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Tramping through the Himalayan snows to treat patients after the 2005 Pakistan earthquake, internist Félix Báez could never have imagined he would be on the front lines of Ebola in Sierra Leone nine years later....much less that he would contract the deadly virus, live to tell the story and also to return to his team in Africa to continue the fight. At his side in the Geneva University Hospital, where he was airlifted, was Dr Jorge Pérez, today director of Cuba’s Pedro Kourí Tropical Medicine Institute (IPK), but best known as “Cuba’s AIDS doctor.” Times have changed for both physicians, and Ebola is first on their minds as it rages on. At this writing, while there is cautious optimism in Liberia, the epidemic is not yet under control. Ebola has already infected nearly 22,000 people, taken over 8600 lives; Sierra Leone is one of the countries hardest hit. Among the sick and dying have been too many local health workers: 103 of the 138 infected, at last count. The first to sound the global alarm was Doctors Without Borders, which, like Cuba, already had health professionals on the ground in Africa; they were joined by many more, and Cuba was the country that offered the most assistance once WHO called for nations to step up with funds and, most importantly, human resources. Cuba sent 256 volunteers, all with significant international emergency experience: 38 to Guinea, 53 to Liberia and 165 to Sierra Leone. And more wait in the wings, specially-trained disaster medical workers who have already received their first round of Ebola courses at IPK. These Cuban and other international volunteers are bringing patients back from the brink of death, assisting national health workers and community educators. And people like Jorge Pérez are working to get to the bottom of Ebola to help prevent its spread throughout Africa and to other parts of the world. But to keep an epidemic like this from happening again, it will take more, much more. Not only could the global community have done a better job this time around. But as Jim Kim, President of the World Bank admonished, Ebola didn’t start with disease, but rather with historic inequalities, the virus festering within health systems barely able to function. A lesson for us all. Hours before Dr Báez’s return to Sierra Leone—where he is now—MEDICC Review interviewed him and Dr Pérez at IPK in Havana.

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Neonatologist Dr Fernando Domínguez served two years in a remote municipality of Cuba’s Guantánamo Province upon graduation from medical school in 1973. Continuing his commitment to vulnerable populations, he joined the Cuban team in the Democratic Republic of the Congo, serving as a family doctor attending neonates and children. After returning to Cuba, he completed his pediatric residency and later became head of the neurodevelopment department at Havana’s Ramón González Coro University Maternity Hospital, where he has worked for over three decades. Dr Domínguez holds a doctorate in medical sciences, and since 1995 has served on the board of the Cuban Society of Pediatrics, where he was President from 2005–2011. He is also a member of the Ministry of Public Health’s National Bioethics Commission; President of the Scientific Council of the Manuel Fajardo Medical School; on the Executive Board of the Latin American Association of Pediatrics; and a member of the Permanent Commission of the International Pediatric Association (IPA). Since 2010, he has served on IPA’s Commission for Child Environmental Health and is the Editor-in-Chief of the pediatric section of Infomed, Cuba’s national health portal.

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INTRODUCTION Improved survival rates of neonates with very low birth weight (<1500 g) have led to a higher incidence of neurodevelopmental sequelae. OBJECTIVE Examine neurodevelopment outcomes over the first two years of life of infants who weighed <1500 g at birth, in relation to birth weight, gestational age and 1-minute and 5-minute Apgar scores, in a Havana tertiary care hospital. METHODS A case-series study was conducted to assess neurodevelopment outcomes of very low birth weight infants over their first two years of life. The study population comprised 116 surviving neonates with very low birth weight (<1500 g), born in the Dr Ramón González Coro University Maternity Hospital in Havana, Cuba, 2006–2010. A longitudinal, multidisciplinary and interdisciplinary follow up of all infants’ neurodevelopment was performed, from hospital discharge to age two years, corrected for gestational age at birth. Data on each infant’s perinatal variables were collected: birth weight in grams, gestational age at birth, and 1-minute and 5-minute Apgar scores. Patients were classified as having normal neurodevelopment, mild abnormalities and moderate-to-severe abnormalities. Pearson’s chi-square test was used to determine possible relationships between perinatal variables studied and neurodevelopment, with exact sampling distribution and 95% confidence level. RESULTS Normal neurodevelopment was observed in 69% of very low birth weight infants, 25.9% had mild abnormalities, and 5.2% displayed moderate-to-severe abnormalities. The results demonstrate a statistically significant relationship between gestational age and neurodevelopmental outcomes; more neurodevelopmental abnormalities were found in infants born at earlier gestational age (<30 weeks). CONCLUSIONS Surviving very low birth weight neonates with lower gestational age at birth face a higher risk of neurodevelopmental abnormalities.

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INTRODUCTION Birth weight is considered to be the best predictor of an infant's health status in the neonatal phase. In the Americas, several studies have set the foundation for determining references birth weights. In Cuba there is a report on anthropometric patterns in neonates in 1990 from a maternity ward in Havana, but there are no updated neonatal weight distribution curves by gestational age and sex, as suggested by WHO. OBJECTIVE Create birth weight percentile distribution tables and curves for neonates by gestational age and sex in Holguín Municipality, capital of the eastern Cuban province of the same name. METHODS A retrospective longitudinal study was designed in a universe of 16,018 neonates born alive, delivered within a gestational range of 30 to 42 weeks in the maternity unit of the V.I. Lenin University General Hospital in Holguín Municipality between January 2008 and December 2012. Included were neonates born in the study hospital living in Holguín Municipality; neonates from multiple births were excluded. Variables included gestational age, sex, and birth weight. Gestational age- and sex-specific weight percentile distribution tables and curves were constructed based on observed values. A third-degree polynomial was applied via weighted least squares regression to smooth distribution curves. Analysis of varinance was conducted to compare four years (2008, 2009, 2010 and 2011) and the coefficient of variation was calculated for each week of gestation. RESULTS The average weight of neonates of both sexes rose from week 30 to week 42. The coefficient of variation between weeks 34 and 42 was 11.6%–19% in girls and 12.1%–21.3% in boys. The 10th percentile value at 36 weeks of gestation was 2140 g for girls and 2200 g for boys. For girls, cutoff points for the 10th percentile (small for gestational age infant) were higher at 34–42 weeks and for boys at 36–42 weeks. Applying our cutoff points to this population identified 47% more low birth weight infants than did previously applied standards. CONCLUSIONS Marked differences were found when comparing our tables with tables from other countries. The higher references values for the 10th percentile (compared to previous ones in Cuba) in mean more neonates fall in the low birth weight category, providing greater opportunities to reduce morbidity and mortality in this high-risk group.

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INTRODUCTION Hyperphenylalaninemias are inborn errors of phenylalanine metabolism caused by deficiency of L-phenylalanine hydroxylase (the enzyme that converts phenylalanine to tyrosine), resulting in increased serum phenylalanine (>4 mg/dL or 240 μmol/L). Phenylketonuria, or PKU, is the most common form. Untreated PKU is associated with progressive neurodevelopmental delay, evolving towards intellectual impairment. Cuba introduced a national newborn screening program for PKU in 1986. It has enabled early diagnosis and initiation of dietary treatment, reducing appearance of intellectual impairment in these patients. Originally, confirmatory diagnosis was done only by quantifying serum phenylalanine. In 2010, however, an HPLC method for quantifying serum phenylalanine and tyrosine simultaneously was validated at the National Medical Genetics Center, to perform confirmatory and differential diagnosis of hyperphenylalaninemias, as well as biochemical monitoring of patients diagnosed. OBJECTIVES Describe experience using HPLC confirmatory diagnosis for positive cases from the National Neonatal Screening Program for Phenylketonuria and in biochemical monitoring of diagnosed patients after initiation of dietary treatment. METHODS A descriptive retrospective case-series study was conducted from June 2010 through June 2012. The study population comprised 531 infants who tested positive in the National Neonatal Screening Program for Phenylketonuria. Variables used were serum phenylalanine concentration (first criterion of positivity) and tyrosine, phenylalanine/tyrosine ratio (second criterion, both detected by reverse-phase HPLC with direct fluorescence), hyperphenylalaninemia classification, year of diagnosis, sex, and province of origin. RESULTS Of the samples, 97.7% (519/531) were confirmed as false positives, and 10.4% (55/531) had transient neonatal tyrosinemia. Hyperphenylalaninemia was diagnosed in 12 infants (2.2%): 1.3% (7/531) presented classical PKU, with 34.7 ± 14.7 mg/dL phenylalanine in serum and phenylalanine/tyrosine ratio of 18.9 ± 12.7; and 0.9% (5/531) had persistent hyperphenylalaninemia, with 8.9 ± 3.4 mg/dL of phenylalanine and phenylalanine/tyrosine ratio of 4.5 ± 1.6. Matanzas Province contributed more cases than any of Cuba's 14 other provinces (3/12, 25%) and there was a slight predominance of male sex (7/12, 58.3%). During biochemical monitoring, 83.3% of patients (10/12) reduced their levels of phenylalanine (<5 mg/dL or 300 μmol/L): 5 with classical PKU and all 5 with persistent hyperphenylalaninemia. The incidence of neonatal hyperphenylalaninemias was 1/22,503 live births and 1/38,577 for classical PKU. CONCLUSIONS HPLC for simultaneous quantification of phenylalanine and tyrosine in serum meets the needs of a confirmatory test for patients testing positive in Cuba's National Neonatal Screening Program for Phenylketonuria (which has high false positive rates). It has enabled introduction in Cuba of a second PKU diagnostic criterion of positivity for both the classification of hyperphenylalaninemias and the biochemical monitoring of diagnosed patients.

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INTRODUCTION Cytomegalovirus and herpes simplex virus are associated with congenital or perinatal infection, causing potential damage to the newborn. OBJECTIVES Determine the prevalence of active or latent infection by cytomegalovirus and herpes simplex virus in a population of mothers, congenital infection by these agents in their infants, and association between prevalence of virus infection in mothers and in their newborns. METHODS A cross-sectional study was conducted from June to September 2012 in a population of 95 pregnant women admitted to the Dr Ramón González Coro University Maternity Hospital during the third trimester of pregnancy, and their infants (98). Patients were tested for antibodies specific to these viruses; vaginal swabs and urine from the women and serum and urine from the newborns were tested for viral genome. The Fisher exact test with 95% confidence interval was used for comparisons. RESULTS Of the women studied, 89.5% tested positive for cytomegalovirus and 83.2% for herpes simplex. Active infection from cytomegalovirus was detected in 16.7%, and from herpes simplex in 3.2%. Congenital cytomegalovirus infection was detected in 4.1% of newborns; no herpes simplex virus infection was found in this group. Two newborns of women with active cytomegalovirus infection were congenitally infected. CONCLUSIONS Serology demonstrated that most of the women were immune to both viruses. Active cytomegalovirus infections are common in this population, and newborns of women with active cytomegalovirus infection during pregnancy are at increased risk of congenital infection.

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INTRODUCTION In recent years, global initiatives to address the AIDS epidemic have produced promising advances through access to effective treatment programs. However, lack of adherence to antiretroviral therapy is a problem for pediatric patients. OBJECTIVES Explore antiretroviral therapy adherence in children and adolescents living with HIV/AIDS in Cuba and examine its relationship with psychosocial, individual and treatment factors. METHODS A qualitative study was carried out of 21 caregivers of children and adolescents with HIV/AIDS. Demographics and information on treatment regimen were collected by chart review. Indepth interviews were conducted to assess adherence and examine its relationship with psychosocial, individual and treatment factors. Interviews were transcribed and the information was grouped by factor category. Adherence was analyzed in relation to these three sets of factors. RESULTS Caregivers interviewed reported adequate adherence in 17 of the 21 children. Lack of adherence was linked primarily to psychosocial factors such as additional responsibility taken on by the caregiver while grappling with his or her own illness, the presence of untreated psychological symptoms in the caregiver, perceived difficulties with family support, the child’s age, and assigning treatment responsibilities to the child without taking into account his/her psychological maturity. CONCLUSIONS The study revealed a high level of antiretroviral therapy adherence. It reconfirmed the fundamental importance of the caregiver and family support for therapeutic success in children and adolescents living with HIV/AIDS. These results, as well as the factors identified in cases of nonadherence, can contribute to a framework for assessment and specialized interventions to optimize pediatric antiretroviral adherence.

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INTRODUCTION Primary hypertension has its origins in childhood and is a risk factor for atherosclerosis; it is considered an important health problem because of its high prevalence worldwide. OBJECTIVE Describe the development of hypertension during adolescence, including some factors that influence its persistence and progression in Cuban adolescents. METHODS A cohort study was conducted in an intentional sample of 252 apparently healthy adolescents from the catchment area of the Héroes del Moncada Polyclinic in Plaza de la Revolución Municipality, Havana. They were assessed in two cross-sectional studies in 2004 and 2008. Mean age at first assessment was 13.2 years, 17.1 years at the second. Variables were weight, height, body mass index, waist circumference, blood pressure, smoking, family history of hypertension and birth weight. Correlation coefficients and growth curve analyses were applied to assess blood pressure persistence. Risk of developing prehypertension and hypertension was estimated in the second assessment, based on predictors identified in the 2004 cut. Forecasting models with these factors were developed using classification trees as analytical tools. RESULTS Of the six adolescents categorized as hypertensive in the first assessment, five still showed blood pressure alterations after four years. The main factors related to hypertension in those aged 16–19 were blood pressure itself and a body mass index >90th percentile, followed by low birth weight and abdominal obesity. Prognostic models for predicting this condition at the end of adolescence demonstrated the importance of blood pressure alterations at age 12–15 years. CONCLUSIONS High rates of persistence and progression of hypertension during adolescence highlights the need for systematic blood pressure screening at the primary health care level and adoption of primary prevention strategies beginning in childhood.

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INTRODUCTION Acute liver failure is rare in pediatric patients and is one of the most challenging medical emergencies due to its prognostic and therapeutic implications. The best scientific evidence worldwide comes from multicenter studies in developed countries. In Cuba, there are no prior studies of this disorder in children. OBJECTIVES Describe the main clinical features of Cuban children treated at a national referral center for acute liver failure, as defined by recognized diagnostic criteria for pediatric patients. METHODS A case series study was conducted comprising patients diagnosed with acute liver failure treated from 2005 to 2011 in the hepatology and liver transplant service at Havana’s William Soler University Children’s Hospital. Variables were age group, etiology of acute liver failure, grade of hepatic encephalopathy, blood chemistry variables, and clinical outcome (whether or not spontaneous recovery of liver function occurred). Associations between variables were assessed using contingency tables, and case fatality was calculated, as well as relative risk with its 95% confidence interval. The Mann-Whitney U test was used to compare means of laboratory test results. RESULTS Median age of the 31 patients studied (14 boys and 17 girls) was 24 months (range 1–180). Time between symptom onset and diagnosis of acute liver failure was 25.1 days (SD 16.8). Infection was the most common etiology, present in 61.3% of cases (19/31); nonhepatotropic viruses, especially cytomegalovirus, predominated in infants. Spontaneous recovery occurred in 15 patients (48.4%), 3 (9.7%) received transplants, and 13 died, for a case fatality of 41.9%. Outcome was not associated with etiology (p = 0.106), but was statistically associated with degree of hepatic encephalopathy (p <0.01): 77.8% of patients (7/9) with grades III-IV encephalopathy died, for a relative risk of 4.0 (95% CI 1.15–13.8), versus 11.1% (1/9) with grade II or less encephalopathy. Cholesterol levels were significantly lower in patients who failed to recover spontaneously (p <0.01). CONCLUSIONS Patients’ clinical characteristics in this case series were similar to those described in developed countries.The fact that nonhepatotropic viruses (basically, cytomegalovirus in infants) are the main cause of acute liver failure in Cuban children calls for further epidemiologic study and identification of local underlying determinants of this phenomenon.

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INTRODUCTION Lung cancer is one of the leading causes of death worldwide and in Cuba, where its incidence and mortality are on the rise. Diagnostic delay is a variable linked to survival and prognosis. Quantifying this delay and comparing it with data from other national and international sources may lead to planning actions to reduce its impact. OBJECTIVE Assess diagnostic delay of lung cancer in patients at the Joaquín Albarrán Clinical-Surgical Teaching Hospital, Havana, Cuba, from 2007 to 2010. METHODS A retrospective descriptive study was conducted based on administrative data from patients diagnosed with lung cancer. The length of overall diagnostic delay was determined, as well delay between symptom onset and the patient's first contact with the health system, and delay at the primary and secondary levels of the national health system. Descriptive statistics were used to summarize the different time intervals. RESULTS The study comprised a total of 54 patients; 74.1% were men; the largest age group was 51–60 years. Of the total, 61.1% sought care first at the primary level. Total diagnostic delay for these patients was 67.4 days: 24.3 days due to patient delay (SD 32.8), 16.2 days due to primary care delay (SD 5.2), and 26.9 days due to secondary care delay (SD 20.1). The total delay for patients first seen at the secondary care level was 79.1 days (SD 81.8): 47.8 days due to patient delay (SD 25.6), and 31.3 days due to secondary level delay (SD 14.4). CONCLUSIONS Diagnostic delay in lung cancer is high. Patients who went directly to hospital did not benefit from shorter delay in diagnosis.

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A review/analysis of current literature on exemplary multicenter registries of clinical dementias was conducted as a comparative basis for a proposed Cuban registry on cognitive impairment and dementia. The study of mental health disorders has been predominantly based on clinical concepts and criteria, and only in recent years a public health approach has been applied. Traditional epidemiological studies do not reveal patterns of cognitive impairment and behavioral disorders (particularly dementias) in routine clinical practice in a defined geographic area, which would provide essential information for longterm planning and allocation of health and social resources. Thus, multicenter clinical registries have become an important source of clinical and epidemiological data on dementias in recent decades. This article addresses the Cuban proposal for an automated national dementia registry, comparing it to others internationally. The registry would be housed in the Neurology and Neurosurgery Institute, and would include a duly protected surveillance network hosted on the Institute's website. Such a multicenter dementia registry based on epidemiological surveillance methods and limited to a defined area would provide new, valid, representative and current data on dementia occurrence patterns by subtype, flow of case identification and referral from primary care, as well as the main clinical features of patients at the time of their first contact with health services. This information would support development of health planning policies for implementation of programs aimed at improved distribution of social and health resources in the affected population, monitoring of the disorder's natural evolution and identification of preventive measures. The scientific benefits would be equally important: production of new knowledge, generation of hypotheses for clinical research projects, standardization of diagnostic criteria, and promotion of multicenter research in both national and multinational centers.