Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

OBJECTIVE: To describe the patient population, priority diseases and outcomes in newborns admitted <48 hours old to neonatal units in both Kenya and Nigeria. STUDY DESIGN: In a network of seven secondary and tertiary level neonatal units in Nigeria and Kenya, we captured anonymised data on all admissions <48 hours of age over a 6-month period. RESULTS: 2280 newborns were admitted. Mean birthweight was 2.3 kg (SD 0.9); 57.0% (1214/2128) infants were low birthweight (LBW; <2.5kg) and 22.6% (480/2128) were very LBW (VLBW; <1.5 kg). Median gestation was 36 weeks (interquartile range 32, 39) and 21.6% (483/2236) infants were very preterm (gestation <32 weeks). The most common morbidities were jaundice (987/2262, 43.6%), suspected sepsis (955/2280, 41.9%), respiratory conditions (817/2280, 35.8%) and birth asphyxia (547/2280, 24.0%). 18.7% (423/2262) newborns died; mortality was very high amongst VLBW (222/472, 47%) and very preterm infants (197/483, 40.8%). Factors independently associated with mortality were gestation <28 weeks (adjusted odds ratio 11.58; 95% confidence interval 4.73-28.39), VLBW (6.92; 4.06-11.79), congenital anomaly (4.93; 2.42-10.05), abdominal condition (2.86; 1.40-5.83), birth asphyxia (2.44; 1.52-3.92), respiratory condition (1.46; 1.08-2.28) and maternal antibiotics within 24 hours before or after birth (1.91; 1.28-2.85). Mortality was reduced if mothers received a partial (0.51; 0.28-0.93) or full treatment course (0.44; 0.21-0.92) of dexamethasone before preterm delivery. CONCLUSION: Greater efforts are needed to address the very high burden of illnesses and mortality in hospitalized newborns in sub-Saharan Africa. Interventions need to address priority issues during pregnancy and delivery as well as in the newborn.

A Novel Icterometer for Hyperbilirubinemia Screening in Low-Resource Settings.

BACKGROUND: Severe neonatal hyperbilirubinemia (>20 mg/dL) affects ∼1 million infants annually. Improved jaundice screening in low-income countries is needed to prevent bilirubin encephalopathy and mortality. METHODS: The Bili-ruler is an icterometer for the assessment of neonatal jaundice that was designed by using advanced digital color processing. A total of 790 newborns were enrolled in a validation study at Brigham and Women's Hospital (Boston) and Sylhet Osmani Medical College Hospital (Sylhet, Bangladesh). Independent Bili-ruler measurements were made and compared with reference standard transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) concentrations. RESULTS: Bili-ruler scores on the nose were correlated with TcB and TSB levels (r = 0.76 and 0.78, respectively). The Bili-ruler distinguished different clinical thresholds of hyperbilirubinemia, defined by TcB, with high sensitivity and specificity (score ≥3.5: 90.1% [95% confidence interval (CI): 84.8%-95.4%] and 85.9% [95% CI: 83.2%-88.6%], respectively, for TcB ≥13 mg/dL). The Bili-ruler also performed reasonably well compared to TSB (score ≥3.5: sensitivity 84.5% [95% CI: 79.1%-90.3%] and specificity 83.2% [95% CI: 76.1%-90.3%] for TSB ≥11 mg/dL). Areas under the receiver operating characteristic curve for identifying TcB ≥11, ≥13, and ≥15 were 0.92, 0.93, and 0.94, respectively, and 0.90, 0.87, and 0.86 for identifying TSB ≥11, ≥13, and ≥15. Interrater reliability was high; 97% of scores by independent readers fell within 1 score of one another (N = 88). CONCLUSIONS: The Bili-ruler is a low-cost, noninvasive tool with high diagnostic accuracy for neonatal jaundice screening. This device may be used to improve referrals from community or peripheral health centers to higher-level facilities with capacity for bilirubin testing and/or phototherapy.

A Low-Cost, Community Knowledge Approach to Estimate Maternal and Jaundice-Associated Mortality in Rural Bangladesh.

In the absence of a civil registration system, a house-to-house survey is often used to estimate cause-specific mortality in low- and middle-income countries. However, house-to-house surveys are resource and time intensive. We applied a low-cost community knowledge approach to identify maternal deaths from any cause and jaundice-associated deaths among persons aged ≥ 14 years, and stillbirths and neonatal deaths in mothers with jaundice during pregnancy in five rural communities in Bangladesh. We estimated the method's sensitivity and cost savings compared with a house-to-house survey. In the five communities with a total of 125,570 population, we identified 13 maternal deaths, 60 deaths among persons aged ≥ 14 years associated with jaundice, five neonatal deaths, and four stillbirths born to a mother with jaundice during pregnancy over the 3-year period before the survey using the community knowledge approach. The sensitivity of community knowledge method in identifying target deaths ranged from 80% for neonatal deaths to 100% for stillbirths and maternal deaths. The community knowledge approach required 36% of the staff time to undertake compared with the house-to-house survey. The community knowledge approach was less expensive but highly sensitive in identifying maternal and jaundice-associated mortality, as well as all-cause adult mortality in rural settings in Bangladesh. This method can be applied in rural settings of other low- and middle-income countries and, in conjunction with hospital-based hepatitis diagnoses, used to monitor the impact of programs to reduce the burden of cause-specific hepatitis mortality, a current World Health Organization priority.

Identification of pathogens for differential diagnosis of fever with jaundice in the Central African Republic: a retrospective assessment, 2008-2010.

BACKGROUND: Febrile jaundice results clinically in generalized yellow coloration of the teguments and mucous membranes due to excess plasma bilirubin, accompanied by fever. Two types are found: conjugated and unconjugated bilirubin jaundice. Jaundice is a sign in several diseases due to viruses (viral hepatitis and arbovirus), parasites (malaria) and bacteria (leptospirosis). In the Central African Republic (CAR), only yellow fever is included on the list of diseases for surveillance. The aim of this study was to identify the other pathogens that can cause febrile jaundice, for better management of patients. METHODS: Between 2008 and 2010, 198 sera negative for yellow fever IgM were randomly selected from 2177 samples collected during yellow fever surveillance. Laboratory analyses targeted four groups of pathogens: hepatitis B, C, delta and E viruses; dengue, chikungunya, Zika, Crimean-Congo haemorrhagic fever, West Nile and Rift Valley arboviruses; malaria parasites; and bacteria (leptospirosis). RESULTS: Overall, 30.9% sera were positive for hepatitis B, 20.2% for hepatitis E, 12.3% for hepatitis C and 8.2% for malaria. The majority of positive sera (40.4%) were from people aged 16-30 years. Co-infection with at least two of these pathogens was also found. CONCLUSION: These findings suggest that a systematic investigation should be undertaken of infectious agents that cause febrile jaundice in the CAR.

'Halving the heel pricks': evaluation of a neonatal jaundice protocol incorporating the use of a transcutaneous bilirubinometer.

AIM: This study aimed to assess the impact of implementing a new jaundice protocol incorporating the use of the Konica Minolta/Air Shields JM 103 Jaundice Meter (JM103) (Konica Minolta Sensing Inc., Osaka, Japan) in the setting of an Australian post-natal ward. METHODS: A before-and-after study was completed following the introduction of a protocol integrating the use of the JM103 monitor on to the post-natal ward. Eligible infants were ≥ 36 weeks gestation, > 24 h and < 8 days of age. The number of Total Serum Bilirubin tests (TSBRs) were compared for the 12 months prior (T1) with a 6-month period and 6 months after protocol introduction (T2). Transcutaneous bilirubin (TcBR) results were also collected in T2. Rates of phototherapy and peak TSBRs at commencement were also compared as measures of safety. RESULTS: Four hundred and twenty-six of the 2197 live births in T1 required one or more TSBRs compared with 119 of the 1169 live births in T2. This represents an odds ratio of 0.47 (95% confidence interval 0.38-0.58) for infants in T2 having ≥ 1 TSBR compared with T1. There was no difference between the groups for rates of phototherapy (3.8% vs. 3.0%; P= 0.2) nor any difference between the groups for peak SBR during phototherapy (301.9 µmol/L (standard deviation, SD 58) for T1 vs. 303.2 µmol/L (SD 54) for T2; P= 0.45). The estimated cost saving per year is $6966.00. CONCLUSION: TcBR measurement in conjunction with our protocol significantly reduces painful procedures and costs without increasing the risk of delaying treatment with phototherapy.

Clinical and regulatory protocol for the treatment of jaundice in adults and elderly subjects: a support for the health care network and regulatory system / Protocolo clínico e de regulação para o tratamento de icterícia no adulto e idoso: subsídio para as redes assistenciais e o complexo regulador

PURPOSE: Clinical interventions and controlled access to the health care system can be improved by a Regulatory System (RS) and Clinical and Regulatory Protocols (CRPs). The objective of the present paper is to present the methodology used for elaborating the CRPs. METHODS: The process used to elaborate the CPRs involved a scientific co-operation between university and health care system. Workshops were held and attended by primary care practitioners, RS team, and matrix team (university specialists supporting primary care practitioners). RESULTS: The treatment of jaundice in adults and elderly subjects is amongst the themes selected for elaborating the CRPs since jaundice is a medical sign frequently seen in four clinical scenarios involving distinctive diagnostic and therapeutic interventions which can be performed in different health care settings. Evaluation guidelines as well as the clinical and regulatory procedures were established for different health care settings. The most relevant clinical and regulatory interventions were expressed as algorithms in order to facilitate the use of CRPs by health care practitioners. CONCLUSION: It is expected that the implementation of this protocol will minimise the imbalance between the icteric patients' needs and the treatment modalities being offered, thus contributing to a more co-operative health care network.

OBJETIVO: As ações clínicas e de ordenação do acesso à rede de saúde podem ser aperfeiçoadas pelo Complexo Regulador (CR) e pelos Protocolos Clínicos e de Regulação (PCR). Nesse trabalho apresenta-se a metodologia de elaboração dos PCR mediante cooperação entre universidade e sistema de saúde. MÉTODOS: O processo utilizado para a elaboração dos PCR envolve oficinas com a participação de profissionais da atenção básica, do CR e das equipes matriciais (especialistas da universidade que dão suporte às equipes de atenção básica). RESULTADOS: Dentre os temas selecionados para elaboração dos PCR, incluiu-se a icterícia no adulto e no idoso. Trata-se de um sinal clínico que comporta quatro cenários de apresentação com distintos percursos diagnósticos e terapêuticos passíveis de serem executados em diferentes pontos da rede assistencial. As diretrizes de avaliação, bem como as decisões e ações clínicas e reguladoras cabíveis para os diferentes cenários foram estabelecidas desde a atenção básica até o hospital terciário. As ações clínicas e reguladoras mais relevantes foram colocadas em algoritmo para facilitar o emprego do protocolo pelos profissionais de saúde. CONCLUSÃO: Há a expectativa que a implementação desse protocolo possa minimizar o descompasso entre as necessidades dos pacientes ictéricos e a modalidade de serviço oferecida e, assim, contribuir para a configuração de uma rede assistencial mais cooperativa.

Objective assessment of the contribution of each diagnostic test and of the ordering sequence in jaundice caused by pancreatobiliary carcinoma.

BACKGROUND: Computer-assisted diagnostic systems are not substantially more accurate than the clinician in the differential diagnosis of jaundice but may help in optimal selection and sequencing of tests. The present study aimed to assess with an electronic diagnostic tool the pattern of ordering tests and the diagnostic contribution and related financial cost of each test in jaundiced patients with pancreatobiliary carcinoma, in an effort to make the clinician's diagnostic behaviour more efficient and economical. METHODS: Clinical and diagnostic test data were prospectively gathered from 356 jaundiced patients with pancreatobiliary carcinoma and entered in a Bayesian diagnostic programme. The test results were added to the existing diagnostic evidence, and the programme calculated the diagnostic contribution of each test. RESULTS: A total of 1804 diagnostic tests were ordered. Quantitative assessment of the diagnostic contribution of each test showed that percutaneous transhepatic cholangiography and computed tomography were associated with the highest provision of information. The most cost-effective tests were ultrasonography and liver function tests. CONCLUSIONS: It is possible to determine objectively the diagnostic contribution of each test in establishing the diagnosis of pancreatobiliary carcinoma. The observed physician behaviour in ordering the various diagnostic tests might be improved with regard to its efficacy and its cost-effectiveness profile.

Assessment of liver cirrhosis severity in 1015 patients of the Euricterus database with Campbell-Child, Pugh-Child and with ascites and ascites-nutritional state (ANS) related classifications. Euricterus Project Management Group.

BACKGROUND/AIMS: The assessment of disease stage in cirrhosis is important for the individual patient (prognosis, timing and risk for requiring surgical intervention) and also for population comparisons and trials. There are several established methods, and we have aimed at comparison of the methods within a large cirrhosis population. METHODOLOGY: In the European Union Euricterus database, there are 1015 patients with a "certain" diagnosis of cirrhosis, each of whom in one session had a protocol work-up of history, physical examination and all laboratory investigations needed for this study. The Child-Turcotte (CT), Campbell-Child (C) and Pugh-Child (P) classifications, as well as ascites/no ascites, ascites 1, 2, 3 (no, therapy responsive, nonresponsive) and ascites/nutritional state (ANS, 1-9) scores were used. CT and C have the same 5 variables, P has prothrombin time instead of nutritional state. CT, C and P variables score 1-3 each. C and P furthermore have variable range scores of 5-15. CT, C and P have classes A-C. The variables used were ascites, nutritional state, encephalopathy, bilirubin, albumin and prothrombin time. RESULTS: Only 53 patients (5%) fit within the CT criteria. C and P variable range scores (5-15) correlated strongly (r = 0.84). Cross-over calculation showed slightly different results in the P and C choice of variables, while the variable ranges (1-3) did not matter. Different selection of score ranges for the A-C classes in C and P resulted in 69% class C in P (35% in C) and 3% A in P (19% in C). The patients with ascites (70%) had worse bilirubin, albumin, nutritional states and C and P 5-15 scores (p < 0.0001). Patients with ascites 3 had all variables and also C, P 5-15 scores worse than those with ascites 2 (p < 0.02). ANS scoring showed wasting in 33% of the patients without ascites (ANS 3), 50% of the patients with ascites 2 (ANS 6) and 60% with ascites 3 (ANS 9) (p < 0.0003), and C and P scores were higher in the 3 ANS scores with wasting. CONCLUSIONS: Campbell and Pugh 5-15 scores correlated closely and can be used interachangeably. As C does not contain the more elaborate prothrombin time determination, it probably can be used anywhere in the world. Ascites (degree) and Ascites/Nutritional State (ANS) scoring only use history and physical examination and are, or remain, although less refined, clinically relevant.

The value of clinical assessment in the diagnosis of icterus and cholestasis.

We studied the reliability of the clinical assessment and the discriminatory value of different symptoms and signs in diagnosing obstructive and non-obstructive diseases causing icterus and/or cholestasis. During a period of two-and-a-half years, clinical assessment done by both physicians-in-training and by senior physicians was completed for 266 patients, and the usefulness of different symptoms and signs was tested in 220 of these. Clinical assessment was found to be a reliable method in distinguishing between obstructive and non-obstructive conditions causing icterus, with the sensitivity of 92% and specificity of 86%. In cases of anicteric cholestasis, the sensitivity and specificity of clinical assessment were 74% and 80%, respectively. Abdominal pain and abdominal tenderness were significantly (p less than 0.01) associated with obstructive diseases, whereas an enlarged liver, fever and excessive consumption of alcohol were associated with non-obstructive diseases (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Itching, vomiting, intolerance to fatty foods, previous cholecystectomy, abdominal tumour and clinical icterus had no discriminatory value. Clinical evaluation is a reliable method in the diagnostic workup of a patient with icterus or anicteric cholestasis, and it is still of crucial importance in directing further investigations.

A decision tree for early differentiation between obstructive and non-obstructive jaundice.

We present a method for early differentiation between obstructive and non-obstructive jaundice. On the basis of 14 variables (clinical data and clinical chemical tests, all available within 48 h) a simple decision tree or flow chart has been constructed. The diagnostic yield was as follows: 857 of 982 consecutive jaundiced patients (87%) in a data base and 98 of 108 patients in an independent test sample (91%) were correctly classified. Decision trees for the differentiation between benign or malignant causes within the obstructive group and between acute or chronic causes within the non-obstructive group are also presented. The resulting four-way classification was correct for 77% of the patients in the data base and for 72% of the patients in the test sample. The decision trees are compared with previous methods founded on Bayes' rule and logistic discrimination. The decision trees enable a quick and reliable classification of jaundiced patients, thus providing a valid basis for rational planning of the further diagnostic study.

The utility of ancillary tests in the diagnosis of jaundice.

The helpfulness of technological tests in the diagnosis of diseases presenting as jaundice was examined using a measure of expected utility derived from decision theory. Data from 243 patients admitted with jaundice yielded a total of 2260 test-results from twenty seven tests used. The results were partitioned into a total of 123 bands. Forty-three bands had a sufficient number of results to be considered for calculation. Eleven out of the 27 tests and 16 of 123 bands gave information recognized to be worthwhile. They contributed to the diagnosis of the 7 commonest diseases, and would permit the selection of the best combination of tests to be performed. The frequency of use of tests did not reflect their utility. A test-sequencing proforma might be a useful aid in the work-up of patients.

Síndrome ictérico: valoración clinica y de laboratorio en el diagnóstico / Jaundice syndrome: clinic and laboratory valuation in the diagnosis

Se hace un estudio de 50 pacientes hospitalizados en el Servicio de Medicina del Hospital Central SFP, con el diagnóstico de síndrome ictérico de etiología a determinar durante el periodo comprendido entre Enero a Junio de 1986. El objeto es valorar el aporte de los exámenes auxiliares de laboratorio de uso rutinario en el diagnóstico etiológico. El 48% (24 casos) correspondían al sexo femenino y el 52% (26 casos) al masculino siendo la mayor incidencia de patología entre los 20 y 30 años (40%). Los síntomas y signos que predominaron fueron : ictericia (100%), fiebre (74%), coluria (70%), hepatomegalia (64%), dolor abdominal (54%), hipoacolia (32%). Los exámenes de laboratorio de mayor orientación diagnóstica fueron: Dosaje sérico de biblirrubinas, dosaje sérico de transaminasas, dosaje sérico de fosfatasa alcalina y determinación del antígeno de superficie. las causas del síndrome ictérico observadas en el presente trabajo fueron: Hepatitis viral 42% (21 casos), patologías de vías bibliares 30% (15 casos), hepatitis salmonelósica 16% (08 casos), otras causas 12% (06 casos). El manejo terapéutico en el presente trabajo fue de tipo médico 70% (35 casos) y de tipo quirúrgico 30% (15 casos)

Suspected obstructive jaundice: a decision analysis of diagnostic strategies.

Clinical decision analysis and a computer model were used to evaluate ten diagnostic strategies for the diagnosis of extrahepatic obstructive jaundice. The sensitivity, specificity, complications, and costs of currently used individual tests were used to determine the overall sensitivity, specificity, complications, and costs of each strategy at different disease prevalences. In patients with a low probability of extrahepatic obstructive jaundice (less than or equal to 20%), the optimal strategy begins with ultrasonography, followed by a cholangiogram when dilated ducts are present. When dilated ducts are not present, patients may be observed clinically and endoscopic retrograde cholangiopancreatography is done if the jaundice does not resolve. In patients with a higher probability of extrahepatic obstructive jaundice, a cholangiogram is needed for an accurate diagnosis. In patients with a low probability of extrahepatic obstructive jaundice, the optimal strategy has an overall sensitivity of 92% and a specificity of 99%. About 40% of patients need a cholangiogram at an average cost of $1000 per patient. In patients with a higher probability of extrahepatic obstructive jaundice, the optimal strategy has an overall sensitivity of 97%, specificity of 98%, and cost of $1000 to $1200 per patient.

Dagnostic imaging of the upper part of the abdomen.

The new diagnostic procedures developed during the last several years present a confusing dilemma. The state of the art of ultrasound, computed tomography and nuclear scintigraphy is progressing so rapidly that what one says today is generally out of date tomorrow. However, certain guidelines should be followed in evaluating various organ systems. Generally, ultrasound is the procedure of choice in the upper part of the abdomen in most patients who are not extremely obese or filled with intestinal gas. A sonogram is less expensive than computed tomography and, at the present time, is considered noninvasive compared with compound tomography, which produces a small, but significant, radiation exposure. The accuracy of the two modalities is quite similar. Using the slight advantage that computed tomography may have in a given organ system does not generally override other factors, such as cost and radiation dose. However, mitigating factors, such as obesity, presence or absence of intestinal gas or barium, should be taken into account when selecting patients for either procedure. In many clinical situations, neither computed tomography nor ultrasound should be used until other modalities, such as conventional radiography or scintigraphy, have first been tried. Should the problem not be resolved by these more conventional techniques, an ultrasound or computer tomographic examination may be indicated to delineate further the pathologic condition of the abdomen.

Laparoscopic assessment of the jaundiced patient: a review of 53 patients.

Laparoscopy in the investigation of patients with jaundice allows visualization of intra-abdominal pathology, target biopsy of intra-abdominal lesions and percutaneous fine-needle cholangiography, all to be carried out at the one procedure. Formal laparotomy can then be planned electively or avoided completely in appropriate cases. In our experience we have found laparoscopy with percutaneous fine-needle cholangiography and biopsy to be a useful procedure in the diagnosis and management of jaundiced patients.

[The economical use of methods employed in the diagnosis of jaundice: decisional attitude as opposed to diagnostic attitude (author's transl)]. / Economie de moyens dans le diagnostic des ictères: attitude décisionnelle contre attitude diagnostique.

For the diagnosis of jaundice, a comparison is established between a classical diagnostic attitude and a decisional attitude which consists in guiding and restricting the investigations according to the therapeutic possibilities. It appears from the comparative study of the two groups of patients that the decisional attitude is better, resulting in a treatment which occurs earlier, is less expensive and probably of a better quality.