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1.
PLoS Med ; 19(9): e1004087, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36074760

ABSTRACT

BACKGROUND: Treatment for gestational diabetes mellitus (GDM) aims to reduce maternal hyperglycaemia. The TARGET Trial assessed whether tighter compared with less tight glycaemic control reduced maternal and perinatal morbidity. METHODS AND FINDINGS: In this stepped-wedge, cluster-randomised trial, identification number ACTRN12615000282583, 10 hospitals in New Zealand were randomised to 1 of 5 implementation dates. The trial was registered before the first participant was enrolled. All hospitals initially used less tight targets (fasting plasma glucose (FPG) <5.5 mmol/L (<99 mg/dL), 1-hour <8.0 mmol/L (<144 mg/dL), 2 hour postprandial <7.0 mmol/L (<126 mg/dL)) and every 4 months, 2 hospitals moved to use tighter targets (FPG ≤5.0 mmol/L (≤90 mg/dL), 1-hour ≤7.4 mmol/L (≤133 mg/dL), 2 hour postprandial ≤6.7 mmol/L) (≤121 mg/dL). Women with GDM, blinded to the targets in use, were eligible. The primary outcome was large for gestational age. Secondary outcomes assessed maternal and infant health. Analyses were by intention to treat. Between May 2015 and November 2017, data were collected from 1,100 women with GDM (1,108 infants); 598 women (602 infants) used the tighter targets and 502 women (506 infants) used the less tight targets. The rate of large for gestational age was similar between the treatment target groups (88/599, 14.7% versus 76/502, 15.1%; adjusted relative risk [adjRR] 0.96, 95% confidence interval [CI] 0.66 to 1.40, P = 0.839). The composite serious health outcome for the infant of perinatal death, birth trauma, or shoulder dystocia was apparently reduced in the tighter group when adjusted for gestational age at diagnosis of GDM, BMI, ethnicity, and history of GDM compared with the less tight group (8/599, 1.3% versus 13/505, 2.6%, adjRR 0.23, 95% CI 0.06 to 0.88, P = 0.032). No differences were seen for the other infant secondary outcomes apart from a shorter stay in intensive care (P = 0.041). Secondary outcomes for the woman showed an apparent increase for the composite serious health outcome that included major haemorrhage, coagulopathy, embolism, and obstetric complications in the tighter group (35/595, 5.9% versus 15/501, 3.0%, adjRR 2.29, 95% CI 1.14 to 4.59, P = 0.020). There were no differences between the target groups in the risk for pre-eclampsia, induction of labour, or cesarean birth, but more women using tighter targets required pharmacological treatment (404/595, 67.9% versus 293/501, 58.5%, adjRR 1.20, 95% CI 1.00 to 1.44, P = 0.047). The main study limitation is that the treatment targets used may vary to those in use in some countries. CONCLUSIONS: Tighter glycaemic targets in women with GDM compared to less tight targets did not reduce the risk of a large for gestational age infant, but did reduce serious infant morbidity, although serious maternal morbidity was increased. These findings can be used to aid decisions on the glycaemic targets women with GDM should use. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12615000282583.


Subject(s)
Diabetes, Gestational , Australia , Blood Glucose , Cesarean Section , Diabetes, Gestational/drug therapy , Diabetes, Gestational/epidemiology , Female , Humans , Infant , Morbidity , Pregnancy
3.
Nutrients ; 14(17)2022 Sep 03.
Article in English | MEDLINE | ID: mdl-36079903

ABSTRACT

While probiotics are reported to reduce the risks of neonatal morbidities, less is known about probiotics and feeding tolerance. With this retrospective cohort study, we investigate whether introduction of probiotic supplementation as the standard of care was associated with fewer neonatal morbidities and improved feeding tolerance in very preterm infants. Using the Swedish Neonatal Quality Register, 345 live-born very preterm infants (28-31 weeks' gestation), from January 2019-August 2021, in NICUs in Stockholm, Sweden, either received probiotic supplementation (Bifidobacterium infantis, Bifidobacterium lactis, Streptococcusthermophilus) (139) or no supplementation (206); they were compared regarding a primary composite outcome of death, sepsis, and/or necrotising enterocolitis and secondary outcomes: time to full enteral feeding and antibiotics use. Probiotics seemed associated with a reduced risk of the composite outcome (4.3% versus 9.2%, p = 0.08). In the subgroup of 320 infants without the primary outcome, probiotics were associated with shorter time to full enteral feeding (6.6 days versus 7.2 days) and less use of antibiotics (5.2 days versus 6.1 days). Our findings suggest that probiotics improve feeding tolerance and further support that very preterm infants may benefit from probiotic supplementation.


Subject(s)
Enterocolitis, Necrotizing , Infant, Premature, Diseases , Probiotics , Anti-Bacterial Agents/therapeutic use , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/prevention & control , Female , Fetal Growth Retardation , Humans , Infant , Infant, Newborn , Infant, Premature , Morbidity , Probiotics/therapeutic use , Retrospective Studies
4.
Cardiovasc Diabetol ; 21(1): 179, 2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36085031

ABSTRACT

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes and has maternal health implications reaching beyond the perinatal period. We aimed to investigate the incidence and severity of cardiovascular and metabolic morbidity in women with previous GDM in a Danish population and to study whether proxies of impaired beta cell function-insulin treatment during GDM pregnancy and development of subsequent manifest diabetes mellitus-influence incident risk of cardiovascular and metabolic morbidity. METHODS: A nationwide register-based cohort study was conducted on the complete cohort of 700,648 women delivering in Denmark during 1997-2018. The exposure variable was GDM and primary outcome was overall cardiovascular and metabolic morbidity. Secondary outcomes were major cardiovascular disease (ischemic heart disease, heart failure, and/or stroke/transient cerebral ischemia), hypertension, dyslipidemia, and venous thrombosis. Severity of morbidity was assessed using number of hospital contacts with diagnosis codes related to cardiovascular and metabolic morbidity and number of redemptions of prescribed medication related to cardiovascular and metabolic morbidity in women who developed cardiovascular and metabolic morbidity after pregnancy. RESULTS: The median follow-up period was 10.2-11.9 years with a total range of 0-21.9 years. GDM was associated with increased risk of any cardiovascular and metabolic morbidity (adjusted HR 2.13 [95% CI 2.07-2.20]), major cardiovascular disease (adjusted HR 1.69 [95% CI 1.55-1.84]), hypertension (adjusted HR 1.89 [95% CI 1.82-1.96], dyslipidemia (adjusted HR 4.48 [95% CI 4.28-4.69]), and venous thrombosis (adjusted HR 1.32 [95% CI 1.16-1.50]). Insulin treatment during pregnancy and subsequent development of manifest diabetes exacerbated the risk estimates. Previous GDM was associated with more hospital contacts and more redeemed prescriptions in women developing cardiovascular and metabolic morbidity (p < 0.001). CONCLUSIONS: Previous GDM was associated with significantly higher risk of cardiovascular and metabolic morbidity, especially incident dyslipidemia. Risks were exacerbated by proxies of beta cell impairment. Severity of morbidity was significantly worse if GDM preceded cardiovascular and metabolic morbidity.


Subject(s)
Cardiovascular Diseases , Diabetes, Gestational , Hypertension , Insulins , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cohort Studies , Diabetes, Gestational/diagnosis , Diabetes, Gestational/drug therapy , Diabetes, Gestational/epidemiology , Female , Humans , Hypertension/epidemiology , Morbidity , Pregnancy , Risk Factors
5.
Respir Res ; 23(1): 230, 2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36064404

ABSTRACT

BACKGROUND: Imbalance in L-arginine and nitric oxide (NO) metabolism has been implicated in the pathophysiology of asthma and obstructive sleep apnea (OSA), and both diseases impact the other's morbidity. We sought to determine whether L-arginine/NO metabolism differs between adults with asthma with or without comorbid OSA, and its association with asthma morbidity. METHODS: This is a cross-sectional study of 322 adults with asthma recruited in Denver, CO and New York City, NY. Data were collected on OSA status, spirometry, and metrics of asthma control and morbidity. L-Arginine metabolites were quantified in patient serum. Bivariate analyses and multiple regression were performed to determine differences between L-arginine metabolism, OSA and association with asthma morbidity. RESULTS: Among the 322 participants, 92 (28.5%) had OSA. The cohort was 81.6% female, 23.4% identified as Black and 30.6% as Latino. Patients with asthma and OSA had significantly higher serum concentrations of NO synthase inhibitor asymmetric dimethylarginine (ADMA) (p-value = 0.019), lower L-arginine to ornithine ratios (p-value = 0.003), and increased ornithine (p-value = 0.001) and proline levels (p-value < 0.001) compared to those without OSA. In adjusted models, OSA was associated with worse asthma control, adjusted mean difference in asthma control questionnaire of 0.36 (95% confidence interval [CI]: 0.06 to 0.65), and asthma quality of life questionnaire, adjusted mean difference: - 0.53 (95% CI: - 0.85 to - 0.21), after adjusting for relevant covariates including body mass index and L-arginine metabolites. CONCLUSIONS: Adults with asthma and OSA had increased ADMA, an inhibitor of nitric oxide synthase, and greater metabolism of L-arginine via the arginase pathway compared to those with asthma alone, indicating a possible shared pathophysiological mechanism of these diseases.


Subject(s)
Asthma , Sleep Apnea, Obstructive , Adult , Arginine , Asthma/diagnosis , Asthma/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Morbidity , Ornithine , Quality of Life , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology
6.
Front Public Health ; 10: 957576, 2022.
Article in English | MEDLINE | ID: mdl-36062122

ABSTRACT

Introduction: To mitigate morbidity, mortality, and impacts of heat-related illnesses (HRIs) on health, it was vital to implement a comprehensive framework for HRI prevention and control. A recognized tool from the field of trauma prevention known as the Haddon matrix was applied. The matrix states that any event is affected by three factors: host, agent, and environment. In addition, another recognized tool known as the combined model was used in this study. The combined model is a three-dimensional model that includes the idea for the three axes of Haddon's matrix with the methodology of the community risk reduction (CRR) model. Aim of the study: To identify the environmental and individual risk factors of HRIs based on the Haddon matrix and the recommended prevention strategies by the CRR tool by using the combined model. Methodology: An extensive literature review was conducted to assess all the risk factors associated with HRI, as well as preventive measures. Then the Haddon matrix was used to structure, separating human factors from technical and environmental details and timing. After that, the combined model was used to set all responses and mitigation measures for each element obtained from the Haddon matrix tool. Conclusion: Projected increases in heat stress over the globe require the formulation and implementation of evidence-based HRI mitigation and preventive measures. In this study, we implemented the combined model that was utilized as a systematic strategy for the more theoretical framework of Haddon's matrix. Using the Haddon matrix to determine the HRI risk factors and the combined model to mitigate its impact was practical and helpful in planning, preparedness, and mitigating the HRIs during Hajj, provided a broad approach equivalent to the Swiss cheese model, and would facilitate an informed decision.


Subject(s)
Mass Gatherings , Humans , Morbidity , Risk Factors
7.
Rev Med Inst Mex Seguro Soc ; 60(5): 548-555, 2022 Aug 31.
Article in Spanish | MEDLINE | ID: mdl-36048807

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has provoked one of the greatest health crises of our time, which is why risk stratification at the time of hospitalization is essential to identify in good time patients with high morbidity and mortality risk. Dysnatremia as an independent predictor of mortality in patients with COVID-19 has recently become relevant. Objective: To find out if there is an association of dysnatremia with 28-day mortality, and as secondary objectives, its association with hospital stay, invasive mechanical ventilation (IMV) requirement and presence of acute kidney injury (AKI) during hospital stay. Material and methods: Retrospective, descriptive and analytical cohort study. All consecutive patients of 16 years or older of any gender, admitted to a third level hospital from March 1, 2020 to March 2021, who have a diagnosis of COVID-19 with positive PCR were included. Results: The study included a total of 722 patients. The prevalence of dysnatremia was as follows: 18 patients presented hypernatremia (2.49%) and 153 hyponatremia (21.19%). The presence of hypernatremia once sodium was corrected for glucose was associated with higher mortality (p < 0.05, OR 3.446; 95% CI 1.776-6.688), an increased probability of presenting AKI (p <0.05, OR 2.985; 95% CI 1.718-5.184) and a greater requirement for IMV (p < 0.05, OR 1.945; 95% CI 1.701-5.098). Conclusions: Hypernatremia was associated with higher mortality, higher risk of presenting AKI and the requirement for IMV during hospitalization.


Introducción: la enfermedad por coronavirus 2019 (COVID-19) ha provocado una de las mayores crisis sanitarias de nuestros tiempos, por lo que la estratificación pronóstica al momento de la hospitalización es fundamental para identificar de manera temprana a los pacientes con alto riesgo de morbimortalidad. La disnatremia como predictor independiente de mortalidad en pacientes con COVID-19 ha tomado relevancia recientemente. Objetivo: encontrar si existe asociación de disnatremias con mortalidad a 28 días y como secundarios su asociación con estancia hospitalaria, requerimiento de ventilación mecánica invasiva (VMI) y presencia de lesión renal aguda (LRA) durante la estancia hospitalaria. Material y métodos: estudio de tipo cohorte retrospectivo, descriptivo y analítico. Se incluyeron de manera consecutiva todos los pacientes mayores de 16 años de cualquier género, ingresados en un hospital de tercer nivel de marzo de 2020 a marzo de 2021, los cuales presentaron diagnóstico de COVID-19 con PCR positiva. Resultados: el estudio incluyó un total de 722 pacientes. La prevalencia de disnatremia fue la siguiente: 18 pacientes presentaron hipernatremia (2.49%) y 153 hiponatremia (21.19%). La presencia de hipernatremia una vez corregido el sodio para la glucosa se asoció con mayor mortalidad (p < 0.05, RM 3.446; IC 95%, 1.776-6.688), un aumento de la probabilidad de presentar LRA (p < 0.05, RM 2.985; IC 95%, 1.718-5.184) y mayor requerimiento de VMI (p < 0.05, RM 1.945; IC 95%, 1.701-5.098). Conclusiones: la hipernatremia se asoció a una mayor mortalidad, mayor riesgo de presentar LRA y requerimiento de VMI durante la hospitalización.


Subject(s)
Acute Kidney Injury , COVID-19 , Hypernatremia , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , COVID-19/complications , COVID-19/epidemiology , Cohort Studies , Hospital Mortality , Humans , Hypernatremia/complications , Hypernatremia/epidemiology , Morbidity , Retrospective Studies , Risk Factors
8.
Front Public Health ; 10: 887714, 2022.
Article in English | MEDLINE | ID: mdl-36091544

ABSTRACT

Adults with intellectual or developmental disability (IDD) comprise 1-2% of the population worldwide. IDD is a significant risk factor for premature morbidity or mortality. This is likely due in part to preventable health conditions, which are modifiable with the intervention of direct care providers in areas including nutrition, promotion of an active lifestyle and effective identification of health or functional deterioration. Adults with IDD are also at increased risk for neglect or mistreatment, a finding that has been documented across multiple countries and in a variety of care settings. Contributing factors include resource availability, lack of person-centered care, management culture and care worker training. Practical and economical interventions may address the known disparities and challenges facing the large community of adults with IDD. To promote person-centered care, improve record-keeping/documentation, and aid in protecting the health and safety of this vulnerable population, we propose incorporation of a video into the evaluation of adults with IDD living outside the home.


Subject(s)
Developmental Disabilities , Intellectual Disability , Adult , Child , Humans , Morbidity , Risk Factors
9.
BMJ Paediatr Open ; 6(1)2022 07.
Article in English | MEDLINE | ID: mdl-36053577

ABSTRACT

OBJECTIVE: To establish short-term and medium-term complications 1-year postdiagnosis, of acute pancreatitis (AP) in children aged 0-14 years. DESIGN: One-year follow-up of a prospective monthly surveillance of new cases of AP in children under 15 years through the British Paediatric Surveillance Unit (BPSU) from April 2013 to April 2014. SETTING: A monthly surveillance of >3700 consultant paediatricians and paediatric surgeons in the UK and Ireland using the BPSU. PATIENTS: Children aged 0-14 years with a new diagnosis of AP. MAIN OUTCOME MEASURES: The outcomes following AP, including the incidence of complications and comorbidity at diagnosis and at 1 year. RESULTS: Of the 94 new confirmed cases of AP identified in the UK during the study period, 90 cases (96%) were included in the 1-year follow-up. 30 patients (32%) developed further episode(s) of AP. Over one-fifth of patients developed one or more major complication. At initial admission, the most common of these was pancreatic necrosis (n=8, 9%), followed by respiratory failure (n=7, 7%). Reported complications by 1 year were pseudocyst formation (n=9, 10%), diabetes requiring insulin therapy (n=4, 4%) and maldigestion (n=1, 1%). At 1-year postdiagnosis, only 59% of children made a full recovery with no acute or chronic complications or recurrent episodes of AP. Two patients died, indicating a case fatality of ~2.0%. CONCLUSIONS: AP in childhood is associated with significant short-term and medium-term complications and comorbidities including risk of recurrence in approximately a third of cases.


Subject(s)
Pancreatitis, Acute Necrotizing , Acute Disease , Child , Humans , Morbidity , Pancreatitis, Acute Necrotizing/epidemiology , Prospective Studies
10.
Salud Publica Mex ; 64(5, sept-oct): 453-463, 2022 Aug 26.
Article in Spanish | MEDLINE | ID: mdl-36130351

ABSTRACT

OBJETIVO: Analizar la asociación de la concentración de con-taminantes atmosféricos y los indicadores epidemiológicos de Covid-19 en la Zona Metropolitana del Valle de México (ZMVM). Material y métodos. Se diseñó un estudio epidemiológico ecológico. Se utilizaron modelos lineales tipo Poisson para variables de conteo y modelos lineales de efectos aleatorios en variables continuas para cuantificar la asociación entre los contaminantes atmosféricos y los indicadores de Covid-19. Los datos obtenidos fueron del 28 de febrero de 2020 al 30 de junio de 2021. La exposición a contaminantes se estratificó por estaciones climáticas. RESULTADOS: Los contaminantes que tuvieron asociación significativa con indicadores de morbilidad y mortalidad fueron CO, NOX, O3 y PM10. En la estación seca fría el CO y el NOX tuvieron efecto sobre los casos diarios confirmados y las defunciones diarias. Las PM10 se asociaron con efecto en los indicadores de casos diarios confirmados, incidencia diaria, porcentaje de hospitalizados y la tasa de letalidad. CONCLUSIONES: Los resultados sugieren una asociación entre el comportamiento epidemiológico de Covid-19 y la exposición a CO, NOX, O3 y PM10, en la que se encontró un mayor efecto en la estación seca-fría en la ZMVM.


Subject(s)
Air Pollutants , COVID-19 , COVID-19/epidemiology , Humans , Mexico/epidemiology , Morbidity , Retrospective Studies
11.
Pan Afr Med J ; 42: 142, 2022.
Article in English | MEDLINE | ID: mdl-36160279

ABSTRACT

Introduction: to date in Africa, there is limited evidence regarding the role of prophylactic antibiotics to prevent post (adeno) tonsillectomy ((A)TE) morbidity in children. As (A)TE is the most performed surgery in the pediatric population, the use of prophylactic antibiotics is likely a major factor in the development of AMR. In Tanzania, as in many other settings with limited resources antibiotics are misused and overprescribed. Potential reasons include limited stewardship and widespread use of postsurgical prophylactic antibiotics. Misuse of antibiotics might contribute significantly to the development of antimicrobial resistance (AMR). Methods: a two-centre, double-blinded randomized controlled non-inferiority trial. Subjects included children from 2-14 years of age with recurrent chronic tonsillitis and/or obstructive sleep apnoea due to adenotonsillar hypertrophy who were electively scheduled for (A)TE in two tertiary hospitals. Participants were randomly allocated to receive either placebo or amoxicillin for five days postoperatively. Primary outcome was non-inferiority of placebo compared with amoxicillin for postoperative haemorrhage (margin 5%; at 14 days) postoperative fever (margin 5%; at 7 days), and pain (margin 1 point; at 7 days). Secondary outcomes included the times required for resumption of normal diet and normal activities, and microbial recolonization of the tonsillar beds. Data were analysed according to intention-to-treat principle. Follow-up was 14 days. Results: between March 13, 2019 and September 20, 2019 270 children were enrolled. All children were randomly assigned to receive placebo (n = 136) or amoxicillin (n = 134). By 14t hday post-operatively, total of 8 children were lost to follow-up in each arm. No major postoperative haemorrhage was registered. By 14th day post-operatively, 22 (17.5%) children in the amoxicillin arm and 19 (14.8%) children in the placebo arm had reported minor haemorrhage (risk difference (RD) -2.6% (95%CI -10.2 - 5.0); pnon-inferiority = 0.045). By 7th day post operatively, 8 (6.3%) children in amoxicillin arm and 4 (3.1%) children in placebo arm reported fever during the first week (RD -3.2% (95%CI -7.6 - 1.2); pnon-inferiority = 0.001). By 7th day post operatively, mean pain score (mean (SD)) was 3.25 (1.53) in the amoxicillin arm and 3.56 (1.68) in the placebo arm (mean difference 0.31, (95% CI -0.02 - 0.65); pnon-inferiority < 0.001). No statistically significant differences between the two groups were found in any of the secondary outcomes. Findings shows, placebo is non-inferior to amoxicillin for post-operative morbidities in Tanzanian children undergoing (A)TE. Conclusion: it is recommended that antibiotics should only be used when clinically necessary to treat a specific infection. Unnecessary use of antibiotics contributes to the development of antimicrobial resistance. Trial Registration: Pan African Clinical Trials Registry PACTR201905466349317. Retrospectively registered on 15 May 2019.


Subject(s)
Amoxicillin , Tonsillectomy , Amoxicillin/therapeutic use , Anti-Bacterial Agents , Child , Double-Blind Method , Humans , Morbidity , Pain/drug therapy , Postoperative Hemorrhage , Tanzania , Tonsillectomy/adverse effects
12.
BMC Anesthesiol ; 22(1): 301, 2022 Sep 22.
Article in English | MEDLINE | ID: mdl-36138340

ABSTRACT

BACKGROUND: The revised-Risk Analysis Index (RAI-rev) can accurately predict postoperative mortality risk. However, the association of RAI-rev with composite outcome of major morbidity and mortality (MMM) among older surgical patients is largely unknown. This study investigated the association between RAI-rev and postoperative MMM in older patients undergoing abdominal surgery. It also assessed the predictive value of RAI-rev combined with other preoperative risk factors. METHODS: This retrospective cohort study reviewed the medical records of all patients aged 65 and older who underwent abdominal surgery between January 2018 and December 2019. The primary outcome was the postoperative MMM during hospitalization, and its association with preoperative RAI-rev scores was assessed using multivariable logistic regression analysis. The prediction of postoperative outcomes was used the receiver-operating characteristic curve analysis. RESULTS: A total of 2225 older patients were analyzed, and 258 (11.6%) developed postoperative MMM. After adjusting for confounders, each unit increase in RAI-rev scores resulted in a 2.3% increase in the MMM risk and a 3.0% increase in the odds of life-threatening complications and mortality (both P < 0.05). The area under the curves (AUCs) of RAI-rev scores in predicting MMM and life-threatening complications and mortality was 0.604 (95% CI: 0.567 to 0.640) and 0.633 (95% CI: 0.592 to 0.675), respectively (both P < 0.001); when the RAI-rev was combined with age, gender, American Society of Anesthesiologists (ASA) classification, operative stress, and urgency status of surgery (emergency or elective), the AUCs were 0.694 (95% CI: 0.659 to 0.729) and 0.739 (95% CI: 0.702 to 0.777), respectively (both P < 0.001). CONCLUSIONS: Higher RAI-rev scores were independently associated with increased risk of MMM. When combined with age, gender, ASA classification, operative stress, and urgency status of surgery, RAI-rev had improved performance in predicting the risk of MMM, particularly the life-threatening complications and mortality.


Subject(s)
Postoperative Complications , Aged , Humans , Morbidity , Postoperative Complications/etiology , Retrospective Studies , Risk Assessment/methods , Risk Factors
13.
Medicina (Kaunas) ; 58(9)2022 Aug 27.
Article in English | MEDLINE | ID: mdl-36143844

ABSTRACT

Background and Objectives: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease. Arterial stiffness is an independent prognostic marker for cardiovascular disease development. We aimed at determining the effect of two different sodium-glucose co-transporter-2 (SGLT-2) inhibitors on ambulatory arterial stiffness in individuals with T2DM. Materials and Methods: In this single-center, single-arm, prospective study performed from January 2020 to August 2021, we planned to enroll adult subjects with T2DM and stable antidiabetic and antihypertensive treatment, assigned either to empagliflozin or dapagliflozin for 6 months. All eligible subjects underwent ambulatory blood pressure monitoring. We set as the primary efficacy outcome the change in ambulatory pulse wave velocity (PWV) from baseline to week 24. Results: We finally enrolled 46 diabetic subjects, with a mean age of 62.89 (8.53) years and mean T2DM duration of 9.72 (6.37) years. Thirty patients received dapagliflozin, while sixteen patients received empagliflozin. Due to COVID-19 pandemic restrictive measures during the study, the mean follow-up period extended from 6 months to 9.98 (3.27) months. Regarding the prespecified primary efficacy outcome, we found that the SGLT-2 inhibitor treatment did not have a significant effect on PWV (p = 0.65). Prior history of cardiovascular disease did not significantly affect the observed effects. Other indices of arterial stiffness, such as augmentation index and central pulse pressure, were not significantly affected, neither by empagliflozin nor by dapagliflozin. Conclusions: SGLT-2 inhibitor treatment with empagliflozin or dapagliflozin in subjects with T2DM failed to improve ambulatory PWV over a mean follow-up of 10 months. Registration number: ISRCTN88851713.


Subject(s)
COVID-19 , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Symporters , Vascular Stiffness , Antihypertensive Agents/pharmacology , Benzhydryl Compounds , Blood Pressure Monitoring, Ambulatory , Cardiovascular Diseases/chemically induced , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucose , Glucosides , Humans , Hypoglycemic Agents/adverse effects , Middle Aged , Morbidity , Pandemics , Prospective Studies , Pulse Wave Analysis , Sodium , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Symporters/pharmacology , Treatment Outcome
14.
Front Immunol ; 13: 978760, 2022.
Article in English | MEDLINE | ID: mdl-36172383

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Comorbidity , Humans , Immune Checkpoint Inhibitors , Immunologic Memory , Morbidity , SARS-CoV-2 , Transcriptome , Tumor Microenvironment/genetics
15.
JAMA Netw Open ; 5(9): e2233331, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36156145

ABSTRACT

Importance: The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials. Objective: To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids. Design, Setting, and Participants: This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of Child Health and Human Development Neonatal Research Network. Infants who did not receive intensive care and infants with antenatal steroid exposure after GA 22 6/7 weeks were excluded. Exposure: Infants were classified as having no, partial, or complete exposure to antenatal steroids. Main Outcomes and Measures: The primary outcome was survival to discharge. The main secondary outcome was survival without major neonatal morbidity. The associations of differential exposures to antenatal steroids with outcomes were evaluated using logistic regression, adjusting for GA, sex, race, maternal education, small for GA status, mode of delivery, multiple birth, prolonged rupture of membranes, year of birth, and Neonatal Research Network center. Results: A total of 431 infants (mean [SD] GA, 22.6 [0.5] weeks; 232 [53.8%] boys) were included, with 110 infants (25.5%) receiving no antenatal steroids, 80 infants (18.6%) receiving partial antenatal steroids, and 241 infants (55.9%) receiving complete antenatal steroids. Seventeen infants were exposed to antenatal steroids at GA 21 weeks. Among infants exposed to complete antenatal steroids, 130 (53.9%) survived to discharge, compared with 30 infants (37.5%) with partial antenatal steroid exposure and 239 infants (35.5%) with no antenatal steroids. Infants born after complete antenatal steroid exposure, compared with those without antenatal steroid exposure, were more likely to survive to discharge (adjusted odds ratio [aOR], 1.95 [95% CI, 1.07-3.56]) and to survive without major morbidity (aOR, 2.74 [95% CI, 1.19-6.30]). Conclusions and Relevance: In this retrospective cohort study, among infants born between GA 22 0/7 and 23 6/7 weeks who received intensive care, exposure to a complete course of antenatal steroids at GA 22 6/7 weeks or less was independently associated with greater odds of survival and survival without major morbidity. These data suggest that the use of antenatal steroids in patients at GA 22 6/7 weeks or less could be beneficial when active treatment is considered.


Subject(s)
Infant Mortality , Steroids , Adrenal Cortex Hormones/therapeutic use , Child , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Morbidity , Pregnancy , Retrospective Studies , Steroids/adverse effects
16.
J Exp Med ; 219(12)2022 Dec 05.
Article in English | MEDLINE | ID: mdl-36156707

ABSTRACT

Neonatal herpes simplex virus (nHSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally transferred herpes simplex virus (HSV)-specific antibodies reduce the risk of clinically overt nHSV, but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human mAbs can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo via vectored immunoprophylaxis or recombinantly. Through these maternally derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load in mouse pups. Together these studies support the notion that HSV-specific mAb-based therapies could prevent or improve HSV infection outcomes in neonates.


Subject(s)
Herpes Simplex , Animals , Animals, Newborn , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral , Antiviral Agents , Glycoproteins , Humans , Mice , Morbidity , Pregnancy Complications, Infectious
17.
Medicine (Baltimore) ; 101(36): e30390, 2022 Sep 09.
Article in English | MEDLINE | ID: mdl-36086699

ABSTRACT

Total pancreatectomy (TP) is performed for diseases of the entire pancreas. However, reluctance remains regarding TP because of the fear of high morbidity and mortality. Our retrospective study aimed to evaluate the postoperative outcomes of TP performed at a high-volume single center and to identify the risk factors associated with major morbidities and mortality after TP. A total of 142 patients who underwent elective TP at Samsung Medical Center between 1995 and 2015 were included. TP was usually planned before surgery or decided during surgery [one-stage TP], and there were some completion TP cases that were performed to manage tumors that had formed in the remnant pancreas after a previous partial pancreatectomy [2-stage TP]. The differences between the 1-stage and 2-stage TP groups were analyzed. Chronological comparison was also conducted by dividing cases into 2 periods [the early and late period] based on the year TP was performed, which divided the total number of patients to almost half for each period. Among all TP patients, major morbidity occurred in 25 patients (17.6%), the rate of re-admission within 90-days was 20.4%, and there was no in-hospital and 30-days mortality. Between the 1-stage and 2-stage TP groups, most clinical, operative, and pathological characteristics, and postoperative outcomes did not differ significantly. Chronological comparison showed that, although the incidence of complications was higher, hospitalization was shorter due to advanced managements in the late period. The overall survival was improved in the late period compared to the early period, but it was not significant. A low preoperative protein level and N2 were identified as independent risk factors for major morbidity in multivariable analysis. The independent risk factors for poor overall survival were R1 resection, adenocarcinoma, and high estimated blood loss (EBL). TP is a safe and feasible procedure with satisfactory postoperative outcomes when performed at a high-volume center. More research and efforts are needed to significantly improve overall survival rate in the future.


Subject(s)
Pancreatectomy , Pancreatic Neoplasms , Humans , Morbidity , Pancreatectomy/methods , Retrospective Studies , Treatment Outcome
19.
Front Immunol ; 13: 941977, 2022.
Article in English | MEDLINE | ID: mdl-36119098

ABSTRACT

Non-communicable diseases (NCDs) like cardiovascular disease, chronic respiratory diseases, cancers, diabetes, and neuropsychiatric diseases cause significant global morbidity and mortality which disproportionately affect those living in low resource regions including low- and middle-income countries (LMICs). In order to reduce NCD morbidity and mortality in LMIC it is imperative to understand risk factors associated with the development of NCDs. Certain infections are known risk factors for many NCDs. Several parasitic helminth infections, which occur most commonly in LMICs, have been identified as potential drivers of NCDs in parasite-endemic regions. Though understudied, the impact of helminth infections on the development of NCDs is likely related to helminth-specific factors, including species, developmental stage and disease burden. Mechanical and chemical damage induced by the helminth in combination with pathologic host immune responses contribute to the long-term inflammation that increases risk for NCD development. Robust studies from animal models and human clinical trials are needed to understand the immunologic mechanisms of helminth-induced NCDs. Understanding the complex connection between helminths and NCDs will aid in targeted public health programs to reduce helminth-induced NCDs and reduce the high rates of morbidity that affects millions of people living in parasite-endemic, LMICs globally.


Subject(s)
Helminths , Noncommunicable Diseases , Animals , Cost of Illness , Humans , Morbidity , Noncommunicable Diseases/epidemiology , Risk Factors
20.
Can J Surg ; 65(5): E619-E621, 2022.
Article in English | MEDLINE | ID: mdl-36130804

ABSTRACT

Morbidity and Mortality Conferences (MMCs) are considered to be one of the most powerful education tools for clinicians; however, their current structure in many health care facilities focuses predominantly on quality and outcome improvement, and their retrospective approach limits their educational component. This article discusses how MMCs can be modified to enhance the educational outcomes and provide a valuable training session that adds to the quality control value.


Subject(s)
Internship and Residency , Medical Errors , Humans , Morbidity , Quality Improvement , Retrospective Studies
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