Sickle cell disease-related organ damage occurs irrespective of pain rate: implications for clinical practice

In daily clinical practice, the frequency of painful crises (pain rate) is an important parameter of sickle cell disease severity. We assessed the prevalence of sickle cell disease-related organ damage and complications and their relation to pain rate. Organ damage and history of vaso-occlusive complications were obtained via systematic screening of consecutive patients and by chart review. In 104 adult sickle cell patients pain rate was related to a history of acute chest syndromes, avascular osteonecrosis, iron overload, priapism and cholelithiasis. However, major disease-related complications, such as microalbuminuria and pulmonary hypertension, were detected in 23% and 24% respectively of patients without painful crises in the study period underlining the importance of systematic screening for developing organ damage in sickle cell patients irrespective of pain rate.     

Homozygous sickle cell disease in patients above 20 years of age: follow-up of 108 patients in Dakar

CONTEXT: The progress realized in the treatment of sickle cell anemia has resulted to a better and longer life for these patients in developed countries. Ongoing challenge are to manage complication and social living for these patients. The purpose of this study was to determine morbidity, mortality and socioprofessional insertion of homozygous sickle cell patients, followed up in Dakar university hospital. PATIENTS AND METHODS: We performed a longitudinal and prospective study including 108 homozygous sickle cell anemia patients, whose age were above 20 years, followed in a regular basis (at least 3 times per year), during 5 years on average (3 to 12 years). All patients had a quarterly hematological check-up and a annual statement to detect chronic complications. Clinic and paraclinical data, as information in socioprofessional insertion were noted in medical records for analysis. RESULTS: Mean age was 27 years (20-51 years). The age between 20-29 years was represented by 67.5%, 26.9% aged 30-39 years and 5.6% were above 40 years of age. Men were slightly predominant with a sex-ratio of 1.25. Concerning morbidity, 96.3% of patients had at least 1 vaso-occlusive crisis per year, 26.9% were transfused and 64.8% had been hospitalized during the follow-up. A chronic complication was found in 49% of patients (53/108). The more frequent of these complications were gall stone (10%), femoral head necrosis (9.2%), priapism (11.6% of men), chronic leg ulceration (4.6%), ophthalmic involvement (3.7%), renal and cardiac complications (2.7% for each one). The presence of complications was not significantly influenced by patient's sex. Five patients died during a mean follow-up of 5 years. Concerning school attendance, 13% reach university level whereas 47% stop their education on the secondary level and 40% on primary level. Professionally, 36.2% of patients had no exercise any activity. CONCLUSION: Our results emphasize that life expectancy can be prolonged in sickle cell anemia patients in Africa, when they have a benefit of a regular follow-up. We show also the respective frequency of chronic complications and then, the necessity of multidisciplinary teams to optimize the take care of sickle cell anemia patients in Africa.     

Is the Medical Home for Adult Patients with Sickle Cell Disease a Reality or an Illusion?

Abstract

Recently, the patient-centered medical home (PCMH) emerged as a viable method to improve delivery of medical care. Due to all the promotion about the effectiveness of the PCMH, patients with sickle cell disease, their families and the community hoped that this could be a possible solution to the problems that arise in the treatment of adult patients with sickle cell disease. Review of the literature and review of the criteria for the establishment of a PCMH show that the PCMH is not an ideal model for patients with sickle cell disease because finding a personal physician, which is the first criteria of a functional PCMH, is a major problem in the process of transitioning the care of patients with sickle cell disease from pediatrics to adult care. Moreover, garnering hospital support to defray the initial costs to establish a PCMH for adults with sickle cell disease is unlikely given the already high costs of care for patients with sickle cell disease. Moreover, recent studies have shown insufficient evidence to determine the presumed beneficial effects of the PCMH, especially in patients with chronic disease.     

Mortality and causes of death in children with sickle cell disease in the Netherlands, before the introduction of neonatal screening

This study analyzed the mortality and causes of death in sickle cell disease patients in the Netherlands, to provide a baseline for monitoring the effect of the recently introduced neonatal screening programme and to indicate areas of improvement in the care for these patients. All children (<18 years) diagnosed with sickle cell disease in a tertiary hospital from 1985 to 2007 were included. Vital status was determined up to March 2008. A total of 298 children were included: 189 (63%) patients had HbSS, 17 (6%) HbSβ(0) thalassaemia, 72 (24%) HbSC and 20 (7%) HbSβ(+) thalassaemia. Twelve patients (4%) died during a total follow-up of 3896 patient years. All known deaths were sickle cell disease-related. Meningitis/sepsis (n=4; 33%), stroke (n=3; 25%) and death during a visit to the country of origin (n=3; 25%) were the most common causes of death. The overall mortality rate was 0·27 deaths/100 patient years [95% confidence interval (CI): 0·15-0·43]. The estimated survival at the age of 18 years was 97·3% (95% CI: 95-99%). This report confirms that the burden of mortality in sickle cell disease is increasingly shifting to adults. It is recommended that compliance to antibiotic prophylaxis, thorough counselling and support for patients travelling abroad and specialized peri-operative care should receive continuous attention.     

Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality

OBJECTIVE: To determine the incidence, clinical course, and risk factors associated with the onset of chronic renal failure in sickle cell anemia and sickle C disease. DESIGN: A prospective, 25-year longitudinal demographic and clinical cohort study. A matched case-control study was conducted to determine risk factors. PATIENTS: A total of 725 patients with sickle cell anemia and 209 patients with sickle C disease who received medical care from the hematology service in a large municipal hospital. Most were observed from birth or early childhood. MEASUREMENTS: Thirty-six patients developed sickle renal failure: 4.2% of patients with sickle cell anemia and 2.4% of patients with sickle C disease. The median age of disease onset for these patients was 23.1 and 49.9 years, respectively. Survival time for patients with sickle cell anemia after the diagnosis of sickle renal failure, despite dialysis, was 4 years, and the median age at the time of death was 27 years. Relative risk for mortality was 1.42 (95% Cl, 1.12 to 1.81; P = 0.02) compared with patients who did not develop renal insufficiency. MAIN RESULTS: Histopathologic studies showed characteristic lesions of glomerular "drop out" and glomerulosclerosis. Case-control analysis showed that ineffective erythropoiesis with increasingly severe anemia, hypertension, proteinuria, the nephrotic syndrome, and microscopic hematuria were significant pre-azotemic predictors of chronic renal failure. The risk for sickle renal failure was increased in patients who had inherited the Central African Republic beta s-gene cluster haplotype. CONCLUSIONS: The pre-azotemic manifestations of hypertension, proteinuria, and increasingly severe anemia predict end-stage renal failure in patients with sickle cell disease. The rate of progression of renal insufficiency is genetically determined. Treatment of the uremic phase has been dismal, underscoring the need for the development of useful pre-azotemic therapeutic modalities.     

Reasons for admission of individual with diabetes to the Tripoli Medical Center in 2015

BackgroundDiabetes mellitus is a complex, chronic, metabolic disease manifested in hyperglycemia and associated with various complications, Consequently, people with diabetes have higher rates of hospital admissions than the general population. There is little information about the burden of hospitalizations of diabetic patients in Libya.AimThe aim was to identify the causes of admission of individual with diabetes and to identify the risk factors for hospitalization.Patients and methodsThis is a retrospective case-series study conducted in Tripoli Medical Center, Tripoli. It covers 1037 individual with diabetes admitted between 1 January 2015 and 31 December 2015. All the data were collected from the patient files.ResultsThe mean age of the patients was 60.7 years ±15.1 standard deviation. The male-to-female ratio was 1:1. Type 2 diabetes accounted for 90.2% of the patients, 56.5% of whom had diabetes for >10 years, 40.5% had no prior chronic illness, 26.7% had hypertension, and 26.4% had multiple co-morbidities. The mean hospital stay was 6.1 days, and 60.8% of the patients were on insulin therapy. The main causes of admission were infection (23%), mainly in the chest, followed by lower extremity disease (22.4%), cardiovascular disease (19.3%), cerebrovascular disease (14.4%) and renal disease (11.8%).ConclusionsThe main causes of hospitalization as shown by this study were infections, and chronic complications of diabetes in the lower extremities and cardiovascular system. Most of the patients were >60 years old, had diabetes type 2 for >10 years, were on insulin treatment, and had no other comorbidity.     

Anemia is Associated with Bone Mineral Density in Chronic Obstructive Pulmonary Disease

Abstract

Objective: Patients with chronic obstructive pulmonary disease (COPD) often suffer from systemic co-morbidities, including anemia. However, anemia is related to multiple outcomes in COPD and in other chronic diseases, but it's impact is underestimated in COPD. The objective of the present study was to relate anemia in patients with COPD with disease-related outcomes, systemic inflammation and COPD related co-morbidities. Methods: Data of 321 patients with COPD admitted for pulmonary rehabilitation were analysed. Besides general characteristics, lung function, body composition, arterial gases and plasma haemoglobin concentration, disease-related outcomes (health-related quality of life by St. George's Respiratory Questionnaire, 6-minute walking distance, mMRC dyspnea scale, and BODE index), systemic inflammation (C-reactive protein (CRP)) and self-reported and objectified co-morbidities (low muscle mass, osteoporosis, renal failure, risk for undernutrition) were taken into account. Results: First, 20% of the patients were anemic, and 8% was polycythemic. Polycythemic patients had a lower proportion of men and a lower proportion of low muscle mass compared to the other groups. Anemic patients had higher plasma CRP levels and lower total body bone mineral density compared to the other groups. There was no difference in disease-related outcomes or other co-morbidities in the patients with and without anemia. Even after adjustment for confounders, anemia was an independent determinant for higher CRP levels and lower bone mineral density. Conclusion: Anemia is frequently present in patients with COPD and there is evidence that it is associated with lower whole body bone mineral density.     

Risk factor management of type 2 diabetic patients in primary care in the Scandinavian countries between 2003 and 2015

AimsTo observe and report population demography, comorbidities, risk factor levels and risk factor treatment in a sample of individuals treated for type 2 diabetes in primary care in Norway, Sweden and Denmark.MethodsRetrospective observational cohort using extraction of data from electronic medical records linked with national health care registries.ResultsSixty primary care clinics participated with annual cross-sectional data (2003 to 2015). In 2015 the sample consisted of 31,632 individuals. Mean age (64.5–66.8 years) and proportion of women (43–45%) were similar. The prevalence of cardiovascular disease in 2015 was 40.7%, 41.6% and 38.0% for Norway, Sweden and Denmark, respectively and 84% to 89% of patients were receiving a pharmacological anti-diabetic treatment. More Danish patients reached targets for HbA_1c and LDL cholesterol, while more patients in Sweden and Denmark met the blood pressure target of <130/80 mmHg as compared to Norway.ConclusionsIn three comparable public primary health care systems we found a high prevalence of cardiovascular disease and differences in risk factor treatment and attainment of risk factor goals. With recent guideline changes there is potential for further prevention of diabetes complications in primary care in the future.     

Challenge of Managing Sickle Cell Disease in a Pediatric Population Living in Kinshasa,Democratic Republic of Congo: A Sickle Cell Center Experience

In the Democratic Republic of Congo (DRC), sickle cell disease is not yet really regarded as a health care priority. The patterns of sickle cell disease in patients living in Kinshasa, DRC are discussed and the difficulties encountered in their management are highlighted. The cross-sectional survey is of sickle cell patients and their families attending the Centre de Médecine Mixte et d’Anémie SS de Yolo (CMMASS), Kinshasa, DRC, between January and April 2009. Completed questionnaires were received from 168 respondents (111 girls; 57 boys). Seventy-one percent of the subjects were diagnosed before the age of 2 years but none in the neonatal period. Sickle cell disease was diagnosed in 54.8% of the patients after they had suffered pain crises. Of the 168 subjects, 74.0% had previously received blood transfusions. Seventy-five (45.0%) had more than three severe pain crises per year. A minority of 35.0% reported that they regularly took an antibioprophylaxis. Seventy-five (45.0%) subjects were eligible for hydroxyurea (HU) therapy but in all cases this drug was taken irregularly. Eighty-two percent of drugs were purchased by the parents. One hundred and sixty-three children (97.0%) were vaccinated according to the Expanded Programme on Immunization (EPI), 61.0% against Streptococcus pneumoniae and 16.0% against the Hepatitis B virus (HBV). No case of immunization against Hemophilus influenzae and Salmonella sp was reported. Neonatal screening programs, early educational detection programs for families, use of current method treatments and an implementation of a health insurance system for sickle cell disease will improve detection and management for these and future patients in our population.     

The pathophysiology, prevention, and treatment of stroke in sickle cell disease

PURPOSE OF REVIEW: Stroke is one of the most devastating complications of sickle cell disease, but current research has led to improved understanding of its pathogenesis and to new approaches in the prevention of both primary and secondary stroke. This review focuses on advances reported in the past 2 years. RECENT FINDINGS: New concepts in the pathophysiology of central nervous system events in sickle cell disease have centered around hemolytic anemia and nitric oxide metabolism. Genetic risk factors are now being explored. Major improvement in primary stroke prevention has occurred through transcranial Doppler ultrasonography screening, but utilization of this technique is far from optimal. Hydroxyurea is now being tested as an alternative approach to chronic transfusion for secondary stroke prevention through a multicenter trial. Other studies are addressing the management of silent infarcts and nocturnal hypoxemia. SUMMARY: Increased understanding of the etiology and pathogenesis of stroke in sickle cell disease should eventually lead to improved management of all central nervous system complications. Alternative secondary stroke prevention with hydroxyurea may allow patients to avoid dependence on life-long chronic transfusion. Primary stroke prevention through transcranial Doppler ultrasonography screening may ultimately yield a dramatic reduction in the incidence of stroke in sickle cell disease.     

Sickle cell disease: Reducing the global disease burden

Sickle cell disease has been largely an invisible global health issue, especially in regions of high incidence mainly due to lack of awareness among both the local health policy makers and the public. Public health interventions, such as screening of newborns, provision of prophylaxis against bacterial infections, and immunizations against pneumococcal infections can have the greatest impact. Family education on assessment of spleen size and subsequent detection of splenic sequestration and promptness to seek medical attention for a febrile child is also important in the control of the morbidity and mortality of children with SCD living in resource‐poor countries. In addition to these affordable interventions, hydroxyurea therapy is necessary to decrease both the acute and chronic complications of sickle cell anemia. Sickle cell disease has been recognized to have global health significance by key institutions including the World Health Organization in 2006 and the United Nation is 2008. In 2010, the WHO released national health care management goals and set targets to be achieved by the countries in sub‐Saharan Africa for the control and management of SCD. These are yet to be translated into action. To do, this would require active and sustainable public‐private partnerships for sustainable program development in these regions. Effective interventions should be integrated into existing health systems, the best examples linking primary healthcare facilities to specialized sickle cell disease centers in regional and tertiary healthcare institutions.     

New results in clinical severity of homozygous sickle cell anemia in Dakar, Senegal

Despite the unicity of its genetic mutation, Sickle cell homozygosity presents different clinical features. Our objectives were to evaluate disease severity in Senegalese patients. Sixty (60) homozygous sickle cell patients were followed up monthly during one year and disease severity was assessed using the "severity index" (SI) which is resulting from epidemiologic, clinic and biological data. Mean age was 20.13, sex ratio was 0.87 and mean age of diagnosis was 9.8 years. 90% of patients presented vaso-occlusive crisis (2.53 per patient), 73.3% had infectious episodes (1.9 per patient), 69.3% had never been transfused and 25% of patients had presented chronic complications linked to anemia or ischemia. Mean hemoglobin value was 8.1 g/dl and mean Hb F was 8.2%. Low seric ferritin was found in 1.7% of patients. Benign form of homozygous sickle cell anemia (SI< or =6) was found in 48.3% of patients. Our data confirm the relative good tolerance of homozygous sickle cell disease in Senegal. The haplotype Senegal may play an important role but others host and environmental factors operate certainly because some severe cases were identified in our patients. The identification of all these factors might contribute to a better follow up of sickle cell disease.     

Current strategies for the management of children with sickle cell disease

Children with sickle cell disease may present to doctors anywhere in the world. In developed countries, neonatal screening allows early identification and management of the disease, mostly through daily antibioprophylaxis, immunizations and education of the parents. Stroke prevention relies on the detection of high-risk patients by annual transcranial Doppler ultrasonography from 2 to 16 years of age. Annual check-ups aim to detect early organ deficiencies. The most frequent complications are pain, infections and acute anemia; they may occur in combination. Approximately 10% of children have severe sickle cell disease that may require chronic blood transfusion, hydroxyurea or hematopoietic stem cell transplantation. Comprehensive management programs have dramatically increased survival, and most patients now reach adulthood.     

Causes of death in sickle cell disease: an autopsy study

More precise analysis of causes of death is needed to focus research efforts and improve morbidity and mortality in sickle cell disease. In this study, the morphological evidence of the cause of death was studied in 306 autopsies of sickle cell disease, which were accrued between 1929 and 1996. The most common cause of death for all sickle variants and for all age groups was infection (33-48%). The terminal infection was heralded by upper respiratory tract syndromes in 72.6% and by gastroenteritis in 13.7%. The most frequent portal of entry in children was the respiratory tract but, in adults, a site of severe chronic organ injury. Other causes of death included stroke 9.8%, therapy complications 7.0%, splenic sequestration 6.6%, pulmonary emboli/thrombi 4.9%, renal failure 4.1%, pulmonary hypertension 2.9%, hepatic failure 0.8%, massive haemolysis/red cell aplasia 0.4% and left ventricular failure 0.4%. Death was frequently sudden and unexpected (40.8%) or occurred within 24 h after presentation (28.4%), and was usually associated with acute events (63.3%). This study shows that the first 24 h after presentation for medical care is an especially perilous time for patients with sickle cell disease and an acute event. Close monitoring and prompt aggressive treatment are warranted.     

Allogeneic stem cell transplantation for sickle cell disease. A study of patients' decisions

Allogeneic stem cell transplantation is increasingly considered as a curative though risky treatment option for adults with sickle cell disease. Little is known about attitudes of adult patients and their health care providers regarding the risks and benefits of transplantation. A survey of 100 patients and their health care providers was undertaken. Assessment of risk was by a reference gamble paradigm. Comparison was made of the characteristics of those accepting substantial risk vs those not accepting risk, as well as assessment of agreement on risks recommended by health care providers and accepted by patients. Sixty-three of 100 patients were willing to accept some short-term risk of mortality in exchange for the certainty of cure. Fifteen patients were willing to accept more than 35% mortality risk. No differences in patient or disease-related variables were identified between those accepting risk and those not accepting risk. There was no agreement between the recommendations of health care providers and the risk accepted by patients. A substantial proportion of adults with sickle cell disease are interested in curative treatment, at the expense of considerable risk. The decision to accept risk is influenced by individual patient values that cannot be easily quantified and that do not correlate with the assessment of the health care provider. Given the substantial interest in curative therapy, education about and consultation for allogeneic stem cell transplantation in sickle cell patients should be encouraged.     

Sickle cell disease in Madhya Pradesh,Central India: A comparison of clinical profile of sickle cell homozygote vs. sickle-beta thalassaemia individuals

Background and objectives: The clinical manifestation in sickle cell disease (SCD) patients varies from one individual to another due to factors like the presence of alpha-thalassaemia mutation, foetal haemoglobin, and β-globin gene haplotype. The present study enumerates the clinical profile of sickle cell anaemia patients from Central India.

Methods: Seven hundred seventy-six SCD patients from Jabalpur and surrounding districts (Madhya Pradesh) in central India were registered with the sickle cell clinic of NIRTH, Jabalpur. The present study reveals recorded signs and symptoms of genetically confirmed sickle cell anaemia (404) and sickle beta thalassaemia (92) patients.

Results: Majority of the patients were from scheduled caste communities (47.9%) and Gond tribal community (13.8%). Splenomegaly was the most common clinical manifestation observed (71.4%). Overall, 63.5% patients had a history of blood transfusion. The most frequent signs and symptoms observed were Pallor, Icterus, Joint pain, Fever, and Fatigue. Majority of the patients revealed onset of disease prior to attaining the age of 3 years (sickle cell anaemia 44.3% and sickle beta thalassaemia 35.9%). Mean haemoglobin levels among SCA individuals were marginally higher than SBT patients. On the other hand, mean foetal haemoglobin levels among SBT individuals showed the reverse trend. Notably, the present study reports the first incidence of priapism recorded in Central India.

Conclusions: The study revealed a high prevalence of SCD among scheduled caste, backward caste, and tribal communities. Dissemination of study findings, screening, pre-marriage counselling, and pre-natal diagnosis are fundamental to preventing or lowering of birth of sickle cell anaemia children in the affected populations.     

Red cell transfusion and alloimmunization in sickle cell disease

Red cell transfusion remains a critical component of care for acute and chronic complications of sickle cell disease. Randomized clinical trials demonstrated the benefits of transfusion therapy for prevention of primary and secondary strokes and postoperative acute chest syndrome. Transfusion for splenic sequestration, acute chest syndrome, and acute stroke are guided by expert consensus recommendations. Despite overall improvements in blood inventory safety, adverse effects of transfusion are prevalent among patients with sickle cell disease and include alloimmunization, acute and delayed hemolytic transfusion reactions, and iron overload. Judicious use of red cell transfusions, optimization of red cell antigen matching, and the use of erythrocytapheresis and iron chelation can minimize adverse effects. Early recognition and management of hemolytic transfusion reactions can avert poor clinical outcomes. In this review, we discuss transfusion methods, indications, and complications in sickle cell disease with an emphasis on alloimmunization.     

Direct medical cost of type 1 and type 2 diabetes in Turkey

Diabetes mellitus (DM) is a common chronic metabolic disease with an estimated prevalence of 13.8 % in Turkey. The care and management of patients with DM and its complications consume a substantial proportion of healthcare expenditures. In this study, we aimed to analyse the direct medical cost of type 1 and type 2 diabetes in Turkey. 211 diabetes patients, 36 with type 1 diabetes and 175 with type 2 diabetes, were included in this retrospective study. Their demographic characteristics, laboratory test results, co-morbidities, length of hospital stay, and disease complications were recorded, and their invoices, received from the billing department of the institute, were analysed. The average cost of treatment of diabetes patients was calculated as 607.4 USD. No statistically significant difference was found between the cost of type 1 and type 2 diabetes (P?>?0.05). The costs increased with co-morbidities and complications (P?<?0.05). To reduce the cost of DM treatment, not only health professionals but also patients and their relatives must contribute toward DM management.