Pulmonary function indices in children with sickle cell anemia in Enugu,south-east Nigeria

Objectives:

To determine the pulmonary function indices of children with sickle cell anemia (SCA) attending the pediatric sickle cell clinic at the University of Nigeria Teaching Hospital, Enugu, south-east Nigeria and to compare these indices with the results obtained from other regions.

Methods:

A case control study of lung function in children with SCA aged 6-20 years. The study was carried out in the University of Nigeria/University of Nigeria Teaching Hospital, Enugu State, Nigeria between October 2014 and January 2015. Measurements of the peak expiratory flow rate, forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were evaluated.

Results:

A total of 80 subjects were recruited into the study, comprising 40 homozygous HbSS (hemoglobin SS) patients and an equal number of controls. Children with SCA had statistically lower values of FEV1 (1.6±0.52), FVC (1.76±0.95), and peak expiratory flow rate (PEFR) (309.00±82.64) when compared with normal hemoglobin genotype FEV1 (12.01±0.53), FVC (2.12±0.54), and PEFR (364.10±87.85). The mean FVC, FEV1/FVC, and PEFR were also higher in the male control group compared with the HbSS male group, but these differences were not statistically significant. Female controls had significantly larger FEV1, FVC, and PEFR values compared with the HbSS females.

Conclusion:

The lung function indices were significantly lower in children and adolescents with SCA compared with the matched controls with a hemoglobin genotype AA.Sickle cell anemia (SCA) is a genetic hematological disorder characterized by red blood cells that assume an abnormal, rigid, sickle shape.1 This hereditary disorder contributes the equivalent of 3.4% mortality in children aged <5 years worldwide or 6.4% in Africa.2 The prevalence of SCA in Nigeria ranges from 0.4-3%.3 Approximately 85% of sickle cell disorders and >70% of all affected births occur in Africa.4 It is worth noting that at least 5.2% of the world population carry a significant trait. The clinical consequence of SCA results from obstruction of the microvasculature by the sickle cells and red blood cell hemolysis, which causes multi-systemic manifestation. The lungs are affected in a variety of ways by these pulmonary insults, and recurrence overtime may leave the lungs with chronic interstitial, parenchymal, or vascular damage that compromises pulmonary function.5,6 It has been documented that the prevalence of hypoxemia among SCA children was 13%.4 This prevalence was attributable to the chronic anemic state, micro vascular occlusion of the circulation by sickle hemoglobin, and constant pertubation of the endothelial membrane, and consequent elaboration of endothelial molecules, which are commonly seen among SCA children, especially those with various types of vaso-occlusive episodes.7 This is defined as bone and joint pain or multiple sites of pain needing analgesics or hospitalization.8 Acute and chronic pulmonary complications occur frequently in patients with SCA, and contribute to morbidity and mortality later in life. Although the pathogenesis of chronic pulmonary disease in sickle cell disease (SCD) has not been clearly defined, recurrent microvascular obstruction resulting in the development of pulmonary hypertension, endothelial dysfunction, and parenchymal fibrosis are probably the primary mechanisms.6 There is increasing evidence that repeated episodes of acute chest syndrome (ACS) may cause permanent damage to the pulmonary parenchyma and vasculature. Repeated attacks of ACS are a major risk factor for the development of sickle cell chronic lung disease. Studies of lung function in SCD have also demonstrated a restrictive defect,8,9 while a reduction in the total lung capacity (TLC) of 50% has been reported in advanced forms. Acute chest syndrome refers to a spectrum of pulmonary pathology having in common, chest pain, fever, dyspnea with abnormal clinical, and radiologic chest signs as well as leucocytosis.10,11 It is the most common cause of death in children with sickle cell anemia over 10 years of age.12 The etiology of ACS is not clear, lung and bone infarction, infection, and acute pulmonary sequestration, among other possible causes have been proposed.10 In children with sickle anemia in steady state, the major abnormality in pulmonary function is a restrictive pathology, characterized by a slight decrease in total lung capacity, with attendant ventilation perfusion mismatch.10 This can cause a defect in diffusion capacity for carbon monoxide.10 These abnormalities worsen with age and are associated with increases in pulmonary-artery pressures.11 Whereas some studies have documented impaired lung function in SCA (hemoglobin SS) patients,8-10 previous studies8-10 reported what appears to be contrasting findings when the lung function in children with SCA and those of healthy controls with normal hemoglobin genotype were compared. It is therefore necessary that ventilatory function studies be undertaken in this parts of the world to see if there is any difference with known values in other part of the world. In this study, we determine the impact of SCA on the pulmonary function indices in patients attending the pediatric sickle cell clinic at the University of Nigeria Teaching Hospital (UNTH) Enugu, south-east Nigeria and compare it with matched controls and other studies. Many studies have described and assessed the pattern of pulmonary function in SCD from childhood to adulthood, but much is not known on this topic in South Eastern Nigeria. Most of the original studies are from western Nigeria.13,14 This study could therefore corroborate or refute regional or ethnic differences in lung function in children with SCD. The study hypothesis seeks to answer the following questions? Do children with SCA attending UNTH Enugu present with any alteration in lung function? If they do, is there any gender and age difference? Are these lung volume findings similar to that obtained from other region?     

Effect of Age on Survival Benefit of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

OBJECTIVES: To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer.
DESIGN: Observational, retrospective cohort study using two samples: an overall sample of 7,182 patients to provide externally valid analyses and a propensity score–matched sample of 3,016 patients to provide more internally valid analyses by reducing the presence of treatment endogeneity. An interval-censored survival model with a complementary log-log link was used. Hazard ratios and 95% confidence intervals were obtained for all regressions.
SETTINGS: Data from the National Cancer Institute's Surveillance, Epidemiology and End Results database and the linked Medicare enrollment and claims database were used.
PARTICIPANTS: Selected patients were aged 66 and older and had a diagnosis of Stage III colon cancer. Patients were followed from surgery to time of death or censorship.
MEASUREMENTS: The outcome was colon cancer–specific death during the follow-up period. Receipt of adjuvant chemotherapy was measured according to the presence of a claim for 5-fluorouracil or leucovorin within 6 months after surgery.
RESULTS: All elderly patients had a significant survival benefit associated with adjuvant chemotherapy receipt, although the survival benefit of adjuvant chemotherapy was not uniform across all age groups.
CONCLUSION: These findings have important clinical and policy implications for the risk–benefit calculation induced by treatment in older patients with Stage III colon cancer. The results suggest that there is a benefit from chemotherapy, but the benefit is lower with older age.     

Specialist visits and initiation of cancer-directed treatment among a large cohort of men diagnosed with prostate cancer

Background

The urologist generally manages the treatment of men immediately following the diagnosis of prostate cancer (PCa). The role of other physician specialists in this setting is less clear. We investigated whether involvement of other physician specialty types immediately following diagnosis affects initiation of cancer-directed treatment.

Comparative and cost-effectiveness of oxaliplatin-based or irinotecan-based regimens compared with 5-fluorouracil/leucovorin alone among US elderly stage IV colon cancer patients

BACKGROUND:

Clinical trials have shown a statistically significant disease‐free survival benefit of oxaliplatin‐based or irinotecan‐based combination regimens for stage IV colon cancer. Less is known regarding the comparative effectiveness and cost‐effectiveness of these agents among elderly patients. Whether the benefits of these agents justify the additional costs for elderly Medicare recipients is particularly policy relevant after US health care reform.

METHODS:

A cost‐effectiveness analysis of oxaliplatin‐based or irinotecan‐based combination therapy versus 5‐fluorouracil/leucovorin alone in elderly stage IV colon cancer patients was performed from a US Medicare perspective. Survival and direct medical costs were estimated using Surveillance, Epidemiology, and End Results‐Medicare data sets for patients diagnosed from 2002 to 2005 with follow‐up through 2007. Incremental cost‐effectiveness ratios (ICERs) were calculated as costs per life‐year gained, with sensitivity analysis estimating the cost per quality‐adjusted life‐year (QALY).

RESULTS:

Median improved overall survival with 5‐fluorouracil/leucovorin alone, or irinotecan‐based or oxaliplatin‐based combination therapy was 0.99, 1.07, and 1.47 life‐years, respectively. Costs per life‐year gained for oxaliplatin‐based or irinotecan‐based combination regimens compared with 5‐fluorouracil/leucovorin alone were $78,181 and $267,938, respectively. ICERs comparing oxaliplatin‐based to irinotecan‐based regimens were $40,230 per life‐year gained or $160,920 per QALY.

CONCLUSIONS:

Oxaliplatin‐based or irinotecan‐based combination therapy improves overall survival but also substantially increases direct medical costs compared with 5‐fluorouracil/leucovorin alone when used in elderly US patients with stage IV colon cancer. Oxaliplatin‐based regimens are more cost‐effective than irinotecan‐based regimens for treatment of elderly stage IV colon cancer patients in terms of cost per life‐year gained, but not in terms of cost per QALY. Cancer 2012;118: 3173–81. © 2011 American Cancer Society.     

The potential impact of comparative effectiveness research on the health of minority populations

Minorities suffer more frequently and more severely from many diseases than do non-Hispanic whites, and they often receive lower-quality care, which leads to poorer health outcomes. Given the diversity of the US population, comparative effectiveness research should capture the health outcomes of racial and ethnic minority groups and investigate whether disparities reflect variations in care or different responses to treatment. We recommend a number of measures to ensure that this research addresses the needs of minorities, including greater attention to subgroup analysis. We also recommend the increased recruitment of minorities for clinical trials, and such measures as using community health workers to translate research results in ways that will increase their relevance to minority patients.     

Physician visits and the timing of skeletal-related events among men newly diagnosed with metastatic prostate cancer: A cohort analysis

Introduction

Men diagnosed with metastatic prostate cancer (PCa) are at increased risk for skeletal complications which are associated with significant morbidity and mortality. Although both the urologist and the medical oncologist play important roles in the management of patients with advanced PCa, there is limited information regarding their role in the context of skeletal complications. The current study investigated these relationships among newly diagnosed metastatic patients with PCa.