Incidence of thyroid dysfunction following initiation of amiodarone treatment in patients with and without heart failure: a nationwide cohort study.

AIMS: Thyroid dysfunction is considered the most frequent complication to amiodarone treatment, but data on its occurrence outside clinical trials are sparse. The present study aimed to examine the incidence of thyroid dysfunction following initiation of amiodarone treatment in a nationwide cohort of patients with and without heart failure (HF). METHODS AND RESULTS: In Danish registries, we identified all patients with first-time amiodarone treatment during the period 2000-18, without prior thyroid disease or medication. The primary outcome was a composite of thyroid diagnoses and initiation of thyroid drugs. Outcomes were assessed at 1-year follow-up, and for patients free of events in the first year, in a landmark analysis for the subsequent 5 years. We included 43 724 patients with first-time amiodarone treatment, of whom 16 939 (38%) had HF. At 1-year follow-up, the cumulative incidence and adjusted hazard ratio (HR) of the primary outcome were 5.3% and 1.37 (95% confidence interval 1.25-1.50) in patients with a history of HF and 4.2% in those without HF (reference). In the 1-year landmark analysis, the subsequent 5-year cumulative incidences and adjusted HRs of the primary outcome were 5.3% (reference) in patients with 1-year accumulated dose <27.38 g [corresponding to average daily dose (ADD <75 mg)], 14.0% and HR 2.74 (2.46-3.05) for 27.38-45.63 g (ADD 75-125 mg), 20.0% and HR 4.16 (3.77-4.59) for 45.64-63.88 g (ADD 126-175 mg), and 24.5% and HR 5.30 (4.82-5.90) for >63.88 g (ADD >175 mg). CONCLUSION: Among patients who initiated amiodarone treatment, around 5% had thyroid dysfunction at 1-year follow-up, with a slightly higher incidence in those with HF. A dose-response relationship was observed between the 1-year accumulated amiodarone dose and the subsequent 5-year cumulative incidence of thyroid dysfunction.

Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: A prospective cohort study.

OBJECTIVE: We aimed to determine the prevalence of abnormal umbilical artery (UA), uterine artery (UtA), middle cerebral artery (MCA) and cerebroplacental ratio (CPR) Doppler, and their relationship with adverse perinatal outcomes in women undergoing routine antenatal care in the third trimester. DESIGN: Prospective cohort. SETTING: Kagadi Hospital, Uganda. POPULATION: Non-anomalous singleton pregnancies. METHODS: Women underwent an early dating ultrasound and a third-trimester Doppler scan between 32 and 40 weeks of gestation, from 2018 to 2020. We handled missing data using multiple imputation and analysed the data using descriptive methods and a binary logistic regression model. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome (CAPO), perinatal death and stillbirth. RESULTS: We included 995 women. The mean gestational age at Doppler scan was 36.9 weeks (SD 1.02 weeks) and 88.9% of the women gave birth in a health facility. About 4.4% and 5.6% of the UA pulsatility index (PI) and UtA PI were above the 95th percentile, whereas 16.4% and 10.4% of the MCA PI and CPR were below the fifth percentile, respectively. Low CPR was strongly associated with stillbirth (OR 4.82, 95% CI 1.09-21.30). CPR and MCA PI below the fifth percentile were independently associated with CAPO; the association with MCA PI was stronger in small-for-gestational-age neonates (OR 3.75, 95% CI 1.18-11.88). CONCLUSION: In late gestation, abnormal UA PI was rare. Fetuses with cerebral blood flow redistribution were at increased risk of stillbirth and perinatal complications. Further studies examining the predictive accuracy and effectiveness of antenatal Doppler ultrasound screening in reducing the risk of perinatal deaths in low- and middle-income countries are warranted. TWEETABLE ABSTRACT: Blood flow redistribution to the fetal brain is strongly associated with stillbirths in low-resource settings.

Antenatal Doppler ultrasound implementation in a rural sub-Saharan African setting: exploring the perspectives of women and healthcare providers.

BACKGROUND: The World Health Organization recommends research to evaluate the effects of a single third trimester Doppler ultrasound examination on preventable deaths in unselected-risk pregnancies, particularly in low- and middle-income countries (LMICs) where the evidence base is scarce. While evaluating such technologies, researchers often ignore women and health care provider perspectives. This study explored the views and experiences of women and healthcare providers regarding the use of advanced ultrasound technology to optimize the health of mothers and their babies in a rural community in mid-western Uganda. METHODS: We enrolled 53 mothers and 10 healthcare providers, and captured data on their perceptions, barriers, and facilitators to the use of Doppler ultrasound technology using focus group discussions, semi-structured interviews and observations. Using qualitative content analysis, we inductively coded the transcripts in ATLAS.ti 8.0, detecting emerging themes. RESULTS: Women were afraid that ultrasound would harm them or their fetuses and many of them had never seen an ultrasound scan. The majority of the women found their partners supportive to attend antenatal care and use ultrasound services. Healthcare providers in Kagadi Hospital were unfamiliar with Doppler technology and using it to guide clinical decisions. Other barriers to the implementation of Doppler ultrasound included shortage of trained local staff, insufficient equipment, long distance to and from the hospital, and frequent power cuts. CONCLUSIONS: We found limited exposure to Doppler ultrasound technology among women and healthcare providers in mid-western Uganda. Engaging male partners may potentially influence the likelihood of accepting and using it to improve the health of women and their fetuses while wide spread myths and misconceptions about it may be changed by community engagement. Healthcare workers experienced difficulties in offering follow-up care to mothers detected with complications and Doppler ultrasound required a high level of training. While introducing advanced ultrasound machines to weak health systems, it is important to adequately train healthcare providers to avoid inappropriate interventions based on misinterpretation of the findings, consider where it is likely to be most beneficial, and embed it with realistic clinical practice guidelines.

Globally, nearly three million babies are stillborn every year, but most especially in low- and middle-income countries like Uganda. One of the factors contributing to a high number of stillbirths in low-income countries is the difficulty in identifying complications and accessing high quality care during pregnancy. Although antenatal Doppler scans are being widely used to diagnose complications in high-risk pregnancies in developed countries, studies evaluating it in LMICs are needed before it is implemented on a wide scale. We engaged 53 mothers, eight health workers from a hospital and two healthcare managers from a local government in Uganda to attain their opinions about Doppler ultrasound. We found that spousal involvement may promote acceptance and use of ultrasound services. However, the health workers did not have adequate knowledge about Doppler technology and using it for the benefit of mothers and the mothers feared that ultrasound procedures might harm them or their unborn babies. Making matters worse, the hospital faced frequent power cuts that affected the use of the equipment. Further, mothers must cover a long distance to access the hospital and its services. To reduce the number of babies dying during pregnancy or a few days after birth in Uganda and similar low-resource settings using Doppler technology, it is essential to strengthen the health systems. Starting with the training of healthcare providers to equipping and stabilizing power supply in health facilities, and educating the public about critical health procedures to break myths and misconceptions.

Measurement error of mean sac diameter and crown-rump length among pregnant women at Mulago hospital, Uganda.

BACKGROUND: Ultrasonography is essential in the prenatal diagnosis and care for the pregnant mothers. However, the measurements obtained often contain a small percentage of unavoidable error that may have serious clinical implications if substantial. We therefore evaluated the level of intra and inter-observer error in measuring mean sac diameter (MSD) and crown-rump length (CRL) in women between 6 and 10 weeks' gestation at Mulago hospital. METHODS: This was a cross-sectional study conducted from January to March 2016. We enrolled 56 women with an intrauterine single viable embryo. The women were scanned using a transvaginal (TVS) technique by two observers who were blinded of each other's measurements. Each observer measured the CRL twice and the MSD once for each woman. Intra-class correlation coefficients (ICCs), 95% limits of agreement (LOA) and technical error of measurement (TEM) were used for analysis. RESULTS: Intra-observer ICCs for CRL measurements were 0.995 and 0.993 while inter-observer ICCs were 0.988 for CRL and 0.955 for MSD measurements. Intra-observer 95% LOA for CRL were ± 2.04 mm and ± 1.66 mm. Inter-observer LOA were ± 2.35 mm for CRL and ± 4.87 mm for MSD. The intra-observer relative TEM for CRL were 4.62% and 3.70% whereas inter-observer relative TEM were 5.88% and 5.93% for CRL and MSD respectively. CONCLUSIONS: Intra- and inter-observer error of CRL and MSD measurements among pregnant women at Mulago hospital were acceptable. This implies that at Mulago hospital, the error in pregnancy dating is within acceptable margins of ±3 days in first trimester, and the CRL and MSD cut offs of ≥7 mm and ≥ 25 mm respectively are fit for diagnosis of miscarriage on TVS. These findings should be extrapolated to the whole country with caution. Sonographers can achieve acceptable and comparable diagnostic accuracy levels of MSD and CLR measurements with proper training and adherence to practice guidelines.

Overlap between Osteosarcopenia and Frailty and their Association with Poor Health Conditions: The Bushehr Elderly Health Program.

BACKGROUND: The aim of this study was to investigate the association of osteosarcopenia with frailty and poor health conditions among older Iranian adults. METHODS: This cross-sectional study analyzed data from the Bushehr Elderly Health Program. Osteosarcopenia was defined as the presence of osteopenia/osteoporosis and sarcopenia, while the Fried criteria were used to assess frailty. We assessed the history of falls and health-related quality of life (HRQoL), including physical and mental component summaries (PCS and MCS, respectively), history of fractures, activities of daily living (ADL), and instrumental activities of daily living (IADL), as indicators of poor health conditions. RESULTS: This study included a total of 2,371 older adults. The prevalence rates of osteosarcopenia-only, frailty-only, and osteosarcopenia with frailty were 17.4%, 3%, and 4.8%, respectively. The prevalence of a history of falls, poor ADL, and poor IADL was significantly higher in the frailty-only and osteosarcopenia with frailty groups. Osteosarcopenia with frailty was significantly associated with a history of falls (adjusted odds ratio [adjOR]=1.94; 95% confidence interval [CI], 1.20-3.15), poor ADL (adjOR=2.85; 95% CI, 1.81-4.50), and poor IADL (adjOR=5.09; 95% CI, 2.85-9.11). However, the frailty-only group also showed an association with falls and poor ADL and IADL. Only osteosarcopenia was associated with an increased OR for fracture. Frailty had the greatest effect on the MCS and PCS scores, whereas osteosarcopenia with frailty had a moderate impact. CONCLUSION: Osteosarcopenia with frailty significantly increased the odds of falls, poor ADL, poor IADL, and lower HRQoL compared with the robust group. Combined osteosarcopenia and frailty were not associated with poor health. These findings indicate the importance of diagnosing osteosarcopenia and frailty as separate entities to provide appropriate interventions and treatment.

Factors Associated With Acute Kidney Injury After Cardiopulmonary Bypass in Children.

Background: Acute kidney injury (AKI) is a common complication after cardiovascular surgery in children, noted in approximately 40% of children undergoing cardiopulmonary bypass (CPB). We sought to determine the risk factors including inflammatory and vascular endothelial markers associated with AKI in children undergoing cardiac surgery. Methods: A secondary analysis of a prospective observational cohort study of paediatric patients with a cardiac defect requiring CPB and a weight of >2.5 kg was performed. AKI was defined as a 1.5 times increase from the preoperative value in serum creatinine or an absolute increase by ≥0.3 mg/dL (≥26.5 µmol/L). Plasma inflammatory markers (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and tumour necrosis factor α) and vascular endothelial markers (vascular endothelial growth factor, von Willebrand factor, regulated on activation, normal T-cell expressed and secreted, granulocyte macrophage colony-stimulating factor, monocyte chemoattractant protein-1, platelet-derived growth factor, and microparticles) were assessed at 5 perioperative time points. Associations with AKI were found using generalized linear regression models adjusted for repeated measures. Results: A total of 207 patients were assessed, of whom 56% (n = 116) were male. Thirty-three percent (n = 68) developed AKI. In univariable analyses, adverse outcomes significantly related to the presence of AKI included increased intensive care unit stay (3.0 vs 5.6 hours, P < 0.001). In multivariable analysis, independent factors that were significantly associated with AKI included longer duration of CPB (111 vs 154 minutes, P < 0.001) and lower preoperative creatinine. Inflammatory and vascular endothelial biomarkers were not associated with AKI. Conclusions: AKI remains a prevalent problem after cardiac surgery, and renal ischemia related to longer bypass time potentially plays a key role in the etiology. Inflammatory and vascular endothelial biomarkers were not significantly related to AKI.

Contexte: L'insuffisance rénale aiguë (IRA) est une complication fréquente qui survient chez les enfants après une intervention chirurgicale cardiovasculaire. Environ 40 % des enfants chez qui une circulation extracorporelle (CEC) est mise en place durant l'intervention présentent ultérieurement une IRA. Nous avons tenté de définir les facteurs de risque, y compris les marqueurs inflammatoires et endothéliaux vasculaires, qui sont associés à l'IRA chez les enfants qui subissent une intervention chirurgicale cardiaque. Méthodologie: Nous avons réalisé une analyse secondaire d'une étude de cohorte observationnelle prospective menée auprès d'enfants qui étaient atteints d'une anomalie cardiaque nécessitant une CEC et qui pesaient plus de 2,5 kg. L'IRA était définie comme une hausse du taux de créatinine sérique par un facteur de 1,5 par rapport à la valeur préopératoire ou comme une augmentation absolue de ≥ 0,3 mg/dL (≥ 26,5 µmol/l). Les marqueurs inflammatoires plasmatiques (interleukine [IL]-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, facteur de nécrose tumorale alpha) et les marqueurs endothéliaux vasculaires (facteur de croissance de l'endothélium vasculaire, facteur de von Willebrand, chimiokine exprimée et sécrétée après l'activation des lymphocytes T normaux, facteur de stimulation des granulocytes et macrophages, protéine chimiotactique des monocytes-1, facteur de croissance dérivé des plaquettes, microparticules) ont été évalués à 5 moments périopératoires différents. Les associations avec l'IRA ont été établies au moyen de modèles de régression linéaire généraux, qui ont été ajustés pour tenir compte des mesures répétées. Résultats: L'évaluation a porté sur 207 patients, dont 56 % (n = 116) étaient des garçons, et une IRA a été observée chez 33 % (n = 68) d'entre eux. Les résultats d'analyses univariées ont montré que les issues indésirables associées de façon significative à la présence d'une IRA comprenaient un séjour prolongé à l'unité de soins intensifs (3,0 c. 5,6 heures, p < 0,001). Dans les analyses multivariées, les facteurs indépendants associés de façon significative à une IRA comprenaient une CEC prolongée (111 c. 154 minutes, p < 0,001) et un faible taux de créatinine préopératoire. Les biomarqueurs inflammatoires et endothéliaux vasculaires n'ont pas été associés à l'IRA. Conclusions: L'IRA demeure un problème répandu après une intervention chirurgicale cardiaque. L'ischémie rénale associée à une CEC prolongée joue potentiellement un rôle clé dans son étiologie. Par ailleurs, les biomarqueurs inflammatoires et endothéliaux vasculaires n'ont pas été associés de façon significative à l'IRA.

The use of lung ultrasound in COVID-19.

This review article addresses the role of lung ultrasound in patients with coronavirus disease 2019 (COVID-19) for diagnosis and disease management. As a simple imaging procedure, lung ultrasound contributes to the early identification of patients with clinical conditions suggestive of COVID-19, supports decisions about hospital admission and informs therapeutic strategy. It can be performed in various clinical settings (primary care facilities, emergency departments, hospital wards, intensive care units), but also in outpatient settings using portable devices. The article describes typical lung ultrasound findings for COVID-19 pneumonia (interstitial pattern, pleural abnormalities and consolidations), as one component of COVID-19 diagnostic workup that otherwise includes clinical and laboratory evaluation. Advantages and limitations of lung ultrasound use in COVID-19 are described, along with equipment requirements and training needs. To infer on the use of lung ultrasound in different regions, a literature search was performed using key words "COVID-19", "lung ultrasound" and "imaging". Lung ultrasound is a noninvasive, rapid and reproducible procedure; can be performed at the point of care; requires simple sterilisation; and involves non-ionising radiation, allowing repeated exams on the same patient, with special benefit in children and pregnant women. However, physical proximity between the patient and the ultrasound operator is a limitation in the current pandemic context, emphasising the need to implement specific infection prevention and control measures. Availability of qualified staff adequately trained to perform lung ultrasound remains a major barrier to lung ultrasound utilisation. Training, advocacy and awareness rising can help build up capacities of local providers to facilitate lung ultrasound use for COVID-19 management, in particular in low- and middle-income countries.

Quercetin and Its Role in Reducing the Expression of Pro-inflammatory Cytokines in Osteoarthritis.

Osteoarthritis is the most common human joint disease in the world. It is also one of the most common skeletal muscle defects, destructive joint changes, and the leading cause of disability and reduced quality of life. Destructive changes in inflammatory joints are associated with a range of biochemical events, including the overproduction of inflammatory cytokines. Cytokines are protein compounds that play an essential role in causing and regulating inflammation. A balance between pro-inflammatory and anti-inflammatory cytokines is crucial in maintaining a stable body. In some inflammatory diseases, including osteoarthritis, the balance between these compounds is disturbed, and the balance shifts to pre-inflammatory cytokines. For this reason, researchers today are trying to find an effective way to reduce inflammation and treat osteoarthritis by using certain compounds. Current treatments for osteoarthritis, including nonsteroidal antiinflammatory drugs, glucocorticoids, and hyaluronic acid, are mainly based on reducing pain and inflammation. However, they have limited effects in controlling symptoms and improving the patient's quality of life. Also, due to the high level of side effects, synthetic drugs have led to the identification of compounds of natural origin to give patients a chance to use painkillers and antiinflammatory drugs with fewer side effects. This review study aimed to present the role of quercetin as a natural compound in reducing the expression of pro-inflammatory cytokines in osteoarthritis. This study also discusses the relationship between inflammation and cartilage destruction and other inflammation-related factors caused by cytokines.

Fighting against amyotrophic lateral sclerosis (ALS) with flavonoids: a computational approach to inhibit superoxide dismutase (SOD1) mutant aggregation.

Protein aggregation is a biological process that occurs when proteins misfold. Misfolding and aggregation of human superoxide dismutase (hSOD1) cause a neurodegenerative disease called amyotrophic lateral sclerosis (ALS). Among the mutations occurring, targeting the E21K mutation could be a good choice to understand the pathological mechanism of SOD1 in ALS, whereof it significantly reduces life hopefulness in patients. Naturally occurring polyphenolic flavonoids have been suggested as a way to alleviate the amyloidogenic behavior of proteins. In this study, computational tools were used to identify promising flavonoid compounds that effectively inhibit the pathogenic behavior of the E21K mutant. Initial screening identified Pelargonidin, Curcumin, and Silybin as promising leads. Molecular dynamics (MD) simulations showed that the binding of flavonoids to the mutated SOD1 caused changes in the protein stability, hydrophobicity, flexibility, and restoration of lost hydrogen bonds. Secondary structure analysis indicated that the protein destabilization and the increased propensity of ß-sheet caused by the mutation were restored to the wild-type state upon binding of flavonoids. Free energy landscape (FEL) analysis was also used to differentiate aggregation, and results showed that Silybin followed by Pelargonidin had the most therapeutic efficacy against the E21K mutant SOD1. Therefore, these flavonoids hold great potential as highly effective inhibitors in mitigating ALS's fatal and insuperable effects.Communicated by Ramaswamy H. Sarma.

Prognostic accuracy of antenatal Doppler ultrasound for adverse perinatal outcomes in low-income and middle-income countries: a systematic review.

OBJECTIVES: This systematic review examined available literature on the prognostic accuracy of Doppler ultrasound for adverse perinatal outcomes in low/middle-income countries (LMIC). DESIGN: We searched PubMed, Embase, Cochrane Library and Scopus from inception to April 2020. SETTING: Observational or interventional studies from LMICs. PARTICIPANTS: Singleton pregnancies of any risk profile. INTERVENTIONS: Umbilical artery (UA), middle cerebral artery (MCA), cerebroplacental ratio (CPR), uterine artery (UtA), fetal descending aorta (FDA), ductus venosus, umbilical vein and inferior vena cava. PRIMARY AND SECONDARY OUTCOME MEASURES: Perinatal death, stillbirth, neonatal death, expedited delivery for fetal distress, meconium-stained amniotic fluid, low birth weight, fetal growth restriction, admission to neonatal intensive care unit, neonatal acidosis, Apgar scores, preterm birth, fetal anaemia, respiratory distress syndrome, length of hospital stay, birth asphyxia and composite adverse perinatal outcomes (CAPO). RESULTS: We identified 2825 records, and 30 (including 4977 women) from Africa (40.0%, n=12), Asia (56.7%, n=17) and South America (3.3%, n=01) were included. Many individual studies reported associations and promising predictive values of UA Doppler for various adverse perinatal outcomes mostly in high-risk pregnancies, and moderate to high predictive values of MCA, CPR and UtA Dopplers for CAPO. A few studies suggested that the MCA and FDA may be potent predictors of fetal anaemia. No randomised clinical trial (RCT) was found. Most studies were of suboptimal quality, poorly powered and characterised by wide variations in outcome classifications, the timing for the Doppler tests and study populations. CONCLUSION: Local evidence to guide how antenatal Doppler ultrasound should be used in LMIC is lacking. Well-designed studies, preferably RCTs, are required. Standardisation of practice and classification of perinatal outcomes across countries, following the international standards, is imperative. PROSPERO REGISTRATION NUMBER: CRD42019128546.

Accurate IMRT fluence verification for prostate cancer patients using 'in-vivo' measured EPID images and in-room acquired kilovoltage cone-beam CT scans.

BACKGROUND: To investigate for prostate cancer patients the comparison of 'in-vivo' measured portal dose images (PDIs) with predictions based on a kilovoltage cone-beam CT scan (CBCT), acquired during the same treatment fraction, as an alternative for pre-treatment verification. For evaluation purposes, predictions were also performed using the patients' planning CTs (pCT). METHODS: To get reliable CBCT electron densities for PDI predictions, Hounsfield units from the pCT were mapped onto the CBCT, while accounting for non-rigidity in patient anatomy in an approximate way. PDI prediction accuracy was first validated for an anatomical phantom, using IMRT treatment plans of ten prostate cancer patients. Clinical performance was studied using data acquired for 50 prostate cancer patients. For each patient, 4-5 CBCTs were available, resulting in a total of 1413 evaluated images. Measured and predicted PDIs were compared using γ-analyses with 3% global dose difference and 3 mm distance to agreement as reference criteria. Moreover, the pass rate for automated PDI comparison was assessed. To quantify improvements in IMRT fluence verification accuracy results from multiple fractions were combined by generating a γ-image with values halfway the minimum and median γ values, pixel by pixel. RESULTS: For patients, CBCT-based PDI predictions showed a high agreement with measurements, with an average percentage of rejected pixels of 1.41% only. In spite of possible intra-fraction motion and anatomy changes, this was only slightly larger than for phantom measurements (0.86%). For pCT-based predictions, the agreement deteriorated (average percentage of rejected pixels 2.98%), due to an enhanced impact of anatomy variations. For predictions based on CBCT, combination of the first 2 fractions yielded gamma results in close agreement with pre-treatment analyses (average percentage of rejected pixels 0.63% versus 0.35%, percentage of rejected beams 0.6% versus 0%). For the pCT-based approach, only combination of the first 5 fractions resulted in acceptable agreement with pre-treatment results. CONCLUSION: In-room acquired CBCT scans can be used for high accuracy IMRT fluence verification based on in-vivo measured EPID images. Combination of γ results for the first 2 fractions can largely compensate for small accuracy reductions, with respect to pre-treatment verification, related to intra-fraction motion and anatomy changes.