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BACKGROUND: The relation between prepregnancy average glucose concentration and a woman's risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM). METHODS AND FINDINGS: A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16-50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks' gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14-1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13-1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07-1.14; p < 0.001) and without (1.15, 95% CI 1.02-1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11-1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04-1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06-1.62; p = 0.01) in those with a preconception A1c of 5.8%-6.4%, and 2.84 (95% CI 2.31-3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76-6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women. CONCLUSIONS: Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.
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Edad Gestacional , Hemoglobina Glucada/metabolismo , Mortalidad Materna , Complicaciones del Embarazo/epidemiología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Nacimiento Vivo/epidemiología , Masculino , Edad Materna , Persona de Mediana Edad , Periodo Posparto/fisiología , Embarazo , Factores de Riesgo , Adulto JovenRESUMEN
As of September 21, 2020, the coronavirus disease 2019 (COVID-19) pandemic had resulted in 6,786,352 cases and 199,024 deaths in the United States.* Health care personnel (HCP) are essential workers at risk for exposure to patients or infectious materials (1). The impact of COVID-19 on U.S. HCP was first described using national case surveillance data in April 2020 (2). Since then, the number of reported HCP with COVID-19 has increased tenfold. This update describes demographic characteristics, underlying medical conditions, hospitalizations, and intensive care unit (ICU) admissions, stratified by vital status, among 100,570 HCP with COVID-19 reported to CDC during February 12-July 16, 2020. HCP occupation type and job setting are newly reported. HCP status was available for 571,708 (22%) of 2,633,585 cases reported to CDC. Most HCP with COVID-19 were female (79%), aged 16-44 years (57%), not hospitalized (92%), and lacked all 10 underlying medical conditions specified on the case report form (56%). Of HCP with COVID-19, 641 died. Compared with nonfatal COVID-19 HCP cases, a higher percentage of fatal cases occurred in males (38% versus 22%), persons aged ≥65 years (44% versus 4%), non-Hispanic Asians (Asians) (20% versus 9%), non-Hispanic Blacks (Blacks) (32% versus 25%), and persons with any of the 10 underlying medical conditions specified on the case report form (92% versus 41%). From a subset of jurisdictions reporting occupation type or job setting for HCP with COVID-19, nurses were the most frequently identified single occupation type (30%), and nursing and residential care facilities were the most common job setting (67%). Ensuring access to personal protective equipment (PPE) and training, and practices such as universal use of face masks at work, wearing masks in the community, and observing social distancing remain critical strategies to protect HCP and those they serve.
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Infecciones por Coronavirus/epidemiología , Personal de Salud/estadística & datos numéricos , Enfermedades Profesionales/epidemiología , Neumonía Viral/epidemiología , Vigilancia de la Población , Adolescente , Adulto , Anciano , COVID-19 , Infecciones por Coronavirus/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/mortalidad , Pandemias , Neumonía Viral/mortalidad , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections.
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Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades , Neumonía Viral/epidemiología , Adolescente , Adulto , Anciano , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , Niño , Preescolar , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/terapia , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/mortalidad , Neumonía Viral/terapia , SARS-CoV-2 , Adulto JovenRESUMEN
Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED). These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.
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Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/mortalidad , Neumonía Viral/complicaciones , Neumonía Viral/mortalidad , Adolescente , COVID-19 , Causas de Muerte/tendencias , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pandemias , Estados Unidos/epidemiología , Adulto JovenRESUMEN
During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).
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Infecciones por Coronavirus/mortalidad , Disparidades en el Estado de Salud , Neumonía Viral/mortalidad , Vigilancia en Salud Pública , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Enfermedad Crónica , Infecciones por Coronavirus/etnología , Etnicidad/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/etnología , Grupos Raciales/estadística & datos numéricos , Factores de Riesgo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection.
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Feto/virología , Placenta/virología , Complicaciones Infecciosas del Embarazo/diagnóstico , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , District of Columbia , Femenino , Humanos , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa , Estados UnidosRESUMEN
mRNA localisation coupled to translational regulation provides an important means of dictating when and where proteins function in a variety of model systems. This mechanism is particularly relevant in polarised or migrating cells. Although many of the models for how this is achieved were first proposed over 20 years ago, some of the molecular details are still poorly understood. Nevertheless, advanced imaging, biochemical and computational approaches have started to shed light on the cis-acting localisation signals and trans-acting factors that dictate the final destination of localised transcripts. In this Cell Science at a Glance article and accompanying poster, we provide an overview of mRNA localisation, from transcription to degradation, focusing on the microtubule-dependent active transport and anchoring mechanism, which we will use to explain the general paradigm. However, it is clear that there are diverse ways in which mRNAs become localised and target protein expression, and we highlight some of the similarities and differences between these mechanisms.
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ARN Mensajero/metabolismo , Transporte Activo de Núcleo Celular , Animales , Biología Celular , Núcleo Celular/metabolismo , Humanos , Biosíntesis de Proteínas , ARN Mensajero/genética , Fracciones Subcelulares/metabolismoRESUMEN
For cells the passage from life to death can involve a regulated, programmed transition. In contrast to cell death, the mechanisms of systemic collapse underlying organismal death remain poorly understood. Here we present evidence of a cascade of cell death involving the calpain-cathepsin necrosis pathway that can drive organismal death in Caenorhabditis elegans. We report that organismal death is accompanied by a burst of intense blue fluorescence, generated within intestinal cells by the necrotic cell death pathway. Such death fluorescence marks an anterior to posterior wave of intestinal cell death that is accompanied by cytosolic acidosis. This wave is propagated via the innexin INX-16, likely by calcium influx. Notably, inhibition of systemic necrosis can delay stress-induced death. We also identify the source of the blue fluorescence, initially present in intestinal lysosome-related organelles (gut granules), as anthranilic acid glucosyl esters--not, as previously surmised, the damage product lipofuscin. Anthranilic acid is derived from tryptophan by action of the kynurenine pathway. These findings reveal a central mechanism of organismal death in C. elegans that is related to necrotic propagation in mammals--e.g., in excitotoxicity and ischemia-induced neurodegeneration. Endogenous anthranilate fluorescence renders visible the spatio-temporal dynamics of C. elegans organismal death.
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Caenorhabditis elegans/química , Fluorescencia , ortoaminobenzoatos/química , Animales , Ésteres/química , Estrés OxidativoRESUMEN
A routine investigation by the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) identified a nonpregnant woman in her twenties who reported she had engaged in a single event of condomless vaginal intercourse with a male partner the day she returned to NYC (day 0) from travel to an area with ongoing Zika virus transmission. She had headache and abdominal cramping while in the airport awaiting return to NYC. The following day (day 1) she developed fever, fatigue, a maculopapular rash, myalgia, arthralgia, back pain, swelling of the extremities, and numbness and tingling in her hands and feet. In addition, on day 1, the woman began menses that she described as heavier than usual. On day 3 she visited her primary care provider who obtained blood and urine specimens. Zika virus RNA was detected in both serum and urine by real-time reverse transcription-polymerase chain reaction (rRT-PCR) performed at the DOHMH Public Health Laboratory using a test based on an assay developed at CDC (1). The results of serum testing for anti-Zika virus immunoglobulin M (IgM) antibody performed by the New York State Department of Health Wadsworth Center laboratory was negative using the CDC Zika IgM antibody capture enzyme-linked immunosorbent assay (Zika MAC-ELISA) (2).
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Enfermedades Virales de Transmisión Sexual , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/transmisión , Virus Zika/aislamiento & purificación , Adulto , Femenino , Humanos , Masculino , Ciudad de Nueva York , ARN Viral/sangre , ARN Viral/aislamiento & purificación , ARN Viral/orina , ViajeRESUMEN
As the number of pacemaker insertions increases to manage numerous cardiac arrhythmias, the number of complications is also increasing as a result. More common complications such as infection and lead displacement are routinely discussed with patients before they undergo the procedure. However rare complications such as superior vena cava syndrome are not discussed during the consenting period. But they do occur, as seen in this case of a 69-year-old male. This fit and active man had a right-sided dual-chamber pacemaker inserted due to sinus node disease and presented 5 years later with symptoms suggestive of superior vena cava obstruction (SVCO). Despite anticoagulation and before surgical intervention could be performed, the patient developed a right-sided chylothorax which was drained. An autologous pericardial patch repair of the SVC and a thrombectomy of SVC clots was subsequently performed. This was only partially successful and the SVCO recurred. A low fatty chain diet was initiated to manage the chylothorax, which remains stable. This rare complication has left the patient with a small pleural effusion and chronic pleural thickening. They can still exercise with mild breathlessness. The management of such a complication, which requires the input of many specialists, is challenging and often does not completely resolve all symptoms. For this reason, superior vena cava obstruction should be considered as a risk during the consenting procedure for a pacemaker insertion.
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The European Centre for Disease Prevention and Control (ECDC) defines a case of tick-borne encephalitis (TBE) as an infection by the TBE virus (TBEV) with clinical manifestations of central nervous system inflammation (e.g., meningitis, encephalitis). To better understand the TBE surveillance landscape, online searches were conducted to determine if cases of TBE, TBEV infection, acute meningitis or encephalitis, or viral meningitis or encephalitis were subject to statutory reporting in European countries in 2023. In countries with statutory reporting, notification responsibility and available information on surveillance-reported cases were determined. The number of TBE cases reported to ECDC were compared with the number of cases recorded in national surveillance reports. Of 44 countries of the Europe Region of the United Nations, 37 (84 %) mandated statutory reporting of cases of TBE, TBEV infection, or acute/viral meningitis/encephalitis. Twenty-six (87 %) of 30 countries with identified surveillance reports recorded TBE cases in 2020-2023. Of these countries, 17 (65 %) required TBE reporting by clinicians and laboratories, 5 (19 %) by clinicians only, and 4 (15 %) by laboratories only. Twenty-four countries reported on TBE cases to ECDC in 2020; however, surveillance for TBE in Europe is heterogeneous. Standardization of TBE surveillance would enhance the understanding of TBE disease burden in Europe.
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Borrelia burgdorferi sensu lato (Bb) are a complex of bacteria genospecies that can cause Lyme disease (LD) in humans after the bite of an infected Ixodes spp. vector tick. In Canada, incidence of LD is increasing in part due to the rapid geographic expansion of Ixodes scapularis across the southcentral and eastern provinces. To better understand temporal and spatial (provincial) prevalence of Bb infection of I. scapularis and how tick surveillance is utilized in Canada to assess LD risk, a literature review was conducted. Tick surveillance studies published between January 1975 to November 2023, that measured the prevalence of Bb in I. scapularis via "passive surveillance" from the public citizenry or "active surveillance" by drag or flag sampling of host-seeking ticks in Canada were included for review. Meta-analyses were conducted via random effects modeling. Forty-seven articles, yielding 26 passive and 28 active surveillance studies, met inclusion criteria. Mean durations of collection for I. scapularis were 2.1 years in active surveillance studies (1999-2020) and 5.5 years by passive surveillance studies (1990-2020). Collectively, data were extracted on 99,528 I. scapularis nymphs and adults collected between 1990-2020 across nine provinces, including Newfoundland & Labrador (33 ticks) and Alberta (208 ticks). More studies were conducted in Ontario (36) than any other province. Across nine provinces, the prevalence of Bb infection in I. scapularis collected by passive surveillance was 14.6% with the highest prevalence in Nova Scotia at 20.5% (minimum studies >1). Among host-seeking I. scapularis collected via active surveillance, Bb infection prevalence was 10.5% in nymphs, 31.9% in adults, and 23.8% across both life stages. Host-seeking I. scapularis nymphs and adults from Ontario had the highest Bb prevalence at 13.6% and 34.8%, respectively. Between 2007-2019, Bb infection prevalence in host-seeking I. scapularis was positively associated over time (p<0.001) which is concurrent with a â¼25-fold increase in the number of annually reported LD cases in Canada over the same period. The prevalence of Bb-infection in I. scapularis has rapidly increased over three decades as reported by tick surveillance studies in Canada which coincides with increasing human incidence for LD. The wide-ranging distribution and variable prevalence of Bb-infected I. scapularis ticks across provinces demonstrates the growing need for long-term standardized tick surveillance to monitor the changing trends in I. scapularis populations and best define LD risk areas in Canada.
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Ixodes , Enfermedad de Lyme , Ixodes/microbiología , Animales , Canadá/epidemiología , Prevalencia , Enfermedad de Lyme/epidemiología , Enfermedad de Lyme/microbiología , Enfermedad de Lyme/transmisión , Grupo Borrelia Burgdorferi/aislamiento & purificación , HumanosRESUMEN
BACKGROUND: COVID-19 mortality studies have primarily focused on persons aged ≥ 65 years; less is known about decedents aged <65 years. METHODS: We conducted a case-control study among NYC residents aged 21-64 years hospitalized with COVID-19 diagnosed March 13-April 9, 2020, to determine risk factors for death. Case-patients (n=343) were hospitalized decedents with COVID-19 and control-patients (n=686) were discharged from hospitalization with COVID-19 and matched 2:1 to case-patients on age and residential neighborhood. Conditional logistic regression models were adjusted for patient sex, insurance status, and marital status. Matched adjusted odds ratios (aORs) were calculated for selected underlying conditions, combinations of conditions, and race/ethnic group. RESULTS: Median age of both case-patients and control-patients was 56 years (range: 23-64 years). Having ≥ 1 selected underlying condition increased odds of death 4.45-fold (95% CI: 2.33-8.49). Patients with diabetes; morbid obesity; heart, kidney, or lung disease; cancer; neurologic/neurodevelopmental conditions; mental health conditions; or HIV had significantly increased odds of death. Compared with having neither condition, having both diabetes and obesity or diabetes and heart disease was associated with approximately threefold odds of death. Five select underlying conditions were more prevalent among non-Hispanic Black control-patients than among control-patients of other races/ethnicities. CONCLUSIONS AND RELEVANCE: Selected underlying conditions were risk factors for death, and most prevalent among racial/ethnic minorities. Social services; health care resources, including vaccination; and tailored public health messaging are important for COVID-19 prevention. Strengthening these strategies for racial/ethnic minority groups could minimize COVID-19 racial/ethnic disparities.
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COVID-19 , Adulto , Estudios de Casos y Controles , Etnicidad , Humanos , Persona de Mediana Edad , Grupos Minoritarios , Ciudad de Nueva York/epidemiología , Factores de Riesgo , SARS-CoV-2 , Adulto JovenRESUMEN
ABSTRACT: We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.
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Cannabinoides , Cannabis , Neuralgia , Analgésicos/uso terapéutico , Animales , Cannabinoides/uso terapéutico , Endocannabinoides , Masculino , Modelos Animales , Neuralgia/tratamiento farmacológicoRESUMEN
Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence as the general population ages. Poorly managed heart failure symptoms of decompensated HFpEF is one of the most common reasons for prolonged hospital admission. The high rate of morbidity and mortality associated with HFpEF is compounded by a poor understanding of the underpinning pathophysiology. Randomized controlled trials have so far been unable to identify an evidence base for reducing morbidity and mortality in patients with HFpEF, although there is some evidence to support quality of life (QOL) improvement. In this review, we described the recent advances on the pathophysiological understanding of HFpEF, the current and emerging treatment strategies, and what this may mean for individual patients. Potential treatments for HFpEF were divided into their relative management strategies and the current evidence assessed for effect on HFpEF mortality, hospital admission frequency, and QOL improvement. Overall, the understanding of HFpEF pathophysiology is improving and has been made a priority in identifying potential therapeutic targets. There is growing evidence that patients with ejection fractions (EF) of less than 60% may obtain a mortality benefit from ACE-inhibitors, angiotensin-neprilysin inhibitors, Angiotensin Receptor Blockers, and Mineralocorticoid Receptor Antagonists. However, this covers only a small proportion of the HFpEF spectrum. Therefore, currently there are no universal treatment strategies recommended for HFpEF, and management should focus on an individualised approach and this should take into account the comorbidities of each patient.
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BACKGROUND: Severe maternal morbidity (SMM) comprises an array of conditions and procedures denoting an acutely life-threatening pregnancy-related condition. SMM may further compromise fetal well-being. Empirical data are lacking about the relation between SMM and infant mortality. METHODS: This population-based cohort study included 1 892 857 singleton births between 2002 and 2017 in Ontario, Canada, within a universal health care system. The exposure was SMM as an overall construct arising from 23 weeks' gestation up to 42 days after the index delivery. The primary outcome was infant mortality from birth to 365 days. Multivariable modified Poisson regression generated relative risks and 95% confidence intervals (CIs), adjusted for maternal age, income, rurality, world region of origin, diabetes mellitus, and chronic hypertension. RESULTS: Infant mortality occurred among 174 of 19 587 live births with SMM (8.9 per 1000) vs 5289 of 1 865 791 live births without SMM (2.8 per 1000) (an adjusted relative risk of 2.93 [95% CI 2.51-3.41]). Of 19 587 pregnancies with SMM, 4523 (23.1%) had sepsis. Relative to births without SMM, the adjusted odds ratio for infant death from sepsis was 1.95 (95% CI 1.10-3.45) if SMM occurred without maternal sepsis and 6.36 (95% CI 3.50-11.55) if SMM included sepsis. CONCLUSIONS: SMM confers a higher risk of infant death. There is also coupling tendency (concurrent event of interest) between SMM with sepsis and infant death from sepsis. Identification of preventable SMM indicators, as well as the development of strategies to limit their onset or progression, may reduce infant mortality.
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Mortalidad Infantil/tendencias , Salud Materna/tendencias , Complicaciones del Embarazo/epidemiología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Morbilidad , Ontario/epidemiología , Embarazo , Complicaciones del Embarazo/diagnóstico , Adulto JovenRESUMEN
BACKGROUND: TREPROSTINIL IS A PROSTACYCLIN ANALOG USED FOR TREATMENT OF PULMONARY HYPERTENSION (PH) IN ADULTS AND CHILDREN, CURRENTLY AWAITING CLINICAL ASSESSMENT FOR USE IN NEONATES.: OBJECTIVES: WE AIMED TO INVESTIGATE THE USE OF TREPROSTINIL IN NEONATES WITH PH ON EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) SUPPORT AND MEASURE PLASMA CONCENTRATIONS OF THE DRUG.: METHODS: THIS IS A RETROSPECTIVE CASE-SERIES WITH PROSPECTIVELY COLLECTED BLOOD SAMPLES, CONDUCTED IN A QUATERNARY CARE NEONATAL INTENSIVE CARE UNIT. BRAIN NATRIURETIC PEPTIDE, CARDIAC FUNCTION ON DOPPLER ECHOCARDIOGRAPHY, AND THE OCCURRENCE OF ADVERSE EFFECTS WAS MONITORED. PLASMA CONCENTRATIONS WERE MEASURED USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY AND MASS SPECTROMETRY.: RESULTS: FOUR PATIENTS WITH PH REQUIRING ECMO THERAPY WERE STUDIED. TREPROSTINIL DOSES OF 20-58 NG/KG/MIN REACHED CONCENTRATIONS OF 0.99-4.39 NG/ML AND INDUCED CLINICAL IMPROVEMENT. INFUSION OF TREPROSTINIL WAS ASSOCIATED WITH IMPROVED RIGHT VENTRICULAR FUNCTION, REVERSED RIGHT-TO-LEFT SHUNTING THROUGH THE DUCTUS ARTERIOSUS, AND STABLE OR DECREASING NEED FOR VASOPRESSOR SUPPORT. NO ADVERSE EFFECTS WERE OBSERVED: CONCLUSIONS: THIS IS THE FIRST STUDY TO REPORT CLINICALLY THERAPEUTIC TREPROSTINIL CONCENTRATIONS IN CIRCULATING PLASMA AFTER TREPROSTINIL ADMINISTRATION IN NEONATES ON ECMO, WITH ASSOCIATED CLINICAL IMPROVEMENT OF PH AND NO SIGNS OF HEMODYNAMIC INSTABILITY.
Asunto(s)
Antihipertensivos/farmacocinética , Epoprostenol/análogos & derivados , Oxigenación por Membrana Extracorpórea , Hipertensión Pulmonar/terapia , Antihipertensivos/administración & dosificación , Epoprostenol/administración & dosificación , Epoprostenol/farmacocinética , Femenino , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/tratamiento farmacológico , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Importance: Prepregnancy diabetes is associated with higher perinatal and maternal morbidity, especially if periconception glycemic control is suboptimal. It is not known whether improved glycemic control from preconception to early pregnancy and midpregnancy periods can reduce the risk of adverse perinatal and maternal outcomes. Objective: To determine whether a net decline in glycated hemoglobin A1c (HbA1c) from preconception to the first half of pregnancy is associated with a lower risk of adverse outcomes for mother and child. Design, Setting, and Participants: This population-based cohort study was completed in all of Ontario, Canada, from 2007 to 2018. Included were births among women with prepregnancy diabetes whose HbA1c was measured within 90 days preconception and again from conception through 21 weeks completed gestation (early pregnancy to midpregnancy). Statistical analysis was performed from July to September 2020. Exposures: Net decrease in HbA1c from preconception to early pregnancy and midpregnancy. Main Outcomes and Measures: The main outcome was a congenital anomaly from birth to age 1 year. Other outcomes included preterm birth or perinatal mortality among offspring as well as severe maternal morbidity (SMM) or death among mothers. Adjusted relative risks (aRRs) were calculated per 0.5% absolute net decline in HbA1c from preconception up to early pregnancy and midpregnancy, adjusting for maternal age at conception, preconception HbA1c and hemoglobin concentration, and gestational age at HbA1c measurement. Results: A total of 3459 births were included, with a mean (SD) maternal age of 32.6 (5.0) years at conception. Overall, the mean (SD) HbA1c decreased from 7.2% (1.6%) preconception to 6.4% (1.1%) in early pregnancy to midpregnancy. There were 497 pregnancies (14.4%) with a congenital anomaly, with an aRR of 0.94 (95% CI, 0.89-0.98) per 0.5% net decrease in HbA1c, including for cardiac anomalies (237 infants; aRR, 0.89; 95% CI, 0.84-0.95). The risk was also reduced for preterm birth (847 events; aRR, 0.89; 95% CI, 0.86-0.91). SMM or death occurred among 191 women (5.5%), with an aRR of 0.90 (95% CI, 0.84-0.96) per 0.5% net decrease in HbA1c. Conclusions and Relevance: These findings suggest that women with prepregnancy diabetes who achieve a reduction in HbA1c may have improved perinatal and maternal outcomes. Further study is recommended to determine the best combination of factors, such as lifestyle changes and/or glucose-lowering medications, that can influence periconception HbA1c reduction.