INTRODUCTION Silent myocardial ischemia is frequent in type 2 diabetics, therefore, symptoms cannot be relied upon for diagnosis and followup in these patients. Various studies relate blood lipid levels to cardiovascular diseases, and several authors describe certain lipoproteins as independent predictors of ischemia.

OBJECTIVE Identify blood lipid levels that predict silent myocardial ischemia in a type 2 diabetic population in Havana.

METHODS From May 2005 through May 2009, assessment was done of 220 asymptomatic type 2 diabetics in ten polyclinics in Havana using laboratory tests and Single-Photon Emission-Computed Tomography, synchronized with electrocardiogram, known as gated SPECT (gSPECT). Coronary angiography was used for confirmation when gSPECT detected ischemia. Patients were classified into two groups: gSPECT positive and gSPECT negative. Descriptive statistics (mean and standard deviation) were calculated for all variables and mean comparison tests were conducted. Classification trees were developed relating lipid values to gSPECT results, identifying optimal cutoff points for their use as indicators of silent myocardial ischemia in the total study population and for each sex separately.

RESULTS GSPECT found silent myocardial ischemia in 29.1% of those examined, and 68.4% of angiograms found multivessel disease. gSPECT-positive diabetics had higher levels of total cholesterol, LDL, and triglycerides (p < 0.05). HDL levels were lower in this group (p < 0.05). Classification trees showed optimal cutoff points, indicators for silent ischemia, for: HDL ≤44 mg/dL, LDL >119.9 mg/dL, and triglycerides >107.2 mg/d; 80.4% of diabetics with these HDL and triglyceride values had ischemia. HDL was the most important normalized variable when the entire population was analyzed. Analysis by sex showed a greater percentage of silent ischemia in men (33.3%) than in women (24.8%). The most important normalized variables were LDL of >100.8 mg/dL for men and HDL of ≤44 mg/dL for women.

CONCLUSIONS A considerable percentage of the study population had silent myocardial ischemia. Type 2 diabetics with ischemia had higher levels of total cholesterol, LDL and triglycerides. HDL levels were significantly lower in these patients. The association of low HDL with high triglycerides was a strong indicator of myocardial ischemia in type 2 diabetics without clinical cardiovascular signs.

KEYWORDS Lipids, type 2 diabetes, silent myocardial ischemia, decision trees, diagnostic imaging, Single-Photon Emission-Computed Tomography, cardiac-gated SPECT, early detection, Cuba

INTRODUCTION Recombinant human erythropoietin is used primarily to treat anemia. There is evidence of its neuroprotective capacity from preclinical studies in Parkinson’s disease and other neurodegenerative diseases. Recombinant human erythropoietin produced in Cuba (ior-EPOCIM) is registered and approved for use in humans in Cuba and in a number of other countries.

OBJECTIVE Assess safety and possible neuroprotective effect of ior-EPOCIM in a group of Parkinson’s disease patients.

METHODS A three-phase exploratory study (proof of concept) was conducted from August 2008 to April 2009: preliminary assessment, treatment (weeks 1–5), and post-treatment (weeks 6–35). Participants were 10 Parkinson’s disease patients (8 men, 2 women) from the outpatient clinic at the International Neurological Restoration Center, all at least one year post onset, aged 47–65 years. The ior-EPOCIM was administered subcutaneously in a once-weekly dose (60 IU/kg body weight) for five weeks. Therapy with patients’ antiparkinsonian drugs was maintained throughout the study, except during motor examination, conducted following a 12-hour withdrawal (OFF condition). Safety was evaluated primarily by recording adverse events (by intensity and causality) from start of treatment until the study’s completion. Hematological parameters and blood pressure were also measured because of their direct relationship to the medication’s action. To evaluate possible neuroprotective activity, variables were included related to patients’ motor function and cognitive and affective status, measured using internationally recognized scales. All variables were evaluated before, during and after treatment. Data were processed using a fixed-effects linear model, with a repeated-measures design (significance level p ≤ 0.05).

RESULTS Three patients experienced mild adverse events (precordial discomfort and hypertension in one; leg fatigue in another; renal colic in a third), with a possible causal relationship in the first two that was neither life threatening nor required hospitalization. Hemoglobin was the only hematological parameter that showed a growing and significant increase (p < 0.001), but without reaching pathological levels. The other variables presented clinically positive and statistically significant changes compared to pretreatment assessment: motor function (p < 0.001), cognitive status (p < 0.001) and mood (p = 0.013).

CONCLUSIONS At the dosage used, ior-EPOCIM was safe and well tolerated in these Parkinson’s disease patients. Further studies are needed to corroborate these results and evaluate the medication’s possible neuroprotective effect.

KEYWORDS Parkinson disease, erythropoietin, recombinant proteins, neuroprotective agents, clinical trial, safety, ior-EPOCIM, Cuba

Popular belief has it that alcohol, particularly red wine, protects against atherosclerosis and associated cardio- and cerebrovascular conditions. That presumption motivates this paper, which describes the mechanisms underlying the J-shaped risk curve for alcohol use, with benefits for vascular disease risk at low consumption levels and harmful effects—both directly on the user and indirectly on the bystander—at higher levels. The importance of further exploring alcohol use in patients with cardiovascular risk factors and of intervening to modify non-social use of alcohol to prevent serious adverse health consequences is also addressed.

KEYWORDS Alcohol-related disorders, burden of illness, atherosclerosis, atherogenesis, vascular disease, risk factors, Cuba

INTRODUCTION Following a tripling of tuberculosis incidence in Cuba between 1991 and 1994 (from 4.7 to 14.7 per 100,000), the National TB Control Program was revamped in 1995 and the National Reference Center for Childhood TB and Provincial Childhood TB Commissions were created as a strategy for addressing this emerging health problem.

OBJECTIVE Assess the impact of Cuba’s new strategy for TB control in children aged <15 years during the period 1995–2005.

METHODS A descriptive review of health services and systems was conducted in Cuba, examining 157 cases of TB diagnosed in children aged <15 years during the period 1995–2005 and comparing impact and process indicators for selected years (1995, 2000, and 2005). Impact indicators included reduction in: a) incidence; b) serious forms (peritoneal, meningeal, miliary, combined); c) mortality; and d) case outcomes (cure, death, treatment drop-out, treatment failure). Process indicators were proportion of cases with: a) microbiological tests; b) knowledge of infection source; c) diagnoses obtained through adult case contact tracing; d) time to diagnosis <60 days; and e) post-mortem diagnoses.

RESULTS During the period 1995–2005, TB rates in children aged <15 years fell by 50% (from 1.0 to 0.5 per 100,000), more evident in children <10 years. The Havana rate was three times the national rate. Diagnosis was post-mortem in three serious cases (1.9%); there were four deaths (2.5%), none after 2000. Only seven children (4.5%) had serious forms, none after 2002. Except for cases diagnosed post-mortem, all children received treatment directly supervised by health personnel. Cure rate was 99.4%; there were no treatment drop-outs or chronic cases; one relapse was reported (0.6%). Knowledge of infection source increased to 90% over the selected years. Microbiological tests were conducted in 90% of cases, with isolation in 30.9%. No isolate was drug‑resistant, nor were there reports of infectious contacts with resistance. We found no HIV coinfection. At the end of the study, time to diagnosis of ≥60 days persisted in 40% of cases.

CONCLUSIONS Creation of a National Reference Center for Childhood TB and Provincial Childhood TB Commissions has contributed to improved TB diagnosis and control in children aged <15 years, achieving incidence similar to that during the period prior to TB re-emergence and to those of some developed countries. Improvements are needed in the work and systematic training of health personnel, especially at the primary health care level, in order to eliminate TB as a national health problem by 2015.

KEYWORDS Tuberculosis, tuberculosis/diagnosis, tuberculosis/epidemiology, tuberculosis/mortality, tuberculosis/prevention and control, tuberculosis/therapy, child health services, Cuba

The article presents global data on access to pharmaceuticals and discusses underlying barriers. Two are highly visible: pricing policies and intellectual property rights; two are less recognized: the regulatory environment and scientific and technological capacities. Two ongoing transitions influence and even distort the problem of universal access to medications: the epidemiologic transition to an increasing burden of chronic non-communicable diseases; and the growing role of biotechnology products (especially immunobiologicals) in the pharmacopeia. Examples from Cuba and Brazil are used to explore what can and should be done to address commercial, regulatory, and technological aspects of assuring universal access to medications.

KEYWORDS Biotechnology, biological products, clinical trials, drug costs, economics, pharmaceutical, pharmaceutical preparations, intellectual property, patents, access to health care, world health, Cuba, Brazil

INTRODUCTION Co-infections between hepatitis B and HIV viruses are frequent due to their similar epidemiological characteristics. Worldwide, hepatitis B infection is one of the main causes of hepatocellular carcinoma and cirrhosis. In Cuba as elsewhere, prevalences of hepatitis B and hepatitis C viral infections are higher in persons with HIV. These hepatitis viruses act as opportunistic infections in persons with HIV. In other contexts, persons with HIV have been found to be at higher risk for occult hepatitis B, defined as the presence in serum or plasma of hepatitis B virus DNA and antibodies to its core antigen, in the absence of hepatitis B surface antigen.

OBJECTIVES Describe occult hepatitis B prevalence in Cuban HIV-positive patients and explore possible associations with their clinical characteristics.

METHODS A total of 325 serum samples from patients positive for HIV and negative for hepatitis B surface antigen were studied, divided into two groups, Group 1, negative for hepatitis C virus; and Group 2, positive for hepatitis C virus. Exposure to hepatitis B was determined by testing for hepatitis B core antigen; samples positive for hepatitis B core antigen were then examined for presence of antibodies to hepatitis B surface antigen. Both determinations were done by ultramicroELISA. In samples positive for hepatitis B core antigen with levels of antibodies to hepatitis B surface antigen of <50 IU/L, real-time polymerase chain reaction was used to detect hepatitis B DNA and its presence examined in relation to several clinical variables. All data were obtained from patients’ clinical records.

RESULTS In the hepatitis-C–negative group, 27.9% (68/243) of serum samples tested were positive for hepatitis B core antigen. In the hepatitis-C–positive group, 37.8% (31/82) were positive for hepatitis B core antigen. Total hepatitis B virus exposure prevalence was 30.4% (99/325); 54.5% (54/99) showing low immunity (hepatitis B virus surface antigen <50 IU/L) and 24% of these (13/54), occult hepatitis. There was no statistically significant association between hepatitis B virus DNA and any of the clinical variables studied.

CONCLUSIONS Low-immunity HIV-positive persons in our study were exposed to hepatitis B virus. Diagnosis of occult hepatitis B infection is frequent in these patients. This study suggests that diagnostic protocols for persons with HIV and without hepatitis B surface antigen should include testing for hepatitis B core antigen, with positive results followed by molecular techniques to detect occult hepatitis B. This study makes a useful contribution to prevention and control of hepatitis B in Cuba.

KEYWORDS Hepatitis B, hepatitis B antigens, hepatitis C, AIDS, AIDS-related opportunistic infections, Cuba

INTRODUCTION The use of highly active antiretroviral therapy has reduced progression to AIDS and increased survival among seropositive persons; yet, appearance of resistant viruses may jeopardize these benefits. In Cuba, HIV mainly affects adults; at the end of 2009 of the 41 children infected, 25 were still alive; of these, 22 were under antiretroviral treatment. Until now, nothing was known about HIV-1 antiviral resistance and viral subtypes in the pediatric population in Cuba.

OBJECTIVE This study aims to identify presence of antiretroviral-resistant HIV-1 strains in Cuban children and their mothers, and to provide a phylogenetic characterization and comparison of pol gene sequences in the same.

METHODS Plasma samples were collected from 22 children and their mothers, all HIV-1–infected, from 2004 through 2009. Reverse transcription polymerase chain reaction was used to amplify the pol gene fragment coding for HIV protease and reverse transcriptase enzymes; this was then sequenced and subjected to phylogenetic analysis of HIV subtypes and recombinant forms to compare sequences between mothers and children. HIV mutations conferring antiretroviral resistance were determined.

RESULTS Viral amplification was achieved in samples from 11 children and 8 mothers. Subtypes detected were: CRF19_cpx in five children, subtype B in three, CRF18_cpx in two, and subtype C in one child. In all mother–child pairs, samples were grouped within the same viral subtype in the phylogenetic tree. One mother was under treatment and five children had been treated before the sample was collected. In viruses amplified from samples of children under treatment, resistance was most frequently found to lamivudine (3 cases) and nevirapine (4 cases). Two untreated children carried resistant viruses possibly acquired from their mothers.

CONCLUSIONS This is the first study to describe HIV-1 antiviral resistance in the pediatric population in Cuba; it also identified viral subtypes infecting the mother−child pairs studied. We recommend antiretroviral resistance assays before initiating treatment in pregnant seropositive women and their newborns.

KEYWORDS HIV, AIDS, antiretroviral therapy, antiviral drug resistance, phylogeny, infectious disease transmission, vertical, Cuba

The following errata have been corrected in all versions of this article

Page 24: Byline, ”Joan Alemán” should read “Yoan Alemán.”

Page 31, The Authors: ”Joan Alemán” should read “Yoan Alemán Campos.”

Translated from the Spanish and reprinted with permission from the Revista Cubana de Farmacia. Vol. 44 No. 2 (special supplement), Apr–Jun 2010.
Original available at: http://bvs.sld.cu/revistas/far/vol44_sup2_10/Surgimiento,%20evolucion%20y%20principales%20resultados%20del%20CENCEC.pdf

ABSTRACT
The rapid development of Cuba’s pharmaceutical industry in the 1990s created a need for structures to ensure clinical evaluation of products before their introduction into medical practice and subsequent marketing. One of the centers founded for this purpose was the National Clinical Trials Coordinating Center. This paper summarizes the factors that motivated the creation of the Center and presents a brief history of its organizational development over the last 17 years. It also describes the main components of the system for designing and conducting clinical trials, and the most significant contributions of each toward achieving the Center’s objectives.

KEYWORDS Contract research organization, clinical evaluation, drug industry, clinical trial, Cuba

INTRODUCTION Chronic myeloid leukemia is the first malignant disease to be associated with a genetic lesion and is the first leukemia to provide a genotype model conducive to targeted molecular therapy. It is a chronic clonal myeloproliferative disorder, originating in a pluripotent stem cell common to all three hematopoietic lineages, characterized by overproduction of myeloid cells in all stages of maturation.

Approval of the use of imatinib in the United States in 2001 and its introduction in the treatment of chronic myeloid leukemia changed the evolution and prognosis of the disease and began the era of molecular therapy for malignancies. Imatinib is highly effective and causes fewer adverse reactions than earlier treatments based on interferon and hydroxyurea.

In Cuba, chronic myeloid leukemia has been treated with interferon since 1998. Starting in 2003, imatinib was gradually introduced for use in newly-diagnosed chronic myeloid leukemia patients.

OBJECTIVE Evaluate the use of imatinib as first-line therapy for chronic myeloid leukemia in a group of Cuban patients, based on hematologic, cytogenetic, and molecular response; overall and event-free survival rates; and most frequency and severity of adverse reactions.

METHODS During May 2003 to May 2008, 33 newly-diagnosed chronic myeloid leukemia patients (25 adults, 8 children; <6 months from diagnosis) received a single daily oral dose of imatinib 400 mg from the time of study enrollment. Variables used: (1) to evaluate treatment efficacy: hematologic, cytogenetic, and molecular response; overall and event-free survival; and (2) to evaluate safety: presence of adverse reactions leading to definitive interruption of treatment or death.

RESULTS Complete hematologic response occurred in 100% of patients, major cytogenetic response in 90.9%, and complete cytogenetic response in 48.5%. Molecular response occurred in 36.4% of patients. With a mean follow-up of 39 months, overall survival was 96% and estimated five-year event-free survival was 85%. No adverse reactions occurred in 39.5% of patients. Adverse reactions most frequently observed were myelosuppression (24.2%) and digestive disorders (21.2%). These were followed, in decreasing order, by edema, primarily orbital (9.1%), skin depigmentation (3%), and cardiac arrhythmias (3%).

CONCLUSIONS In the present study, imatinib was effective first-line therapy for patients with newly-diagnosed chronic myeloid leukemia, as determined by overall and event-free survival rates. No severe adverse reactions were observed.

KEYWORDS Imatinib, chronic myeloid leukemia, cytogenetic response, molecular response, Cuba

INTRODUCTION Congenital ptosis is malpositioning of the eyelids that, when moderate or severe, can negatively affect visual development during its critical period, resulting in amblyopia: diminished visual acuity with no apparent organic cause. Early diagnosis and timely treatment are essential for preventing amblyopia. Congenital ptosis is uncommon but poses a challenge to any ophthalmologist; the only treatment is surgical. Among these patients in Cuba, those with the most complex clinical characteristics are generally referred to the Ramón Pando Ferrer Ophthalmology Institute in Havana.

OBJECTIVE Characterize visual acuity outcomes obtained in patients seen at this Institute who received surgery for simple congenital ptosis using the frontalis sling procedure.

METHOD A descriptive prospective longitudinal study was conducted to describe visual acuity outcomes in 11 patients with a diagnosis of isolated congenital ptosis seen in the Oculoplastic Service of the Ramón Pando Ferrer Ophthalmology Institute between January and July 2009 and operated on using the frontalis sling procedure. The majority exhibited severe visual acuity impairment (0.1–0.5) prior to surgery. Variables employed were age, sex, degree of ptosis, degree of ptosis correction, visual acuity, and complications during surgery and postoperatively.

RESULTS Male patients aged 1–4 years predominated. Visual acuity improved in 100% of patients, to varying degrees. Prior to surgery, 72% had visual acuity of 0.1–0.5. Six months post-surgery, with visual rehabilitation, 90.9% exhibited visual acuity of >0.5. In 81.8% of patients, palpebral ptosis was fully corrected. Complications were minimal: injury to the palpebral tarsus and undercorrection were the most common and did not affect final surgical outcome or interfere with rehabilitation.

CONCLUSIONS Correction of congenital ptosis using the frontalis sling technique yielded satisfactory visual acuity outcomes, contributing to visual rehabilitation of the affected patients.

KEYWORDS Blepharoptosis/congenital, blepharoplasty, frontalis sling, amblyopia, Cuba