Diagnosis patterns of sickle cell disease in Ghana: a secondary analysis.

BACKGROUND: Despite having the highest prevalence of sickle cell disease (SCD) in the world, no country in Sub-Saharan Africa has a universal screening program for the disease. We sought to capture the diagnosis patterns of SCD (age at SCD diagnosis, method of SCD diagnosis, and age of first pain crisis) in Accra, Ghana. METHODS: We administered an in-person, voluntary survey to parents of offspring with SCD between 2009 and 2013 in Accra as a part of a larger study and conducted a secondary data analysis to determine diagnosis patterns. This was conducted at a single site: a large academic medical center in the region. Univariate analyses were performed on diagnosis patterns; bivariate analyses were conducted to determine whether patterns differed by participant's age (children: those < 18 years old whose parents completed a survey about them, compared to adults: those > = 18 years old whose parents completed a survey about them), or their disease severity based on SCD genotype. Pearson's chi-squared were calculated. RESULTS: Data was collected on 354 unique participants from parents. Few were diagnosed via SCD testing in the newborn period. Only 44% were diagnosed with SCD by age four; 46% had experienced a pain crisis by the same age. Most (66%) were diagnosed during pain crisis, either in acute (49%) or primary care (17%) settings. Children were diagnosed with SCD at an earlier age (74% by four years old); among the adults, parents reflected that 30% were diagnosed by four years old (p < 0.001). Half with severe forms of SCD were diagnosed by age four, compared to 31% with mild forms of the disease (p = 0.009). CONCLUSIONS: The lack of a robust newborn screening program for SCD in Accra, Ghana, leaves children at risk for disease complications and death. People in our sample were diagnosed with SCD in the acute care setting, and in their toddler or school-age years or thereafter, meaning they are likely being excluded from important preventive care. Understanding current SCD diagnosis patterns in the region can inform efforts to improve the timeliness of SCD diagnosis, and improve the mortality and morbidity caused by the disease in this high prevalence population.

Hospital Medicine Providers' Transfusion Knowledge: A Survey Study.

Blood transfusion is one of the most common procedures performed in the inpatient setting. Although ordering a transfusion is a component of routine practice for most hospitalists, prior literature has shown that non-transfusion medicine physicians have poor to intermediate transfusion medicine knowledge (TMK). No recent study has evaluated TMK among hospitalists, including both attending hospitalists and advanced practice providers (APPs). Using a validated exam and a truncated version of a validated survey, we obtained an initial impression of attitudes, perceived and actual TMK. A total of 183 hospital medicine providers nation-wide completed the 12-question online survey and 20 question exam, including 155 attending hospitalists and 28 APPs. The overall mean score was 52% (range 20%-85%). Forty-one percent of participants reported less than 1 hour of training in transfusion medicine. Five of the seven questions with the worst performance (<25% correct) were on transfusion reactions. Almost all respondents reported consenting a patient for blood transfusion and 60% believed that TMK was very or extremely important in order to provide appropriate care for patients. More than 80% believed that having additional transfusion medicine education would be at least moderately helpful. Although routinely consenting patients for transfusion, hospital medicine providers may have insufficient TMK particularly as it pertains to transfusion reactions. The majority of hospitalists rated TMK important to clinical practice and had an interest in additional training, thus continuing medical education has the potential to improve TMK and patient care.

Blocking a rash diagnosis: a rare case of infective endocarditis.

We report a case of a previously healthy, afebrile patient who presented with subacute bilateral lower extremity rash and complete heart block, which was later found to be secondary to infective endocarditis. His transoesophageal echocardiogram detected multiple vegetations and blood cultures were positive for Granulicatella adiacens, a nutritionally variant streptococcus that is a normal component of oral flora and thought to be responsible for approximately 5% of all cases of streptococcal endocarditis. Due to concerns for renal failure, the patient was treated with an unconventional regimen of ampicillin and ceftriaxone. He underwent a valve replacement and pacemaker placement and has done well since hospital discharge.

Chlamydia ascites: a call for sexually transmitted infection testing.

A 26-year-old gravida 2, para 2-0-0-2 woman with a recent uncomplicated vaginal delivery 10 weeks prior presented to our hospital with 5 weeks of abdominal swelling and discomfort. Four weeks after delivery, the patient began having right upper quadrant pain and was found to have cholelithiasis. She underwent an elective laparoscopic cholecystectomy 6 weeks prior to admission, but started to develop worsening abdominal swelling 1 week postoperatively. Abdominal distension and shifting dullness were present on examination. CT of the abdomen and pelvis was remarkable for moderate-volume ascites and mild enhancement of the pelvic peritoneum. Paracentesis removed 2.46 L of ascites fluid with 76% lymphocytic predominance. Results for Chlamydia trachomatis were positive in urine, cervical swab and ascitic fluid. Doxycycline was prescribed for a diagnosis of pelvic inflammatory disease exudative ascites. Since discharge, she has completed her antibiotic course and reports resolution of all symptoms without recurrence of ascites.

Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes.

Sickle cell disease (SCD) is a hematologic disorder caused by a missense mutation in the adult ß-globin gene. Higher fetal hemoglobin (HbF) levels in red blood cells of SCD patients have been shown to improve morbidity and mortality. We previously found that nuclear receptors TR2 and TR4 repress expression of the human embryonic ε-globin and fetal γ-globin genes in definitive erythroid cells. Because forced expression of TR2/TR4 in murine adult erythroid cells paradoxically enhanced fetal γ-globin gene expression in transgenic mice, we wished to determine if forced TR2/TR4 expression in a SCD model mouse would result in elevated HbF synthesis and thereby alleviate the disease phenotype. In a "humanized" sickle cell model mouse, forced TR2/TR4 expression increased HbF abundance from 7.6% of total hemoglobin to 18.6%, accompanied by increased hematocrit from 23% to 34% and reticulocyte reduction from 61% to 18%, indicating a significant reduction in hemolysis. Moreover, forced TR2/TR4 expression reduced hepatosplenomegaly and liver parenchymal necrosis and inflammation in SCD mice, indicating alleviation of usual pathophysiological characteristics. This article shows that genetic manipulation of nonglobin proteins, or transcription factors regulating globin gene expression, can ameliorate the disease phenotype in a SCD model animal. This proof-of-concept study demonstrates that modulating TR2/TR4 activity in SCD patients may be a promising therapeutic approach to induce persistent HbF accumulation and for treatment of the disease.