Developmental screening in South Africa: comparing the national developmental checklist to a standardized tool

BackgroundWorldwide, more than 200 million children in low- and middle-income countries have developmental delays and/or disabilities. In South Africa the only nationally implemented developmental ‘screening’ tool is integrated as part of ''The Road to Health Booklet (RTHB).MethodThe study employed a comparative cross-sectional within-subject design to evaluate the accuracy of the RTHB developmental checklist against a standardized international tool i.e. the PEDS tools, consisting of the PEDS and PEDS:DM. A total of 201 participants were included through convenience sampling at primary health care facilities in Tshwane, South Africa.ResultsSensitivity of the RTHB developmental checklist is low, but specificity is high. The RTHB developmental checklist failed to identify more than half the infants at risk of delays or disorders. The nationally implemented developmental checklist is ineffective to identify at-risk infants. It should be adapted and validated or replaced in order to improve identification of at-risk infants.     

Epstein–Barr virus-associated acute cholecystitis in a teenager

A 14-year-old girl was admitted to hospital with fever, headache, sore throat and abdominal pain. Her blood lymphocyte count and inflammatory markers were raised. Acute Epstein–Barr virus (EBV) infection was suspected and confirmed serologically and by measuring the viral load. On day 7, she developed jaundice with abnormal liver function tests. An abdominal ultrasound scan revealed thickening of the gallbladder and bile duct walls without calculi suggesting acute acalculous cholecystitis. The patient improved slowly with symptomatic treatment, and a repeat ultrasound scan six months later was normal. Acalculous cholecystitis is a rare complication of EBV infection and usually has a good prognosis.     

Outcome predictors in acute surgical admissions for lower gastrointestinal bleeding

Aim The BLEED criterion is a triaging model for lower gastrointestinal bleeding (LGIB), which was developed and validated in the USA. We assessed the BLEED criteria in a UK population and aimed to elucidate factors that can be implemented for early risk stratification. Method Patients were identified from a prospectively maintained surgical admission database at a central London teaching hospital. Data were collected on 26 clinical factors available on initial presentation. The primary‐outcome end‐points included severe bleeding (persistent bleeding within the first 24 h, blood transfusion, a decrease in haematocrit of ≥ 20% or recurrent bleeding after ≥ 24 hours of stability) and adverse outcome (emergency surgery to control bleeding, intensive care unit [ITU] admission or death). Results One hundred and eighty‐four clinical episodes were identified, representing 3% of all surgical referrals. Twelve patients with upper gastrointestinal bleeding were excluded. Severe bleeding occurred in 110 (64%) patients. An adverse outcome was recorded in 20 (11.6%) patients, and 10 (5.4%) patients died during admission. The commonest aetiologies were diverticular disease, haemorrhoids and malignancy. Four prognosticators of adverse outcome were identified, these being: creatinine > 150μm (P = 0.002); age > 60 years (P = 0.001); abnormal haemodynamic parameters on presentation (P = 0.05); persistent bleeding within the first 24 h (P = 0.05); and area under the receiver–operating characteristics curve (AUC) = 0.79. The BLEED criteria were shown to be nonpredictive (AUC = 0.60). Conclusion The BLEED criterion was not shown to have any predictive value in this patient cohort. Our study has determined an independent set of prognostic factors that could be incorporated into initial triaging of patients presenting with LGIB. This may facilitate the early identification of patients requiring more aggressive resuscitation, admission to a monitored bed and consideration for early radiological or surgical intervention.     

Cerebrospinal fluid markers of neuroinflammation in delirium: A role for interleukin-1β in delirium after hip fracture

Objective

Exaggerated central nervous system (CNS) inflammatory responses to peripheral stressors may be implicated in delirium. This study hypothesised that the IL-1β family is involved in delirium, predicting increased levels of interleukin-1β (IL-1β) and decreased IL-1 receptor antagonist (IL-1ra) in the cerebrospinal fluid (CSF) of elderly patients with acute hip fracture. We also hypothesised that Glial Fibrillary Acidic Protein (GFAP) and interferon-γ (IFN-γ) would be increased, and insulin-like growth factor 1 (IGF-1) would be decreased.

Methods

Participants with acute hip fracture aged > 60 (N = 43) were assessed for delirium before and 3–4 days after surgery. CSF samples were taken at induction of spinal anaesthesia. Enzyme-linked immunosorbent assays (ELISA) were used for protein concentrations.

Results

Prevalent delirium was diagnosed in eight patients and incident delirium in 17 patients. CSF IL-1β was higher in patients with incident delirium compared to never delirium (incident delirium 1.74 pg/ml (1.02–1.74) vs. prevalent 0.84 pg/ml (0.49–1.57) vs. never 0.66 pg/ml (0–1.02), Kruskal–Wallis p = 0.03). CSF:serum IL-1β ratios were higher in delirious than non-delirious patients. CSF IL-1ra was higher in prevalent delirium compared to incident delirium (prevalent delirium 70.75 pg/ml (65.63–73.01) vs. incident 31.06 pg/ml (28.12–35.15) vs. never 33.98 pg/ml (28.71–43.28), Kruskal–Wallis p = 0.04). GFAP was not increased in delirium. IFN-γ and IGF-1 were below the detection limit in CSF.

Conclusion

This study provides novel evidence of CNS inflammation involving the IL-1β family in delirium and suggests a rise in CSF IL-1β early in delirium pathogenesis. Future larger CSF studies should examine the role of CNS inflammation in delirium and its sequelae.     

Bradykinin antagonist counteracts the acute effect of both angiotensin-converting enzyme inhibition and of angiotensin receptor blockade on the lower limit of autoregulation of cerebral blood flow

The lower limit of autoregulation of cerebral blood flow (CBF) can be modulated with both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The influence of bradykinin antagonism on ARB-induced changes was the subject of this study. CBF was measured in Sprague–Dawley rats with laser Doppler technique. The blood pressure was lowered by controlled bleeding. Six groups of rats were studied: a control group and five groups given drugs intravenously: an ACE inhibitor (enalaprilat), an ARB (candesartan), a bradykinin-2 receptor antagonist (Hoe 140), a combination of enalaprilat and Hoe 140, and a combination of candesartan and Hoe 140. In the control group, the lower limit of CBF autoregulation was 54±9 mm Hg (mean±s.d.), with enalaprilat it was 46±6, with candesartan 39±8, with Hoe 140 53±6, with enalaprilat/Hoe 140 52±6, and with candesartan/Hoe 140 50±7. Both enalaprilat and candesartan lowered the lower limit of autoregulation of CBF significantly. The bradykinin antagonist abolished not only the effect of the ACE inhibitor but surprisingly also the effect of the ARB on the lower limit of CBF autoregulation, the latter suggesting an effect on intravascular bradykinin.     

Management of osteoporosis in rheumatoid arthritis patients

Introduction: In rheumatoid arthritis (RA) patients, the risk of both vertebral and non-vertebral fractures is roughly doubled, which is for an important part caused by inflammation-mediated amplification of bone loss and by immobilization. New treatments have become available in the last two decades to treat both RA and osteoporosis.

Areas covered: Epidemiology and assessment of osteoporosis and fracture risk (including the influence of RA disease activity and bone-influencing medications such as glucocorticoids), the importance of vertebral fracture assessment in addition to bone density measurement in patients with RA, the use of disease-modifying antirheumatic drugs and their effects on generalized bone loss, and current and possible future anti-osteoporotic pharmacotherapeutic options are discussed with special focus on RA.

Expert opinion: Assessment of osteoporosis in RA patients should include evaluation of the effects of disease activity and bone-influencing medications such as (the dose of) glucocorticoids, above standard risk factors for fractures or osteoporosis as defined by the FRAX instrument. Disease-modifying antirheumatic drugs are now well able to control disease activity using treat to target strategies. This lowering of disease activity by antirheumatic medications such as anti-TNF-α results in hampering of generalized bone loss; however, no fracture data are currently available. When treating osteoporosis in RA patients, additional focus should be on calcium supplementation, particularly in glucocorticoid users, and also on sufficient vitamin D use. Several anti-osteoporotic medications are now on the market; oral bisphosphonates are most commonly used, but in recent years, more agents have entered the market such as the parenteral antiresorptives denosumab (twice yearly) and zoledronic acid (once yearly), and the anabolic agent parathyroid hormone analogues. New agents, such as odanacatib and monoclonal antibodies against sclerostin, are now being tested and will most likely enlarge the possibilities of osteoporosis treatment in RA patients.     

Glucocorticoid safety for treating rheumatoid arthritis

Introduction: Glucocorticoids (GCs) are often used in the treatment of rheumatoid arthritis and many other inflammatory diseases. Besides strong favorable effects on disease activity, GCs can cause (serious) side effects as well.

Areas covered: Side effects of GCs that are ranked as most important by rheumatologists as well as by patients are bone loss and fractures, cardiovascular events, hypertension, and diabetes mellitus. In evaluating these side effects, confounding by indication is a disturbing factor: not only the use of GCs can increase the risk of several side effects, but so can the activity of the underlying disease, which in turn is related to the amount of GCs that is prescribed to the patient.

Expert opinion: Generally, side effects predominantly occur in patients with a high disease activity and when used in high doses and for a long period of time. For these patients, caution and monitoring are most warranted. However, monitoring is not only recommended in patients with a high disease activity, and high-dose or long-term use of GCs, but in all GC users, since side effects may also occur in patients treated with low-dose GCs. When detecting possible negative effects in time, they might be managed and serious damage due to side effects might hopefully be prevented.     

Estimation of 10-year risk of fatal cardiovascular disease and coronary heart disease in Iceland with results comparable with those of the Systematic Coronary Risk Evaluation project.

BACKGROUND: No data are available on the comparison between an absolute 10-year risk of fatal cardiovascular disease (CVD) and coronary heart disease (CHD) morbidity using the risk assessments of the Systematic Coronary Risk Evaluation (SCORE) project. DESIGN: Data from the prospective Reykjavik Study of 15,782 patients were used to estimate the 10-year risk of fatal CVD and CHD morbidity in Iceland. METHODS: Survival to fatal CVD event was defined as in the SCORE project. Survival to CHD morbidity was defined as having a myocardial infarction, coronary artery bypass graft, or angioplasty. The statistical methodology of SCORE was used. RESULTS: Relative risk in Iceland was comparable with SCORE results but baseline risk was similar to the low-risk version of SCORE, which contradicted previous suggestions for the countries of northern Europe. Correlation between absolute risk of CHD morbidity and risk for fatal CVD was high (r=0.96), resulting in similar ranking of individuals by risk and discriminatory capacity. This is the first published comparison between total fatal CVD risk and CHD morbidity in a population-based cohort using the current risk assessment guidelines of the European Societies on Coronary Prevention. CONCLUSIONS: Risk for fatal CVD in Iceland has the same characteristics as those in a European nation with results varying in accordance with the SCORE project. The risk estimate to be used, CHD morbidity or fatal CVD, is a choice of clinical preference. The data, however, suggest that 5% high-risk threshold of fatal CVD corresponds to a 12% CHD-morbidity risk, which is a significant change from the conventional reference value of 20%.     

Kaolin clotting time and dilute Russell's viper venom time distinguish between prothrombin-dependent and beta 2-glycoprotein I-dependent antiphospholipid antibodies

Antiphospholipid (aPL) antibodies include anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies. LA antibodies recognize the complex of lipid-bound (human) prothrombin, in this way inhibiting the phospholipid-dependent coagulation reactions, whereas aCL antibodies are directed towards beta 2-glycoprotein I (beta 2-GPI) bound to an anionic lipid surface. According to their behavior in coagulation reactions, we have divided aCL antibodies into two groups: aCL-type A, which inhibit the phospholipid-dependent coagulation reactions because they enhance the binding of beta 2-GPI to the procoagulant phospholipid surface; and aCL-type B antibodies, which are devoid of anticoagulant properties. We report the distinctive laboratory and clinical profiles of 25 patients with well-characterized, phospholipid-dependent inhibitor of coagulation. Fourteen patients had LA antibodies (aCL-type B were concomitantly present in 10 cases, while in the other four, aCL titer was normal), and the other 11 had aCL-type A antibodies. The laboratory evaluation of the two groups showed the dilute Russell viper venom time (dRVVT) to be the most abnormal coagulation test in the aCL- type A-positive group, whereas the kaolin clotting time (KCT) was the most abnormal assay in the LA-positive group. In fact, the ratios of the coagulation times of patient plasma over normal pooled plasma (mean +/- standard deviation) for LA versus aCL-type A antibodies were 1.48 +/- 0.27 versus 2.20 +/- 0.42, P = .0001, and 2.22 +/- 0.42 versus 1.50 +/- 0.42, P = .0003, for the dRVVT and KCT, respectively. No differences were observed either in the ratios of the activated partial thromboplastin times and the prothrombin times or the plasma levels of beta 2-GPI and prothrombin. Conversely, aCL titers were significantly higher in aCL-type A-positive patients (147 +/- 44 U) than in the LA- positive group (61 +/- 55 U; P = .0003). We ruled out the possibility that platelet contamination of plasma could account for the observed coagulation profiles, as the two patterns were reproduced in platelet- free plasma. In addition, we performed clotting tests in plasma in the presence of phospholipids and calcium after addition of factor IXa or factor Xa. The assay performed with factor Xa was more sensitive to the presence of aCL-type A antibodies, while the assay performed with factor IXa was preferentially sensitive to LA-containing plasmas, supporting the earlier findings with the dRVVT and KCT assays.(ABSTRACT TRUNCATED AT 400 WORDS)