Diabetic and hypertensive disorders following early pregnancy loss: a systematic review and meta-analysis.

Background: Spontaneous and induced abortions are common outcomes of pregnancy. There is inconsistent evidence of an association between early pregnancy loss and subsequent diabetic and hypertensive disorders in women. This systematic review and meta-analysis evaluated evidence on the risk of the subsequent development of pregnancy and non-pregnancy related diabetic and hypertensive disorders in women who experienced an early pregnancy loss. Methods: Systematic searches were conducted in seven electronic databases (CINAHL Plus, Ovid/EMBASE, Ovid/MEDLINE, ProQuest, PubMed, Scopus, and Web of Science) from inception to 22nd December 2023. Studies were included if they reported an exposure of spontaneous abortion (SAB), induced abortion (IA) or recurrent pregnancy loss (RPL) with an outcome of gestational diabetes mellitus, pre-eclampsia, gestational hypertension, and non-pregnancy related diabetic and hypertensive disorders. Risk of bias was assessed using Risk of Bias Instrument for Non-Randomized Studies of Exposures (ROBINS-E). Random effects meta-analysis was used to pool odds of developing diabetic and hypertensive disorders following an early pregnancy loss. This study is registered with PROSPERO (CRD42022327689). Findings: Of 20,176 records, 60 unique articles were identified for full-text review and 52 met the inclusion criteria, representing a total population of 4,132,895 women from 22 countries. Thirty-five studies were suitable for meta-analysis, resulting in a pooled odds ratio (OR) of 1.44 (95% confidence interval (CI) 1.23-1.68) for gestational diabetes mellitus following a prior SAB and a pooled OR of 1.06 (95% CI 0.90-1.26) for pre-eclampsia following a prior SAB. RPL increased the odds of developing pre-eclampsia (OR 1.37 95% CI 1.05-1.79). There was no association between IA and diabetic and hypertensive disorders. Interpretation: A prior SAB was associated with increased odds of gestational diabetes mellitus, but not pre-eclampsia. However, women who experienced RPL had an increased risk of subsequent pre-eclampsia. Future research is required to establish evidence for an association between early pregnancy loss with non-pregnancy related diabetic and hypertensive disorders. Funding: National Health and Medical Research Council.

A 2.2 NEF Neural-Recording Amplifier Using Discrete-Time Parametric Amplification.

This paper proposes a 2.2 noise efficiency factor (NEF) instrumentation amplifier for neural recording applications. A parametric amplifier based on the MOS C-V characteristic is designed as a pre-amplifier stage, lowering the input referred noise of the following stages by 3.4×. Sampling noise is minimized by oversampling the input signal and switching power is reduced by adopting an 8-phase soft-charging technique.

Management of globus pharyngeus.

Globus pharyngeus is a common ENT condition. This paper reviews the current evidence on globus and gives a rational guide to the management of patients with globus. The aetiology of globus is still unclear though most ENT surgeons believe that reflux whether acidic or not plays a significant role. Though proton pump inhibitors are used extensively in practice, there is little evidence to support their efficacy. Most patients with globus can be discharged after simple office investigations. The role of pepsin-induced laryngeal injury is an exciting concept that needs further study. Given the benign nature of globus pharyngeus, in most cases, reassurance rather than treatment or extensive investigation with rigid oesophagoscopy or contrast swallows is all that is needed. We need more research into the aetiology of globus.

Antiplatelet therapy in ENT surgery: a review.

INTRODUCTION: Antiplatelet agents such as aspirin and clopidogrel are increasingly encountered in clinical practice. Otorhinolaryngological surgeons are involved in the peri-operative decision of whether to continue treatment and risk haemorrhage or to discontinue treatment and risk thrombosis. METHODS: Literature relating to the risk of spontaneous or operative haemorrhage was reviewed. The morbidity and mortality associated with cessation of agents was evaluated. Published guidelines were also evaluated. A protocol for the management of antiplatelet agents in the peri-operative period, with particular reference to ENT operations, is presented. CONCLUSION: SIGNIFICANT morbidity and mortality is associated with the premature cessation of antiplatelet agents. Data from cardiac surgery suggest that operative blood loss only marginally increases in patients on aspirin and clopidogrel. However, the management of antiplatelet agents in the peri-operative period should be made after multidisciplinary consultation.

The use of ice-lollies for pain relief post-paediatric tonsillectomy. A single-blinded, randomised, controlled trial.

OBJECTIVES: To assess whether the use of ice-lollies after tonsillectomy with or without adenoidectomy in children aged 2-12 reduces pain in the immediate postoperative period. DESIGN: A prospective, randomised, single-blinded study design consisting of two groups with an intention to treat analysis. SETTING: Tertiary referral centre. PARTICIPANTS: Children aged 2-12 undergoing tonsillectomy with or without adenoidectomy. MAIN OUTCOME MEASURES: Pain assessment by nursing staff in the form of the validated modified Children's Hospital of Eastern Ontario Pain Scale at 15, 30 and 60 min and 4 h. RESULTS: Ninety-two patients were recruited into the study with 46 allocated to receive an ice-lolly and 41 not to receive an ice-lolly after exclusion of those with incomplete data. The two groups were comparable for number, age, sex and diagnosis. The pain score at every time interval was lower in the group that had received the ice-lolly compared with the group that had not. This was statistically significant at 30 (P = 0.008) and 60 min (P = 0.049). CONCLUSION: Our data suggest that ice-lollies are a cheap, effective and safe method of reducing postoperative pain up to one hour following paediatric tonsillectomy.

Statistical modeling of hemodynamic changes during orthotopic liver transplantation: predictive value for outcome and effect of marginal donors.

AIM: This study analyzed hemodynamic recordings collected on a beat-to-beat basis during orthotopic liver transplantation (OLT). The first aim was to construct a graphic that will represent hemodynamic profile during OLT. The second aim was to compare the intraoperative hemodynamic pattern of survivors versus nonsurvivors and those who received a liver from normal versus marginal donors. METHODS: Hemodynamic data (including cardiac output, cardiac index, stroke volume [SV] and SV index, systemic vascular resistance [SVR] and SVR index, mean arterial pressure, and heart rate) were collected from 100 consecutive adult OLT patients with the use of a lithium dilution cardiac output (LiDCO plus) monitor. A LOESS (Robust Locally Weighted Regression and Smoothing Scatterplots) smoother was used to give a more easily interpreted graph. Patients were grouped with respect to survival at 30 days (survivors vs nonsurvivors) and quality of graft (marginal vs normal). RESULTS: We constructed graphics that represented all intraopetative hemodynamic data during OLT for 100 consecutive procedures. It confirmed hyperdynamic circulation during OLT. Statistical analysis did not reveal significant differences regarding intraoperative hemodynamic data between survivors and nonsurvivors, or between patients receiving normal versus marginal grafts. CONCLUSION: This study shows changes in the hemodynamic profile during OLT, measured on a beat-to-beat basis. Intraoperative hemodynamic changes did not predict patients who did not survive OLT. Beat-to-beat monitoring did not reveal significant hemodynamic instability following transplantation of marginal grafts.

Aggressive angiomyxoma of larynx: case report and literature review.

OBJECTIVE: We report the second known case of aggressive angiomyxoma of the larynx. METHOD: Case report and a review of the world literature concerning angiomyxoma of the larynx and recent advances in the immunohistochemical, cytogenic and clinical study of its female pelvic counterpart. RESULTS: Aggressive angiomyxoma is a rare mesenchymal tumour originally thought only to occur in the female pelvis and peritoneum, or rarely in the male genital tract. A 47-year-old man presented with a one-month history of dysphonia. He was found to have a supraglottic mass on endoscopic examination, and underwent a laryngofissure approach excision biopsy and covering tracheostomy. Histological analysis showed a characteristic proliferation of spindle cells widely separated by loose, myxoid stroma with a prominent vascular component. Aggressive angiomyxoma was diagnosed. CONCLUSION: To our knowledge, this is the second report in the world literature of aggressive angiomyxoma of the larynx. Comparison with the female pelvic counterpart facilitates diagnosis, aided by recent advances, and suggests that complete surgical excision with a wide margin is the treatment of choice.

Mannose-binding lectin variant associated with severe malaria in young African children.

Mannose-binding lectin (MBL) is a serum protein which initiates innate immune responses to microbial pathogens by binding to non-self surface oligosaccharides. MBL deficiency is the most common congenital immunodeficiency of human and has been shown to predispose to infections, particularly in children and immune compromised. In a matched case-control study among 870 Ghanaian children, we examined the influence of six polymorphisms of the MBL2 gene on Plasmodium falciparum infection and severe malaria. A missense mutation resulting in low MBL activity (MBL2*C) was found in 35% of healthy controls, but in 42% of asymptomatically infected children (P=0.01), and in 46% of patients with severe malaria (P=0.007). Heterozygosity for MBL2*C was associated with increased odds of infection (odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.1), severe malaria (OR, 1.7; 95% CI, 1.2-2.4), and of severe anemia in particular (OR, 2.3; 95% CI, 1.4-3.8). The population attributable fraction of severe malaria cases attributable to MBL2*C heterozygosity was 17%. Our results suggest that the MBL pathway of the complement system is a critical determinant of both, susceptibility to P. falciparum infection and manifestation of severe malaria, particularly in young children in whom specific immune responses are weak or absent.

Intermittent preventive treatment in infants as a means of malaria control: a randomized, double-blind, placebo-controlled trial in northern Ghana.

Morbidity and mortality from malaria remain unacceptably high among young children in sub-Saharan Africa. Intermittent preventive treatment in infancy (IPTi) involves the administration of antimalarials alongside routine vaccinations and might be an option in malaria control. In an area of intense, perennial malaria transmission in northern Ghana, 1,200 children received IPTi with sulfadoxine-pyrimethamine or placebo at approximately 3, 9, and 15 months of age. Children were followed up until 24 months of age to assess morbidity and adverse events. During the intervention period (3 to 18 months of age), IPTi reduced the incidences of malaria and severe anemia by 22.5% (95% confidence interval, 12 to 32%) and 23.6% (95% confidence interval, 4 to 39%), respectively, and reduced hospitalizations and episodes of asymptomatic parasitemia by one-third. Protection was pronounced in the first year of life and not discernible in the second. The malaria-protective effect was largely confined to a period of 1 month after sulfadoxine-pyrimethamine treatments. Following the intervention, protection against asymptomatic parasitemia persisted. In contrast, a significant rebound of severe malaria, predominantly severe malarial anemia, occurred among children having received IPTi. Although the treatment was generally well tolerated, one case of moderately severe skin reaction followed sulfadoxine-pyrimethamine treatment. IPTi reduces malaria and anemia in infants in northern Ghana. Extension of IPTi into the second year of life by administering a dose at 15 months of age provided no substantial benefit beyond a 1-month prophylactic effect. Although this simple intervention offers one of the few available malaria-preventive measures for regions where malaria is endemic, the observed rebound of severe malaria advises caution and requires further investigation.

Large-scale surveillance of Plasmodium falciparum crt(K76T) in northern Ghana.

Surveillance of Plasmodium falciparum crt(K76T) [Pfcrt(K76T)], a resistance marker of chloroquine and, limitedly, amodiaquine, in >4,000 children in northern Ghana revealed a prevalence of 79%. Pfcrt(K76T) was heterogeneously distributed and associated with chloroquine use, low parasitemia, and the dry season. Widespread chloroquine resistance challenges the regional life span of amodiaquine as a partner drug in artemisinin combination therapy.

High residual chloroquine blood levels in African children with severe malaria seeking healthcare.

Despite widespread resistance, chloroquine remains widely used in West Africa, particularly in home treatment. We examined chloroquine blood levels on admission to a referral hospital with respect to the manifestation of severe malaria in 290 Ghanaian children. Of the patients, 78% exhibited chloroquine concentrations (subtherapeutic, 35%; therapeutic, 37%; supratherapeutic, 6%) and 11% died. Most parasites (78%) carried the pfcrt-T76 chloroquine resistance mutation. High drug concentrations correlated with reduced parasitaemia but also with selection of resistant parasites, lower respiratory and heart rates, increased plasma lactate levels and impaired consciousness. Geometric mean chloroquine concentrations tended to be higher in children who died than in survivors (1.135 vs. 778nmol/l; P=0.09). Supratherapeutic drug levels (>5000nmol/l) were associated with fatal outcome (odds ratio 8.6; 95% CI 1.4-51.7). Residual chloroquine concentrations were found to be abundant in children with severe malaria and to be associated with alterations in the clinical manifestation of the disease and its case fatality. This may result from toxic effects of the drug and/or reflect preceding overtreatment in children with acute life-threatening disease. In areas of intense chloroquine resistance and frequent pre-treatment, additional administration of chloroquine at hospital admission is not only ineffective but may even further endanger patients.

High levels of circulating cardiac proteins indicate cardiac impairment in African children with severe Plasmodium falciparum malaria.

A role of the heart in the pathophysiology of severe Plasmodium falciparum malaria has recently been suggested. The objective of the present study was to substantiate this finding in a large group of African children and to correlate results with metabolic conditions in these children. Furthermore, the impact of a potential cardiac impairment on outcome in severe cases was assessed. Results may have important implications on the currently ongoing debate on fluid management in severe malaria patients. Plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), myoglobin and creatine kinase muscle-brain (CK-MB) were compared in 400 African children with severe and mild falciparum malaria. Plasma levels of these markers were correlated with lactate and glucose blood levels, indicators for hypovolemia, and with clinical outcome. Children suffering from severe malaria and children who died (n = 22) exhibited high to very high levels of cardiac markers, respectively. Cardiac factors themselves were not predictive of fatal outcome, while, in multivariate analysis, lactic acidosis was the most important biochemical predictor of death in the severe malaria group. Lactic acidosis and hypoglycemia, however, result in cardiac impairment as defined by elevated levels of circulating cardiac proteins. Our results point to hypovolemia as a major underlying cause of lactic acidosis and hypoglycemia in African children with severe falciparum malaria. These deleterious metabolic conditions contribute to myocardial affection which was evident but not predictive per se of fatal outcome.

A randomized, placebo-controlled, double-blind trial on sulfadoxine-pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria.

The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) alone, SP plus amodiaquine (AQ), and SP plus artesunate (AS) was assessed in a randomized, placebo-controlled, and double-blind trial among 438 children with uncomplicated Plasmodium falciparum malaria in northern Ghana. Clinical and parasitological responses were monitored for 28 days following treatment; 86%, 98% and 97% of SP-, SP + AQ-, and SP + AS-treated patients achieved adequate clinical and parasitological response (ACPR) within 2 weeks, respectively. Parasite clearance was better with SP + AS than with SP or SP + AQ treatment but re-infections were more common. Polymerase chain reaction (PCR)-corrected rates of ACPR at day 28 were 72.2% for SP, 94.1% for SP + AQ (P < 0.0001), and 94.5% for SP + AS (P < 0.0001). Gametocyte prevalence and density 1 week after treatment were highest in children treated with SP, and lowest in patients receiving SP + AS. No severe adverse events attributable to study medication were observed. In northern Ghana, more than one of four children suffered SP treatment failure within 4 weeks. Both SP + AQ and SP + AS are efficacious alternative therapeutic options in this region. Although SP + AS and SP + AQ treatments have virtually identical cure rates, rapid parasite clearance and pronounced gametocidal effects are the advantages of the former, whereas cost and a lower rate of late re-infections are those of the latter.

Manifestation and outcome of severe malaria in children in northern Ghana.

The symptoms of severe malaria and their contribution to mortality were assessed in 290 children in northern Ghana. Common symptoms were severe anemia (55%), prostration (33%), respiratory distress (23%), convulsions (20%), and impaired consciousness (19%). Age influenced this pattern. The fatality rate was 11.2%. In multivariate analysis, circulatory collapse, impaired consciousness, hypoglycemia, and malnutrition independently predicted death. Children with severe malaria by the current World Health Organization (WHO) classification, but not by the previous one (1990), showed relatively mild clinical manifestations and a low case fatality rate (3.2%). In hospitalized children with severe malaria in northern Ghana, severe anemia is the leading manifestation, but itself does not contribute to mortality. In this region, malnutrition and circulatory collapse were important predictors of fatal malaria. The current WHO criteria serve well in identifying life-threatening disease, but also include rather mild cases that may complicate the allocation of immediate care in settings with limited resources.

Hemoglobin C and resistance to severe malaria in Ghanaian children.

Hemoglobin (Hb) C has been reported to protect against severe malaria. It is unclear whether relative resistance affects infection, disease, or both. Its extent may vary between regions and with disease pattern. We conducted a case-control study of children with severe malaria, asymptomatic parasitemic children, and healthy children in Ghana. HbAC did not prevent infection but reduced the odds of developing severe malaria and severe anemia. Protection was stronger with HbAS. The frequencies of HbCC and HbSC decreased, from healthy children to asymptomatic parasitemic children to children with severe malaria. These data support the notion that natural selection of HbC occurs because of the relative resistance it confers against severe malaria but argue against the notion that HbC offers resistance to infection.

Alpha(+)-thalassemia protects African children from severe malaria.

The high frequency of alpha(+)-thalassemia in malaria-endemic regions may reflect natural selection due to protection from potentially fatal severe malaria. In Africa, bearing 90% of global malaria morbidity and mortality, this has not yet been observed. We tested this hypothesis in an unmatched case-control study among 301 Ghanaian children with severe malaria and 2107 controls (62% parasitemic). In control children, alpha(+)-thalassemia affected neither prevalence nor density of Plasmodium falciparum. However, heterozygous alpha(+)-thalassemia was observed in 32.6% of controls but in only 26.2% of cases (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.56-0.98). Protection against severe malaria was found to be pronounced comparing severe malaria patients with parasitemic controls (adjusted OR in children < 5 years of age, 0.52; 95% CI, 0.34-0.78) and to wane with age. No protective effect was discernible for homozygous children. Our findings provide evidence for natural selection of alpha(+)-thalassemia in Africa due to protection from severe malaria.

Limited influence of haemoglobin variants on Plasmodium falciparum msp1 and msp2 alleles in symptomatic malaria.

Haemoglobin (Hb) S, HbC, and alpha(+)-thalassaemia confer protection from malaria. Accordingly, these traits may influence the multiplicity of infection (MOI) of Plasmodium falciparum and the presence of distinct parasite genotypes. In 840 febrile children in northern Ghana, we typed the P. falciparum merozoite surface protein genes (msp1, msp2) and examined effects of the Hb variants on MOI and parasite diversity. HbAC, HbAS, heterozygous, and homozygous alpha(+)-thalassaemia occurred in 21, 5, 29 and 4% of the children, respectively. Plasmodium falciparum was detected in 95%. The haemoglobinopathies did not influence MOI, nor did the Hb type bias the distribution of the msp allelic families. However, IC type parasites were most common among patients with homozygous alpha(+)-thalassaemia (93%), less frequent in heterozygotes (89%), and least frequent in alpha-globin normal children (84%, P(chi2 trend) = 0.03). The opposite was seen for Mad20 type parasites (34%, 47%, 53%, P(chi2 trend) = 0.02). Only a few of the 72 individual msp alleles were selected by the haemoglobinopathies. HbC and alpha(+)-thalassaemia are frequent in northern Ghana. In symptomatic children, the effect of Hb variants on parasite multiplicity and diversity appears to be limited. This may reflect an actual lack of influence or indicate abrogation in symptomatic malaria.

Chloroquine blood concentrations and molecular markers of chloroquine-resistant Plasmodium falciparum in febrile children in northern Ghana.

Plasmodium falciparum malaria is a predominant reason for health care utilization among children in sub-Saharan Africa. Despite the spread of resistance, chloroquine (CQ) is the most commonly used antimalarial. Little is known about the pattern of CQ use and resistance to the drug prior to attendance at a health care facility, and its impact on clinical presentation in children attending health care facilities in endemic regions. In a cross-sectional study among 840 febrile children presenting at a primary health care facility in northern Ghana from September to December 2000, CQ blood levels were measured by enzyme-linked immunosorbent assay and parasite isolates were genotyped for the CQ resistance markers pfcrt T76 and pfmdr1 Y86. Plasmodium falciparum was present in 95% by polymerase chain reaction and CQ was detected in 64% of the children. Concentrations of CQ in blood ranged from 31 to 3897 nmol/L (median 198 nmol/L). The pfcrt T76 and pfmdr1 Y86 resistance markers were detected in 84% and 57% of the isolates, respectively, and were selected by CQ. A significant trend for higher frequencies of the resistance markers with increasing CQ concentrations was observed. In this typical primary health care setting in sub-Saharan Africa, CQ use prior to attendance at a health care facility and CQ-resistant P. falciparum are frequent. As CQ selects resistant P. falciparum genotypes, CQ should be omitted as a first-line drug even in primary health care facilities when self-treatment with CQ is common.