Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines.

OBJECTIVE: To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya. METHODS: We followed up children aged 2-59 months with WHO-defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days for TF using two definitions: (i) documentation of pre-defined clinical signs resulting in change of treatment (ii) primary clinician's decision to change treatment with or without documentation of the same pre-defined clinical signs. RESULTS: We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4-5.1) and 12.4% (95% CI 7.9-18.4) for SP and 21.4% (95% CI 15.9-27) and 39.3% (95% CI 32.5-46.4) for VSP depending on the definition applied. Higher rates were associated with early changes in therapy by clinician in the absence of an obvious clinical rationale. Non-adherence to treatment guidelines was observed for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively. Among children with SP, adherence to treatment guidelines was associated with the presence of wheeze on initial assessment (P = 0.02), while clinician non-adherence to guideline-recommended treatments for VSP tended to occur in children with altered consciousness (P < 0.001). Using propensity score matching to account for imbalance in the distribution of baseline clinical characteristics among children with VSP revealed no difference in TF between those treated with the guideline-recommended regimen vs. more costly broad-spectrum alternatives [risk difference 0.37 (95% CI -0.84 to 0.51)]. CONCLUSION: Before revising current pneumonia case management guidelines, standardised definitions of TF and appropriate studies of treatment effectiveness of alternative regimens are required.

n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights.

n-3 Fatty acids (EPA and DHA, from fish oil) are essential fatty acids that are approved for the treatment of severe hypertriacylglycerolaemia and, in some countries, used for reducing the risk of CVD. Because of their inhibitory effects on platelet function, some practitioners have, perhaps unnecessarily, discontinued their use in patients undergoing invasive procedures or being treated with anti-platelet or anticoagulation drugs. Thus, the aim of the present study was to review the effects of n-3 fatty acids on bleeding complications in a wide variety of clinical settings, and to summarise their biochemical mechanism of action in platelet function and coagulation. We surveyed recent publications that either directly studied the effects of n-3 fatty acids on the risk of bleeding or focused on different end-points and also reported the effects on bleeding. n-3 Fatty acid treatment had no effect on the risk of clinically significant bleeding in either monotherapy or combination therapy settings. Although originally believed to operate primarily via the cyclo-oxygenase system, these fatty acids have been shown to affect multiple signalling pathways and thrombotic processes beyond simply affecting platelet aggregation. The present overview found no support for discontinuing the use of n-3 fatty acid treatment before invasive procedures or when given in combination with other agents that affect bleeding. On the contrary, the use of these fatty acids in several settings improved clinical outcomes.

Ketosis-resistant diabetes: a rare case in unlikely territory.

BACKGROUND: Ketosis-resistant diabetes is a syndrome that has undergone numerous classification schemes in the past. In 1979, the National Diabetes Data Group (NDDG) introduced an association of malnutrition and diabetes. In 1985, the World Health Organization (WHO) created a new diabetes category called malnutrition-related diabetes mellitus (MRDM). MRDM consisted of two subclasses: fibrocalculous pancreatic diabetes (FCPD) and protein-deficient pancreatic diabetes (PDPD). Ketosis-resistant diabetes of the young (KRDY) was included in the subclass of PDPD. We report a rare case of a 37-year-old Sudanese immigrant with ketosis-resistant diabetes. CASE: A previously healthy 37-year-old male presented with increased lethargy, polydipsia, polyuria and weight loss for the last seven to eight months. The patient had immigrated to the U.S. from his native country of Sudan about seven years earlier. He was hemodynamically stable. Physical exam was unremarkable with no evidence of retinopathy or neuropathy. Initial laboratory findings revealed a random blood sugar of 1,409 mg/dl and hemoglobin A1C of 17.8 percent. Urinalysis showed negative proteinuria, positive glycosuria, but only trace ketones were detected. Interestingly, the patient's serum ketones were negative. Arterial blood gas revealed PH 7.37, PCO2 47, P02 108 and HCO3 27. Further diagnostic workup revealed C-peptide 0.36, insulin antibodies less than 2, glutamic acid decarboxylase (GAD) antibodies less than 0.5, ICA 512 antibodies 2.9 and negative anti-islet cell antibodies. An abdominal ultrasound did not show any evidence of pancreatic calcifications or any pathology. Aggressive fluid resuscitation and intravenous insulin was initiated. The patient's hospital course was uncomplicated. He responded well to intravenous insulin drip and hydration. He was eventually transitioned to subcutaneous insulin. He was discharged three days later on a home regimen that included Lantus 28 units SQ at night, Novolog 8 units SQ with meals and a sliding scale with Novolog as needed. The patient's recent follow-up appointment revealed adequate glycemic control with HbA1C level of 7 percent. CONCLUSION: Our patient did not meet criteria for either type 1 or type 2 diabetes mellitus. After a literature review of atypical etiologies of diabetes and comparing them to our patient, we concluded that the most likely diagnosis was KRDY. In light of a high influx of refugees and immigrants to the U.S., we should entertain. KRDY and other rare causes of diabetes mellitus in patients not satisfying criteria of either type 1 or type 2 diabetes.

Cardiovascular disease and bridging the diagnostic gap.

Cardiovascular disease (CVD) is now the leading cause of death worldwide. It continues to be on the rise and has become a true pandemic that has no respect to borders.' Coronary artery disease (CAD) is the most common type of CVD. It continues to be the leading cause of mortality both in men and women in the U.S.' Approximately every 25 seconds, an American will suffer an acute coronary syndrome, and approximately every minute someone will die of one. Risk stratification and early disease detection continue to be the bedrock of most preventative strategies. Risk assessment tools like Framingham Heart Score (FHS used in the U.S.), prospective cardiovascular monster (PROCAM used in Germany), or systemic coronary risk evaluation (SCORE used in Europe) are among the common and widely available estimators of a multi-factorial absolute risk of developing CVD.6 Recently, coronary artery calcium (CAC) has emerged as a non-invasive modality that might improve prediction of future cardiovascular events. We have conducted a comprehensive review of CVD risk factors, risk assessment and screening tools being applied to aid in early detection of CVD. As we work on bridging the diagnostic gap of the leading cause of mortality across the globe, utility of accurate and sensitive risk assessment and screening tools for early CVD detection is vital. This will aid in our goal of early detection, modifying risk factors and prevention of CVD incidence.

Doxycycline-induced pancreatitis: a rare finding.

BACKGROUND: Drug-induced pancreatitis (DIP) is a rare problem in medicine. A retrospective study from 45 German centers of gastroenterology concluded that only 22 of 1613 (1.4 percent) cases of acute pancreatitis in 1993 were DIP. Though DIP is a rare etiology of acute pancreatitis compared to other common etiologies like alcohol, gallstones, hypercalcemia, hypertriglyceridemia, infection, trauma or medical procedures like endoscopic retrograde cholangiopancreatography (ERCP), its incidence continues to rise. We report a case of a 21-year-old female with DIP following doxycycline treatment for an upper respiratory infection. CASE: A 21-year-old, otherwise healthy female presented with severe abdominal discomfort associated with nausea and vomiting. She was hemodynamically stable with normal vital signs. Physical exam revealed a soft but tender to palpation epigastric area. Peritoneal signs were negative. Urinalysis was negative for acute infection. Urine human chorionic gonadotrophin was negative for pregnancy. Laboratory findings revealed a mildly elevated lipase level at 128 U/L (normal 13-60) but was otherwise normal. A computed tomography of abdomen and pelvis revealed evidence of fat stranding consistent with acute pancreatitis. A right upper quadrant ultrasound ruled out gallstones. A serum triglyceride was within normal limit at 80mg/dl. She denied any alcohol use. On further questioning, the patient admitted to previously being diagnosed with an upper respiratory infection two weeks earlier. She had consequently finished a 10-day course of doxycycline therapy, with her last dose five days before presentation. After a literature review of drugs implicated in DIP and ruling out other causes of acute pancreatitis, we concluded that our patient had doxycycline-induced pancreatitis. Follow-up visit three weeks post discharge revealed complete resolution of previous symptoms. CONCLUSION: In our vastly evolving pharmacotherapy world, DIP should be entertained as a possible etiology of idiopathic pancreatitis, especially after other common causes have been ruled out.

Cleft lip and palate: a descriptive comparative, retrospective, and prospective study of patients with cleft deformities managed at 2 hospitals in Kenya.

This was a combined retrospective and prospective study in which 2 sets of results from 2 hospitals in Nairobi were analyzed and compared. The retrospective study was conducted at Kenyatta National Hospital, whereas the prospective study was conducted at Metropolitan Hospital.The main objective of the study was to establish the presentation and pattern of patients with cleft lip and palate and complications of repair at the 2 hospitals.In the retrospective arm of the study, files of all patients presenting with clefts at Kenyatta National Hospital between January 1998 and December 2007 were retrieved, and a questionnaire was filled out for each of them, whereas all patients seen and operated on for clefts at the Metropolitan Hospital from January 2007 to October 2008 were recruited into the prospective study.There was a predominance of male participants in both studies, and most clefts were on the left side. The retrospective and prospective studies had positive family history in 3.5% and 30.9%, respectively. Associated congenital malformations were 8.2% for the retrospective study and 25% for the prospective study. In both studies, the central province had the largest number of clefts, whereas the coast province had very few.Cleft lip and palate is a significant congenital malformation in Kenya, and there seems to be a higher incidence of familial tendency and associated congenital malformations than that reported elsewhere.

Frequency and spectrum of outpatient musculoskeletal diagnoses at a pediatric hospital in Kenya.

Chronic pediatric musculoskeletal (MSK) conditions are a major cause of morbidity. The burden of pediatric rheumatic diseases in East Africa is largely unknown. The purposes of this study were to estimate frequencies and assess the spectrum of MSK-related diagnoses using ICD-10 diagnostic codes among outpatients at a pediatric hospital in Kenya and to evaluate the accuracy of the assigned codes used for the 'arthropathies' category. All pediatric outpatient diagnoses classified under the ICD-10 codes for 'diseases of the MSK system and connective tissue' (M00-M99) recorded between January and December 2011 were extracted from the electronic medical record system at Gertrude's Children's Hospital (GCH). For each of the ten MSK disease categories, frequencies were calculated. The assigned ICD10 code for cases in the 'arthropathies' (M00-M25) category was assessed by two rheumatologists. MSK diagnoses (n = 1078) accounted for 0.5% of all GCH outpatient consults available for analysis. 'Soft tissue disorders' were the most frequent MSK diagnoses (n = 614, 57%), followed by 'arthropathies' (n = 332, 30.8%), 'dorsopathies' (n = 81, 7.5%), 'osteopathies and chondropathies' (n = 39, 3.6%), and 'other' disorders (n = 12, 1.1%). No patients were classified in the category of 'systemic connective tissue disorders'. In cases classified as 'arthropathies', there was poor agreement (Kappa 0.136) between the ICD10 code assigned by the treating physicians and that assigned by the rheumatologists. However, when the rheumatologists' classification was loosened, agreement was moderate (Kappa 0.533). This study provides estimates of the frequency of outpatient MSK diagnoses at a pediatric hospital in Kenya in 2011. MSK diagnoses were not rare. Despite limitations of administrative databases to estimate frequencies of specific diagnoses, they provide a snapshot of the overall burden and spectrum of MSK conditions.

The spectrum of rheumatic in-patient diagnoses at a pediatric hospital in Kenya.

BACKGROUND: Pediatric rheumatic diseases are chronic illnesses that can cause considerable disease burden to children and their families. There is limited epidemiologic data on these diseases in East Africa. The aim of this study was to assess the spectrum of pediatric rheumatic diagnoses in an in-patient setting and determine the accuracy of ICD-10 codes in identifying these conditions. METHODS: Medical records from Gertrude's Children's Hospital in Kenya were reviewed for patients diagnosed with "diseases of the musculoskeletal system and connective tissue" as per ICD-10 diagnostic codes assigned at discharge between January and December 2011. Cases were classified as "rheumatic" or "non-rheumatic". Accuracy of the assigned ICD-10 code was ascertained. Death records were reviewed. Longitudinal follow-up of "rheumatic" cases was done by chart review up to March 2014. RESULTS: Twenty six patients were classified as having a "rheumatic" condition accounting for 0.32% of patients admitted. Of these, 11 (42.3%) had an acute inflammatory arthropathy, 6 (23.1%) had septic arthritis, 4 (15.4%) had Kawasaki disease, 2 (7.7%) had pyomyositis, and there was one case each of septic bursitis, rheumatic fever, and a non-specific soft tissue disorder. No cases of juvenile idiopathic arthritis (JIA) were identified. One case of systemic lupus erythematosus was documented by death records. The agreement between the treating physician's discharge diagnosis and medical records ICD-10 code assignment was good (Kappa: 0.769). On follow-up, one child had recurrent knee swelling that was suspicious for JIA. CONCLUSIONS: Pediatric rheumatic conditions represented 0.32% of admissions at a pediatric hospital in Kenya. Acute inflammatory arthropathies, septic arthritis and Kawasaki disease were the most frequent in-patient rheumatic diagnoses. Chronic pediatric rheumatic diseases were rare amongst this in-patient population. Despite limitations associated with the use of administrative diagnostic codes, they can be a first step in evaluating the spectrum of pediatric rheumatic conditions in Kenya and other countries in East Africa.

Cystic Echinococcosis in Turkana, Kenya: The Role of Cross-Sectional Screening Surveys in Assessing the Prevalence of Human Infection.

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus. Infection leads to formation of cysts within the viscera of the human host. In the 1980s, the transhumant population of northwest Turkana, Kenya, was found to have the highest prevalence of CE in the world. In 1983, AMREF Health Africa and the Kenya Medical and Research Institute launched a CE Control Program in northwest Turkana, screening and treating the local people. This epidemiological study of CE in Turkana analyses approximately 30 years of surveillance and surgical data. Cyst data were categorized using the World Health Organization CE ultrasound classification system before being analyzed for cyst, patient, and population characteristics, and surveillance data from 1985 are compared with more recent surveillance data to assess changes in prevalence in the control region since the commencement of control activities. In 1985, the prevalence of CE among the Turkana was 5.6%. In 2010-2011 and 2011-2012, calculated CE prevalence rates were 1.9% and 3.8%, respectively. Since the 1980s, the age distribution of people with CE in Turkana has shifted: initially, cases of CE appeared predominantly within younger age groups, but recent data reveal a higher prevalence within older age groups. The frequency of infection in females also significantly decreased. The reduction in CE prevalence from 5.6% in the 1980s to 1.9-3.8% in 2010-2012 and the shift in age distribution of CE-infected individuals over time indicate that the prevalence of CE in Turkana has decreased since the control program began.

Ultrastructural study of Echnococcus granulosus larval forms.

The larval forms of Echinococcus granulosus were surgically removed from Turkana hydatid patients and studied on the electron microscope. It was found that the larval forms "hydatid cyst" consists of a protective laminated layer that surrounds the germinal layer. The germinal layer is made up of numerous germinal cells that transform to brood capsules within which protoscolices are formed. Protoscolices are formed from accumulations of undifferentiated germinal cells. The brood capsule wall is similar to germinal layer and they were found to contain numerous invaginated protoscolices. The invaginated protoscolices were of various sizes and they were not attached to the wall of the brood capsule. The evaginated protoscolex has two body regions, the head (scolex) and body (soma). The scolex is covered by numerous long microtriches whereas the soma is covered with few short microtriches.

Cellular immunity to Echinococcus granulosus cysts.

A fundamental feature of Echinococcus granulosus infection is its chronicity. There are many reasons for this, including weak natural immunity and the ability of the larval stages to evade or resist elimination by the hosts' specific immune responses. To identify the types of hosts' cellular immune response, a series of ultrastructral studies of hydatid cysts surgically removed from Turkana patients was conducted based on transmission electron microscopy. Ultrastructurally, the ectocyst (adventitial layer) is organised into three layers; an inner layer containing mainly the infiltrating mononuclear leukocytes; a middle, loose connective tissue layer with inflammatory cells mainly plasma cells, fibroblasts, scant neutrophils, eosinophils and lymphocytes, and an outer loose connective tissue layer that blends with the surrounding host tissue. The mast cells and basophils were not observed. This study has showm that the adventitial layer of hydatid cysts infiltrated by leukocytes, principally by macrophages and plasma cells.