Pulmonary artery pressure and iron deficiency in patients with upregulation of hypoxia sensing due to homozygous VHL(R200W) mutation (Chuvash polycythemia).

BACKGROUND: Patients with Chuvash polycythemia, (homozygosity for the R200W mutation in the von Hippel Lindau gene (VHL)), have elevated levels of hypoxia inducible factors HIF-1 and HIF-2, often become iron-deficient secondary to phlebotomy, and have elevated estimated pulmonary artery pressure by echocardiography. The objectives of this study were to provide a comprehensive echocardiographic assessment of cardiovascular physiology and to identify clinical, hematologic and cardiovascular risk factors for elevation of tricuspid regurgitation velocity in children and adults with Chuvash polycythemia. DESIGN AND METHODS: This cross-sectional observational study of 120 adult and pediatric VHL(R200W) homozygotes and 31 controls at outpatient facilities in Chuvashia, Russian Federation included echocardiography assessment of pulmonary artery pressure (tricuspid regurgitation velocity), cardiac volume, and systolic and diastolic function, as well as hematologic and clinical parameters. We determined the prevalence and risk factors for elevation of tricuspid regurgitation velocity in this population and its relationship to phlebotomy. RESULTS: The age-adjusted mean ± SE tricuspid regurgitation velocity was higher in VHL(R200W) homozygotes than controls with normal VHL alleles (2.5±0.03 vs. 2.3±0.05 m/sec, P=0.005). The age-adjusted left ventricular diastolic diameter (4.8±0.05 vs. 4.5±0.09 cm, P=0.005) and left atrial diameter (3.4±0.04 vs. 3.2±0.08 cm, P=0.011) were also greater in the VHL(R200W) homozygotes, consistent with increased blood volume, but the elevation in tricuspid regurgitation velocity persisted after adjustment for these variables. Among VHL(R200W) homozygotes, phlebotomy therapy was associated with lower serum ferritin concentration, and low ferritin independently predicted higher tricuspid regurgitation velocity (standardized beta=0.29; P=0.009). CONCLUSIONS: Children and adults with Chuvash polycythemia have higher estimated right ventricular systolic pressure, even after adjustment for echocardiography estimates of blood volume. Lower ferritin concentration, which is associated with phlebotomy, independently predicts higher tricuspid regurgitation velocity (www.clinicaltrials.gov identifier NCT00495638).

NT-proBNP as a marker of cardiopulmonary status in sickle cell anaemia in Africa.

N-terminal (NT) pro-brain natriuretic peptide (proBNP) > or =160 ng/l has a 78% positive predictive value for pulmonary hypertension and is associated with increased mortality in US sickle cell disease patients, but the importance in sickle cell disease patients in Africa is not known. In a cross-sectional study at Ahmadu Bello University Teaching Hospital, Shika-Zaria, Nigeria, we studied 133 hydroxycarbamide-naïve Nigerian sickle cell anaemia patients aged 18-52 years at steady-state and 65 healthy controls. Twenty-six percent of patients versus 5% of controls had NT-proBNP > or =160 ng/l (P = 0.0006). By logistic regression among the patients, human immunodeficiency virus seropositivity, higher serum ferritin and lower haemoglobin or higher lactate dehydrogenase independently predicted elevated NT-proBNP. After adjustment for haemoglobin concentration, elevated NT-proBNP concentration was associated with an estimated 7.8-fold increase in the odds of severe functional impairment, defined as an inability to walk more than 300 m in 6 min (95% confidence interval 1.5-32.6; P = 0.005). Similarly, elevated tricuspid regurgitation velocity was associated with an estimated 5.6-fold increase in the odds of functional impairment (95% confidence interval 1.5-21.0; P = 0.011). In conclusion, NT-proBNP elevation is common and is associated with markers of anaemia, inflammation and iron status and with severe functional impairment among sickle cell anaemia patients in Nigeria.

Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria.

Pulmonary artery systolic hypertension is common and associated with increased mortality among adult sickle cell disease (SCD) patients in the United States. Although the prevalence of SCD is highest in sub-Saharan Africa, the frequency of pulmonary artery systolic hypertension and the risk factors for the development of pulmonary hypertension have not been reported from Africa. We studied 208 hydroxyurea naïve Nigerian SCD patients at steady state and 94 healthy controls. Pulmonary artery systolic hypertension was defined prospectively as tricuspid regurgitant jet velocity > or =2.5 m/sec. Results were compared with a previously published US prospective SCD cohort. Only 7% of Nigerians compared with 46% of US adults with SCD were >35 years. Tricuspid regurgitant jet velocity was > or =2.5 m/sec in 25% of Nigerian SCD patients. Higher jet velocity was associated with greater serum globulin (P = 0.002), blood urea nitrogen (P = 0.019) and lactate dehydrogenase concentrations (P = 0.026) and with inability to walk >300 m in 6 min (P = 0.042). Compared with the US cohort, Nigerian patients had more hemolysis as indicated by lower hemoglobin and higher lactate dehydrogenase concentrations (P < or = 0.003). Pulmonary hypertension is common among Nigerian SCD patients. The public health implication of this finding is significant considering the potential number of individuals at risk for this complication. Better understanding of the long term outcome of pulmonary hypertension and causes of death in SCD and the institution of preventive measures are major public health challenges for Africa. The inclusion of African sites in sickle cell pulmonary hypertension clinical trials should be encouraged.

Parity effect on preterm birth and growth outcomes among infants with isolated omphalocele.

OBJECTIVE: To assess the association between parity and fetal morbidity outcomes among omphalocele-affected fetuses. STUDY DESIGN: We carried out a retrospective study of 498 cases of isolated omphalocele (210 born to nulliparous and 288 to multiparous mothers) in New York State from 1983 through 1999. Infants of nulliparous mothers were compared to those of multiparous gravidas using adjusted odds ratios generated from a logistic regression. RESULTS: Omphalocele-affected fetuses of nulliparous mothers had a lower risk of being delivered preterm (odds ratio (OR)=0.49; 95% CI=0.27-0.90) but comparable risks for low birth weight (OR=1.01; 95% CI=0.60-1.72), very low birth weight (OR=0.33; 95% CI=0.09-1.20), very preterm birth (OR=0.42; 95% CI=0.15-1.16), and small size for gestational age (SGA) [OR=0.61; 95% CI=0.23-1.63]. CONCLUSION: Omphalocele-affected fetuses of multiparous mothers have double the risk for preterm birth compared to their nulliparous counterparts. This information is potentially useful in counseling parents whose fetuses have omphaloceles.

Advanced maternal age and fetal growth inhibition in triplets.

OBJECTIVE: To determine whether advanced maternal age is associated withfetal growth inhibition in triplets. STUDY DESIGN: We conducted a retrospective cohort study on triplet live births in the United States from 1995 through 1998. The outcomes of fetal growth inhibition measured were low birth weight, very low birth weight, preterm birth, very preterm birth and smallnessfor gestational age. We generated adjusted ORs after taking into account intracluster correlations using the generalized estimating equation framework. RESULTS: As compared to women of younger maternal age (20-29), mature (30-39) and older women (> or =40 years) with triplet gestations tended to have a lower likelihood offetal growth inhibition. Mean birth weight and mean gestational age at delivery increased with increasing maternal age in a dose-dependent pattern (p for trend < 0.0001). As compared to triplets born to younger mothers, those of older women were less likely to have low birth weight (OR=0.51, 95% CI=0.37-0.69) or very low birth weight (OR = 0.58, 95% CI = 0.47-0.72) or to be preterm (OR = 0.39, 95% CI = 0.27-0.56) or very preterm (OR = 0.67, 95% CI = 0.55-0.80). The riskfor small-for-gestational-age infants was comparable. CONCLUSION: Older maternal age is associated with morefavorable triplet fetal growth parameters, although the exact mechanisms of this paradox remain poorly understood.

Survival of "pre-viable" infants in the United States.

OBJECTIVE: We investigated temporal trend in survival of pre-viable (200-499 g) fetuses over the previous decade, and estimated future survival rates based on previous and current survival thresholds. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study on live-born pre-viable fetuses (200-499 g) in the United States comparing two period cohorts; 1985-1988 versus 1995-1999. We computed survival of pre-viable babies (who were still alive at 24 hours) during the two periods and based on these results, we estimated future survival rates for the coming decades. MAIN OUTCOMES: Survival beyond the neonatal period. RESULTS: About 35 million live births were analyzed for the two periods. In the first period (1985-1988), 927 live births among pre-viable fetuses were recorded while in the second period (1995-1999) 2585 were counted, equivalent to a birth rate of 60.6 and 131.9 per million live births respectively. This corresponds to an increase of more than 100% across the decade (p for trend < 0.0001). Survival improved by about 50% across the period, from 12.0% to 17.4% (p < 0.0001). Based on these results, the survival rate among pre-viable fetuses will be expected to rise to about 24.0% within the next 6 years (2010). CONCLUSIONS: Survival among pre-viable fetuses is increasing in the United States. This raises ethical, legal and medical issues concerning the defined viability status of these babies, which is currently described as "non-viable".

Mode of delivery and neonatal survival of infants with isolated gastroschisis.

OBJECTIVE: We sought to compare neonatal survival of infants with gastroschisis by mode of delivery. METHODS: We conducted a retrospective cohort study on infants with gastroschisis who were delivered in New York State from 1983 through 1999. We compared neonatal mortality between infants born vaginally and those delivered by cesarean using adjusted hazard ratios derived from Cox proportional hazards regression models. RESULTS: A total of 354 infants were found to have isolated gastroschisis. Of these, 174 were delivered vaginally, whereas 180 were delivered by cesarean. Neonatal mortality was registered among 18 infants (5.1%); 12 (6.9%) in the vaginal and 6 (3.3%) in the cesarean group. After controlling for potential confounders, the risk for neonatal demise was similar in both the vaginal and cesarean subcohorts (adjusted hazard ratio 0.84, 95% confidence interval [CI] 0.29-2.43). Preterm birth was the morbidity pathway that explained the early demise of infants with gastroschisis, irrespective of mode of delivery (adjusted hazard ratio 3.4, 95% CI 1.10-10.4) whereas small for gestational age did not predict mortality (adjusted hazard ratio 1.04, 95% CI 0.13-8.14). CONCLUSION: In this study the mode of delivery was not found to be associated with neonatal survival of infants with gastroschisis. Preterm birth rather than small for gestational age was the predictor of neonatal death among gastroschisis infants. LEVEL OF EVIDENCE: III

Determinants for hospitalization in " low-risk" community acquired pneumonia.

BACKGROUND: A variable decision in managing community acquired pneumonia (CAP) is the initial site of care; in-patient versus outpatient. These variations persist despite comprehensive practice guidelines. Patients with a Pneumonia Severity Index (PSI) score lower than seventy have low risk for complications and outpatient antibiotic management is recommended in this group. These patients are generally below the age of fifty years, non-nursing home residents, HIV negative and have no major cardiac, hepatic, renal or malignant diseases. METHODS: A retrospective analysis of 296 low-risk CAP patients evaluated within a year one period at St. Agnes Hospital, Baltimore, Maryland was undertaken. All patients were assigned a PSI score. 208 (70%) were evaluated and discharged from the emergency department (E.D.) to complete outpatient antibiotic therapy, while 88 (30%) were hospitalized. Patients were sub-stratified into classes I-V according to PSI. A comparison of demographic, clinical, social and financial parameters was made between the E.D. discharged and hospitalized groups. RESULTS: Statistically significant differences in favor of the hospitalized group were noted for female gender (CI: 1.46-5.89, p= 0.0018), African Americans (CI: 0.31-0.73, p= 0.004), insurance coverage (CI: 0.19-0.63, p= 0.0034), temperature (CI: 0.04-0.09, p= 0.0001) and pulse rate (CI: 0.03-0.14, p= 0.0001). No statistically significant differences were observed between the two groups for altered mental status, hypotension, tachypnea, laboratory/radiological parameters and social indicators (p>0.05). The average length of stay for in-patients was 3.5 days at about eight time's higher cost than outpatient management. There was no difference in mortality or treatment failures between the two groups. The documentation rate and justifications for hospitalizing low risk CAP patients by admitting physicians was less than optimal. CONCLUSIONS: High fever, tachycardia, female gender, African- American race and medical insurance coverage are determinants for hospitalization among low risk CAP patients in our study. The average length of stay for in-patients was 3.5 days (3 to 5 days). The cost of in-patient care was about eight times higher than outpatient management. This study supports the recommendation of using the PSI for E.D evaluation of patients in appropriate social settings.

Assessing compliance of cardiologists with the national cholesterol education program (NCEP) III guidelines in an ambulatory care setting.

INTRODUCTION: The NCEP III -ATP guidelines provide clear clinical directives for lipid management especially statins therapy in appropriate patient groups. Compliance of primary care physicians with these guidelines especially in ambulatory care settings has been shown to be poor. The compliance of cardiologist to these guidelines is less documented. METHODS: A retrospective chart review of 386 patients managed in a large urban cardiology practice was undertaken. Patients with documented contraindications to use of statins were excluded from the study. Only patients with two or more years of follow-up in the practice were included. Demographic variables and medical history including CAD or its equivalent and its major risk factors were identified. The proportion of patients on statins and adequacy of statins therapy were recorded. The lipid profiles of all patients were also analyzed. RESULTS: Fifteen patients with documented contraindications to statins therapy including persistent/severe LFT abnormalities, allergies, and gastrointestinal intolerance were excluded. A total of 371 patients were included in the analysis. The mean age for patients in the study was 65 years (range: 42-84). 236 (64%) were males while 141 (36%) were females. 161 (43%) patients were on statins while 210 (57%) weren't. 88 (62%) of females were on stain compared to 116 (49%) of males (p = 0.001). 68% of patients below the age of 50 yrs were not on statins compared with 55% of those greater than 50 yrs (p = 0.01). 38% of patients on statins therapy had sub-optimal lipid profile despite greater than two years of therapy. No statistically significant differences in race and use of satins were noted. CONCLUSION: This study demonstrates a higher than expected prevalence of sub-optimal management of dyslipidemia among patients with established coronary heart disease without contraindications to statins managed by cardiologists. Cardiology and primary care practices require similar comprehensive routine lipid management program that is assiduously maintained and evaluated at both in-patient and out patient settings to ensure most patients receive optimal therapy with statins and other lipid lowering agents.

Policy mapping for establishing a national emergency health policy for Nigeria.

BACKGROUND: The number of potential life years lost due to accidents and injuries though poorly studied has resulted in tremendous economic and social loss to Nigeria. Numerous socio-cultural, economic and political factors including the current epidemic of ethnic and religious conflicts act in concert in predisposing to and enabling the ongoing catastrophe of accident and injuries in Nigeria. METHODS: Using the "policymaker", Microsoft-WindowscircledR; based software, the information generated on accidents and injuries and emergency health care in Nigeria from literature review, content analysis of relevant documents, expert interviewing and consensus opinion, a model National Emergency Health Policy was designed and analyzed. A major point of analysis for the policy is the current political feasibility of the policy including its opportunities and obstacles in the country. RESULTS: A model National Emergency Health Policy with policy goals, objectives, programs and evaluation benchmarks was generated. Critical analyses of potential policy problems, associated multiple players, diverging interests and implementation guidelines were developed. CONCLUSIONS: "Political health modeling" a term proposed here would be invaluable to policy makers and scholars in developing countries in assessing the political feasibility of policy managing. Political modeling applied to the development of a NEHP in Nigeria would empower policy makers and the policy making process and would ensure a sustainable emergency health policy in Nigeria.

Sickle cell disease and pulmonary hypertension in Africa: a global perspective and review of epidemiology, pathophysiology, and management.

Secondary pulmonary hypertension (PAH) has been shown to have a prevalence of 30% in patients with sickle cell disease (SCD) with mortality rates of 40% at 40 months after diagnosis in the United States. The burden of SCD is highest in sub-Saharan Africa, especially in Nigeria (West Africa), where approximately 6 million people are afflicted. The true global incidence, prevalence, and burden of SCD and its associated end organ complications however remain unknown. Chronic hemolysis represents a prominent mechanistic pathway in the pathogenesis of SCD-associated pulmonary hypertension via a nitric oxide (NO) scavenging and abrogation of NO salutatory effects on vascular function, including smooth muscle relaxation, downregulation of endothelial adhesion molecules and inhibition of platelet activation. Many known infectious risk factors for PAH are also hyperendemic in Africa, including Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS), chronic hepatitis B and C, and possibly malaria. Interactions between these infectious complications and SCD-related hemolysis could yield an even higher prevalence of pulmonary hypertension and compound the existing global health systems challenges in managing SCD. Indeed, our preliminary analysis of African immigrants currently in the United States suggests that pulmonary hypertension represents a significant complication of SCD in the African subcontinent. There is clearly a need to include Africa and other parts of the world with high SCD prevalence in future comprehensive studies on the epidemiology and treatment of end organ complications of an aging SCD population world-wide.

Saw palmetto-induced pancreatitis.

Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.

Pseudo-Meig's syndrome with multiple synchronous benign and malignant pelvic tumors.

BACKGROUND: Meig's and Pseudo-Meig's syndromes have been reported in association with several malignancies but the concomitant existence of multiple synchronous benign and malignant tumors in association with Pseudo-Meigs' syndrome has not been reported in the published literature. CASE: A 55-year old African American woman presented with mild asthma exercebation, right ovarian mass, hydrothorax and elevated CA-125 levels. Histological examination confirmed a right ovarian carcinoid tumor embedded within a mature cystic teratoma while the left ovary, fallopian tube and the uterus contained a poorly differentiated adenocarcinoma of the endometrium. CONCLUSION: This is the first case report of Pseudo-Meig's syndrome in association with ovarian carcinoid tumor and multiple synchronous benign and malignant pelvic tumors.

Gastroschisis, low maternal age, and fetal morbidity outcomes.

OBJECTIVE: To determine if the risk for fetal growth inhibition among gastroschisis-afflicted fetuses is heightened among younger gravidas (teen mothers). METHOD: This was a retrospective cohort study on live-born infants with isolated gastroschisis delivered in New York State from 1983 through 1999. We compared infants of mature (>20 years) mothers with those of younger (<20 years) mothers with respect to the following indices of fetal morbidity outcomes: low birth weight and very low birth weight, preterm and very pre-term, and small for gestational age. We used adjusted odds ratios to approximate relative risks. RESULTS: A total of 368 infants with isolated gastroschisis were analyzed. The two groups differed in terms of mean gestational age at delivery [Mean + standard deviation(SD) for infants with gastroschisis born to mature mothers = 37.2 weeks +/- 2.8 versus 36.3 weeks + 3.6 for those of teenage mothers(p = 0.01)], as well as mean birth weight [mean birth weight +/- SD for infants with gastroschisis born to mature mothers = 2562.4 grams +548.8 versus 2367.9 grams +/- 645.2 for those of younger mothers (p = 0.004)]. Infants of teen mothers were about twice as likely to be of low birth weight (OR = 1.70; 95% CI = 1.05-2.77) and about three times as likely to be born very preterm when compared to those of mature mothers (OR = 2.80; 95% Cl = 1.02-8.00). No significant differences were observed with respect to very low birth weight, pre-term and small for gestational age. CONCLUSION: Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.

Omphalocele, advanced maternal age, and fetal morbidity outcomes.

In this study we wanted to determine if the risk for adverse neonatal outcome among omphalocele-affected fetuses is increased among older gravidas. This was a retrospective cohort study on live-born infants with omphalocele delivered in New York State from 1983 through 1999. We compared infants of older (>or=35 years) with those of younger (<35 years) mothers with respect to the following fetal morbidity indices: low birth weight and very low birth weight, preterm and very preterm, and small for gestational age. We used adjusted odds ratios to approximate relative risks. Data on a total of 1,010 infants with omphalocele were analyzed. Mean gestational age and birth weight were similar in both maternal age categories: mean+/-standard deviation (SD) for infants with omphalocele born to older mothers=37.4 weeks+/-3.9 versus 38.0 weeks+/-5.1 for those of younger mothers (P=0.2); mean birth weights+/-SD for infants with omphalocele born to older mothers=2,813+/-871.1 versus 2,958+/-809.9 for those of younger mothers (P=0.08). Also, the two maternal age sub-groups did not differ with respect to the fetal morbidity outcome: low birth weight (OR=0.95; 95% CI=0.60-1.51), very low birth weight (OR=0.78; 95% CI=0.36-1.69), preterm (OR=0.95; 95% CI=0.58-1.57), very preterm (OR=0.73; 95% CI=0.34-1.58), and SGA (OR=1.00; 95% CI=0.44-2.27). Thus, advanced maternal age does not appear to be a risk factor for fetal morbidity outcomes among omphalocele-affected fetuses. This information is potentially useful in counseling affected parents.

Omphalocele and gastroschisis: Black-White disparity in infant survival.

BACKGROUND: Racial/ethnic variations in the occurrence of abdominal wall defects have been previously noted but it remains poorly understood whether race/ethnicity is a determinant of survival among affected infants. METHODS: Study was conducted on cases of gastroschisis and omphalocele recorded for the years 1983-1999 at the New York Congenital Malformation Registry. Adjusted and unadjusted hazard ratios were generated from a Proportional Hazards Regression model to compare survival among affected Blacks, Hispanics and Whites. The major end point of analysis was differences in all cause mortality among infants with abdominal wall birth defects across different racial/ethnic groups. RESULTS: Among the three racial/ethnic groups, 1481 infants were diagnosed with either omphalocele (978 or 66%) or gastroschisis (503 or 34%). Overall infant mortality rate (IMR) was 182 per 1000, with 74% of the deaths occurring within the first 28 days of life. Omphalocele infants had significantly higher infant mortality (IMR = 215 per 1000) than infants with gastroschisis (IMR = 118 per 1000)[p < 0.0001]. Overall, Black infants with abdominal wall defects had lower mortality indices than Whites and Hispanics. However, when considered as separate disease entities, Black infants were twice as likely to survive as compared to Whites if they had omphalocele [Adjusted Hazard Ratio (AHR) = 0.52; 95% Confidence Interval (CI) = 0.37-0.74], and twice as likely to die as Whites if they had gastroschisis instead (AHR = 2.23; 95% CI = 1.16-4.28). For both defect subtypes, Hispanics have risks for infant mortality comparable to Whites. CONCLUSIONS: The natural history of omphalocele and gastroschisis co-varies with race. Black infants with gastroschisis have worse survival outcomes while those with omphalocele have better chances of survival than their White or Hispanic counterparts.