Double-blind placebo-controlled randomized clinical trial evaluating doxycycline effects on chemotherapy-induced oral mucositis.

WHAT IS KNOWN AND OBJECTIVE: Chemotherapy (CT)-associated oral mucositis (OM) is one of the most debilitating and painful side effects in oncology patients, with limited effective management options. During CT, matrix metalloproteinases (MMPs) are upregulated, causing damage in mucosal and submucosal tissues, and playing a key role in OM; therefore, the use of subantimicrobial doxycycline as a MMP inhibitor may represent a potential approach for OM management. The aim of this clinical trial was to evaluate the efficacy and safety of low doses of doxycycline in OM development in individuals with acute leukaemia (AL) during CT. METHODS: Randomized controlled clinical trial (Registration No. NCT01087476) performed in adult AL patients scheduled to receive CT (September 2010-October 2014). Individuals were stratified by leukaemia type and assigned randomly to receive doxycycline hyclate (50 mg/d) (doxycycline group: DG) or placebo (placebo group: PG) before and during CT. Included subjects had a baseline oral examination and thereafter 3 times a week during 21 days. The primary outcome was OM development. RESULTS AND DISCUSSION: One hundred and forty-seven AL subjects were enrolled: 74 in DG and 73 in PG; baseline characteristics between groups were comparable. During follow-up, 15 (10.2%) individuals developed OM; no differences between treatment groups were found (DG:8.1%, PG:12.3%; P = .59). The mean OM Assessment Scale score was 2.51, without differences between groups (DG:2.7, PG:2.4; P = .65). Low baseline blood albumin levels in the OM-affected individuals were identified, revealing the effect of systemic deterioration as a predisposing factor for OM development. No adverse effects were observed. WHAT IS NEW AND CONCLUSION: Subantimicrobial doses of doxycycline did not reduce the incidence, onset, duration or severity of OM.

TNF as marker of oral candidiasis, HSV infection, and mucositis onset during chemotherapy in leukemia patients.

OBJECTIVE: To assess changes in the salivary expression of IL-1α, IL-1ß, IL-2, IL-6, IL-10, IL-17, and TNF in acute leukemia (AL) patients before and during chemotherapy, and its association with HSV infection, oral candidiasis (OC), and oral mucositis (OM) onset. METHODS: Cohort study in AL patients >15 years starting induction chemotherapy at a Mexican oncological center (2013-2014). Onset of oral lesions (OLs) was assessed during follow-up, and saliva was obtained at baseline, at visit 2 (days 4-12), and at visit 3 (days 13-21) after chemotherapy, treated with a protease inhibitor and stored at -70°C. An enzyme-linked immunosorbent assay was performed. Cox proportional hazards regression models were constructed to estimate hazard ratios and its 95% CI (HR, 95% CI) for OL development. RESULTS: Forty-one patients were followed up, and 17 (41.5%) developed OLs. OL patients had higher baseline salivary IL-1α than those without lesions (p = 0.040). During visit 2, OL patients had higher levels of IL-1α (p = 0.033), IL-1ß (p = 0.016), IL-6 (p = 0.035), and TNF (p = 0.019) than those who did not develop OLs. Patients with HSV infection, OC, and OM showed higher salivary TNF levels during follow-up (HR: 3.52, 95% CI: 1.35-9.14, p = 0.010). CONCLUSION: AL patients undergoing chemotherapy with high salivary TNF levels were more likely to develop HSV infection, OC, and OM.

Prevalence of tuberculin reactivity among healthcare workers from a Mexican hospital.

The prevalence of tuberculosis (TB) infection in healthcare workers (HCWs) is completely unknown in Mexico. To evaluate the frequency of TB infection in our hospital, we performed a prevalence study of tuberculin reactivity among a random sample of asymptomatic HCWs. Our results showed an extremely high prevalence of PPD reactivity (70%) among 175 HCWs, probably related to the high incidence of active TB in the general population and to the absence of preventive programs.

PIP: Tuberculosis (TB) is again a fast growing health problem in the world. Recent data from the World Health Organization revealed 1.7 billion persons are infected with TB in the world, with at least 8 million new cases of active pulmonary TB and 2.9 million deaths every year. A prevalence study of tuberculin reactivity was performed among a random sample of 200 asymptomatic National Institute of Nutrition (NIN) health care workers (HCWs) in a Mexican hospital in order to evaluate the frequency of TB infection. Trained nurses inoculated purified protein derivative (PPD) using the Mantoux technique. All HCWs tested completed a questionnaire about demographic data, previous TB infection, previous contact with active tuberculous patients, Bacillus Calmette-Guerin (BCG) vaccine scar, previous PPD testing, and immunosuppressive conditions. 175 (87.5%) returned for test reading, including 51 nurses, 49 physicians, 36 office workers, 28 lab workers, and 11 janitors. There were 52 males and 123 females, with a median age of 25 years (range, 18-60). Overall, 123 (70%) of 175 HCWs were PPD reactive. The rate of reactivity was higher among persons with a history of BCG vaccination than those without such history (105/139 [75.5%] versus 18/36 [50%]; P 0.01) and was higher among HCWs at least 30 years old than among those younger than 30 years (45/64 [70%] versus 78/120 [65%]; P 0.05). The rate of PPD positivity was not influenced by sex, area of work, or reported contact with TB patients. Median induration among reactors was 17.5 mm, whereas it was 0 mm among nonreactors. Results showed an extremely high prevalence of PPD reactivity among our HCWs, which probably is explained by the high incidence of active TB in the general population and to the absence of preventive programs. It is useful to establish the PPD reactivity of HCWs for early recognition of active disease among symptomatic reactors and for follow up of nonreactors to detect subsequent conversions among them in order to prevent the nosocomial dissemination of tuberculosis.

Tuberculosis and tuberculin quality: best intentions, misleading results.

OBJECTIVE: To compare the performance of three purified protein derivative (PPD) formulations: Tubersol (Connaught); RT23, Statens Serum Institut (SSI); and RT23, Mexico, tested in Mexican populations at low and high risk for tuberculosis (TB). DESIGN: A double-blinded clinical trial. SETTING: A university hospital in Mexico City. PARTICIPANTS: The low-risk population was first or second-year medical students with no patient contact; the high-risk population was healthcare workers at a university hospital. METHODS: Each of the study subjects received the three different PPD preparations. Risk factors for TB, including age, gender, occupation, bacille Calmette-Guérin (BCG) status, and TB exposure, were recorded. A 0.1-mL aliquot of each preparation was injected in the left and right forearms of volunteers using the Mantoux technique. Blind readings were done 48 to 72 hours later. Sensitivity and specificity were calculated at 10 mm of induration using Tubersol as the reference standard. The SSI tested the potency of the different PPD preparations in previously sensitized guinea pigs. RESULTS: The low-risk population had a prevalence of positive PPD of 26%. In the low-risk population, RT23 prepared in Mexico, compared to the 5 TU of Tubersol, had a sensitivity of 51%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 86%. The RT23 prepared at the SSI had a sensitivity of 69%, a specificity of 99%, a positive predictive value of 95%, and a negative predictive value of 90%. In the high-risk population, the prevalence of positive PPD was 57%. The RT23 prepared in Mexico had a sensitivity of 33%, a specificity of 100%, and a positive predictive value of 53%; the RT23 prepared at the SSI had a sensitivity of 91%, a specificity of 98%, a positive predictive value of 98%, and a negative predictive value of 89%. RT23 used in Mexico had a potency of only 23% of that of the control. There was no statistical association among those with a positive PPD, irrespective of previous BCG vaccination (relative risk, 0.97; 95% confidence interval, 0.76-1.3;P=.78). CONCLUSIONS: Healthcare workers had twice the prevalence of positive PPD compared to medical students. RT23 prepared in Mexico had a low sensitivity in both populations compared to 5 TU of Tubersol and RT23 prepared at the SSI. Previous BCG vaccination did not correlate with a positive PPD. Low potency of the RT23 preparation in Mexico was confirmed in guinea pigs. Best intentions in a TB program are not enough if they are not followed by high-quality control.

Pediatric primary gram-negative nosocomial bacteremia: a possible relationship with infusate contamination.

OBJECTIVE: To evaluate the potential contribution of "extrinsic" contamination of intravenous fluids in hospital bacteremia and infection. DESIGN: Prospective cross-sectional survey of infusate contamination, December 1992 to December 1993. SETTING: A pediatric department (1,500 admissions per year) in a general, urban teaching hospital, serving low-income patients. SAMPLES AND PATIENTS: Infusate samples (0.5 to 1.0 mL) from the injection port used by the staff were taken for cultures from all febrile or septic patients in hospital wards. At least four samples were taken each day; if no febrile or septic patients were available, other patients were sampled at convenience. RESULTS: A 6.8% positive culture rate (87 contaminates in 1,277 infusates) was obtained, without significant differences among the wards. Gram-negative organisms were recovered from 56 samples (62.9%), mainly of the tribe Klebsielleae (56.1%). Coagulase-negative staphylococci were isolated in 30 samples (33.7%). There was no significant difference between the febrile-septic group and the asymptomatic group in the rate of infusate contamination (P = .59). In eight patients, the same organisms were recovered from infusate and blood culture. The overall bacteremia rate was 2.5 per 100 discharges. CONCLUSIONS: Compared to previous reports, higher infusate contamination rates and different organisms (mainly gram-negative) were observed. In hospitals of underdeveloped countries, nosocomial infection control frequently is disregarded. Infusate contamination may be common and could lead to gram-negative bacteremia. In such settings, it seems advisable to perform surveillance studies to identify infusate contamination, because a single infusate contamination could be a signal for an epidemic.

Mycobacterium tuberculosis infection in patients with systemic rheumatic diseases. A case-series.

OBJECTIVE: To describe the clinical characteristics of patients with systemic rheumatic diseases and tuberculosis. A retrospective case series from 1987 to 1994, drawn from a tertiary-care hospital in Mexico City, was studied. RESULTS: Thirty patients were included (20 women, 10 men), with mean age of 39.8 years (range 14-66), and a mean duration of the systemic rheumatic disease of 44 months (1-372). The rheumatic diseases included systemic lupus erythematosus (SLE) (n = 13), rheumatoid arthritis (7), polymyositis or dermatomyositis (5), and other diseases (5). During the six months previous to the diagnosis of tuberculosis, 22 patients had received corticosteroids, and 13 others immunosuppressants. Mycobacterium tuberculosis was isolated from 18 patients. Pulmonary tuberculosis was found in 10 patients, and extrapulmonary tuberculosis in 20, seven of these with miliary disease. SLE was seen in 6 of the patients with miliary tuberculosis. The clinical manifestations were: fever (67%), weight loss (67%), diaphoresis (60%), cough and sputum (53%), lymph node enlargement (43%), and dyspnea (33%). Sixteen patients had an abnormal chest film. Of 18 patients tested by PPD RT-2, 8 had an induration > 10 mm. Patients were initially treated with 3 or 4 anti-tuberculosis drugs for 15 days to 6 months, followed by 6 to 10 months of isoniazid plus rifampicin. Three relapsed, and 2 died of respiratory failure. CONCLUSIONS: This case series showed a particular pattern of tuberculosis in patients with systemic rheumatic diseases.

Tuberculosis prophylaxis in patients with steroid treatment and systemic rheumatic diseases. A case-control study.

OBJECTIVE: The aim of this study was to assess the impact of isoniazid prophylaxis in patients with systemic rheumatic diseases who attended a teaching hospital in Mexico City between 1987 and 1992. METHODS: In this case-control study, patients with systemic rheumatic diseases and tuberculosis (cases) were compared with patients with systemic rheumatic diseases without tuberculosis (controls). The groups were matched by year of hospital admission and rheumatic disease. Clinical charts were reviewed for: 1) isoniazid prophylaxis, defined as the administration of isoniazid 300 mg/day for 6 or more months in patients with exposure to steroids (prophylaxis with isoniazid was defined as complete, incomplete or any prophylaxis); 2) exposure to steroids: defined as the administration of prednisone > 15 mg/day (or its equivalent of another steroid) for 3 or more months before tuberculosis or recruitment into the study; 3) exposure to immunosuppressants, defined as the administration of any dose of azathioprine, methotrexate, cyclophosphamide, and/or 6-mercaptopurine, before tuberculosis in the cases or recruitment date in the controls; 4) reactivity to PPD; and 5) other relevant variables. RESULTS: Twenty cases and 66 controls were studied. A 70% decrease in the risk of developing tuberculosis was found among patients who received any prophylaxis with isoniazid as compared to controls: OR 0.31, 95% CI 0.09-0.98, p = 0.03. A 97% decrease was seen in those patients who received complete prophylaxis: OR 0.034, 95% CI 0.0001-0.216, p < 0.0001. The protective effect of complete prophylaxis persisted even after controlling for other potential confounders, such as age, gender, rheumatic disease, duration of rheumatic symptoms, and exposure to steroids and/or immunosuppressants. CONCLUSION: The results of this study suggest that in countries with a high prevalence of tuberculosis the use of isoniazid (300 mg/day for 6 months) in rheumatic patients with exposure to prednisone (> 15 mg/day for three or more months) may be useful to prevent tuberculosis, independently of the results of the PPD reactivity test. However, a controlled clinical trial will be required to confirm these results.

Clinical manifestations and survival trends during the first 12 years of the AIDS epidemic in Mexico.

BACKGROUND: Our objective was to evaluate survival trends (1984-1995), the prevalence of AIDS-defining conditions, and the role of treatment with zidovudine and/or prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) in survival following AIDS diagnosis. METHODS: We reviewed the clinical charts and postmortem studies of all patients admitted to the HIV Clinic from 1984-1995. Three groups were identified according to the following dates of HIV diagnosis: 1) 1984-1988; 2) 1989-1992, and 3) 1993-1995. RESULTS: We studied 909 charts. During the study period, 744 (81.6%) patients developed AIDS. Median survival increased from 11.7 months in group 1 to 15.4 and 17.5 months in groups 2 and 3, respectively (p <0.05). We observed the following important changes in the frequency of AIDS-defining conditions over the study period: Pneumocystis carinii pneumonia (PCP) decreased from 24.8 to 17 and 14% in groups 1, 2, and 3, respectively, (p = 0.008), and Kaposi's sarcoma (KS), from 31.1 to 10.5 and 13.5% (p <0.001). On the other hand, there was an increase in cytomegalovirus disease with 12.4, 20.4, and 18.6% (p = 0.04) and wasting syndrome with 36, 45, and 57% (p <0.001). In the proportional hazard model for death, zidovudine or TMP-SMX use was associated with a protective effect. CONCLUSIONS: Survival is improving among patients with HIV infection at our institution. The prevalence of AIDS-defining conditions has changed over the last 12 years. There has been a diminution of PCP and KS, whereas cases of CMV disease and wasting syndrome increased.

Application of an autopsy report specifically designed for cardiovascular diseases.

After modifying the format and content of the autopsy report traditionally used at the Instituto Nacional de Cardiología of México, Tlalpan, we present the results of the new, revised autopsy protocol here. The new autopsy protocol (model report) was designed as a "fixed format" to describe the cardiovascular diseases observed at our institution, thus pretending to collect more and better data, providing useful information, and contributing to better clinicopathologic correlations. The comparison between the model and traditional reports demonstrated an improvement in the autopsy data collection system--achieving better clinicopathologic correlations of the main disease and the cause of death, and identifying morphologic alterations that would explain it in more cases. The model report was also considered more accessible and useful since it permitted the answering of more questions raised by clinicians.

Validity of height and weight self-report in Mexican adults: results from the national health and aging study.

BACKGROUND: An adequate nutritional status is essential for maintaining the independence in the elderly. The height and weight self-report is considered a useful alternative for the estimation of body mass index (BMI). The validity of the self-report is an issue that has not been dealt with in developing countries. AIM: To assess the validity of the height and weight self-report in adults Mexican citizens. DESIGN: Transversal study. STUDY POPULATION: 1707 persons (836 males, 871 females) were asked for their height and weight and were measured. RESULTS: Mean (+/- standard deviation) age was 59.09 +/- 9.86 SD; mean years of education was 5.51 +/-4.67 years. We found a high correlation between self-reported and measured weight (R2= 0.837); the difference between both values rose along with the age (from 0.4 kg to 1.74 kg). A systematic difference between self-reported and measured height was found. Self-reported height was over-estimated, and the bias increased along with the age of the subjects (from 1.57 cm to 2.57 cm); further, over-estimation was larger in female individuals (+2.22 cm in female vs. +1.21 cm in male subjects). We calculated a linear model that predicts real height from self-reported height with moderate, although statistically significant results (R2= 0.39 y 0.50, for female and male, respectively, p < 0.0001). Knee height was also used to estimate "adulthood height" and thus, BMI. This method showed age-related dissimilarities, and the linear regression model yielded an unacceptably low correlation (R2= <0.10). The best method to estimate real BMI was to consider self-reported parameters. DISCUSSION: Height and weight estimation using self-reported parameters is an acceptable method. Its precision is not so high in subjects > 75 years. Height over-estimation is an expected finding congruent with age-related corporal changes. The estimation of height using knee height is not a useful method. CONCLUSION: Height and weight self-report is a valid method that may be used to accurately estimate height and weight in Mexican people.

[Measuring the impact of medical interventions at the individual level]. / Medición del impacto de intervenciones médicas a nivel individual.

Medical interventions have a variable response among individuals. It is desirable to detect patients who are getting a therapeutic benefit. Any medical intervention has to show a favorable effect in survival and/or control of symptoms in order to be considered useful. In many clinical scenarios, laboratory test results are not enough to be confident of the effectiveness of a treatment. In order to do a clinical evaluation focused on patients' interests, we suggest the use of instruments to measure quality of life. Currently there are quality of life scales that have undergone a rigorous process of validation and reliability. Sub-group analysis is frequently used to predict an individual benefit of medical interventions. In the interpretation of sub-group analysis, it is important to be aware of the risk of misinterpretation, making false positive or false negative conclusions about the effect of the treatment. The N-of-1 trial is a valid scientific alternative to define individual effectiveness of therapy. Defining the degree of therapeutic benefit timely we avoid useless therapies, unnecessary side effects, and sequelae secondary to the lack of opportune treatment.

[The use of antibiotics at the outpatient clinic of the "Salvador Zubirán" National Institute of Nutrition]. / Uso de antibióticos en la consulta externa del Instituto Nacional de la Nutrición "Salvador Zubirán".

We conducted a survey of the prescription of antibiotics among the outpatient clinics of the Instituto Nacional de la Nutrición "Salvador Zubirán", a third level hospital in México City. We made an auditory of the medical record and prescriptions given to every patient treated for an infectious episode, accounting for at least six questions to evaluate the quality of the prescription: 1) if the patient should had received antibiotics; 2) if the antibiotic prescribed was adequate; 3) if the dose was sufficient; 4) if the frequency of administration was correct; 5) if the route of administration was adequate; and 6) if the length of the treatment was sufficient. We validated the concordance among two evaluators and found that it was 89% for the whole questionnaire. In the evaluation we found that the patients should had received antibiotic 94% of the time: the antibiotic selected was a right choice 80% of the time; the dose was adequate 45% of the time; the frequency of administration was adequate 70% of the time; the route of administration was adequate 79% of the time; and the length of treatment was adequate 38% of the time. The worst findings were seen in two of the most important issues of antibiotic prescription which directly affect the appearance of antibiotic resistance.

[Pediatric nosocomial bacteremia. Potential usefulness of culturing infusion liquids]. / Bacteriemia nosocomial pediátrica. Utilidad potencial del cultivo de los líquidos de infusión.

Hospital-acquired bacteremia is a common cause of morbidity and mortality, mainly in pediatric units. In a 25 month retrospective study, we analyzed the blood cultures from the Hospital General Regional of the city of Leon, Guanajuato State, Mexico, in order to establish the causal agents of nosocomial bacteremia and infer some associations with contaminated intravenous infusion fluids. In addition we performed a two month study to culture the flasks and intravenous tubing used in our infusions. Five hundred and fifty one blood cultures drawn from August 1990 to September 1992 were analyzed. A total of 135 (24.5%) were positive, most of them (51.8%) with strains of the Klebsielleae tribe (SKT) (Klebsiella, Enterobacter, Serratia). The global incidence of bacteremia in the two year period was 4.3%. In the infusion study, 230 intravenous fluids were cultured, with 68 isolates (30%) most from the SKT tribe. A final consideration is made on the role that inadequate management of intravenous liquids could play in the development of endemic and epidemic nosocomial bacteremia in our hospital, and the eventual utility of making cultures of the i.v. liquids.

Salmonella gastroenteritis outbreak among workers from a tertiary care hospital in Mexico City.

OBJECTIVE: To describe an outbreak of Salmonella gastroenteritis among employees of the National Institute of Nutrition (INNSZ) of Mexico City during July, 1994. METHODS: Employees who developed diarrhea or fever associated with gastrointestinal symptoms starting on July 14th were included for study as well as 50 healthy controls. A questionnaire was applied to all, and they also provided a stool sample, along with other 80 asymptomatic people (included the kitchen workers) in whom only stool culture was done. RESULTS: Ninety-seven employees that ate regularly at the Hospital's cafeteria were affected by the outbreak, and 67 of them (69%) could be evaluated. Most of them were nurses (34%), and handymen (27%). Most common symptoms were abdominal pain (97%), diarrhea (95%), nausea (91%), and fever (89%). Cultures from suspicious food items were all negative, but stool cultures from 10/70 cases were positive for Salmonella enteritidis vs. 0/133 in the controls. The ten S. enteritidis isolates resulted identical either by serotyping and by rapid amplified polymorphic DNA (RAPD) analysis. Cultures from all kitchen employees were negative for S. enteritidis. Breakfast meal on July 14th was associated with the development of gastroenteritis (61/67 cases vs 26/50 controls, p < 0.001), and particularly with an egg-covered meat plate (61/62 vs 13/26 controls, p < 0.0001). CONCLUSIONS: This outbreak was probably caused by eggs contaminated with Salmonella, since no one of the kitchen personnel was found to be an asymptomatic carrier, and the implicated recipe allows for inappropriate cooking. Recommendations to improve cooking procedures must be added to the usual regulations to diminish the frequency of foodborne disease outbreaks in hospitals.