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Cardiovascular Diabetology Mar 2022We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).
METHODS
We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).
RESULTS
A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion.
CONCLUSIONS
Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diabetic Nephropathies; Female; Heart Failure; Humans; Kidney; Male; Myocardial Infarction; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 35321742
DOI: 10.1186/s12933-022-01476-x -
BMJ Open Aug 2017To summarise incidence and prevalence of diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D) for the overall patient population and different subgroups... (Review)
Review
OBJECTIVES
To summarise incidence and prevalence of diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D) for the overall patient population and different subgroups (age, sex, geographical region, ethnicity and type of insulin administration).
DESIGN
Systematic literature review (SLR).
DATA SOURCES
Medline (via PubMed) and Embase (1 January 2000 to 23 June 2016).
STUDY SELECTION
Peer-reviewed observational studies with reported data on the incidence or prevalence of DKA in T1D adults were included. A single reviewer completed the study screening and selection process and a second reviewer performed an additional screening of approximately 20% of the publications; two reviewers independently conducted the quality assessment; the results were narratively synthesised.
RESULTS
Out of 1082 articles, 19 met the inclusion and exclusion criteria, with two additional studies identified that did not specify the patient age range and are therefore not included in the SLR. Overall, eight studies reported incidence with a range of 0-56 per 1000 person-years (PYs), with one outlying study reporting an incidence of 263 per 1000 PYs. Eleven studies reported prevalence with a range of 0-128 per 1000 people. Prevalence of DKA decreased with increasing age. Subgroup analyses were performed using data from no more than two studies per subgroup. There was a higher prevalence of DKA reported in women, non-whites and patients treated with insulin injections compared with men, whites and patients using continuous subcutaneous insulin infusion pumps, respectively.
CONCLUSIONS
To our knowledge, this is the first SLR on the epidemiology of DKA in T1D adults. Despite an increasing prevalence of T1D in recent years, DKA in adults has been poorly characterised. In an era when the benefit-risk profiles of new antidiabetic therapies are being evaluated, including the potential risk of DKA, there is a clear need to better elucidate the expected rate of DKA among T1D adults.
Topics: Adult; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Hypoglycemic Agents; Infusion Pumps; Injections; Insulin; Male
PubMed: 28765134
DOI: 10.1136/bmjopen-2017-016587 -
Rheumatology (Oxford, England) Dec 2015To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS.
OBJECTIVE
To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS.
METHODS
The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features.
RESULTS
The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ.
CONCLUSION
The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines.
Topics: Adult; Advisory Committees; Europe; Evidence-Based Medicine; Female; Humans; Joint Diseases; Kidney Diseases; Lung Diseases; Male; Middle Aged; Prevalence; Prognosis; Severity of Illness Index; Sjogren's Syndrome; Skin Diseases
PubMed: 26231345
DOI: 10.1093/rheumatology/kev200 -
Diabetologia Apr 2022The aim of this work was to assess the effectiveness of continuous glucose monitoring (CGM) vs self-monitoring of blood glucose (SMBG) in maintaining glycaemic control... (Meta-Analysis)
Meta-Analysis Review
Effectiveness of continuous glucose monitoring in maintaining glycaemic control among people with type 1 diabetes mellitus: a systematic review of randomised controlled trials and meta-analysis.
AIMS/HYPOTHESIS
The aim of this work was to assess the effectiveness of continuous glucose monitoring (CGM) vs self-monitoring of blood glucose (SMBG) in maintaining glycaemic control among people with type 1 diabetes mellitus.
METHODS
Cochrane Library, PubMed, Embase, CINAHL, Scopus, trial registries and grey literature were searched from 9 June 2011 until 22 December 2020 for RCTs comparing CGM intervention against SMBG control among the non-pregnant individuals with type 1 diabetes mellitus of all ages and both sexes on multiple daily injections or continuous subcutaneous insulin infusion with HbA levels, severe hypoglycaemia and diabetic ketoacidosis (DKA) as outcomes. Studies also included any individual or caregiver-led CGM systems. Studies involving GlucoWatch were excluded. Risk of bias was appraised with Cochrane risk of bias tool. Meta-analysis and meta-regression were performed using Review Manager software and R software, respectively. Heterogeneity was evaluated using χ and I statistics. Overall effects and certainty of evidence were evaluated using Z statistic and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) software.
RESULTS
Twenty-two studies, involving 2188 individuals with type 1 diabetes, were identified. Most studies had low risk of bias. Meta-analysis of 21 studies involving 2149 individuals revealed that CGM significantly decreased HbA levels compared with SMBG (mean difference -2.46 mmol/mol [-0.23%] [95% CI -3.83, -1.08], Z = 3.50, p=0.0005), with larger effects experienced among higher baseline HbA >64 mmol/mol (>8%) individuals (mean difference -4.67 mmol/mol [-0.43%] [95% CI -6.04, -3.30], Z = 6.69, p<0.00001). However, CGM had no influence on the number of severe hypoglycaemia (p=0.13) and DKA events (p=0.88). Certainty of evidence was moderate.
CONCLUSIONS/INTERPRETATION
CGM is superior to SMBG in improving glycaemic control among individuals with type 1 diabetes in the community, especially in those with uncontrolled glycaemia. Individuals with type 1 diabetes with HbA >64 mmol/mol (>8%) are most likely to benefit from CGM. Current findings could not confer a concrete conclusion on the effectiveness of CGM on DKA outcome as DKA incidences were rare. Current evidence is also limited to outpatient settings. Future research should evaluate the accuracy of CGM and the effectiveness of CGM across different age groups and insulin regimens as these remain unclear in this paper.
PROSPERO REGISTRATION
Registration no. CRD42020207042.
FUNDING
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Insulin; Male
PubMed: 35141761
DOI: 10.1007/s00125-021-05648-4 -
Critical Care (London, England) Jan 2021Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical... (Meta-Analysis)
Meta-Analysis
Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.
BACKGROUND
Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation.
METHODS
We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.
RESULTS
Eleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94-1.09; P = 0.77; I = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23-1.63; P < 0.00001; I = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01-1.78; P = 0.04; I = 0%).
CONCLUSIONS
This meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.
Topics: Acute Kidney Injury; Critical Illness; Humans; Incidence; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Time Factors; Time-to-Treatment
PubMed: 33407756
DOI: 10.1186/s13054-020-03451-y -
The Cochrane Database of Systematic... Feb 2017Cardiotocography (CTG) records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiotocography (CTG) records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of oxygen (hypoxic) to guide additional assessments of fetal wellbeing, or determine if the baby needs to be delivered by caesarean section or instrumental vaginal birth. This is an update of a review previously published in 2013, 2006 and 2001.
OBJECTIVES
To evaluate the effectiveness and safety of continuous cardiotocography when used as a method to monitor fetal wellbeing during labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 November 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials involving a comparison of continuous cardiotocography (with and without fetal blood sampling) with no fetal monitoring, intermittent auscultation intermittent cardiotocography.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility, quality and extracted data from included studies. Data were checked for accuracy.
MAIN RESULTS
We included 13 trials involving over 37,000 women. No new studies were included in this update.One trial (4044 women) compared continuous CTG with intermittent CTG, all other trials compared continuous CTG with intermittent auscultation. No data were found comparing no fetal monitoring with continuous CTG. Overall, methodological quality was mixed. All included studies were at high risk of performance bias, unclear or high risk of detection bias, and unclear risk of reporting bias. Only two trials were assessed at high methodological quality.Compared with intermittent auscultation, continuous cardiotocography showed no significant improvement in overall perinatal death rate (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.59 to 1.23, N = 33,513, 11 trials, low quality evidence), but was associated with halving neonatal seizure rates (RR 0.50, 95% CI 0.31 to 0.80, N = 32,386, 9 trials, moderate quality evidence). There was no difference in cerebral palsy rates (RR 1.75, 95% CI 0.84 to 3.63, N = 13,252, 2 trials, low quality evidence). There was an increase in caesarean sections associated with continuous CTG (RR 1.63, 95% CI 1.29 to 2.07, N = 18,861, 11 trials, low quality evidence). Women were also more likely to have instrumental vaginal births (RR 1.15, 95% CI 1.01 to 1.33, N = 18,615, 10 trials, low quality evidence). There was no difference in the incidence of cord blood acidosis (RR 0.92, 95% CI 0.27 to 3.11, N = 2494, 2 trials, very low quality evidence) or use of any pharmacological analgesia (RR 0.98, 95% CI 0.88 to 1.09, N = 1677, 3 trials, low quality evidence).Compared with intermittent CTG, continuous CTG made no difference to caesarean section rates (RR 1.29, 95% CI 0.84 to 1.97, N = 4044, 1 trial) or instrumental births (RR 1.16, 95% CI 0.92 to 1.46, N = 4044, 1 trial). Less cord blood acidosis was observed in women who had intermittent CTG, however, this result could have been due to chance (RR 1.43, 95% CI 0.95 to 2.14, N = 4044, 1 trial).Data for low risk, high risk, preterm pregnancy and high-quality trials subgroups were consistent with overall results. Access to fetal blood sampling did not appear to influence differences in neonatal seizures or other outcomes.Evidence was assessed using GRADE. Most outcomes were graded as low quality evidence (rates of perinatal death, cerebral palsy, caesarean section, instrumental vaginal births, and any pharmacological analgesia), and downgraded for limitations in design, inconsistency and imprecision of results. The remaining outcomes were downgraded to moderate quality (neonatal seizures) and very low quality (cord blood acidosis) due to similar concerns over limitations in design, inconsistency and imprecision.
AUTHORS' CONCLUSIONS
CTG during labour is associated with reduced rates of neonatal seizures, but no clear differences in cerebral palsy, infant mortality or other standard measures of neonatal wellbeing. However, continuous CTG was associated with an increase in caesarean sections and instrumental vaginal births. The challenge is how best to convey these results to women to enable them to make an informed decision without compromising the normality of labour.The question remains as to whether future randomised trials should measure efficacy (the intrinsic value of continuous CTG in trying to prevent adverse neonatal outcomes under optimal clinical conditions) or effectiveness (the effect of this technique in routine clinical practice).Along with the need for further investigations into long-term effects of operative births for women and babies, much remains to be learned about the causation and possible links between antenatal or intrapartum events, neonatal seizures and long-term neurodevelopmental outcomes, whilst considering changes in clinical practice over the intervening years (one-to-one-support during labour, caesarean section rates). The large number of babies randomised to the trials in this review have now reached adulthood and could potentially provide a unique opportunity to clarify if a reduction in neonatal seizures is something inconsequential that should not greatly influence women's and clinicians' choices, or if seizure reduction leads to long-term benefits for babies. Defining meaningful neurological and behavioural outcomes that could be measured in large cohorts of young adults poses huge challenges. However, it is important to collect data from these women and babies while medical records still exist, where possible describe women's mobility and positions during labour and birth, and clarify if these might impact on outcomes. Research should also address the possible contribution of the supine position to adverse outcomes for babies, and assess whether the use of mobility and positions can further reduce the low incidence of neonatal seizures and improve psychological outcomes for women.
Topics: Cardiotocography; Cesarean Section; Female; Heart Auscultation; Heart Rate, Fetal; Humans; Infant; Infant Mortality; Infant, Newborn; Labor, Obstetric; Pregnancy; Randomized Controlled Trials as Topic; Seizures
PubMed: 28157275
DOI: 10.1002/14651858.CD006066.pub3 -
Diabetes, Obesity & Metabolism Sep 2020To assess the effects of sodium-glucoseco-transporter-2 (SGLT2) inhibitors on diabetic ketoacidosis (DKA) in patients with type 2 diabetes. (Meta-Analysis)
Meta-Analysis
Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.
AIM
To assess the effects of sodium-glucoseco-transporter-2 (SGLT2) inhibitors on diabetic ketoacidosis (DKA) in patients with type 2 diabetes.
MATERIALS AND METHODS
We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to 13 June 2019 for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with control in patients with type 2 diabetes. Paired reviewers independently screened citations, assessed the risk of bias and extracted data. Peto's method was used as the primary approach to pool the effect of SGLT2 inhibitors on DKA. Sensitivity analyses with the alternative effect measure (risk ratio) or pooling method (Mantel-Haenszel), the use of continuity correction of 0.5 for zero-event trials or a generalized linear mixed model were conducted. Six preplanned subgroup analyses were performed to explore heterogeneity. The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence.
RESULTS
A total of 39 RCTs were included, involving 60 580 patients and 85 DKA events. SGLT2 inhibitors were statistically associated with an increased risk of DKA versus control (SGLT2 inhibitors: 62/34 961 [0.18%] vs. control: 23/25 211 [0.09%], Peto odds ratio [OR] 2.13, 95% confidence interval [CI] 1.38 to 3.27, I = 8%; RD 1.7 more events, 95% CI 0.6 more to 3.4 more events per 1000 over 5 years; high-quality evidence). Sensitivity analyses showed similar results. The subgroup analyses by mean age (interaction P = 0 .02) and length of follow-up (interaction P = 0 .03) showed a larger relative effect among older patients (aged ≥60 years) and those with longer use of SGLT2 inhibitors (>52 weeks).
CONCLUSIONS
High-quality evidence suggests that SGLT2 inhibitors may increase the risk of DKA in patients with type 2 diabetes. The apparent differences in treatment effects among patients of a different age or follow-up were probable, suggesting the advisability of caution in patients with long-term use of SGLT2 inhibitors or in older patients.
Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Glucose; Humans; Hypoglycemic Agents; Middle Aged; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 32364674
DOI: 10.1111/dom.14075 -
The Cochrane Database of Systematic... Jul 2020Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious risks to the mother (unconsciousness, pulmonary aspiration) and baby (hypoxia, acidosis, neurological injury).
OBJECTIVES
To assess the effects of prophylactic interventions for hypotension following spinal anaesthesia for caesarean section.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (9 August 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials, including full texts and abstracts, comparing interventions to prevent hypotension with placebo or alternative treatment in women having spinal anaesthesia for caesarean section. We excluded studies if hypotension was not an outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted data from eligible studies. We report 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 125 studies involving 9469 women. Interventions were to prevent maternal hypotension following spinal anaesthesia only, and we excluded any interventions considered active treatment. All the included studies reported the review's primary outcome. Across 49 comparisons, we identified three intervention groups: intravenous fluids, pharmacological interventions, and physical interventions. Authors reported no serious adverse effects with any of the interventions investigated. Most trials reported hypotension requiring intervention and Apgar score of less than 8 at five minutes as the only outcomes. None of the trials included in the comparisons we describe reported admission to neonatal intensive care unit. Crystalloid versus control (no fluids) Fewer women experienced hypotension in the crystalloid group compared with no fluids (average risk ratio (RR) 0.84, 95% confidence interval (CI) 0.72 to 0.98; 370 women; 5 studies; low-quality evidence). There was no clear difference between groups in numbers of women with nausea and vomiting (average RR 0.19, 95% CI 0.01 to 3.91; 1 study; 69 women; very low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (60 babies, low-quality evidence). Colloid versus crystalloid Fewer women experienced hypotension in the colloid group compared with the crystalloid group (average RR 0.69, 95% CI 0.58 to 0.81; 2009 women; 27 studies; very low-quality evidence). There were no clear differences between groups for maternal hypertension requiring intervention (average RR 0.64, 95% CI 0.09 to 4.46, 3 studies, 327 women; very low-quality evidence), maternal bradycardia requiring intervention (average RR 0.98, 95% CI 0.54 to 1.78, 5 studies, 413 women; very low-quality evidence), nausea and/or vomiting (average RR 0.89, 95% CI 0.66 to 1.19, 14 studies, 1058 women, I² = 29%; very low-quality evidence), neonatal acidosis (average RR 0.83, 95% CI 0.15 to 4.52, 6 studies, 678 babies; very low-quality evidence), or Apgar score of less than 8 at five minutes (average RR 0.24, 95% CI 0.03 to 2.05, 10 studies, 730 babies; very low-quality evidence). Ephedrine versus phenylephrine There were no clear differences between ephedrine and phenylephrine groups for preventing maternal hypotension (average RR 0.92, 95% CI 0.71 to 1.18; 401 women; 8 studies; very low-quality evidence) or hypertension (average RR 1.72, 95% CI 0.71 to 4.16, 2 studies, 118 women, low-quality evidence). Rates of bradycardia were lower in the ephedrine group (average RR 0.37, 95% CI 0.21 to 0.64, 5 studies, 304 women, low-quality evidence). There was no clear difference in the number of women with nausea and/or vomiting (average RR 0.76, 95% CI 0.39 to 1.49, 4 studies, 204 women, I² = 37%, very low-quality evidence), or babies with neonatal acidosis (average RR 0.89, 95% CI 0.07 to 12.00, 3 studies, 175 babies, low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (321 babies; low-quality evidence). Ondansetron versus control Ondansetron administration was more effective than control (placebo saline) for preventing hypotension requiring treatment (average RR 0.67, 95% CI 0.54 to 0.83; 740 women, 8 studies, low-quality evidence), bradycardia requiring treatment (average RR 0.49, 95% CI 0.28 to 0.87; 740 women, 8 studies, low-quality evidence), and nausea and/or vomiting (average RR 0.35, 95% CI 0.24 to 0.51; 653 women, 7 studies, low-quality evidence). There was no clear difference between the groups in rates of neonatal acidosis (average RR 0.48, 95% CI 0.05 to 5.09; 134 babies; 2 studies, low-quality evidence) or Apgar scores of less than 8 at five minutes (284 babies, low-quality evidence). Lower limb compression versus control Lower limb compression was more effective than control for preventing hypotension (average RR 0.61, 95% CI 0.47 to 0.78, 11 studies, 705 women, I² = 65%, very low-quality evidence). There was no clear difference between the groups in rates of bradycardia (RR 0.63, 95% CI 0.11 to 3.56, 1 study, 74 women, very low-quality evidence) or nausea and/or vomiting (average RR 0.42, 95% CI 0.14 to 1.27, 4 studies, 276 women, I² = 32%, very-low quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (130 babies, very low-quality evidence). Walking versus lying There was no clear difference between the groups for women with hypotension requiring treatment (RR 0.71, 95% CI 0.41 to 1.21, 1 study, 37 women, very low-quality evidence). Many included studies reported little to no information that would allow an assessment of their risk of bias, limiting our ability to draw meaningful conclusions. GRADE assessments of the quality of evidence ranged from very low to low. We downgraded evidence for limitations in study design, imprecision, and indirectness; most studies assessed only women scheduled for elective caesarean sections. External validity also needs consideration. Readers should question the use of colloids in this context given the serious potential side effects such as allergy and renal failure associated with their administration.
AUTHORS' CONCLUSIONS
While interventions such as crystalloids, colloids, ephedrine, phenylephrine, ondansetron, or lower leg compression can reduce the incidence of hypotension, none have been shown to eliminate the need to treat maternal hypotension in some women. We cannot draw any conclusions regarding rare adverse effects associated with use of the interventions (for example colloids) due to the relatively small numbers of women studied.
Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Antiemetics; Cesarean Section; Colloids; Crystalloid Solutions; Ephedrine; Female; Humans; Hypotension; Intraoperative Complications; Isotonic Solutions; Ondansetron; Phenylephrine; Postoperative Nausea and Vomiting; Pregnancy; Randomized Controlled Trials as Topic; Vasoconstrictor Agents; Walking
PubMed: 32619039
DOI: 10.1002/14651858.CD002251.pub4 -
BMJ Open Feb 2019To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies.
DESIGN
We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs).
INTERVENTION
SGLT2 inhibitors, compared with placebo or active comparators.
PRIMARY OUTCOMES
Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations.
RESULTS
We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture.
CONCLUSIONS
Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear.
PROSPERO REGISTRATION NUMBER
CRD42016038715.
Topics: Acute Kidney Injury; Amputation, Surgical; Benzhydryl Compounds; Canagliflozin; Diabetic Ketoacidosis; Fractures, Bone; Glucosides; Humans; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Urinary Tract Infections
PubMed: 30813108
DOI: 10.1136/bmjopen-2018-022577 -
Pulmonology 2019Chronic Obstructive Pulmonary Disease (COPD) history is characterized by episodes of exacerbation of varying severity, featured by acute worsening of respiratory...
Chronic Obstructive Pulmonary Disease (COPD) history is characterized by episodes of exacerbation of varying severity, featured by acute worsening of respiratory symptoms, commonly precipitated by respiratory tract infection. The recent ERS/ATS clinical practice guidelines strongly recommend the application of non invasive ventilation (NIV) for patients with acute respiratory failure (ARF) leading to acute or acute-on-chronic respiratory acidosis (pH 7.35) and not for those patients with acute exacerbation of COPD (AECOPD) and hypercapnia who are not acidotic. In recent years, High-Flow through Nasal Cannula (HFNC) has been introduced in the clinical practice. We designed the present systematic review of the literature to assess all effects of HFNC use reported in exacerbated COPD patients. In this setting, HFNC is able to keep PaCO2 unmodified, while oxygenation slightly deteriorates as opposed to NIV. Furthermore, the work of breathing is reduced with HFNC by a similar extent to NIV, while it increases by 40-50% during conventional oxygen therapy (COT). HFNC is also reported to be more comfortable than COT and NIV. Despite these results, little and limited evidence for improved clinical outcomes is currently available.
Topics: Acidosis, Respiratory; Blood Gas Analysis; Disease Progression; Humans; Hypercapnia; Noninvasive Ventilation; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Respiratory Rate; Respiratory Therapy; Treatment Outcome; Work of Breathing
PubMed: 31591056
DOI: 10.1016/j.pulmoe.2019.08.001