Systemic Ozone Therapy by Rectal Insufflation for Immunoglobulin A Deficiency
January 2018, Vol 20, No. 1

INTRODUCTION IgA deficiency is a primary immunodeficiency predominantly due to an antibody defect, for which there is no replacement therapy. Treatment consists of prevention and treatment of infections and other associated conditions. Given the immunomodulatory and regulatory properties of the redox balance of ozone therapy in infectious and inflammatory conditions, evaluation of its effect on IgA deficiency is of interest.

OBJECTIVE Assess the benefits and possible adverse effects of ozone treatment in patients with IgA deficiency.

METHODS A monocentric randomized controlled phase 2 clinical trial (RPCEC 00000236) was carried out, after approval by the Institutional Ethics Committee of the Roberto Rodríguez Fernández Provincial General Teaching Hospital in Morón, Ciego de Ávila Province, Cuba. Included were 40 patients aged 5–50 years, distributed in 2 groups of 20, after agreeing to participate and signing informed consent. The experimental group received 2 cycles of ozone by rectal insufflation for 20 days (5 times a week for 4 weeks each cycle) with a 3-month interval between cycles, for a total of 40 doses, with age-adjusted dose ranges. The control group was treated with leukocyte transfer factor (Hebertrans), 1 U per m<sup>2</sup> of body surface area subcutaneously, once weekly for 12 weeks. Frequency of appearance and severity of clinical symptoms and signs of associated diseases, serum immunoglobulin concentrations and balance of pro-oxidant and antioxidant biomarkers were recorded at treatment initiation and one month after treatment completion. Therapeutic response was defined as complete, partial, stable disease or progressive disease. Descriptive statistics and significance were calculated to compare groups and assess effect size.

RESULTS One month after treatment completion, 70% of patients in the experimental group experienced significant increases in IgG
(p = 0.000) and IgM (p = 0.033). The experimental group also displayed decreased pro-oxidation biomarkers, glutathione modulation and increased antioxidant enzymes, with reduced oxidative stress; none of these occurred in the control group. Complete therapeutic response was achieved in 85% of patients in the experimental group and only 45% in the control group. Mild, transient adverse events were reported in both groups.

CONCLUSIONS Ozone therapy by rectal insufflation is a suitable therapeutic option for treating IgA deficiency because it produces antioxidant and immunomodulatory effects and is feasible, safe and minimally invasive.

KEYWORDS Ozone therapy, IgA deficiency, primary immunodeficiency, oxidative stress, antioxidants, pro-oxidants, Cuba

CONTRIBUTION OF THIS RESEARCH This paper introduces in Cuba a new treatment a for IgA deficiency, with immunomodulatory and antioxidant effects offering substantial clinical benefits to patients with this immunodeficiency.

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Liver Stiffness Reference Values for Healthy Cuban Adults
January 2018, Vol 20, No. 1

INTRODUCTION Reference values for liver stiffness for healthy individuals vary worldwide. Different optimal cutoff values correspond to the stages of fibrosis in chronic liver disease.

OBJECTIVES Characterize the distribution of liver stiffness in Cuban adults without liver disease and its association with age, serum uric acid and body mass index.

METHODS A cross-sectional study was performed of 110 plasma donors recruited from the Havana Province Blood Bank January 2016 through February 2017. Measurements of liver stiffness were performed using a FibroScan elastography device on the same day of laboratory analyses and abdominal ultrasound. The Pearson coefficient was used to assess correlations, and the reference range was calculated using the mean and its 95% confidence interval.

RESULTS Liver stiffness values observed ranged from 2.2–6.3 kPa. The reference range (95% CI) for the 110 subjects without known liver disease was 4.2–4.6 kPa (mean 4.4). A positive correlation was observed between liver stiffness measurements and body mass index (r = 0.255, p <0.01) and serum uric acid (r = 0.266, p <0.01). There was no correlation between liver stiffness and age. Liver stiffness in women was similar to that of men, 4.3 (2.4–6.1) and 4.5 (2.2–6.3) kPa, respectively (p = 0.086).

CONCLUSIONS Liver stiffness in Cuban adults without liver disease ranges from 2.2–6.3 kPa. The reference range is 4.2–4.6 kPa. Body mass index and serum uric acid levels are positively associated with liver stiffness.

KEYWORDS Liver disease, liver fibrosis, hepatic cirrhosis, hepatic fibrosis, diagnostic imaging, elastography, sonoelastography, elasticity imaging techniques, tissue elasticity imaging, technology assessment, Cuba

CONTRIBUTION OF THIS RESEARCH This is the first Cuban study using FibroScan to measure liver stiffness; its results will enable better assessment of liver disease in clinical practice.

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Brain Metastases in Havana Cancer Patients
January 2018, Vol 20, No. 1

INTRODUCTION Cancer is a major public health problem worldwide and in Cuba. Approximately one third of cancer patients develop a brain metastasis. Despite this, epidemiological studies are scarce, internationally and in Cuba; published research is mainly limited to autopsy studies and hospital case series.

OBJECTIVE Characterize patients with brain metastases residing in Habana del Este Municipality, Havana, Cuba, with respect to demographics, metastasis location and primary tumor site.

METHODS A retrospective descriptive study was carried out with data for all patients with histologically confirmed cancer diagnosed in 2014 and registered in primary health care in Habana del Este Municipality. Diagnostic reports from computed tomography and/or magnetic resonance imaging were used to identify patients with brain metastases. Study variables were age, sex, skin color, number and location of brain metastases, control of primary tumor, and presence of extracranial metastases. Percentages were calculated and presented in tables.

RESULTS We identified 832 cancer patients in the Habana del Este population of 181,473 (prevalence 458.5 per 100,000 population). Among patients with cancer, 27.6% (230/832) had brain tumors, among which 83% (191/230) were brain metastases and 17% (39/230) primary tumors, a ratio of 4.9:1. Brain metastases appeared in 23% (191/832) of cancer patients (prevalence 105.2 per 100,000 population). Among patients with brain metastases, 48.2% (92/191) were aged 41–60 years and 61.3% (117/191) were female sex. The majority, 59.7% (114/191) had multiple metastases. The most frequent primary tumor location was the breast (40.8%, 78/191), followed by the lung (31.9%; 61/191); 46.8% (211/451) of brain metastases were in the parietal lobe.

CONCLUSIONS Brain metastases are more prevalent in this Cuban municipality than reported in other countries, but they constitute a higher proportion of cancer cases than seen in other population-based studies. The study’s results underline the importance of detecting brain metastasis early, to permit timely interventions to improve quality of life and survival.

KEYWORDS Cancer, neoplasm metastasis, tumor metastasis/brain, epidemiology, prevalence, Cuba

CONTRIBUTION OF THIS RESEARCH This is the first epidemiological study of brain metastases in Cuba and one of the few carried out internationally.

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Treatment of Basal Cell Carcinoma with Interferons Alpha-2b and Gamma in Primary Care
January 2018, Vol 20, No. 1

INTRODUCTION Interferons have been used to treat basal cell carcinoma with positive results. Cuba’s Genetic Engineering and Biotechnology Center developed HeberPAG, a combined formulation of interferons alpha-2b and gamma, for treatment of basal cell carcinoma of any size, subtype and location.

OBJECTIVE Evaluate the safety and effectiveness of using HeberPAG in primary care to treat basal cell carcinomas.

METHODS A descriptive observational study was conducted of basal cell carcinoma treated with HeberPAG. The sample comprised 21 tumors in 19 patients who met selection criteria. The dose was 3.5 million international units of antiviral activity administered by perilesional infiltration 3 times a week for 3 weeks. Clinical monitoring and laboratory testing of patients was conducted before treatment initiation and at 4, 8, 16 and 52 weeks. Variables recorded were: age, sex, skin phototype, clinical and histologic type, clinical response to treatment, changes in tumor diameters and adverse events. Four response categories were included: complete response, partial response, stable disease and progressive disease. Data were recorded in medical dossiers. Microsoft Excel and SAS were used for data management and calculation of measures of frequency, central tendency and dispersion.

RESULTS Of 19 patients studied, 63% were male, and 63% aged 61–80 years. At 16 weeks, there was an objective response in 76% of tumors (8 complete and 8 partial responses). Fewer objective responses were seen in rodent ulcer, advanced invasive and sclerosing clinical types and in the sclerodermiform histologic type. Mean sum of diameters decreased from 36.9 mm (SD 4.1 mm) to 10.3 mm (SD 18.3 mm). One-year recurrence was 10%. The most common adverse reaction was flu-like syndrome, consisting of fever, malaise, joint pain and muscle pain.

CONCLUSIONS Basal cell carcinoma can be successfully treated in primary care settings with a combination of interferons alpha-2b and gamma administered by trained personnel. At the dose employed in this study, the formulation produces a favorable response in basal cell carcinomas of low clinical and histologic risk, and is well tolerated, with only mild side effects.

KEYWORDS Basal cell carcinoma, interferons, interferon alpha-2b, interferon gamma, primary care, Cuba

CONTRIBUTION OF THIS RESEARCH This study demonstrates the feasiblity of treating basal cell carcinoma in primary care settings with a combined formulation of interferons alpha-2b and gamma, enabling management in primary care of a cancer usually treated in hospital.

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Human Evolutionary Carcinogenesis and Effects of Demographic and Epidemiologic Transitions in Low- and Middle-Income Countries
October 2017, Vol 19, No 4

INTRODUCTION In many countries cancer is or threatens to become the leading cause of death, although incidence and mortality rates differ between high-income and low- and middle-income countries. Developments in evolutionary biology have revealed that carcinogenesis is even more complex than previously thought. Several theories attempt to integrate the various existing points of view about what is known to date.

OBJECTIVES Analyze and explain the main current theories of carcinogenesis and explore their possible application to understanding the demographic and epidemiologic transitions’ effects on cancer population dynamics in low- and middle-income countries.

EVIDENCE ACQUISITION A systematic literature review was carried out in MEDLINE (via PubMed), SCOPUS (via ScienceDirect) and SciELO. Consistency and quality of evidence in articles reviewed were taken into account; we excluded studies with consistency levels of IV and V, and those with limited or insufficient quality of evidence.

DEVELOPMENT Human evolution has led to a type of life history characterized by numerous tradeoffs with oncogenic implications. Cultural coevolution and socioeconomic development have affected cancer population dynamics. Several theories explain carcinogenesis from an ecological and evolutionary perspective, among them somatic mutation, adaptive oncogenesis, life history theories, and the Noble and Hochberg model. The human environmental effect on cancer risk is manifested in the influence of demographic and epidemiologic transitions in low- and middle-income countries, where cancer represents a high disease burden due to the effects of recently introduced environmental factors in native environments, accentuation of adaptive decoupling, and diversification of genetic polymorphisms for cancer susceptibility.

CONCLUSIONS The Noble and Hochberg model best explains the population dynamics of cancer in low- and middle-income countries, especially regarding the effects of recently introduced environmental factors on native environments, adaptive decoupling and genetic diversity (manifest in differences in clinical and biological tumor expression by level of economic development), in response to demographic and epidemiologic transitions.

KEYWORDS Carcinogenesis, oncogenesis, tumorigenesis, population dynamics, health transition, biological evolution, cultural evolution, life history theory, Cuba

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Determinants of Virulence and Antimicrobial Susceptibility in Non-O1, Non-O139 Vibrio cholerae Isolates
October 2017, Vol 19, No 4

INTRODUCTION In the Caribbean region, acute diarrheal diseases caused by the Vibrio genus have increased in recent years, following the 2010 earthquake in Haiti. Based on its capsular lipopolysaccharide, Vibrio cholerae is classified into more than 200 serogroups, divided into O1, O139 and non-O1, non-O139. Non-O1 serogroups produce clinical features ranging from mild diarrhea to severe dehydration. In Cuba, circulation of non-O1, non-O139 V. cholerae has been reported both in outbreaks and sporadic cases.

OBJECTIVE Describe the antimicrobial susceptibility of V. cholerae to the drugs of interest used in its treatment and verify the presence of enzymatic virulence factors.

METHODS A descriptive, cross-sectional study was conducted in January through November 2014, based on 125 non-O1, non-O139 V. cholerae isolates obtained during 2013 and 2014 from patients with acute diarrheal disease (isolates from the National Reference Laboratory for Acute Diarrheal Diseases of the Pedro Kourí Tropical Medicine Institute, Havana). Bacteriological identification was performed according to conventional methods. Antimicrobial susceptibility was determined by the Bauer-Kirby agar diffusion method. The technique described by Robinson in 1986 was used to determine virulence factors, hemolytic activity and enzyme factors (DNase, elastase, gelatinase), and Karagozova’s method for the enzyme lecithinase.

RESULTS Highest percentages of sensitivity were obtained for azithromycin (98.4%), doxycycline (97.6%) and ciprofloxacin (96.8%), and highest resistance values for ampicillin (60%), sulfonamide (46.4%) and trimethoprim–sulfamethoxazole (32%). Six resistance patterns were detected, four found in Cuba for the first time, as well as six patterns of multidrug resistance (4.8%). All isolates had at least two extracellular enzymes as virulence factors. The most frequent were gelatinase (90.4%) and lecithinase (77.6%). The percentage of virulence factors was lower in the group of isolates resistant to ≥2 antimicrobials. An inverse relationship was found between presence of enzymatic virulence factors and resistance in the isolates studied.

CONCLUSIONS The results suggest that azithromycin, doxycycline and ciprofloxacin should continue to be used for treatment of V. cholerae-caused infections, and confirmed the presence of four new resistance patterns in isolates circulating in Cuba.

KEYWORDS Vibrio cholerae, cholera, antimicrobial resistance, multiple drug resistance, multidrug resistance, virulence, virulence factors, pathogenicity, Cuba

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Predicting Abdominal Surgery Mortality: A Model Based on Intra-abdominal Pressure
October 2017, Vol 19, No 4

INTRODUCTION Early assessment of prognosis following major abdominal surgery is associated with decreased risk of complications and death. While scoring systems are useful in this regard, there is no index that enables comprehensive individual patient assessment and is also applicable in ICUs with limited resources.

OBJECTIVES Demonstrate that a model based on intra-abdominal pressure is effective in predicting death after major abdominal surgery.

METHODS A prospective observational study was done of 300 post–abdominal-surgery patients admitted to the ICU of a university hospital affiliated with the General Calixto García Medical Faculty, in January 2008 through January 2010. Patients were randomly assigned (2:1) to two groups: test and validation. The independent variable was vital status at discharge (alive or deceased); independent variables were age, sex, malignancy, APACHE II score and intra-abdominal pressure. In the test group, three mathematical models were fit to predict death (APACHE II, intra-abdominal pressure, and APACHE II plus intra-abdominal pressure), which were later validated in the second group. Each model’s capacity to discriminate between living and deceased was evaluated according to sensitivity and specificity of receiver operating characteristic curves. Calibration was assessed with the Hosmer–Lemeshow goodness-of-fit test and comparison of receiver operating characteristic curves by chi-square test of homogeneity. Each patient was followed until hospital discharge or death.

RESULTS The three mortality prediction models displayed excellent calibration and discrimination, very similar predictive power, and no differences among their respective areas under the curve (chi square 2.802, p = 0.094). Variables with the most influence on probability of death were age, APACHE II score and intra-abdominal pressure.

CONCLUSIONS The three models show good capacity and similar effectiveness to predict death after major abdominal surgery. The model based on intra-abdominal pressure is the most feasible in limited-resource settings.

KEYWORDS Abdominal surgery, APACHE II, intra-abdominal pressure, mortality, prediction model, evidence-based medicine, decision modeling, decision support techniques, Cuba

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Biosimilars and the Real World
October 2017, Vol 19, No 4

Biotechnology has changed the pharmacopeia. It is expected that in the next five years, 50% of biological products will originate from biotechnology. Yet, treatments based on effective, costly biopharmaceuticals for prolonged use hamper the goals of ensuring universal therapeutic coverage and access to the best treatments. This conflict surfaced 30 years ago with synthetic drugs, and the solution was to create generics once the developers’ patents expired. Biosimilars are not generics, strictly speaking, as it is impossible to guarantee that they are molecularly identical to the original product; nor are they completely new products, as they rely on a great deal of prior work done by other scientists. National strategies are needed to ensure the broadest possible coverage in the best interests of the population. The key to a strategy to ensure access to the best treatment available lies in the concept of “totality of evidence,” which includes all information about a given molecular structure and its mechanism of action; safety and efficacy information from the first clinical trials; and monitoring data from products’ use in medical practice. A strategy of broad biological and molecular categorization plus intense pharmacovigilance would reduce development costs, the main barrier to widespread access.

KEYWORDS Biosimilar pharmaceuticals, biosimilars, biologics, legislation, social control, health services accessibility, health services needs and demand, Cuba

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Statistical Modeling in Health Research: Purpose Drives Approach
April–July 2017, Vol 19, No 2–3

Statistical modeling is commonly used in both predictive and explanatory studies in health research. Its use in Cuba continues to grow, although it is sometimes employed inappropriately, which can lead to errors that imperil validity. This article attempts to shed light on faulty practices in statistical modeling by examining and discussing the main differences between explanatory and predictive models, with reference to the following: study objectives, theoretical considerations in model-building, aspects requiring assessment, variable and algorithm selection, analysis of confounders, treatment of multicollinearity, and reporting results.

KEYWORDS Prognosis, risk factor, protective factor, causality, statistical models, linear models, predictive models, explanatory models, logistic regression, Cuba

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Measuring Health-related Quality of Life in Cuban Patients with Head and Neck Cancer
April–July 2017, Vol 19, No 2–3

INTRODUCTION Quality of life measurement is an important aspect of comprehensive clinical assessment. It does not have a set definition, but changes according to sociocultural context. Head and neck cancer patients experience substantially decreased health-related quality of life. The Cuban public health system needs to develop its own instrument to measure these patients’ quality of life.

OBJECTIVES. Construct and validate an instrument to measure quality of life in Cuban patients with nasopharyngeal, laryngeal, oral or mesopharyngeal cancer.

METHOD The sample comprised adult patients treated for nasopharyngeal, laryngeal, oral or mesopharyngeal cancer in Cuba’s National Oncology and Radiobiology Institute in 2013 and 2014. To construct and validate the instrument, we selected a sample of 520 patients. Initial interviews were held until no substantially new information emerged; 40 patients were selected to participate in focus groups to identify important problems leading to decreased health-related quality of life. Face validity of the preliminary questionnaire was assessed with 40 patients. Internal consistency and validity were assessed with 400 patients. Score stability was assessed with another 40 patients using a test–retest design. There were 24 experts who participated in the process, 15 in the construction phase and 9 in the content validity evaluation of the preliminary version. Assessment of reliability and validity was based on internationally recognized approaches, including Cronbach alpha and empirical verification of convergent, discriminant, clinical and predictive validity. Response burden was also assessed (completion time and item nonresponse).

RESULTS A 65-item questionnaire, CV-IOR-CyC-01, was developed and validated, with three domains (physical functioning, psychosocial functioning and family relationships, disease symptoms and treatment side effects) and two ungrouped questions on perceived general health and perceived health-related quality of life. The instrument displayed satisfactory reliability (homogeneity and stability) and validity (face, content, convergent, discriminant, clinical and predictive). Test–retest correlation was strong. Large differences and a downward trend in health-related quality of life across clinical stages and moderate or high standardized response mean values reflect good clinical and predictive validity. Response burden was acceptable (completion time 6.2 minutes, item nonresponse rate 1.3%–3.8%).

CONCLUSIONS CV-IOR-CyC-01’s psychometric properties justify its use in clinical trial protocols with patients with nasopharyngeal, laryngeal, oral or mesopharyngeal cancer.

KEYWORDS Validation studies, psychometrics, health-related quality of life, head and neck cancer, head and neck neoplasms, qualitative research, Cuba

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Origin and Evolutionary History of HIV-1 Subtype B in Cuba
April–July 2017, Vol 19, No 2–3

INTRODUCTION Cuba’s HIV epidemic is characterized by high genetic diversity, with circulation of several subtypes and recombinant forms. Earlier studies described a predominance of subtype B in the HIV-positive population, but these studies did not take into account patients’ epidemiologic history.

OBJECTIVE Clarify the origin and phylodynamics of HIV-1 subtype B in the Cuban epidemic.

METHODS We analysed phylogenetic relationships among 120 sequences (from different geographic origins) of the pol gene in HIV-1 subtype B isolates from Cuban patients diagnosed from 1987 through 2012. Time of HIV-1 subtype B introduction and viral evolutionary rate were determined using a Bayesian coalescent method.

RESULTS Based on phylogenetic relationships, subtype B was introduced into Cuba multiple times. Subtype B spread in Cuba through dissemination of strains that probably came from the USA, Canada and Europe. The time of the most recent common ancestor of Cuban subtype B was close to 1977 (95% CI 1974–1982), and the evolutionary rate was 2.7 x 10-3 nucleotide substitutions per site per year.

CONCLUSIONS Our results suggest multiple introductions of HIV-1B into Cuba in the late 1970s, predominantly strains from North America and Europe. The results reflect the importance of maintaining, reviewing and updating molecular epidemiology of HIV-1 in Cuba, due to its rapid evolution and possible implications for the National STI/HIV/AIDS Program of Cuba’s Ministry of Public Health.

KEYWORDS HIV-1, subtype B, HAART, molecular epidemiology, molecular evolution, phylodynamics, Cuba

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Association of Antineuronal Antibody Levels with Cognitive Impairment in Older Cuban Adults
April–July 2017, Vol 19, No 2–3

INTRODUCTION Alzheimer disease is the main cause of dementia associated with aging in Cuba and the world. Development of methods for early diagnosis is vital to increasing intervention effectiveness and improving patient quality of life. Recent studies have shown associations between alterations in serum levels of antineuronal antibodies and Alzheimer disease pathology. However, the specific relationship between such antineuronal antibodies and Alzheimer pathogenesis remains unclear because of the great variety of antibodies identified and their heterogeneity among patients and nondemented controls.

OBJECTIVE Assess the association between serum levels of antibodies against neuronal antigens (total brain protein, aldolase and amyloid beta protein) and cognitive performance in older Cuban adults.

METHODS A cross-sectional pilot study was conducted of adults aged ≥65 years living in Havana’s Playa Municipality and Artemisa Province (southwest of Havana). A sociodemographic and risk factor questionnaire was administered, neuropsychological assessment conducted, and physical and neurological examinations performed. A relative or caregiver was also interviewed. Laboratory tests included: complete blood count, glycemia, lipid panel, and apolipoprotein E genotype. Of 143 individuals studied, 33 were cognitively normal, 52 had mild cognitive impairment, and 58, probable Alzheimer disease. Serum antibody levels were determined by ELISA and compared using covariance analysis with a significance level of 0.05. ELISA specificity, sensitivity and predictive value were assessed by analyzing their respective diagnostic performance curves.

RESULTS Patients with probable Alzheimer disease performed least well on the mini mental state examination (cognitively normal 28.8, SD 1.2; mild cognitive impairment 27.4, SD 2.2; probable Alzheimer disease 12.9, SD 6.5; ANOVA p <0.001). The percentage of Apo E4 carriers was seven times greater in the group with probable Alzheimer disease than in the cognitively normal group. Among the antibodies studied, only those against amyloid beta peptide had levels significantly higher in the Alzheimer disease group than in the cognitively normal group (p = 0.007) and the group with mild cognitive impairment (p = 0.002).

CONCLUSIONS Results support the presence of an autoimmune component in Alzheimer disease and suggest that serum anti–amyloid-beta could be used for its diagnosis.

KEYWORDS Dementia, Alzheimer disease, mild cognitive impairment, autoantibodies, E4 apolipoprotein, Apo E4, enzyme-linked immunosorbent assay, ELISA, immunoassay, immunosorbent techniques, amyloid beta protein, Cuba

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Cuban Exogenous Pulmonary Surfactant in Treatment of Pediatric Acute Respiratory Distress Syndrome
April–July 2017, Vol 19, No 2–3

INTRODUCTION Acute respiratory distress syndrome is a complex heterogeneous disorder with low incidence but high case fatality in children. Treatment with pulmonary surfactants is a possible option. Surfacen, a Cuban exogenous pulmonary surfactant, has been proven safe and effective in premature newborns with hyaline membrane disease, but evidence regarding its efficacy in older children is still inconclusive.

OBJECTIVE Determine Surfacen’s efficacy in improving oxygenation and increasing survival in children with acute respiratory distress syndrome.

METHODS A multicenter (five pediatric intensive care units in four provinces), open-label, controlled, randomized phase III clinical trial with two treatment groups was conducted from November 2009 through August 2013, with 19 girls and 23 boys aged 1 month to 18 years. The experimental group (20 patients) received conventional treatment (oxygenation and mechanical ventilation) plus intratracheal instillation of Surfacen (100 mg/4 mL) every eight hours for three days. The control group (22 patients) received only conventional treatment. The primary dependent outcome was patient vital status (alive or deceased) 28 days after study enrollment. Other variables and outcomes analyzed were age, sex, ARDS presentation, Kirby index (arterial oxygen tension over inspired oxygen fraction), oxygenation index, static lung compliance, transcutaneous oxygen saturation, radiographic course, mechanical ventilation time and length of stay in neonatal intensive care. Statistical tests used were the chi-square test and Fisher exact test.

RESULTS On day 28, there was 80% survival in the experimental group versus 38.1% in the control group. There were significant differences between the experimental and the control group in Kirby index, oxygenation index, static lung compliance and radiographic course, all favoring the experimental group. For every 2.38 patients treated in total, there was one additional survivor in the experimental group.

CONCLUSIONS When combined with conventional therapy in the regimen employed, Surfacen improves oxygenation and increases survival in children with ARDS.

KEYWORDS Exogenous pulmonary surfactant, acute pulmonary distress syndrome, ARDS, children, intensive care, Cuba

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Neonatal Surgery Case Fatality and Associated Factors in a Cuban Pediatric Hospital, 2005–2015
April–July 2017, Vol 19, No 2–3

INTRODUCTION Newborns in need of surgery are a challenge to manage and require highly specialized centers with multidisciplinary surgical teams. Since the 1980s, neonatal surgical survival has increased by up to 70% in some countries, mainly due to advances in neonatal intensive care, anesthesia and surgical technique.

OBJECTIVE Describe surgical case fatality and survival in a neonatal reference hospital in Cuba, estimate risk of death, and identify potential risk predictors among neonatal characteristics.

METHODS A retrospective cohort study was conducted based on hospital administrative data and clinical records for a series of surgical cases in the neonatal intensive care unit of Havana’s William Soler University Children’s Hospital from January 2005 to December 2015. All neonates who underwent surgery during the study period were included. The dependent variable was discharge status (alive, deceased); independent variables were: sex, age (in days) at time of surgery, gestational age, birth weight, indication for surgery, surgical order (first, repeat), and presence of sepsis or other postoperative complications. The study used contingency tables to analyze associations between neonatal characteristics and discharge status. A classification tree was used to obtain simple estimates of surgical risk.

RESULTS Survival was 91.3% (675/739) among 739 neonates who underwent surgery. The majority were male (58.7%, 434/739), full term (84.2%, 622/739), and of normal birth weight (80.6%, 596/739). Most surgeries were performed in the first 10 days of life. Digestive system anomalies constituted the most common surgical indication (57.6%, 426/739); among these anorectal malformations (26.8%, 114/426) and esophageal atresia (17.4%, 74/426) predominated. Survival rates were lower for digestive perforation (57.7%, 15/26), gastroschisis (57.1%, 4/7) and intestinal atresia (73%, 27/37). Neonates in the youngest and oldest age groups at time of surgery faced highest risk of death, especially those in the older group. Term infants with normal birth weight operated on for the first time had survival rates >95%.

CONCLUSIONS Survival was high and low birth weight conferred the worst prognosis. Infants with normal birth weight operated on for the first time had the greatest probability of survival.

KEYWORDS Neonatal surgery, intensive care, neonatal; congenital disorders, birth defects, congenital abnormalities, surgery, surgery, mortality, case fatality, Cuba

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Anemia and Iron Deficiency Related to Inflammation, Helicobacter pylori Infection and Adiposity in Reproductive-age Cuban Women
April–July 2017, Vol 19, No 2–3

INTRODUCTION Iron deficiency is the main cause of anemia, but infections, inflammation and other factors also play a role. Anemia in women of childbearing age is a risk for pregnancy, childbirth and childhood development during the first two years of life. In Cuba, per WHO definition, anemia is a moderate public health problem in the third trimester of pregnancy and in preschoolers, with a prevalence of 21.6%, in both cases.

OBJECTIVE Estimate prevalence of anemia and iron deficiency in women of childbearing age and assess its relation to inflammation, overweight, central adiposity, H. pylori infection and ingestion of iron-rich foods and enhancers of iron absorption.

METHODS A cross-sectional, analytical study was performed in 391 women aged 18–40 years in four municipalities of Havana, Cuba, from February through June 2014. Variables (indicators in parentheses) were anemia (hemoglobin), iron deficiency (ferritin), nutritional status (body mass index and waist circumference), inflammation (C-reactive protein, acid alpha 1-glycoprotein and interleukin 6), H. pylori infection and ingestion of iron-rich foods. SPSS 20.0 and Epi Info 7.1.2.0 were used for statistical analysis.

RESULTS Anemia prevalence was 24.6% (96/391); iron deficiency, 68% (266/391); H. pylori infection, 47.1% (184/391); inflammation detected by C-reactive protein, 8.4 % (33/391) and by alpha-1-glycoprotein, 19.9% (78/391). Limited results are included for interleukin 6, which was determined in fewer cases (96). Excess body weight was found in 38.7% (150/388) and increased central adiposity in 26.7% (101/378). Iron deficiency was the main cause of anemia (OR 2.68). Central adiposity, excess body weight, and iron deficiency were positively associated with inflammation (OR of 1.77, 1.23 and 1.72, respectively), whereas H. pylori infection was negatively associated with iron deficiency and anemia (OR 0.75 and 0.94, respectively). Low consumption of meat (OR 1.17) and vegetables (OR 1.36) showed discrete limited positive associations with iron deficiency, as well as low consumption of eggs (OR 1.69) and vegetables (OR 1.56) with anemia.

CONCLUSIONS Anemia is a moderate public health problem in the studied group, but with iron deficiency present in two thirds of the population and associated with anemia. Risk factors for anemia and iron deficiency, such as menorrhagia and bacterial or viral infections, should be assessed in women of childbearing age, to support interventions needed to reduce risks in pregnancy and childbirth.

KEYWORDS Anemia, iron deficiency, women, women of childbearing age, inflammation, Helicobacter pylori, obesity, adiposity, Cuba

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Autism Spectrum Disorder in Cuba: Comprehensive & Coordinated Response
April–July 2017, Vol 19, No 2–3

Challenges abound, however, to guarantee the healthy development of autistic Cubans and the wellbeing of their families and caretakers, while improving awareness and understanding by society at large about this complicated disorder. The most immediate hurdle facing island health authorities is: precisely what is the prevalence of ASD in the country? To date, no national survey has been conducted establishing a baseline for how many people are affected. Without these data, prioritizing programs for this vulnerable population is more difficult, as is resource allocation, defining training needs, and scientific research design. Although all Cubans with disabilities regardless of origin or type are protected by law,[1] a total-population study is needed not only to determine the extent of the health problem, but also the implications for Cuban families, the health and education systems, and the national economy. According to WHO, integrating autistic children and adults into society is a priority requiring “actions for making physical, social, and attitudinal environments more accessible, inclusive and supportive.”[2] An incomplete evidence base slows progress of these actions, hindering Cuba’s goals of social insertion and inclusivity.

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From the Editors ►