulação para Baixo , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Análise de Sequência de RNA
18.
Wilderness Environ Med ; 26(2): 256-60, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25698182

RESUMO

The National Association of Emergency Medical Services Physicians' (NAEMSP) position on the role of medical oversight within an operational Emergency Medical Service (EMS) program highlights the importance of integrating specially trained medical directors within the structure of these programs. In response, the NAEMSP Wilderness EMS (WEMS) Committee recognized the need for the development of an educational curriculum to provide physicians with the unique skills needed to be a medical director for a WEMS agency. This paper describes the Delphi process used to create the subject matter core content, as well as the actual core content developed. This core content was the foundation for the development of a specific WEMS medical director curriculum, the Wilderness EMS Medical Director Course.


Assuntos
Serviços Médicos de Emergência/métodos , Auxiliares de Emergência/educação , Diretores Médicos/educação , Medicina Selvagem/educação , Médicos , Trabalho de Resgate
19.
Clin Infect Dis ; 59 Suppl 2: S76-9, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25151482

RESUMO

Until 1997, the subject of bioterrorism was not discussed within the medical community and deliberately ignored in national planning efforts. Biological weapons were regarded as "morally repulsive." This complacency stemmed from a 1972 Biological Weapons Convention where all countries agreed to cease offensive biological weapons research. In the 1990s, however, the Soviet Union was discovered to have an extensive bioweapons program and a Japanese religious cult sought to launch an anthrax attack on Tokyo. Biological weapons such as smallpox and anthrax had the potential to cause a national catastrophe. However, little was done until John Bartlett in 1997 led a symposium and program to educate the medical community and the country of the need for definitive bioweapons programs. It was highly persuasive and received a final stimulus when the anthrax attack occurred in the United States in 2001.


Assuntos
Bioterrorismo/história , Bioterrorismo/legislação & jurisprudência , Defesa Civil , História do Século XX , História do Século XXI , Humanos , Ataques Terroristas de 11 de Setembro , Estados Unidos
20.
Br J Cancer ; 110(5): 1278-87, 2014 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-24518597

RESUMO

BACKGROUND: Isoforms of the PDE4 family of cAMP-specific phosphodiesterases (PDEs) are expressed in a cell type-dependent manner and contribute to underpinning the paradigm of intracellular cAMP signal compartmentalisation. Here we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression and uncover a role in controlling prostate cancer cell proliferation. METHODS: PDE4 transcripts from 19 prostate cancer cell lines and xenografts were quantified by qPCR. PDE4D7 expression was further investigated because of its significant downregulation between androgen-sensitive (AS) and androgen-insensitive (AI) samples. Western blot analysis, PDE activity assay, immunofluorescent staining and cAMP responsive FRET assays were used to investigate the sub-plasma membrane localisation of a population of PDE4D7 in VCaP (AS) and PC3 (AI) cell lines. Disruption of this localisation pattern using dominant-negative protein expression and siRNA knockdown showed that PDE4D7 acts in opposition to proliferative signalling as assessed by electrical impedance-based proliferation assays. RESULTS: Here we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression. PDE4D7 is highly expressed in AS cells and starkly downregulated in AI samples. The significance of this downregulation is underscored by our finding that PDE4D7 contributes a major fraction of cAMP degrading PDE activity tethered at the plasma membrane and that displacement of PDE4D7 from this compartment leads to an increase in the proliferation of prostate cancer cells. PDE4D7 mRNA expression is not, however, directly regulated by the androgen receptor signalling axis despite an overlapping genomic structure with the androgen responsive gene PART1. PDE4D7, which locates to the plasma membrane, acts to supress aberrant non-steroidal growth signals within the prostate or AS metastasis. CONCLUSIONS: PDE4D7 expression is significantly downregulated between AS and AI cell phenotypes. This change in expression potentially provides a novel androgen-independent biomarker and manipulation of its activity or its expression may provide therapeutic possibilities and insights into contributory aspects of the complex molecular pathology of prostate cancer.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/metabolismo , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Neoplasias de Próstata Resistentes à Castração/enzimologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/genética , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Membrana Celular/genética , Membrana Celular/metabolismo , AMP Cíclico/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Regulação para Baixo , Humanos , Isoenzimas , Masculino , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais
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