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Conventional Cardiotocography Computerized CTG Analysis and Perinatal Outcomes: a Systematic Review.Maedica Sep 2023Cardiotocography (CTG) constitutes a major and generally used tool for the assessment of fetal well-being. Subjectivity is the main difficulty in the interpretation of...
Cardiotocography (CTG) constitutes a major and generally used tool for the assessment of fetal well-being. Subjectivity is the main difficulty in the interpretation of CTG. Inter- and intra-observer variability are substantival features of the interpretation of CTGs. An auspicious answer for reduction of inter- and intra-observer variability is the computerized analysis of fetal heart rate (FHR). Moreover, computerized analysis contributes to the reduction of adverse maternal and fetal outcomes. The aim of the present review was to compare the visual and computerized analysis of CTG for establishing whether computerized CTG was related to better perinatal outcomes. Three electronic medical related databases (PubMed, Scopus and Cochrane) were searched from May to June 2023 in order to find randomized controlled trials (RCTs) in English. Studies were evaluated for their methodological quality with the CONSORT checklist. The target population comprised pregnant or intrapartum women into cardiotocographic monitoring. The intervention was represented by the visual analysis of CTG, and the comparison intervention by the computerized analysis of CTG. Primary outcomes included adverse perinatal outcomes. A total of 47 studies relevant with the topic were examined. However, only five articles met all inclusion and methodological criteria; four of those demonstrated that computerized analysis had no significant reduction in the rate of metabolic acidosis or obstetric interventions, and one study found a lower incidence of adverse perinatal outcome with conventional CTG (with fetal blood sampling). However, all reviews propose further development of decision-support software and more large-scale RCTs in the future. The computerized analysis of FHR is a promising solution for the reduction of adverse perinatal outcomes and elimination of inter- and intra-observer variability.
PubMed: 38023753
DOI: 10.26574/maedica.2023.18.3.483 -
Cureus May 2021Renal and hepatic functions are often mingled through both the existence of associated primary organ diseases and hemodynamic co-relationship. The primary objective of... (Review)
Review
Renal and hepatic functions are often mingled through both the existence of associated primary organ diseases and hemodynamic co-relationship. The primary objective of this study was to sum up the relationship between autoimmune hepatitis (AIH) on renal tubular acidosis (RTA) and the stages of the disease. A systematic review was performed for 24 trials. A total of 3687 patients were included. The incidence of RTA occurring and short-term mortality reduction was seen in two groups; for an overall effect: Z = 2.85 (P = 0.004) a total 95% CI of 0.53 [0.34, 0.82]. Only one patient with alcoholic liver cirrhosis was found to have an incomplete type of RTA. Test for overall effect: Z = 2.28 (P = 0.02) 95% CI of 2.83 [1.16, 6.95]. A reduction in fatal infections with dual therapy of corticosteroid plus N-acetylcysteine (NAC) test for overall effect: Z = 3.07 (P = 0.002) with 95% CI of 0.45 [0.27, 0.75]. Autoimmune diseases are the most frequent underlying cause of secondary RTA in adults. The primary renal disease must be actively excluded in all patients with hepatic failure by aggressive clinical and laboratory evaluations.
PubMed: 34079685
DOI: 10.7759/cureus.15287 -
Diabetes/metabolism Research and Reviews Sep 2020The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly-onset cardiovascular disease (CVD).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly-onset cardiovascular disease (CVD). Mounting studies have shown that metformin may reduce maximal carotidintima-media thickness (cIMT), improve insulin resistance and metabolic control in subjects with T1DM, and thus, may extend cardioprotective benefits. This systematic review and meta-analysis was performed to assess the efficacy and safety of metformin added to insulin therapy on reducing CVD risks and improving metabolism in T1DM.
METHODS
PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared metformin and insulin combination (duration ≥3 months) to insulin treatment alone in T1DM. Data were expressed as weighted/standardized mean differences (MDs/SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, along with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the overall certainty of the evidence.
RESULTS
Nineteen RCTs (n = 1540) met the eligibility criteria. Metformin treatment significantly reduced carotid artery intima-media thickness (MD -0.06 mm [95% CI -0.88, -0.28], P < .001). Though no significant difference was found in insulin sensitivity (SMD 2.21 [95% CI -1.88, 6.29], P = .29), the total daily insulin dosage (SMD -0.81 [95% CI -1.25, -0.36], P < .001) along with traditional CVD risk factors showed improvement by better glycaemic control, partial lipid profiles, diastolic blood pressure, and limited weight gain, with neutral effect on diabetic ketoacidosis, lactic acidosis, and hypoglycaemia. However, metformin therapy increased the incidence of gastrointestinal adverse events.
CONCLUSIONS
Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.
Topics: Diabetes Mellitus, Type 1; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Metformin; Prognosis; Vascular Diseases
PubMed: 32390336
DOI: 10.1002/dmrr.3334 -
Archives of Internal Medicine Nov 2003Metformin therapy for type 2 diabetes mellitus has been shown to reduce total mortality rates compared with other antihyperglycemic treatments but is thought to increase... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metformin therapy for type 2 diabetes mellitus has been shown to reduce total mortality rates compared with other antihyperglycemic treatments but is thought to increase the risk of lactic acidosis. The true incidence of fatal and nonfatal lactic acidosis associated with metformin use is not known.
METHODS
A comprehensive search was performed to identify all comparative trials or observational cohort studies published between January 1, 1959, and March 31, 2002, that evaluated metformin therapy, alone or in combination with other treatments, for at least 1 month. The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years for metformin treatment and for placebo or other treatments. In a second analysis, lactate levels were measured as a net change from baseline or as mean treatment values for metformin and comparison groups.
RESULTS
Pooled data from 194 studies revealed no cases of fatal or nonfatal lactic acidosis in 36 893 patient-years in the metformin group or in 30 109 patients-years in the nonmetformin group. Using Poisson statistics with 95% confidence intervals, the probable upper limit for the true incidence of lactic acidosis in the metformin and nonmetformin groups was 8.1 and 9.9 cases per 100 000 patient-years, respectively. There was no difference in lactate levels for metformin compared with placebo or other nonbiguanide therapies.
CONCLUSION
There is no evidence to date that metformin therapy is associated with an increased risk of lactic acidosis or with increased levels of lactate compared with other antihyperglycemic treatments if the drugs are prescribed under study conditions, taking into account contraindications.
Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Phenformin; Risk Assessment
PubMed: 14638559
DOI: 10.1001/archinte.163.21.2594 -
Journal of Medical Virology Jun 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including... (Meta-Analysis)
Meta-Analysis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark. It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03). Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.
Topics: Child; Humans; Adolescent; COVID-19; Diabetes Mellitus, Type 1; SARS-CoV-2; Diabetic Ketoacidosis; Post-Acute COVID-19 Syndrome; Cohort Studies
PubMed: 37264687
DOI: 10.1002/jmv.28833 -
Cureus Dec 2022Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against... (Review)
Review
Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against using these drugs in severe diabetic kidney disease. Consequently, the choice of anti-diabetic medicine in various stages of diabetic nephropathy should balance the benefits and risks to the patient. We aim to synthesize available evidence on the effectiveness and safety of metformin concerning sulfonylureas in patients with diabetic renal disease. The COSMOS-E (Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology) and MOOSE (Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology) guidelines were followed when designing the systematic review. The present study assessed the effectiveness of metformin and sulphonylurea monotherapy regarding renal function. Studies published from 2001 to 2022 were included. We have identified 570 records from PubMed, BioMed Central, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), ScienceDirect, and PLoS (The Public Library of Science) Medicine databases. Eight cohort studies met the inclusion criteria. All studies reported adjusted hazard ratios with confidence limits. Metformin was found to be more effective in the following events: all-cause mortality, GFR (glomerular filtration rate), ESRD (end-stage renal disease) or death events, one-year risk of death or end-stage renal disease, cardiovascular events, heart failure hospitalization, and hypoglycemic episodes. However, metformin was less effective in acute renal replacement therapy, end-stage renal disease, and/or death, with a one-year risk of acute dialysis. Lactic acidosis was not significant with metformin. The present study recommends that metformin therapy is safe compared to sulfonylurea therapy in diabetic nephropathy patients, provided that the contraindications given in the guidelines are strictly adhered to.
PubMed: 36628027
DOI: 10.7759/cureus.32286 -
Pediatric Nephrology (Berlin, Germany) Apr 2018D-lactic acidosis is an uncommon and challenging form of metabolic acidosis that may develop in short bowel syndrome. It has been documented exclusively in case reports...
BACKGROUND
D-lactic acidosis is an uncommon and challenging form of metabolic acidosis that may develop in short bowel syndrome. It has been documented exclusively in case reports and small case series.
METHODS
We performed a review of the literature in the National Library of Medicine and Excerpta Medica databases.
RESULTS
We identified 84 original reports published between 1977 and 2017. D-lactic acidosis was observed in 98 individuals ranging in age from 7 months to 86 years with short bowel syndrome. The clinical presentation included Kussmaul breathing, confusion, slurred speech, and gait disturbances. Furthermore, among 99 consecutive patients with short bowel syndrome, 21 reported having episodes with symptoms consistent with D-lactic acidosis. In addition, D-lactic acid might also contribute to acidosis in diabetes mellitus. Finally, abnormally high D-lactic acid was documented after administration or ingestion of large amounts of propylene glycol, as paraneoplastic phenomenon and perhaps also in a so far poorly characterized inherited inborn error of metabolism.
CONCLUSIONS
In humans with short bowel syndrome (or carbohydrate malabsorption), D-lactic acidosis is likely rather common and under-recognized. This condition should be included in the differential diagnosis of unexplained high-gap metabolic acidosis where the anion causing the acidosis is not known. Furthermore, diabetic acidosis might be caused by accumulation of both ketone bodies and D-lactic acid. Finally, there are endogenous sources of D-lactic acid in subjects with propylene glycol intoxication.
Topics: Acidosis, Lactic; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Lactic Acid; Male; Middle Aged; Short Bowel Syndrome; Young Adult
PubMed: 29218437
DOI: 10.1007/s00467-017-3844-8 -
Journal of Nephrology Dec 2016Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which... (Review)
Review
BACKGROUND
Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research.
DESIGN
A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved.
RESULTS
Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients.
CONCLUSIONS
This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.
Topics: Biomarkers; Calcium; Consensus; Crystallization; Humans; Interdisciplinary Communication; Nephrolithiasis; Nephrologists; Patient Care Team; Predictive Value of Tests; Recurrence; Risk Factors; Secondary Prevention; Treatment Outcome; Urinalysis; Urologists
PubMed: 27456839
DOI: 10.1007/s40620-016-0329-y -
Drug Safety Dec 2019There is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis. The aims of this research were (1) to formally...
INTRODUCTION AND OBJECTIVES
There is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis. The aims of this research were (1) to formally evaluate the association between metformin therapy and lactic acidosis in published case reports using two causality scoring systems, (2) to determine the frequency of pre-existing independent risk factors in published metformin-associated lactic acidosis cases, (3) to investigate the association between risk factors and mortality in metformin-associated lactic acidosis cases, and (4) to explore the relationship between prescribed metformin doses, elevated metformin plasma concentrations and the development of lactic acidosis in cases with chronic renal impairment.
METHODS
A systematic review was conducted to identify metformin-associated lactic acidosis cases. Causality was assessed using the World Health Organisation-Uppsala Monitoring Centre system and the Naranjo adverse drug reaction probability scale. Compliance to dosing guidelines was investigated for cases with chronic renal impairment as well as the association between steady-state plasma metformin concentrations prior to admission.
RESULTS
We identified 559 metformin-associated lactic acidosis cases. Almost all cases reviewed (97%) presented with independent risk factors for lactic acidosis. The prescribed metformin dose exceeded published guidelines in 60% of cases in patients with impaired kidney function. Metformin steady-state plasma concentrations prior to admission were predicted to be below the proposed upper limit of the therapeutic range of 5 mg/L.
CONCLUSIONS
Almost all cases of metformin-associated lactic acidosis reviewed presented with independent risk factors for lactic acidosis, supporting the suggestion that metformin plays a contributory role. The prescribed metformin dose, on average, exceeded the dosing recommendations by 1000 mg/day in patients with varying degrees of renal impairment but the predicted pre-admission plasma concentrations did not exceed the therapeutic range.
Topics: Acidosis, Lactic; Causality; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic; Risk Factors
PubMed: 31372935
DOI: 10.1007/s40264-019-00854-x -
Journal of Medical Toxicology :... Apr 2020Metformin-associated lactic acidosis (MALA) may occur after acute metformin overdose, or from therapeutic use in patients with renal compromise. The mortality is high,... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Metformin-associated lactic acidosis (MALA) may occur after acute metformin overdose, or from therapeutic use in patients with renal compromise. The mortality is high, historically 50% and more recently 25%. In many disease states, lactate concentration is strongly associated with mortality. The aim of this systematic review and meta-analysis is to investigate the utility of pH and lactate concentration in predicting mortality in patients with MALA.
METHODS
We searched PubMed, EMBASE, and Web of Science from their inception to April 2019 for case reports, case series, prospective, and retrospective studies investigating mortality in patients with MALA. Cases and studies were reviewed by all authors and included if they reported data on pH, lactate, and outcome. Where necessary, authors of studies were contacted for patient-level data. Receiver operating characteristic (ROC) curves were generated for pH and lactate for predicting mortality in patients with MALA.
RESULTS
Forty-four studies were included encompassing 170 cases of MALA with median age of 68.5 years old. Median pH and lactate were 7.02 mmol/L and 14.45 mmol/L, respectively. Overall mortality was 36.2% (95% CI 29.6-43.94). Neither lactate nor pH was a good predictor of mortality among patients with MALA. The area under the ROC curve for lactate and pH were 0.59 (0.51-0.68) and 0.43 (0.34-0.52), respectively.
CONCLUSION
Our review found higher mortality from MALA than seen in recent studies. This may be due to variation in standard medical practice both geographically and across the study interval, sample size, misidentification of MALA for another disease process and vice versa, confounding by selection and reporting biases, and treatment intensity (e.g., hemodialysis) influenced by degree of pH and lactate derangement. The ROC curves showed poor predictive power of either lactate or pH for mortality in MALA. With the exception of patients with acute metformin overdose, patients with MALA usually have coexisting precipitating illnesses such as sepsis or renal failure, though lactate from MALA is generally higher than would be considered survivable for those disease states on their own. It is possible that mortality is more related to that coexisting illness than MALA itself, and many patients die with MALA rather than from MALA. Additional work looking solely at MALA in healthy patients with acute metformin overdose may show a closer relationship between lactate, pH, and mortality.
Topics: Acid-Base Equilibrium; Acidosis, Lactic; Aged; Biomarkers; Female; Humans; Hydrogen-Ion Concentration; Hypoglycemic Agents; Lactic Acid; Male; Metformin; Middle Aged; Prognosis; Risk Assessment; Risk Factors
PubMed: 31907741
DOI: 10.1007/s13181-019-00755-6