The Effect of Hydroxyurea Therapy on Adverse Clinical Events and Haematological Indices in Paediatric Patients with Sickle Cell Anaemia / Efecto de la Terapia con Hidroxiurea en los Eventos Clínicos Adversos y los Indices Haematológicos de Pacientes Paediátricos con Aanemia de Células Falciformes

ABSTRACT Objective: The aim of this study was to determine the effect of hydroxyurea on adverse clinical events and haematological indices in paediatric patients with sickle cell anaemia. Method: This study compared the same cohort of patients before and after hydroxyurea therapy, monitoring the rate of adverse events, pre- and post-treatment and haematological indices. Results: Of the 40 patients, the incidence rate of painful crises post-treatment was 80% lower than pre-treatment. Post-treatment incidence rates of painful crises managed at home, requiring emergency department care or requiring admission to the ward were also lower - 79%, 81% and 84%, respectively. There was no significant difference in the incidence of other clinical events. The haemoglobin concentration increased within the first month and plateaued while the mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) continued to increase until six months before plateauing out. The white blood cell count (WBC) and absolute neutrophil count (ANC) decreased over the first month before levels stabilized. The reticulocyte percentage and the absolute reticulocyte count (ARC) decreased over the first three months before plateauing while the platelet count remained stable. Conclusion: Hydroxyurea significantly reduced the incidence of painful crises. There were significant increases in haemoglobin, MCV and MCHC with decreases in WBC, ANC, ARC, and reticulocyte percentage while the platelet count remained relatively stable.

RESUMEN Objetivo: El objetivo de este estudio fue determinar el efecto de la hidroxiurea sobre los eventos clínicos adversos y los índices hematológicos en pacientes pediátricos con anemia falciforme. Método: Este estudio comparó una misma cohorte de pacientes antes y después del tratamiento con hidroxiurea, monitoreando la tasa de eventos adversos, el tratamiento previo y posterior, y los índices hematológicos. Resultados: En los 40 pacientes, la tasa de incidencia de postratamiento de crisis dolorosas fue 80% inferior a la del pretratamiento. Las tasas de incidencia de postratamientos de crisis dolorosas que fueron tratadas en el hogar, atendidas en el departamento de emergencias, o requirieron ingreso hospitalario, fueron también menores -79%, 81%y 84%, respectivamente. No hubo diferencias significativas en la incidencia de otros eventos clínicos. La concentración de hemoglobina aumentó en el primer mes y se estabilizó, mientras que el volumen corpuscular medio (VCM) y la concentración de hemoglobina corpuscular media (CHCM) continuaron aumentando hasta seis meses antes de estabilizarse. nivelarse. El conteo de glóbulos blancos (CGB) y el conteo absoluto de neutrófilos (CAN) disminuyeron durante el primer mes antes de que los niveles se estabilizaran. El porcentaje de reticulocitos y el conteo absoluto de reticulocitos (CAR) disminuyeron durante los primeros tres meses antes de estabilizarse, mientras que el conteo de plateletas permaneció estable. Conclusión: La hidroxiurea redujo significativamente la incidencia de crisis dolorosas. Hubo aumentos significativos de hemoglobina, VCM y CHCM con disminuciones de CGB, CAN, CAR, y porcentaje de reticulocitos mientras que el conteo plaquetario permaneció relativamente estable.

Psoriatic Arthritis: An Assessment of Clinical; Biochemical and Radiological Features in a Single-Centre South African Cohort

BACKGROUND:Although psoriatic arthritis (PsA) is a well-documented clinical entity; epidemiological; clinical and radiological studies of South African (SA) patients are scarce.OBJECTIVES:To assess clinical; biochemical and radiological features in a single-centre SA cohort.METHODS: We conducted a prospective assessment of the clinical; biochemical and radiological features of 384 consecutive patients with PsA seen at the rheumatology clinic at Prince Mshiyeni Memorial Hospital; Durban; SA; between January 2007 and December 2013. Patients were assessed at enrolment and 6 months after enrolment. They were classified into five groups as described by Moll and Wright; being entered into the group that best described the clinical manifestations. Clinicopathological characteristics recorded at enrolment were age at the time of examination; racial background; personal and family medical history; age and symptoms at the onset of PsA; pattern of joint involvement; joint pain; and the relationship between joint pain and the onset of PsA.RESULTS:Of the patients; 59.1% had a polyarticular presentation indistinguishable from rheumatoid arthritis; 19.0% had distal interphalangeal involvement; 9.1% had spondyloarthropathy; 11.9% had oligoarthritis and 0.9% had arthritis mutilans. The epidemiological trends (male/female ratio 1.45:1; mean age at onset of arthritis 50.2 (standard deviation 11.8) years; female preponderance in the polyarticular group and male preponderance in the spondyloarthropathy and oligoarticular groups) were similar to trends published elsewhere. A notable characteristic of our cohort was the complete absence of black South Africans with PsA.CONCLUSIONS:The complete absence of black South Africans with PsA is interesting. We anticipate that our findings will prompt genetic studies to isolate both protective and susceptibility genes for further elucidating PsA

C-reactive protein: adjunct to cardiovascular risk assessment / Proteína C reactiva: complemento para la evaluación del riesgo cardiovascular

OBJECTIVES: The study aimed to investigate whether elevated plasma high sensitivity C-reactive protein (hs-CRP) levels are independently associated with an increased risk of cardiovascular disease (CVD) and to then assess the effectiveness of the addition of hs-CRP testing to cardiovascular risk assessment by standard lipid screening. METHODS: A retrospective hospital-based case-control study was designed. All patients attending Cross Crossing Medical Centre (CCMC) for routine cardiovascular assessment or emergency treatment were included. Cases were defined as patients with a cardiovascular event and controls as those without an event. Data collected included blood measurements of hs-CRP and cholesterol, demographic data, drug and risk factor history. RESULTS: Odds ratio of 1.84 (95% CI 1.00, 3.38) indicated that a patient with elevated hs-CRP is 1.84 times more at risk of CVD than one with normal hs-CRP. Additionally, the association between hs-CRP and CVD was found to be independent of the other risk factors (p = 0.058). Hs-CRP ranked fourth as an indicator of risk above smoking and diabetes, and patients with both high hs-CRP and high cholesterol (OR = 9.5) were 3.5 times more at risk of CVD than someone with high cholesterol alone (OR = 6.0). CONCLUSIONS: Hs-CRP testing enhanced the clinical identification of patients at risk of cardiovascular events. It can therefore contribute to timely implementation of effective lifestyle modification and pharmaceutical intervention.

OBJETIVOS: El estudio apuntó a investigar si los niveles de proteína C reactiva (PCR-hs) de alta sensibilidad de plasma elevado están independientemente asociados con el aumento del riesgo de la enfermedad cardiovascular (ECV), y luego evaluar la efectividad de añadir la prueba PCR-hs para la evaluación del riesgo cardiovascular mediante detección (screening) estándar de lípidos. MÉTODOS: Se diseñó un estudio caso-control retrospectivo con sede en el hospital. En el mismo fueron incluidos todos los pacientes que asistían al Centro Médico Cross Crossing (CCMC) para una evaluación cardiovascular de rutina o para tratamiento de urgencia. Los casos fueron definidos como pacientes con controles y eventos cardiovasculares, o sin un evento. Los datos recogidos incluyeron mediciones sanguíneas de PRC-hs y colesterol, datos demográficos, historia de factores de riesgo y de drogas. RESULTADOS: El odds ratio de 1.84 (95% CI 1.00, 3.38) indicó que un paciente con PCR-hs elevado tiene un riesgo de ECV 1.84 veces mayor que uno con PCR-hs normal. Además, se halló que la asociación entre el PCR-hs y la ECV era independiente de los otros factores de riesgo (p = 0.058). La PCR-hs alcanzó el cuarto lugar como indicador de riesgo, por encima del hábito de fumar y la diabetes, y los pacientes con alto PCR-hs y alto colesterol (OR = 9.5) presentaban riesgo de ECV 3.5 veces mayor que aquellos que sólo tenían colesterol alto (OR = 6.0). CONCLUSIONES: Las pruebas de PCR-hs mejoraron la identificación clínica de pacientes con riesgo de eventos cardiovasculares. Por lo tanto, estas pruebas pueden contribuir a implementar oportunamente una modificación para un estilo de vida y una intervención farmacéutica que sean efectivos.

Natural immunity to rotavirus infection in children.

Annual deaths in infants and young children due to rotavirus (RV) infection are around 100,000 in India and about 600,000 globally. Development of a vaccine for this disease is a high priority. The protective mechanisms for RV diarrhea in human are not fully understood, but it is known that children develop natural immunity against RV. Early exposure to RV results in most severe episode of diarrhea and subsequent infections are milder or asymptomatic. Of the immune responses measured during natural infection, RV-specific antibodies have been well documented, whereas data on cellular immunity in humans are sparse. It is generally thought that two outer capsid proteins VP4 and VP7 play a critical role in protective immunity by stimulating production of neutralizing antibodies. While serotype- specific protection mediated by antibodies directed against the outer capsid proteins may be a mechanism of protection, such a correlate for protection has been difficult to demonstrate in humans during clinical trials. Increasing evidences suggest that viral proteins that lack a capacity of eliciting neutralizing antibody response also induce protective immunity. Limited efforts have focused on the role of non-structural proteins in protective immunity. This review describes current understanding of antibody responses in children with focus on responses specific to viral antigens with their possible role in protective immunity. We have also briefly reviewed the responses elicited to non-antibody effectors during RV infection in human subjects.

Effect of zinc added to multi-vitamin supplementation containing low-dose vitamin A on plasma retinol level in children--a double-blind randomized, controlled trial.

In a community-based double-blind randomized trial in children aged 6-35 months, both intervention and control groups received a multi-vitamin syrup containing vitamin A, while the intervention group had zinc gluconate (equivalent to 10 mg of elemental zinc) additional in the syrup. There was a significant decrease in diarrhoea and pneumonia in the intervention group. This study was undertaken to investigate if addition of zinc to vitamin A had improved plasma retinol levels, which, in turn, was responsible for the effects observed in the intervention group. In a randomly-selected subsample of 200 children--100 each from the intervention and the control group, plasma retinol levels after 120 days of supplementation were measured. There was no difference in the mean plasma retinol levels [the difference in the mean 0.46 microg/dL (95% confidence interval -1.42-2.36)] between the two groups following supplementation. No difference in plasma retinol levels was observed in the subgroups based on base-line nutritional status and plasma zinc levels. Addition of zinc to low-dose vitamin A in this study did not improve the vitamin A status of children and cannot explain morbidity effects of the intervention.

A cost-benefit analysis of typhoid fever immunization programmes in an Indian urban slum community.

Many economic analyses of immunization programmes focus on the benefits in terms of public-sector cost savings, but do not incorporate estimates of the private cost savings that individuals receive from vaccination. This paper considers the implications of Bahl et al.'s cost-of-illness estimates for typhoid immunization policy by examining how community-level incidence estimates and information on distribution of costs of illness among patients and the public-health sector can be used in the economic analysis of vaccination-programme options. The findings illustrate why typhoid vaccination programmes may often appear to be unattractive to public-health officials who adopt a public budgetary perspective. Under many plausible sets of assumptions, public-sector expenditure on typhoid vaccination does not yield comparable public-sector cost savings. If public-health officials adopt a societal perspective on the economic benefits of vaccination, there are many situations in which different vaccination programmes will make economic sense. The findings show that this is especially true when public decision-makers recognize that (a) the incidence of typhoid fever is underestimated by blood culture-positive cases and (b) avoided costs of illness represent a significant underestimate of the actual economic benefits to individuals of vaccination.

Costs of illness due to typhoid fever in an Indian urban slum community: implications for vaccination policy.

Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to facilitate the use of available anti-typhoid vaccines in developing countries. This one-year prospective surveillance was carried out in an urban slum community in Delhi, India, to estimate the costs of illness for cases of typhoid fever. Ninety-eight culture-positive typhoid, 31 culture-positive paratyphoid, and 94 culture-negative cases with clinical typhoid syndrome were identified during the surveillance. Estimates of costs of illness were based on data collected through weekly interviews conducted at home for three months following diagnosis. Private costs included the sum of direct medical, direct non-medical, and indirect costs. Non-patient (public) costs included costs of outpatient visits, hospitalizations, laboratory tests, and medicines provided free of charge to the families. The mean cost per episode of blood culture-confirmed typhoid fever was 3,597 Indian Rupees (US$ 1=INR 35.5) (SD 5,833); hospitalization increased the costs by several folds (INR 18,131, SD 11,218, p<0.0001). The private and non-patient costs of illness were similar (INR 1,732, SD 1,589, and INR 1,865, SD 5,154 respectively, p=0.8095). The total private and non-patient ex-ante costs, i.e. expected annual losses for each individual, were higher for children aged 2-5 years (INR 154) than for those aged 5-19 years (INR 32), 0-2 year(s) (INR 25), and 19-40 years (INR 2). The study highlights the need for affordable typhoid vaccines efficacious at 2-5 years of age. Currently-available Vi vaccine is affordable but is unlikely to be efficacious in the first two years of life. Ways must be found to make Vi-conjugate vaccine, which is efficacious at this age, available to children of developing-countries.

Pathways to infant mortality in urban slums of Delhi, India: implications for improving the quality of community- and hospital-based programmes.

The study aimed at obtaining insights into the processes underlying infant deaths to help identify preventive interventions which may bring down infant mortality rates further. Verbal autopsies were performed on 162 deaths of liveborn infants that occurred in a birth cohort in two urban slums of Delhi, India, between February 1995 and August 1996. A structured verbal autopsy form was used for ascertaining the cause of death. The narratives of caretakers on seeking of care and treatment received for illness were reviewed to identify the actions and behaviours that might have contributed to death. Seeking of care was less common (57%) for illnesses that led to death in the first week of life than at later ages. The first-week deaths commonly (61%) occurred within 24 hours of recognition of illness which might have been too a short time for effective interventions by care providers. Only six of 45 neonates who had features of sepsis, pneumonia or meningitis, major congenital malformations, birth asphyxia, or prematurity were advised by primary care providers for hospitalization. Similarly, only 25 (41%) of 61 older infants who had severe malnutrition and sepsis or meningitis, diarrhoea or pneumonia, or other illnesses were referred to hospital. Parenteral antibiotics were prescribed less often than warranted. Only two of 16 neonates with serious bacterial infections and eight of 19 postneonates with features of sepsis or meningitis received parenteral antibiotics. Inappropriate healthcare practices were common among the practitioners of modern and indigenous systems of medicine and registered medical practitioners. Forty percent of the neonates and a little over half of the older infants, advised for hospitalization, were taken to hospital. Fifteen percent of the infants taken to hospital were refused admission. Of 21 hospitalized infants discharged alive, five (23%) died within 48 hours and 13 (62%) within a week of returning home. A major effort is required to improve skills of healthcare providers of the biomedical and indigenous systems of medicine in caring for neonates and infants. Development of home-based treatment regimens for young infants and objective criteria for their hospitalization and discharge should receive a high priority.

Ataxia Telangiectasia. A case report

The case of an eight year old girl with Ataxia Telangiectasia (AT) is described. She presented at seven years of age with gait problems and was found to have the neurological, dermatological and immunological features characteristic of AT along with a history of frequent sino-pulmonary infections. This report highlights the refractory nature of the disease, the difficulties in medical management, and the problems posed by late diagnosis which can compromise patient care. This is a rare inherited form of ataxia which has not been previously reported in West Indian literature.

Life-stress events, depression and purpose-in-life in first-admission alcoholics and members of Alcoholics Anonymous

The relationship between alcoholism, depression, life-stress events and purpose-in-life is a very complex one. Thirty-five first admission alcoholics and an equal number of members of Alcoholics Anonymous were assessed, using objective measures of acoholism, depression, stress and purpose-in-life. The results indicate that there were significant differences between the twogroups on drinking behaviour, depression and purpose-in-life. No differences were found between the groups on the stress questionnaire. Positive correlations were found between drinking behavour and depression,life events and purpose-in-life