Reduction of severe acute maternal morbidity and maternal mortality in Thyolo District, Malawi: the impact of obstetric audit

Background

Critical incident audit and feedback are recommended interventions to improve the quality of obstetric care. To evaluate the effect of audit at district level in Thyolo, Malawi, we assessed the incidence of facility-based severe maternal complications (severe acute maternal morbidity (SAMM) and maternal mortality) during two years of audit and feedback.

Methodology/Principal Findings

Between September 2007 and September 2009, we included all cases of maternal mortality and SAMM that occurred in Thyolo District Hospital, the main referral facility in the area, using validated disease-specific criteria. During two- to three-weekly audit sessions, health workers and managers identified substandard care factors. Resulting recommendations were implemented and followed up. Feedback was given during subsequent sessions. A linear regression analysis was performed on facility-based severe maternal complications. During the two-year study period, 386 women were included: 46 died and 340 sustained SAMM, giving a case fatality rate of 11.9%. Forty-five cases out of the 386 inclusions were audited in plenary with hospital staff. There was a reduction of 3.1 women with severe maternal complications per 1000 deliveries in the district health facilities, from 13.5 per 1000 deliveries in the beginning to 10.4 per 1000 deliveries at the end of the study period. The incidence of uterine rupture and major obstetric hemorrhage reduced considerably (from 3.5 to 0.2 and from 5.9 to 2.6 per 1000 facility deliveries respectively).

Conclusions

Our findings indicate that audit and feedback have the potential to reduce serious maternal complications including maternal mortality. Complications like major hemorrhage and uterine rupture that require relatively straightforward intrapartum emergency management are easier to reduce than those which require uptake of improved antenatal care (eclampsia) or timely intravenous medication or HIV-treatment (peripartum infections).     

Home environment and severe asthma in adolescence: a population based case-control study.

OBJECTIVE--To investigate the effects of the home environment on the risk of severe asthma during adolescence. DESIGN--A questionnaire based case-control study drawn from a cross sectional survey of allergic diseases among secondary school pupils in Sheffield in 1991. SUBJECTS--763 children whose parents had reported that over the previous 12 months they had suffered either 12 or more wheezing attacks or a speech limiting attack of wheeze. A further 763 children were frequency matched for age and school class to act as controls. Analysis was restricted to 486 affected children and 475 others born between 1975 and 1980 who had lived at their present address for more than three years. RESULTS--Independent associations with severe wheeze were seen for non-feather bedding, especially foam pillows (odds ratio 2.78; 95% confidence interval 1.89 to 4.17), and the ownership of furry pets now (1.51; 1.04 to 2.20) and at birth (1.70; 1.20 to 2.40). These estimates were derived from subjects whose parents denied making changes in the bedroom or avoiding having a pet because of allergy. Parental smoking, use of gas for cooking, age of mattress, and mould growth in the child''s bedroom were not significantly associated with wheezing. CONCLUSIONS--Either our study questionnaire failed to detect the avoidance or removal of feather bedding by allergic families or there is some undetermined hazard related to foam pillows. Synthetic bedding and furry pets were both widespread in this population and may represent remediable causes of childhood asthma.     

Genetic polymorphisms of cytokine genes and risk for trichloroethylene-induced severe generalized dermatitis: A case-control study

Trichloroethylene (TCE)-induced severe generalized dermatitis (SGD) is considered to be a contact allergic disease and is dependent on a cell-mediated immune response. Little is known about its pathogenesis. Several lines of evidence suggest that tumour necrosis factor (TNF) and interleukin 4 (IL-4) are involved in the immunological and inflammatory reactions. To investigate the relation between polymorphisms of TNF and the IL-4 gene and the risk of TCE-induced SGD, a case-control study was conducted consisting of 111 patients diagnosed with SGD and 152 TCE-exposed workers without SGD. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of TNF-α (G-238A, G-308A), TNF-β (intron 1) and IL-4 (C-590T). Logistic regression was applied to calculate the odds ratios (OR) and 95% confidence intervals. The results reveal that the frequency of TNF α-308 wild allele in cases was significantly higher than that in control subjects (p=0.049). Individuals with a heterozygous genotype of TNF α-308 were associated with the decreased risk of TCE-induced SGD relative to the homozygous genotype (OR=0.398, 95% CI=0.164–0.967). No significant differences in the allele and genotype frequencies could be demonstrated at any other polymorphic loci among both groups. The finding of a possible contribution of a TNF-α genetic polymorphism is a primary result because the pathogenesis of TCE-induced SGD is complex and likely to involve the interaction of a number of genes. A further study should be conducted to illustrate the influence of a link between certain relevant alleles in the assessment of genetic susceptibility.     

Risk factors for severe malaria in Bamako, Mali: a matched case-control study

The aim of this case-control study was to identify epidemiological risk factors for severe malaria among children living in Bamako, a malaria-endemic area. For this, 260 healthy community controls were matched to 130 patients with severe malaria. Conditional multiple logistic regression analysis indicated that all examined independent factors associated with severe malaria are directly related to characteristics of the child's mother, with the exception of the child's own yellow fever vaccination history (odds ratio (OR): 1.93, 95% confidence intervals (CI(95%)) [1.10-3.37]). The following characteristics were all associated with a decreased risk of severe malaria in the child: maternal education (OR: 0.52, CI(95%) [0.31-0.86]), the mother's adequate knowledge about malaria (OR: 0.46, 95% CI(95%) [0.25-0.86]), her use of mosquito bed nets (OR: 0.53, CI(95%) [0.30-0.92]) and breast-feeding for at least 2 years (OR: 0.57, CI(95%) [0.33-0.94]). Conversely, chronic maternal disease (OR: ?3.16, CI(95%) [1.31-7.61]) was associated with an increased risk of severe malaria. These findings strongly support the hypothesis that maternal factors are central to the development of severe malaria in children. Programmes aiming to improve both maternal health and maternal education may reduce the incidence of severe malaria in children and should therefore be advocated in Bamako and in areas with similar epidemiological patterns for malaria.     

Genetic polymorphisms of cytokine genes and risk for trichloroethylene-induced severe generalized dermatitis: a case-control study.

Trichloroethylene (TCE)-induced severe generalized dermatitis (SGD) is considered to be a contact allergic disease and is dependent on a cell-mediated immune response. Little is known about its pathogenesis. Several lines of evidence suggest that tumour necrosis factor (TNF) and interleukin 4 (IL-4) are involved in the immunological and inflammatory reactions. To investigate the relation between polymorphisms of TNF and the IL-4 gene and the risk of TCE-induced SGD, a case-control study was conducted consisting of 111 patients diagnosed with SGD and 152 TCE-exposed workers without SGD. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of TNF-alpha (G-238A, G-308A), TNF-beta (intron 1) and IL-4 (C-590T). Logistic regression was applied to calculate the odds ratios (OR) and 95% confidence intervals. The results reveal that the frequency of TNF alpha-308 wild allele in cases was significantly higher than that in control subjects (p=0.049). Individuals with a heterozygous genotype of TNF alpha-308 were associated with the decreased risk of TCE-induced SGD relative to the homozygous genotype (OR=0.398, 95% CI=0.164-0.967). No significant differences in the allele and genotype frequencies could be demonstrated at any other polymorphic loci among both groups. The finding of a possible contribution of a TNF-alpha genetic polymorphism is a primary result because the pathogenesis of TCE-induced SGD is complex and likely to involve the interaction of a number of genes. A further study should be conducted to illustrate the influence of a link between certain relevant alleles in the assessment of genetic susceptibility     

Risk factors for progression from severe maternal morbidity to death: a national cohort study

Background

Women continue to die unnecessarily during or after pregnancy in the developed world. The aim of this analysis was to compare women with severe maternal morbidities who survived with those who died, to quantify the risk associated with identified factors to inform policy and practice to improve survival.

Methods and Findings

We conducted a national cohort analysis using data from two sources obtained between 2003 and 2009: the Centre for Maternal and Child Enquiries maternal deaths database and the United Kingdom Obstetric Surveillance System database. Included women had eclampsia, antenatal pulmonary embolism, amniotic fluid embolism, acute fatty liver of pregnancy or antenatal stroke. These conditions were chosen as major causes of maternal mortality and morbidity about which data were available through both sources, and include 42% of direct maternal deaths over the study period. Rates, risk ratios, crude and adjusted odd ratios were used to investigate risks factors for maternal death. Multiple imputation and sensitivity analysis were used to handle missing data.We identified 476 women who survived and 100 women who died. Maternal death was associated with older age (35+ years aOR 2.36, 95%CI 1.22–4.56), black ethnicity (aOR 2.38, 95%CI 1.15–4.92), and unemployed, routine or manual occupation (aOR 2.19, 95%CI 1.03–4.68). An association was also observed with obesity (BMI≥30 kg/m² aOR 2.73, 95%CI 1.15–6.46).

Conclusions

Ongoing high quality national surveillance programmes have an important place in addressing challenges in maternal health and care. There is a place for action to reverse the rising trends in maternal age at childbirth, and to reduce the burden of obesity in pregnancy, as well as ongoing recognition of the impact of older maternal age on the risks of pregnancy. Development and evaluation of services to mitigate the risk of dying associated with black ethnicity and lower socioeconomic status is also essential.     

Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study

Background

Severe malaria is a leading cause of childhood mortality in Africa. However, at presentation, it is difficult to predict which children with severe malaria are at greatest risk of death. Dysregulated host inflammatory responses and endothelial activation play central roles in severe malaria pathogenesis. We hypothesized that biomarkers of these processes would accurately predict outcome among children with severe malaria.

Methodology/Findings

Plasma was obtained from children with uncomplicated malaria (n = 53), cerebral malaria (n = 44) and severe malarial anemia (n = 59) at time of presentation to hospital in Kampala, Uganda. Levels of angiopoietin-2, von Willebrand Factor (vWF), vWF propeptide, soluble P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), soluble endoglin, soluble FMS-like tyrosine kinase-1 (Flt-1), soluble Tie-2, C-reactive protein, procalcitonin, 10 kDa interferon gamma-induced protein (IP-10), and soluble triggering receptor expressed on myeloid cells-1 (TREM-1) were determined by ELISA. Receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of individual biomarkers. Six biomarkers (angiopoietin-2, soluble ICAM-1, soluble Flt-1, procalcitonin, IP-10, soluble TREM-1) discriminated well between children who survived severe malaria infection and those who subsequently died (area under ROC curve>0.7). Combinational approaches were applied in an attempt to improve accuracy. A biomarker score was developed based on dichotomization and summation of the six biomarkers, resulting in 95.7% (95% CI: 78.1–99.9) sensitivity and 88.8% (79.7–94.7) specificity for predicting death. Similar predictive accuracy was achieved with models comprised of 3 biomarkers. Classification tree analysis generated a 3-marker model with 100% sensitivity and 92.5% specificity (cross-validated misclassification rate: 15.4%, standard error 4.9%).

Conclusions

We identified novel host biomarkers of pediatric severe and fatal malaria (soluble TREM-1 and soluble Flt-1) and generated simple biomarker combinations that accurately predicted death in an African pediatric population. While requiring validation in further studies, these results suggest the utility of combinatorial biomarker strategies as prognostic tests for severe malaria.     

Incidence of severe acute renal failure in adults: results of a community based study.

OBJECTIVE--To determine the age related incidence of severe acute renal failure in adults in two health districts in England. DESIGN--Prospective study of patients identified as having severe acute renal failure within a two year period; subsequent monitoring of outcome for a further two years. SETTING--Two health districts in Devon. SUBJECTS--Those adults in a population of 444,971 who developed severe acute renal failure (serum creatinine concentration > 500 mumol/l) for the first time during two years, with subsequent fall of the serum creatinine concentration below the index value. MAIN OUTCOME MEASURES AND RESULTS--125 adults (140 per million total population yearly, 172 per million adults) developed severe acute renal failure, of whom 90 (72%) were over 70. Age related incidence rose from 17 per million yearly in adults under 50 to 949 per million yearly in the 80-89 age groups. In 31 patients (25%) the cause was prostatic disease, which was related to a good prognosis (84% (26) alive at three months). Overall survival was 54% (67) at three months and 34% (42) at two years and was not significantly age related. 18 per million total population yearly (22 per million adult population) received acute dialysis. Referral rate for specialised opinion was 51 per million total population yearly with an estimated appropriate referral rate of 70 per million per year. CONCLUSIONS--The incidence of severe acute renal failure in the community is at least twice as high as the incidence reported from renal unit based studies. Prostatic disease, a preventable and treatable problem, is the most common cause. Survival figures indicate that age alone should not be a bar to specialist referral or treatment.     

Incidence and predictors of phantom shocks in implantable cardioverter defibrillator recipients

Background

Implantable cardioverter defibrillators (ICDs) are designed to deliver shocks or antitachycardia pacing (ATP) in the event of ventricular arrhythmias. During follow-up, some ICD recipients experience the sensation of ICD discharge in the absence of an actual discharge (phantom shock). The aim of this study was to evaluate the incidence and predictors of phantom shocks in ICD recipients.

Methods

Medical records of 629 consecutive patients with ischaemic or dilated cardiomyopathy and prior ICD implantation were studied.

Results

With a median follow-up of 35 months, phantom shocks were reported by 5.1 % of ICD recipients (5.7 % in the primary prevention group and 3.7 % for the secondary prevention group; p=NS). In the combined group of primary and secondary prevention, there were no significant predictors of the occurrence of phantom shocks. However, in the primary prevention group, phantom shocks were related to a history of atrial fibrillation (p=0.03) and NYHA class <III (p=0.05). In the secondary prevention group, there were no significant predictors for phantom shocks.

Conclusion

Phantom shocks occur in approximately 5 % of all ICD recipients. In primary prevention patients, a relation with a history of atrial fibrillation and NYHA class <III were significant predictors for the occurrence of phantom shocks. In the secondary prevention patients, no significant predictors were found.     

Incidence and predictors of immediate complications following perioperative non-obstetric epidural punctures

Background

We made a survey among Finnish anesthesiologists concerning the current perioperative anesthetic practice of hip fracture patients for further development in patient care.

Methods

All members of the Finnish Society of Anesthesiologists with a known e-mail address (786) were invited to participate in an internet-based survey.

Results

The overall response rate was 55% (423 responses); 298 respondents participated in the care of hip fracture patients. Preoperative analgesia was mostly managed with oxycodone and paracetamol; every fifth respondent applied an epidural infusion. Most respondents (98%) employed a spinal block with or without an epidural catheter for intraoperative anesthesia. Midazolam, propofol and/or fentanyl were used for additional sedation. General anesthesia was used rarely. Postoperatively, paracetamol and non-steroidal anti-inflammatory drugs and occasionally peroral oxycodone, were prescribed in addition to epidural analgesia.

Conclusions

The survey suggests that the impact of more individualised analgesia regimens, both preoperatively and postoperatively, should be investigated in further studies.     

Anticonvulsant use and fracture: a case-control study

Objectives:We aimed to investigate fracture risk associated with anticonvulsant use in a population-based sample of men and women.Methods:Data from 1,458 participants (51.8% women) with a radiologically confirmed incident fracture (cases) were compared to 1,796 participants (46.5% women) without fracture (controls). Lifestyle factors, medication use and medical history were self-reported. Associations between anticonvulsant use and fracture were explored using binary logistic regression following adjustment for confounders.Results:In men, fracture cases and controls differed in age, smoking history, education, alcohol use, and gonadal hormone supplementation. In women, fracture cases and controls differed by previous fracture history, alcohol use, physical activity levels and use of anti-fracture agents. After adjustment for age, pooled anticonvulsant use was associated with a 3.4-fold higher risk of fracture in men and a 1.8-fold higher risk in women. Following further adjustments for confounders these patterns persisted; a 2.8-fold higher fracture risk in men and a 1.8-fold higher fracture risk in women.Conclusions:Anticonvulsant use was associated with increased fracture risk, independent of demographic, lifestyle, medical and medication related factors. While further studies exploring potential underlying mechanisms are warranted, regular monitoring of bone health in anticonvulsant users with risk factors may be useful.     

Migraine and stroke in young women: case-control study

ObjectiveTo investigate the association between migraine and ischaemic or haemorrhagic stroke in young women.DesignHospital based case-control study.SettingFive European centres participating in the World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.Subjects291 women aged 20-44 years with ischaemic, haemorrhagic, or unclassified arterial stroke compared with 736 age and hospital matched controls.InterventionQuestionnaire.ResultsAdjusted odds ratios associated with a personal history of migraine were 1.78 (95% confidence intervals, 1.14 to 2.77), 3.54 (1.30 to 9.61), and 1.10 (0.63 to 1.94) for all stroke, ischaemic stroke, and haemorrhagic stroke respectively. Odds ratios for ischaemic stroke were similar for classical migraine (with aura) (3.81, 1.26 to 11.5) and simple migraine (without aura) (2.97, 0.66 to 13.5). A family history of migraine, irrespective of personal history, was also associated with increased odds ratios, not only for ischaemic stroke but also haemorrhagic stroke. In migrainous women, coexistent use of oral contraceptives or a history of high blood pressure or smoking had greater than multiplicative effects on the odds ratios for ischaemic stroke associated with migraine alone. Change in the frequency or type of migraine on using oral contraceptives did not predict subsequent stroke. Between 20% and 40% of strokes in women with migraine seemed to develop directly from a migraine attack.ConclusionsMigraine in women of childbearing age significantly increases the risk of ischaemic but not haemorrhagic stroke. The coexistence of oral contraceptive use, high blood pressure, or smoking seems to exert a greater than multiplicative effect on the risk of ischaemic stroke associated with migraine.

Key messages

• A personal history of migraine was associated with increased risk of ischaemic but not haemorrhagic stroke
• Coexistence of risk factors—use of oral contraceptives, high blood pressure, or smoking had more than multiplicative effects on odds ratios for ischaemic stroke associated with migraine alone
• A family history of migraine, irrespective of a personal migraine history, was associated with increased risk of ischaemic and haemorrhagic stroke
• Up to 40% of strokes in migrainous women develop directly out of a migraine attack—so called migrainous strokes
• A change in type or frequency of migraine with use of oral contraceptives did not predict subsequent stroke

     

Incidence and predictors of morphometric vertebral fractures in patients with ankylosing spondylitis

Introduction

Ankylosing spondylitis (AS) is associated with an increased incidence of vertebral fractures (VFs); however the actual incidence and predictors of morphometric VFs are unknown. The present study examined the incidence and predictors of new VFs in a large AS cohort.

Methods

In total, 298 AS patients who fulfilled the modified New York criteria were enrolled and spinal radiographs were evaluated biennially. Clinical and laboratory data and radiographic progression were assessed according to the Bath AS Disease Activity Index, erythrocyte sedimentation rate, C-reactive protein (CRP), and the Stoke AS spine score (SASSS). VF was defined according to the Genant criteria. The incidence of VFs at 2 and 4 years was evaluated using the Kaplan-Meier method. The age-specific standardized prevalence ratio (SPR) for AS patients in comparison with the general population was calculated.

Results

Of 298 patients, 31 (10.8%) had previous VFs at baseline. A total of 30 new VFs occurred in 26 patients over 4 years. The incidence of morphometric VFs was 4.7% at 2 years and 13.6% at 4 years. Multivariate logistic regression analysis showed that previous VFs at baseline and increased CRP levels at 2 years were predictors of new VFs (odds ratio (OR) =12.8, 95% confidence interval (CI) = 3.6-45.3 and OR = 5.4, 95% CI = 1.4–15.9). The age-specific specific standardized prevalence ratio of morphometric VFs in AS was 3.3 (95% CI 2.1–4.5).

Conclusions

The incidence of morphometric VFs increased in AS. Previous VFs and increased CRP levels predicted future VFs. Further studies are needed to identify the effects of treatment interventions on the prevention of new VFs.     

Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study

ABSTRACT: BACKGROUND: The factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM. METHODS: To identify immune responses associated with SM, a sex- and age-matched case-control study was carried out in 134 Mozambican children with SM (cerebral malaria, severe anaemia, acidosis and/or respiratory distress, prostration, hypoglycaemia, multiple seizures) or uncomplicated malaria (UM). IgG and IgM against P. falciparum lysate, merozoite antigens (MSP-119, AMA-1 and EBA-175), a Duffy binding like (DBL)-alpha rosetting domain and antigens on the surface of infected erythrocytes were measured by ELISA or flow cytometry. Plasma concentrations of IL-12p70, IL-2, IFN-gamma, IL-4, IL-5, IL-10, IL-8, IL-6, IL- 1beta, TNF, TNF-beta and TGF-beta1 were measured using fluorescent bead immunoassays. Data was analysed using McNemar's and Signtest. RESULTS: Compared to UM, matched children with SM had reduced levels of IgG against DBLalpha (P < 0.001), IgM against MSP-119 (P = 0.050) and AMA-1 (P = 0.047), TGF-beta1 (P <0.001) and IL-12 (P = 0.039). In addition, levels of IgG against P. falciparum lysate and IL-6 concentrations were increased (P = 0.004 and P = 0.047, respectively). Anti-DBLalpha IgG was the only antibody response associated to reduced parasite densities in a multivariate regression model (P = 0.026). CONCLUSIONS: The lower levels of antibodies found in children with SM compared to children with UM were not attributable to lower exposure to P. falciparum in the SM group. IgM against P. falciparum and specific IgG against a rosetting PfEMP1 domain may play a role in the control of SM, whereas an imbalanced pro-inflammatory cytokine response may exacerbate the severity of infection. A high overlap in symptoms together with a limited sample size of different SM clinical groups reduced the power to identify immunological correlates for particular forms of SM.