Leptospirosis in pregnancy: A systematic review

IntroductionLeptospirosis is a leading zoonotic disease worldwide with more than 1 million cases in the general population per year. With leptospirosis being an emerging infectious disease and as the world’s environment changes with more floods and environmental disasters, the burden of leptospirosis is expected to increase. The objectives of the systematic review were to explore how leptospirosis affects pregnancy, its burden in this population, its effects on maternal and fetal outcomes and the evidence base surrounding treatment options.MethodsWe performed a systematic review of published and unpublished literature using automated and manual methods to screen nine electronic databases since inception, with no language restriction. Two reviewers independently screened articles, completed the data extraction and assessment of risk of bias. Due to significant heterogeneity and paucity of data, we were unable to carry out a meta-analysis, but we conducted a pooled analysis of individual patient data from the case reports and case series to examine the patient and disease characteristics, diagnostic methods, differential diagnoses, antibiotic treatments, and outcomes of leptospirosis in pregnancy. The protocol for this review was registered on the International Prospective Register of Systematic Reviews, PROSPERO: CRD42020151501.ResultsWe identified 419 records, of which we included eight observational studies, 21 case reports, three case series and identified four relevant ongoing studies. Overall the studies were with moderate bias and of ‘fair’ quality. We estimated the incidence of leptospirosis in pregnancy to be 1.3 per 10,000 in women presenting with fever or with jaundice, but this is likely to be higher in endemic areas. Adverse fetal outcomes were found to be more common in pregnant patients who presented in the second trimester compared with patients who presented in the third trimester. There is overlap between how leptospirosis presents in pregnancy and in the general population. There is also overlap between the signs, symptoms and biochemical disturbances associated with leptospirosis in pregnancy and the presentation of pregnancy associated conditions, such as Pre-Eclampsia (PET), Acute Fatty Liver of Pregnancy (AFLP) and HELLP Syndrome (Haemolysis Elevated Liver enzymes Low Platelets). In 94% of identified cases with available data, there was an indicator in the patient history regarding exposure that could have helped include leptospirosis in the clinician’s differential diagnosis. We also identified a range of suitable antibiotic therapies for treating leptospirosis in pregnancy, most commonly used were penicillins.ConclusionThis is the first systematic review of leptospirosis in pregnancy and it clearly shows the need to improve early diagnosis and treatment by asking early, treating early, and reporting well. Ask early—broaden differential diagnoses and ask early for potential leptospirosis exposures and risk factors. Treat early—increase index of suspicion in pregnant patients with fever in endemic areas and combine with rapid field diagnosis and early treatment. Report well—need for more good quality epidemiological studies on leptospirosis in pregnancy and better quality reporting of cases in literature.     

Methodology of assessment and reporting of safety in anti-malarial treatment efficacy studies of uncomplicated falciparum malaria in pregnancy: a systematic literature review

Background

Considering the uncertainty of safety of anti-malarial drugs in pregnancy, efficacy studies are one of the few sources of clinical safety data. Complete safety evaluation is not usually incorporated in efficacy studies due to financial and human resource constraints. This review reports the methods used for the assessment of safety of artemisinin-based and quinine-based treatments in efficacy studies in pregnancy.

Methods

Methodology of assessment and reporting of safety in efficacy studies of artemisinin-based and quinine-based treatment in pregnancy was reviewed using seven databases and two clinical trial registries. The protocol was registered to PROSPERO (CRD42017054808).

Results

Of 48 eligible efficacy studies the method of estimation of gestational age was reported in only 32 studies (67%, 32/48) and ultrasound was used in 18 studies (38%, 18/48). Seventeen studies (35%, 17/48) reported parity, 9 (19%, 9/48) reported gravidity and 13 (27%, 13/48) reported both. Thirty-eight studies (79%, 38/48) followed participants through to pregnancy outcome. Fetal loss was assessed in 34 studies (89%, 34/38), but the definition of miscarriage and stillbirth were defined only in 11 (32%, 11/34) and 7 (21%, 7/34) studies, respectively. Preterm birth was assessed in 26 studies (68%, 26/38) but was defined in 16 studies (62%, 16/26). Newborn weight was assessed in 30 studies (79%, 30/38) and length in 10 studies (26%, 10/38). Assessment of birth weight took gestational age into account in four studies (13%, 4/30). Congenital abnormalities were reported in 32 studies (84%, 32/38). Other common risk factors for adverse pregnancy outcomes were not well-reported.

Conclusion

Incomplete reporting and varied methodological assessment of pregnancy outcomes in anti-malarial drug efficacy studies limits comparison across studies. A standard list of minimal necessary parameters to assess and report the safety component of efficacy studies of anti-malarials in pregnancy is proposed.

     

Obesity in older adults: a systematic review of the evidence for diagnosis and treatment

Objective: Although obesity is increasing in older U.S. adults, treatment is controversial in this age group. We sought to examine evidence concerning obesity's health‐related risks, diagnostic methods, and treatment outcomes in older individuals. Research Methods and Procedures: We searched MEDLINE and Cochrane Library databases, consulted with experts, and examined bibliographies for English language studies discussing obesity in older adults (mean age ≥ 60), published between January 1980 and November 2005. Inclusion criteria were met by 32 longitudinal analyses, seven diagnostic studies, and 17 randomized controlled trial articles. At least two authors independently reviewed and abstracted study design, population, results, and quality information. Results: Correlations between body fat and three anthropometric measures (BMI, waist circumference, waist‐to‐hip ratio) decrease with age but remain clinically significant. Obesity contributes to risk for several cardiovascular endpoints, some cancers, and impaired mobility but protects against hip fracture. The association between obesity and mortality declines as age increases. Intensive counseling strategies incorporating behavioral, dietary, and exercise components promote a weight loss of 3 to 4 kg over 1 to 3.3 years. The loss is linked with improved glucose tolerance, improved physical functioning, reduced incidence of diabetes and a combined hypertension and cardiovascular endpoint, and reduced bone density. Discussion: In older adults, obesity can be diagnosed with standard clinical measures. Intensive counseling can promote modest sustained weight loss, but data are insufficient to evaluate surgical or pharmacological options. Obesity treatment is most likely to benefit individuals with high cardiovascular risk. Limited data suggest possible functional improvement. Treatment should incorporate measures to avoid bone loss.     

Congenital toxoplasmosis: epidemiologic features and control.

Toxoplasmosis is caused by the parasite Toxoplasma gondii. It is acquired from undercooked meat or from food or fomites contaminated by cat feces. The disease can be transmitted to the fetus only during maternal parasitemia, which is associated with primary infection. Extrapolation from current data suggests that there are 140 to 1400 cases of congenital toxoplasmosis per year in Canada and that 70 to 280 of the infants are severely affected at birth; many of the others suffer sequelae later in life. Serologic diagnosis of primary infection in the mother is quite sensitive and specific. Diagnosis in the infant is more difficult and may take several months. Prenatal treatment of the woman and postnatal treatment of the infant are hampered by the lack of proven efficacy as well as ethical and compliance problems. Preventive serologic screening and prophylaxis have the same drawbacks. Educating young women to avoid infection is an inexpensive, low-risk intervention that would be the preferred preventive strategy if it could be shown to be effective. Immunization may prove to be the most cost-effective method of preventing congenital toxoplasmosis if a safe and effective vaccine is developed.     

Long term efficacy of DOTS regimens for tuberculosis: systematic review

Objective To identify published studies assessing tuberculosis recurrence after successful treatment with standard short course regimens for six months to determine the strength and sufficiency of evidence to support current guidelines.Design Systematic review.Data sources Medline, Embase, Cochrane clinical trials register, specialist tuberculosis journals, and reference lists. Only English language publications were eligible.Review methods Studies were included irrespective of methodology or quality. Abstracted information included inclusion and exclusion criteria for participants, duration of follow-up, and definitions of treatment success and disease recurrence. The primary outcome was the proportion of successfully treated patients recorded with recurrent tuberculosis during the follow-up period.Results 17 study arms from 16 studies met the inclusion criteria; 10 were controlled clinical trials and six were either studies done under programmatic conditions or observational studies from functioning tuberculosis programmes. Although several clinical trials supported the use of daily treatment regimens, studies reporting tuberculosis recurrence after intermittent regimens were limited. Few studies carried out under routine programmatic conditions reported disease recurrence. Overall there was wide variation in recurrence after successful treatment, ranging from 0% to 14%. Considerable heterogeneity across studies precluded the systematic assessment of factors contributing to tuberculosis recurrence.Conclusions Despite DOTS (directly observed treatment, short course) being implemented for more than 10 years and millions of patients treated for tuberculosis, few studies have assessed the ability of standard DOTS regimens to result in lasting cure for patients treated under routine programmatic conditions.     

The efficacy and safety of azithromycin in asthma: A systematic review

Azithromycin is a potential therapeutic choice for asthma control, which is a heterogeneous airway inflammatory disease. Because of variable findings, we intend to evaluate the therapeutic effect and safety of azithromycin in asthma. Databases, including PubMed, EMBASE, Cochrane, and CNKI until 31 December 2017, were searched to identify available randomised controlled trials regarding azithromycin treatment for asthma. We identified seven studies involving 1520 cases that met our criteria. The mean difference for lung function (FEV₁, FVC, PEF), symptom assessment (ACQ, AQLQ), airway inflammation, and risk ratios for adverse events were extracted. Chi‐square and I² tests were applied to evaluate the heterogeneity among the studies towards each index with a random effect model or a fixed effect model. Pooled analysis shows that azithromycin administration results in no significant improvement in FEV₁ (MD: 0.09, 95% CI ?0.10 to 0.29, P = 0.36), PEF (MD: 11.76; 95% CI, ?2.86 to 26.38, P = 0.11), total airway inflammatory cells (MD: ?0.29; 95% CI, ?1.38 to 0.80, P =  0.60), ACQ (MD: 0.05; 95% CI, ?0.08 to 0.19, P = 0.44), and AQLQ (MD: 0.12; 95% CI, ?0.02 to 0.26, P =  0.10). Moreover, no significant difference was detected in adverse events (Risk ratio 0.99; 95% CI, 0.82‐1.19, P = 0.90). These findings demonstrate no beneficial clinical outcome of azithromycin in asthma control, and we propose that further prospective cohorts are warranted.     

Pharmacogenetics of glucose-lowering drug treatment: a systematic review

Intensive blood glucose lowering can significantly reduce the risk of micro- and macrovascular complications in patients with diabetes mellitus. However, 30% of all treated patients do not achieve optimal blood glucose levels. Genetic factors may influence the response to glucose-lowering medication. A search of MEDLINE-indexed literature published between January 1966 and July 2007 revealed 37 studies reporting data on genetic polymorphisms and response to glucose-lowering drugs. Most studies involving cytochrome P450 (CYP) genes had small sample sizes (21 studies <50 subjects) and were among healthy volunteers. Multiple studies indicated that the CYP2C9 *3 allele (Ile359Leu polymorphism) was associated with decreased clearance of sulfonylurea drugs. Supporting this, one study reported an increased insulin secretion in CYP2C9*3 allele carriers when using the sulfonylurea agent glyburide. The CYP2C9*3 allele was also associated with a decreased clearance of meglitinides, whereas the CYP2C8*3 (Arg139Lys; Lys399Arg) variant increased the clearance of meglitinides. Polymorphisms in genes encoding the inwardly rectifying potassium channel Kir6.2 (KCNJ11) and the insulin receptor substrate-1 (IRS1) were reported to be associated with an increased risk of (secondary) failure to respond to sulfonylurea therapy. A significant decrease in fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) in response to rosiglitazone was seen in subjects carrying the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma (PPARG) gene. Conversely, carriers of this polymorphism also had a higher conversion to diabetes mellitus when treated with acarbose; this effect was also seen in adiponectin (ADIPOQ) gene polymorphism carriers. Future studies with adequate sample sizes in which several SNPs in multiple candidate genes are genotyped in patients with diabetes should provide reliable information on genetic variants and response to glucose-lowering drugs.     

Congenital transmission of experimental chronic toxoplasmosis in rats.

A 10% transplacental transmission rate was observed in litters from 89 Wistar rats chronically infected with Toxoplasmosis gondii, as judging from bioassays. The rats had been fed T. gondii 2 mo prior to mating. Six of 7 isolates of T. gondii were transplacentally transmitted. The frequency of transmission did not appear to be affected by the strain of T. gondii or the size of the inoculum.     

Congenital toxoplasmosis: An overview of the neurological and ocular manifestations

Toxoplasma gondii is an obligate intracellular parasite which is known to infect one-third of the total world population chronically though it is asymptomatic in immunocompetent patients. However, in an immunocompromised patient or an infected fetus, it may cause devastating effects. The parasite may cross the placenta of an infected pregnant woman and probably infect the fetus congenitally. The severity of the infection depends on the gestational age at which the infection has occurred i.e., if it has occurred in the early phase, the rate of transmission is low but the severity is high if the fetus is infected and if it has occurred in the later phase then transmission rate is higher while the severity would be low. Congenital toxoplasmosis may result in non-specific consequences like abortion, intra-uterine growth restriction, jaundice, hepatosplenomegaly or even intra-uterine death. It may also result in neurological or ocular manifestations like intracranial calcifications, hydrocephalus or retinochoroiditis. The diagnosis may be done by serological screening of anti-Toxoplasma antibodies (IgM and IgG) while PCR of the amniotic fluid or the placenta is the confirmatory test. Acute or chronic infections may be differentiated by IgG avidity tests. The treatment regimens include spiramycin to prevent congenital transmission from an infected mother, pyrimethamine, sulfadoxine and folinic acid to treat the infected fetus, CSF shunting for the treatment of hydrocephalus and a combination of pyrimethamine, azithromycin, and corticosteroids for treating ocular toxoplasmosis.     

The use of research evidence in public health decision making processes: systematic review

Background

The use of research evidence to underpin public health policy is strongly promoted. However, its implementation has not been straightforward. The objectives of this systematic review were to synthesise empirical evidence on the use of research evidence by public health decision makers in settings with universal health care systems.

Methods

To locate eligible studies, 13 bibliographic databases were screened, organisational websites were scanned, key informants were contacted and bibliographies of included studies were scrutinised. Two reviewers independently assessed studies for inclusion, extracted data and assessed methodological quality. Data were synthesised as a narrative review.

Findings

18 studies were included: 15 qualitative studies, and three surveys. Their methodological quality was mixed. They were set in a range of country and decision making settings. Study participants included 1063 public health decision makers, 72 researchers, and 174 with overlapping roles. Decision making processes varied widely between settings, and were viewed differently by key players. A range of research evidence was accessed. However, there was no reliable evidence on the extent of its use. Its impact was often indirect, competing with other influences. Barriers to the use of research evidence included: decision makers'' perceptions of research evidence; the gulf between researchers and decision makers; the culture of decision making; competing influences on decision making; and practical constraints. Suggested (but largely untested) ways of overcoming these barriers included: research targeted at the needs of decision makers; research clearly highlighting key messages; and capacity building. There was little evidence on the role of research evidence in decision making to reduce inequalities.

Conclusions

To more effectively implement research informed public health policy, action is required by decision makers and researchers to address the barriers identified in this systematic review. There is an urgent need for evidence to support the use of research evidence to inform public health decision making to reduce inequalities.     

The effectiveness of evidence summaries on health policymakers and health system managers use of evidence from systematic reviews: a systematic review

Background

Systematic reviews are important for decision makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which make them hard to use for decision-making. There are many organizations that develop and disseminate derivative products, such as evidence summaries, from systematic reviews for different populations or subsets of decision makers. This systematic review aimed to (1) assess the effectiveness of evidence summaries on policymakers’ use of the evidence and (2) identify the most effective summary components for increasing policymakers’ use of the evidence. We present an overview of the available evidence on systematic review derivative products.

Methods

We included studies of policymakers at all levels as well as health system managers. We included studies examining any type of “evidence summary,” “policy brief,” or other products derived from systematic reviews that presented evidence in a summarized form. The primary outcomes were the (1) use of systematic review summaries in decision-making (e.g., self-reported use of the evidence in policymaking and decision-making) and (2) policymakers’ understanding, knowledge, and/or beliefs (e.g., changes in knowledge scores about the topic included in the summary). We also assessed perceived relevance, credibility, usefulness, understandability, and desirability (e.g., format) of the summaries.

Results

Our database search combined with our gray literature search yielded 10,113 references after removal of duplicates. From these, 54 were reviewed in full text, and we included six studies (reported in seven papers) as well as protocols from two ongoing studies. Two studies assessed the use of evidence summaries in decision-making and found little to no difference in effect. There was also little to no difference in effect for knowledge, understanding or beliefs (four studies), and perceived usefulness or usability (three studies). Summary of findings tables and graded entry summaries were perceived as slightly easier to understand compared to complete systematic reviews. Two studies assessed formatting changes and found that for summary of findings tables, certain elements, such as reporting study event rates and absolute differences, were preferred as well as avoiding the use of footnotes.

Conclusions

Evidence summaries are likely easier to understand than complete systematic reviews. However, their ability to increase the use of systematic review evidence in policymaking is unclear.

Trial registration

The protocol was published in the journal Systematic Reviews (2015;4:122)

     

New antiepileptic drugs: a systematic review of their efficacy and tolerability.

OBJECTIVES: To evaluate the efficacy and tolerability of the newly developed antiepileptic drugs gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide in patients with refractory partial epilepsy. DESIGN: Systematic review of published and unpublished randomised controlled trials of add-on treatment with new antiepileptic drugs. SUBJECTS: 20 published and eight unpublished trials representing 3883 patients with refractory partial epilepsy. MAIN OUTCOME MEASURES: Proportion of patients who (a) showed 50% or greater reduction in frequency of seizures (50% responders) and (b) withdrew from each study for any reason. RESULTS: Odds ratios (95% confidence intervals) relative to placebo for 50% responders were 2.29 (1.53 to 3.43) for gabapentin, 2.32 (1.47 to 3.68) for lamotrigine, 3.03 (2.01 to 4.58) for tiagabine, 4.22 (2.80 to 6.35) for topiramate, 3.68 (2.45 to 5.51) for vigabatrin, and 2.47 (1.36 to 4.47) for zonisamide. Odds ratios for withdrawal were 1.36 (0.75 to 2.49) for gabapentin, 1.19 (0.79 to 1.79) for lamotrigine, 1.81 (1.21 to 2.70) for tiagabine, 2.42 (1.43 to 4.11) for topiramate, 2.58 (1.26 to 5.27) for vigabatrin, and 5.70 (1.76 to 18.49) for zonisamide. Comparing results for each drug showed that all of the 95% confidence intervals overlapped, indicating that they were not significantly different in terms of efficacy and tolerability. CONCLUSIONS: All six drugs were significantly better than placebo at reducing frequency of seizures. These results do not allow an evidence based choice between these drugs as we have no conclusive indication of differences in efficacy or tolerability.     

Evolution of human tuberculosis: A systematic review and meta-analysis of paleopathological evidence

Tuberculosis is a re-emerging disease and is a major problem in both developing and developed countries today. An estimated one third of the world's population is infected and almost two million people die from the disease each year. Bone lesions occur in 3–5% of active tuberculosis cases and can be used to diagnose the disease in ancient skeletal remains. A meta-analysis was conducted on 531 palaeopathological tuberculosis cases from 221 sites (7250 BCE to 1899) on all continents for the purpose of testing two hypotheses; (1) the frequency of bone lesions does not change through time and (2) the distribution of lesions throughout the skeleton does not change over time. The frequency of bone lesions was found to significantly decrease over time (P < 0.05). The distribution of bone lesions was found to change from mainly spinal in earlier time periods to include more cases in other regions of the skeleton (long bones, joints, hands, feet) in later time periods. This difference in distribution was evaluated using a Chi-squared test and found to be significant (P < 0.01). These findings are an important addition to the current knowledge of the evolution of the disease and the Mycobacterium tuberculosis.     

Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis

BackgroundNumerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective.Methods and findingsWe carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527).ConclusionsIn this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.

In this meta-analysis, Min Seo Kim and colleagues synthesise results from randomized trials and observational studies on COVID-19 treatments.     

Diagnosis of toxoplasmosis in pregnancy: importance of immunoglobulin G avidity test

The immunoglobulin G (IgG) avidity test has proved to be a highly useful test in the diagnosis of toxoplasmosis during pregnancy, especially in combination with conventional serological assays. Acute infections at the time of gestation predispose the offspring to the risk of congenital toxoplasmosis. The IgG avidity test was developed to differentiate between recent and more distant infection; this method is valuable in the situation in which a single serum sample is obtained in the first trimester of pregnancy. This paper describes the utility of IgG avidity test during pregnancy, and its role in ruling out, by a high avidity, a recently acquired infection. Testing for specific IgG avidity has been reported to be useful for confirmatory testing in patients who have positive IgG and IgM antibodies.     

Ischaemic heart disease during pregnancy or post-partum: systematic review and case series

The risk of manifestations of ischaemic heart disease (IHD) in fertile women is elevated during pregnancy and the post-partum period. With increasing maternal age and a higher prevalence of cardiac risk factors, the incidence of IHD during pregnancy is rising. However, information in the literature is scarce. We therefore performed a retrospective cohort study and systematically reviewed the overall (1975–2013) and contemporary (2005–2013) literature concerning IHD presenting during pregnancy or in the post-partum period. We report two cases of IHD with atypical presentation during pregnancy or post-partum. In our review, we describe 146 pregnancies, including 57 contemporary cases (2005–2013). Risk factors for IHD were present in 80 %. Of the cases of IHD, 71 % manifested in the third trimester or the post-partum period, and 95 % presented with chest pain. The main cause was coronary dissection (35 %), or thrombus/emboli (35 %) in the more contemporary group. Maternal mortality was 8 % (6 % in the contemporary group), and the main cardiac complication was ventricular tachycardia (n = 17). Premature delivery rate was 56 %, and caesarean section was performed in 57 %. Perinatal mortality was 4 %. In conclusion, IHD during pregnancy or in the post-partum period has high maternal mortality and morbidity rates. Also, premature delivery and perinatal mortality rates are high.

Electronic supplementary material

The online version of this chapter (doi:10.1007/s12471-015-0677-6) contains supplementary material, which is available to authorized users.