Issues in the epidemiology and population-based screening of primary angle-closure glaucoma

Among Caucasians, it is well known that 75-95% of primary glaucoma is due to open-angle glaucoma (POAG), with angle-closure (PACG) comprising only a very small minority of cases. These figures are reversed among other groups such as Asians and Eskimos, where PACG makes up 80-90% of primary glaucoma. Among Eskimos, the prevalence of PACG has been reported as 2-8%, as compared to 0.1% among Caucasians. It appears that a population tendency toward shallow anterior chambers may explain the excess burden of PACG morbidity. Among Asians, the prevalence of PACG is intermediate between Caucasians and Eskimos. Existing biometrical data do not show a clear tendency toward shallower anterior chambers among Asians. PACG may be screened for on a population basis by means of various techniques that estimate axial or limbal anterior chamber depth, measure intraocular pressure, or evaluate the optic disc or visual fields. Demographic information and medical and family history will also be of great importance in screening for PACG in large populations. Groups at increased risk for the disease include women, individuals over 50, first-degree relatives of PACG probands, and hyperopes.

Pupil constriction can alter the accuracy of dark room provocative test.

BACKGROUND: Primary angle-closure glaucoma (PACG) is a major cause of visual morbidity in East Asia. Dark-room provocative test (DRPT) has been used to determine which narrow angles have the risk to develop angle closure. However, the accuracy of DRPT might be altered because that after emerging from the dark room, the configuration of the angle is affected by the light of the slit-lamp and the appositionally closed angle reopens. The aim of this study was to examine the pupillary diameter in different light conditions and use it as a parameter to assess the accuracy of dark-room provocative test. METHODS: Patients with suspected primary angle-closure glaucoma undergoing DRPT were recruited. The anterior chamber angle was examined by anterior segment optical coherence tomography under the following conditions: (1) in standard room illumination; (2) after short-term dark-adaptation and (3) after DRPT. Mean values of pupil size and numbers of appositionally closed angle under different conditions were compared. RESULTS: A total of 47 eyes of 47 patients were analyzed. The pupil size after DRPT was smaller than that after short-term dark-adaptation (P < 0.001) and smaller than that in standard room illumination (P = 0.026). The numbers of appositionally closed angles after short-term dark-adaptation were significantly larger than those after DRPT (P < 0.001). There was no significant difference between the numbers of appositionally closed angles in standard room illumination and after DRPT (P = 0.157). CONCLUSIONS: Constriction of pupil size immediately after prolonged dark room provocative test may lead to change in the angle configuration, which may lead to false negative results. We suggest a modified protocol of recording intraocular pressure immediately after DRPT and performing gonioscopy following short-term dark adaptation to improve the accuracy of angle closure assessment.

Efficacy and Long-Term Outcomes of Palivizumab Prophylaxis to Prevent Respiratory Syncytial Virus Infection in Infants with Cystic Fibrosis in Northern Ireland

BACKGROUND: RSV causes considerable morbidity and mortality in children. In cystic fibrosis (CF) viral infections are associated with worsening respiratory symptoms and bacterial colonization. Palivizumab is effective in reducing RSV hospitalization in high risk patient groups. Evidence regarding its effectiveness and safety in CF is inconclusive. CF screening in N. Ireland enabled timely palivizumab prophylaxis, becoming routine in 2002.

OBJECTIVES: To determine the effect of palivizumab on RSV-related hospitalization and compare lung function and bacterial colonization at age 6 years for those born pre- and post-introduction of palivizumab prophylaxis.

METHODS: A retrospective audit was conducted for all patients diagnosed with CF during the period from 1997 to 2007 inclusive. RSV-related hospitalization, time to Pseudomonas aeruginosa (PA) 1st isolate, lung function and growth parameters were recorded. Comparisons were made for outcomes pre- and post-introduction of routine palivizumab administration in 2002. A cost evaluation was also performed.

RESULTS: Ninety-two children were included; 47 pre- and 45 post-palivizumab introduction. The overall RSV-positive hospitalization rate was 13%. The relative risk of RSV infection in palivizumab non-recipients versus recipients was 4.78 (95%CI: 1.1-20.7), P = 0.027. Notably, PA 1st isolate was significantly earlier in the palivizumab recipient cohort versus non-recipient cohort (median 57 vs. 96 months, P < 0.025) with a relative risk of 2.5. Chronic PA infection at 6 years remained low in both groups, with similar lung function and growth parameters. Total costs were calculated at £96,127 ($151,880) for the non-recipient cohort versus £137,954 ($217,967) for the recipient cohort.

CONCLUSION: Palivizumab was effective in reducing RSV-related hospitalization infection in CF patients. Surprisingly, we found a significantly earlier time to 1st isolate of PA in palivizumab recipients which we could not explain by altered or improved diagnostic tests. 

Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome

Sepsis is a common condition that is associated with significant morbidity, mortality and health-care cost. Pulmonary and non-pulmonary sepsis are common causes of the acute respiratory distress syndrome (ARDS). The mortality from ARDS remains high despite protective lung ventilation, and currently there are no specific pharmacotherapies to treat sepsis or ARDS. Sepsis and ARDS are characterised by activation of the inflammatory cascade. Although there is much focus on the study of the dysregulated inflammation and its suppression, the associated activation of the haemostatic system has been largely ignored until recently. There has been extensive interest in the role that platelet activation can have in the inflammatory response through induction, aggregation and activation of leucocytes and other platelets. Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS. This review will discuss the role of the platelet, the mechanisms of action of aspirin in sepsis and ARDS, and aspirin as a potential therapy in treating sepsis and ARDS.

Change in psychological distress in longer-term oesophageal cancer carers: are clusters of illness perception change a useful determinant?

Objective: This study provides a longitudinal assessment of distress in longer-term oesophageal cancer carers, while examining illness perception schema as a possible determinant of change in distress over time.
Methods: Oesophageal cancer carers (n=171), 48-months post-diagnosis, were assessed at baseline and 12-months later with the Illness Perception Questionnaire-Revised, Cancer Coping Questionnaire, Hospital Anxiety and Depression Scale and Concerns About Recurrence Scale.
Results: Findings report deterioration from normal to probable anxiety in 35.7% of carers and probable depression in 28.7% carers over time. Fear of recurrence remained stable. Changes in control, consequence and cause beliefs were identified as key determinants of a change in psychological morbidity.
Conclusions: Illness beliefs appear to be valuable targets for psychological intervention to improve wellbeing among carers of people with oesophageal cancer.

Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial

BACKGROUND: In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10 %), 6-month mortality and relapse (6 %). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted.

METHODS/DESIGN: TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness.

DISCUSSION: If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented.

Persistent endothelial activation and inflammation after Plasmodium falciparum Infection in Malawian children

Endothelial dysregulation is central to the pathogenesis of acute Plasmodium falciparum infection. It has been assumed that this dysregulation resolves rapidly after treatment, but this return to normality has been neither demonstrated nor quantified. We therefore measured a panel of plasma endothelial markers acutely and in convalescence in Malawian children with uncomplicated or cerebral malaria. Evidence of persistent endothelial activation and inflammation, indicated by increased plasma levels of soluble intracellular adhesion molecule 1, angiopoetin 2, and C-reactive protein, were observed at 1 month follow-up visits. These vascular changes may represent a previously unrecognized contributor to ongoing malaria-associated morbidity and mortality.

The spectrum of paediatric cardiac disease presenting to an outpatient clinic in Malawi

BACKGROUND: As progress is made towards attaining Millennium Development Goal 4, further reductions in paediatric mortality will only be achieved by concentrating on the burden of non-communicable or neglected diseases. The literature relating to paediatric cardiac disease in sub-Saharan Africa is sparse. There are no published descriptions of paediatric cardiac disease from Malawi, making it impossible to estimate the contribution it makes to childhood morbidity and mortality.

FINDINGS: In 2008, a paediatric cardiac clinic with echocardiogram scanning was established in Blantyre, southern Malawi. Between January 2009 and February 2011, the age and cardiac diagnosis of every child with an abnormal echocardiogram was recorded in a database. Of 250 children, 139 (55.6%) had congenital heart disease, and 111 (44.4%) acquired heart disease. Ventricular septal defect (VSD) (24%), Tetralogy of Fallot (10%) and patent ductus arteriousus (7.2%) were the commonest forms of congenital heart disease. Rheumatic heart disease (RHD) (22.4%) and dilated cardiomyopathy (13.6%) were the commonest acquired diseases. The mean age of presentation was 3 years 2 months for VSD and 11 years 6 months for RHD.

CONCLUSIONS: In this cohort of children from one centre in Malawi, acquired heart disease - in particular rheumatic heart disease was almost as common as congenital heart disease. Most presented late. It is likely that untreated cardiac disease causes a large number of childhood deaths in Malawi. In addition to renewing secondary preventative efforts against rheumatic heart disease, adequate and accessible cardiothoracic surgical services should be established at a regional level.

Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Novel methods of drug administration for the treatment and care of older patients

The number of older people globally is increasing, contributing to a growing burden of morbidity and mortality. With this shift in population demographic, comes a new challenge in terms of appropriate healthcare for the over 65 years age group. As medication is the principal therapeutic intervention, it is essential that it be fully optimised, to meet the needs of this heterogeneous population. The most common routes of drug administration are oral and injectable, which may display some limitations for older people, in cases of dysphagia or frailty for example. This review considers alternative methods of drug delivery to the norm, specifically discussing the nasal, pulmonary and transdermal routes, as well as novel orally disintegrating tablets. The changing physiology as ageing occurs must be considered in the development of novel drug delivery devices. This review considers the various aspects of ageing that will influence future drug formulation design and development.

Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes.
OBJECTIVES: To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes.
SEARCH STRATEGY: We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity.
MAIN RESULTS: A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful.
CONCLUSIONS: Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy.

Burden of Cancer in a Large Consortium of Prospective Cohorts in Europe

BACKGROUND: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium.

METHODS: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes.

RESULTS: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%).

CONCLUSIONS: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden.