Evolución de la bronquiolitis en los servicios de urgencias extrahospitalarias de la Comunidad de Madrid: estudio observacional 2016-2023 / Bronchiolitis trends in out-of-hospital urgent care services in the Community of Madrid: Observational study, 2016-2023

Introducción: La bronquiolitis se convierte en todo un reto durante su pico estacional, desbordando los recursos materiales y humanos para poder atender los pacientes afectados. A consecuencia de ello, se multiplican exponencialmente los traslados interhospitalarios. No se han encontrado estudios que hayan analizado las características de los pacientes con bronquiolitis aguda (BA) en los servicios de urgencias extrahospitalarios (SUEH) y la influencia de la pandemia en su epidemiología. Objetivo: Conocer las características de los pacientes pediátricos y neonatales con bronquiolitis en los SUEH de la Comunidad de Madrid y analizar la influencia de la pandemia por COVID-19 en su epidemiología. Material y métodos: Estudio observacional descriptivo, transversal y retrospectivo realizado en los SUEH de la Comunidad de Madrid entre 2016 y 2023. Se incluyeron pacientes con diagnóstico de BA según CIE-10 en las historias clínicas de las asistencias y traslados interhospitalarios. Se registraron variables sociodemográficas, clínicas y de tratamiento (ventilatorio y farmacológico). Resultados: Se incluyeron 630 pacientes con BA: 343 atendidos por los SUEH no especializados en neonatología (no-neo) y 287 por el equipo de transporte neonatal (TN). La mediana de edad fue de 3,7meses [2,8-4,7] en SUEH no-neo y de 19días [14,2-23,7] en TN. Hubo un aumento de la edad estadísticamente significativo en la temporada 2020/2021 en el grupo de SUEH no-neo. La escala de gravedad fue estadísticamente mayor en el grupo de TN. Hubo un pico inusual de casos de bronquiolitis en junio de 2021, coincidiendo con el fin de la 4.ª ola de COVID-19. La incidencia de bronquiolitis, tras la 6.ª ola de pandemia, fue la mayor de todas las temporadas (13,5 casos por cada 10.000 niños ≤2años)...(AU)

Introduction: Bronchiolitis poses a considerable challenge during its seasonal peak, overwhelming the material and human resources available to care for affected patients. As a result, interhospital transfers increase exponentially. We did not find any studies analysing the characteristics of patients with bronchiolitis managed in out-of-hospital urgent care (OHUC) services and the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. Objective: To establish the characteristics of paediatric and neonatal patients with acute bronchiolitis (AB) managed in OHUC services in the Community of Madrid and to analyse the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. Methods: Retrospective cross-sectional observational and descriptive study carried out in OHUC settings in the Community of Madrid between 2016 and 2023. We included patients with a diagnosis of acute bronchiolitis based on the ICD-10 codes documented in the electronic records of urgent care visits and interhospital transports. We collected data on sociodemographic, clinical and treatment (ventilation and medication) variables. Results: The sample included 630 patients with AB: 343 managed in non-neonatal OHUC (non-neo) services and 287 by the mobile neonatal intensive care unit transport team (NTT). The median age was 3.7months (IQR: 2.8-4.7) in patients in the non-neo OHUC group and 19days (IQR: 14.2-23.7) in the NTT group. There was a statistically significant increase in age in the 2020/2021 season in the non-neo OHUC group. The severity score was significantly higher in the NTT group. There was an unusual peak in bronchiolitis cases in June 2021, coinciding with the end of the fourth wave of the COVID-19 pandemic. The incidence of bronchiolitis was highest after the sixth wave of the pandemic (13.5 cases per 10,000 children aged <2years)...(AU)

Bronchiolitis trends in out-of-hospital urgent care services in the Community of Madrid: Observational study, 2016-2023.

INTRODUCTION: Bronchiolitis poses a considerable challenge during its seasonal peak, overwhelming the material and human resources available to care for affected patients. As a result, interhospital transfers increase exponentially. We did not find any studies analysing the characteristics of patients with bronchiolitis managed in out-of-hospital urgent care (OHUC) services and the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. OBJECTIVE: To establish the characteristics of paediatric and neonatal patients with acute bronchiolitis (AB) managed in OHUC services in the Community of Madrid and to analyse the impact of the COVID-19 pandemic on the epidemiology of bronchiolitis. METHODS: Retrospective cross-sectional observational and descriptive study carried out in OHUC settings in the Community of Madrid between 2016 and 2023. We included patients with a diagnosis of acute bronchiolitis based on the ICD-10 codes documented in the electronic records of urgent care visits and interhospital transports. We collected data on sociodemographic, clinical and treatment (ventilation and medication) variables. RESULTS: The sample included 630 patients with AB: 343 managed in non-neonatal OHUC (non-neo) services and 287 by the mobile neonatal intensive care unit transport team (NTT). The median age was 3.7 months (IQR, 2.8-4.7) in patients in the non-neo OHUC group and 19 days (IQR, 14.2-23.7) in the NTT group. There was a statistically significant increase in age in the 2020/2021 season in the non-neo OHUC group. The severity score was significantly higher in the NTT group. There was an unusual peak in bronchiolitis cases in June 2021, coinciding with the end of the 4th wave of the COVID-19 pandemic. The incidence of bronchiolitis was highest after the 6th wave of the pandemic (13.5 cases per 10 000 children aged < 2 years). CONCLUSIONS: The median age of paediatric patients with AB managed in OHUC services increased following the end of the lockdown imposed due to the COVID-19 pandemic, which was probably associated with the lack of exposure to the viruses that cause it. This also may explain why the incidence of bronchiolitis was highest in the season following the 6th wave of the pandemic. The severity score was higher in neonatal patients. Epidemiological surveillance, the introduction of protocols and the implementation of an ongoing training programme for non-specialized health care staff involved in the transport of these patients could improve their management.

The elimination of trachoma as a public health problem in Mexico: From national health priority to national success story.

INTRODUCTION: Mexico was the first country in the Americas and the third in the world to eliminate trachoma as a public health problem, as validated by the WHO in 2017. OBJECTIVE: To describe the critical elements that favored the elimination of trachoma as a public health problem in Mexico and the public health impact of this success. METHODOLOGY: A revision and compilation of data and information contained in the dossier presented by the country to PAHO/WHO to obtain the validation of trachoma elimination as a public health problem was conducted by a group of delegates from the national and local trachoma prevention and control program. Data from the national and local surveillance systems and reports of actions conducted after achieving the elimination goal were also included. Critical elements that favored the achievement of the elimination goal from 1896 to 2019 were extracted. RESULTS: Mexico reached the elimination of trachoma in 2016 obtaining the validation in 2017. 264 communities were no longer endemic and 151,744 people were no longer at risk of visual impairment or possible blindness due to trachoma. The key to the success of this elimination process was primarily the local leadership of health authorities with sustained funding for brigades, increased access to potable water and sanitation, and key alliances with indigenous authorities, health authorities, and government institutions that contributed to the achievement of the goal. The SAFE strategy started implementation in Mexico in 2004 as a comprehensive package of interventions. SAFE stands for surgery, antibiotics, facial cleanliness, and improvement of the environmental conditions. These actions impacted drastically on the number of new cases trachmatous trichiasis (TT) and trachomatous inflammation-follicular (TF), which decreased from 1,794 in 2004 to zero in 2016. CONCLUSIONS: The elimination of trachoma as a public health problem in Mexico is a true success story that may serve as a model example for the elimination of other neglected infectious diseases in the Americas.

Health-related quality of life in caregivers of community-dwelling individuals with disabilities or chronic conditions. A gender-differentiated analysis in a cross-sectional study.

BACKGROUND: Most care for people with chronic or disabling conditions living in the community is provided in the family context, and this care is traditionally provided by women. Providing informal care has a negative impact on caregivers' quality of life, which adds to existing health inequalities associated with gender. The aim of this study was to analyze factors associated with the health-related quality of life of caregivers and to determine their differences in a gender-differentiated analysis. METHODS: An observational, cross-sectional, multicenter study was conducted in primary healthcare. A total of 218 caregivers aged 65 years or older were included, all of whom assumed the primary responsibility for caring for people with disabling conditions for at least 6 months per year and agreed to participate in the CuidaCare study. The dependent variable was health-related quality of life, assessed with the EQ-5D. The explanatory variables tested were grouped into sociodemographic variables, subjective burden, caregiving role, social support and variables related to the dependent person. The associations between these variables and health-related quality of life were estimated by fitting robust linear regression models. Separate analyses were conducted for women and men. RESULTS: A total of 72.8% of the sample were women, and 27.2% were men. The mean score on the EQ-5D for female caregivers was 0.64 (0.31); for male caregivers, it was 0.79 (0.23). There were differences by gender in the frequency of reported problems in the dimensions of pain/comfort and anxiety/depression. The variables that were associated with quality of life also differed. Having a positive depression screening was negatively associated with quality of life for both genders: -0.31 points (95% CI: -0.47; -0.15) for female caregivers and -0.48 points (95% CI: -0.92; -0.03) for male caregivers. Perceived burden was associated with quality of life in the adjusted model for women (-0.12 points; 95% CI: -0.19; -0.06), and domestic help was associated in the adjusted model for male caregivers (-0.12 points; 95% CI: -0.19; -0.05). CONCLUSIONS: Gender differences are present in informal caregiving. The impact of providing informal care is different for male and female caregivers, and so are the factors that affect their perceived quality of life. It could be useful it incorporates a gender perspective in the design of nursing support interventions for caregivers to individualize care and improve the quality of life of caregivers. TRIAL REGISTRATION: NCT01478295 [ https://ClinicalTrials.gov ]. 23/11/2011.

Factors associated with in-hospital mortality and readmission in a cohort of patients treated with noninvasive ventilation during emergency department or out-of-hospital emergency care: the VentilaMadrid study. / Factores asociados a la mortalidad intrahospitalaria y reingreso en una cohorte tratada con ventilación no invasiva en urgencias extrahospitalarias y hospitalarias: estudio VentilaMadrid.

OBJECTIVES: To describe clinical, outcome, and risk factors in a cohort of patients treated with noninvasive ventilation (NIV) in a hospital emergency department (ED) or by out-of-hospital emergency medical services (OHEMSs). MATERIAL AND METHODS: Multicenter, prospective cohort study enrolling consecutive patients with acute pulmonary edema and/or exacerbated chronic obstructive pulmonary disease who were treated with NIV between November 2018 and November 2020 in a hospital ED or OHEMS setting in Madrid. We recorded baseline data, variables related to the acute episode, and outcome variables, including in-hospital mortality and 30-day readmission. RESULTS: A total of 317 patients were included; 132 (41.6%) were treated in an OHEMS setting and 185 (58.4%) in a hospital ED. Forty-seven (16.3%) in-hospital deaths occurred, and 78 patients (28.8%) were readmitted within 30 days. Mortality in the hospital ED and OHEMS subsamples did not differ, but the patients who received NIV in an OHEMS setting had a lower 30-day readmission rate. On multivariate analysis, in-hospital mortality was associated with prior dependence in activities of daily living in the multivariate analysis (odds ratio [OR], 2.4; 95% CI, 1.11-5.27) and a low-moderate score on the Simplified Acute Physiology Score II (SAPS II) versus a high-very high one (OR, 2.69; 95% CI, 1.26-5.77). Mortality after OHEMS ventilation was associated with discontinuance of NIV during transfer (OR, 8.57; 95% CI, 2.19-33.60). Readmission within 30 days was associated with group (in-hospital ED application of NIV) (OR, 3.24; 95% CI, 2.62-6.45) and prior dependence (OR, 2.08; 95% CI, 1.02-4.22). CONCLUSION: Patients treated in the hospital ED and OHEMS setting have similar baseline characteristics, although acute episodes were more serious in the OHEMS group. No significant differences were found related to in-hospital mortality. Higher mortality was associated with dependence, a SAPS II score greater than 52, and discontinuance of NIV. Readmission was associated with dependence and NIV treatment in the hospital ED setting.

OBJETIVO: Describir las características clínicas, evolutivas y los factores pronóstico de una cohorte de pacientes tratados con ventilación no invasiva (VNI) en servicios de urgencias extrahospitalarios (SUEH) y hospitalarios (SUH). METODO: Estudio de cohortes multicéntrico, prospectivo con inclusión consecutiva de pacientes con edema agudo de pulmón o agudización de enfermedad pulmonar obstructiva crónica tratados con VNI entre noviembre 2018 y noviembre de 2020 en SUEH y SUH de la Comunidad de Madrid. Se recogieron características basales, del episodio agudo, así como variables de resultado incluyendo la mortalidad hospitalaria y el reingreso a 30 días. RESULTADOS: Se incluyeron 317 pacientes, 132 (41,6%) en SUEH y 185 (58,4%) en SUH. Hubo 47 muertes intrahospitalarias (16,3%) y 78 reingresos a los 30 días (28,8%). No hubo diferencias en la mortalidad, pero el grupo VNI-SUEH tuvo menor reingreso a 30 días. En el análisis multivariado la mortalidad intrahospitalaria se asoció con la dependencia previa (OR = 2,4; IC 95%: 1,11-5,27) y el SAPS-II bajo-moderado frente al alto-muy alto (OR = 2,69; IC 95%: 1,26-5,77). En la cohorte extrahospitalaria, la mortalidad intrahospitalaria se asoció con la retirada de la VNI en la transferencia del paciente (OR = 8,57; IC 95%: 2,19-33,60). Los reingresos a los 30 días se asociaron con inicio de VNI en el hospital (OR = 3,24; IC 95%: 2,62-6,45) y dependencia previa (OR = 2,08; IC 95%: 1,02-4,22). CONCLUSIONES: Los pacientes de ambos grupos, SUH y SUEH, tienen un perfil clínico basal similar, aunque con mayor gravedad del episodio en el grupo SUEH. No se encontraron diferencias estadísticamente significativas en la mortalidad intrahospitalaria. Se asociaron a una mayor mortalidad la dependencia, la escala SAPS-II > 52 y la retirada de la VNI. El reingreso se asoció con la dependencia y pertenecer al grupo SUH.

Factores asociados a la mortalidad intrahospitalaria y reingreso en una cohorte tratada con ventilación no invasiva en urgencias extrahospitalarias y hospitalarias: estudio VentilaMadrid / Factors associated with in-hospital mortality and readmission in a cohort of patients treated with noninvasive ventilation during emergency department or out-of-hospital emergency care: the VentilaMadrid study

Objetivo. Describir las características clínicas, evolutivas y los factores pronóstico de una cohorte de pacientes trata- dos con ventilación no invasiva (VNI) en servicios de urgencias extrahospitalarios (SUEH) y hospitalarios (SUH). Método. Estudio de cohortes multicéntrico, prospectivo con inclusión consecutiva de pacientes con edema agudo de pulmón o agudización de enfermedad pulmonar obstructiva crónica tratados con VNI entre noviembre 2018 y noviembre de 2020 en SUEH y SUH de la Comunidad de Madrid. Se recogieron características basales, del episodio agudo, así como variables de resultado incluyendo la mortalidad hospitalaria y el reingreso a 30 días. Resultados. Se incluyeron 317 pacientes, 132 (41,6%) en SUEH y 185 (58,4%) en SUH. Hubo 47 muertes intrahospi talarias (16,3%) y 78 reingresos a los 30 días (28,8%). No hubo diferencias en la mortalidad, pero el grupo VNI-SUEH tuvo menor reingreso a 30 días. En el análisis multivariado la mortalidad intrahospitalaria se asoció con la dependen- cia previa (OR = 2,4; IC 95%: 1,11-5,27) y el SAPS-II bajo-moderado frente al alto-muy alto (OR = 2,69; IC 95%: 1,26- 5,77). En la cohorte extrahospitalaria, la mortalidad intrahospitalaria se asoció con la retirada de la VNI en la transferencia del paciente (OR = 8,57; IC 95%: 2,19-33,60). Los reingresos a los 30 días se asociaron con inicio de VNI en el hospital (OR = 3,24; IC 95%: 2,62-6,45) y dependencia previa (OR = 2,08; IC 95%: 1,02-4,22). Conclusiones. Los pacientes de ambos grupos, SUH y SUEH, tienen un perfil clínico basal similar, aunque con mayor gravedad del episodio en el grupo SUEH. No se encontraron diferencias estadísticamente significativas en la mortalidad intrahospitalaria. Se asociaron a una mayor mortalidad la dependencia, la escala SAPS-II > 52 y la retirada de la VNI. El reingreso se asoció con la dependencia y pertenecer al grupo SUH.

Objective. To describe clinical, outcome, and risk factors in a cohort of patients treated with noninvasive ventilation (NIV) in a hospital emergency department (ED) or by out-of-hospital emergency medical services (OHEMSs). Methods. Multicenter, prospective cohort study enrolling consecutive patients with acute pulmonary edema and/or exacerbated chronic obstructive pulmonary disease who were treated with NIV between November 2018 and November 2020 in a hospital ED or OHEMS setting in Madrid. We recorded baseline data, variables related to the acute episode, and outcome variables, including in-hospital mortality and 30-day readmission. Results. A total of 317 patients were included; 132 (41.6%) were treated in an OHEMS setting and 185 (58.4%) in a hospital ED. Forty-seven (16.3%) in-hospital deaths occurred, and 78 patients (28.8%) were readmitted within 30 days. Mortality in the hospital ED and OHEMS subsamples did not differ, but the patients who received NIV in an OHEMS setting had a lower 30-day readmission rate. On multivariate analysis, in-hospital mortality was associated with prior dependence in activities of daily living in the multivariate analysis (odds ratio [OR], 2.4; 95% CI, 1.11– 5.27) and a low-moderate score on the Simplified Acute Physiology Score II (SAPS II) versus a high-very high one (OR, 2.69; 95% CI, 1.26–5.77). Mortality after OHEMS ventilation was associated with discontinuance of NIV during transfer (OR, 8.57; 95% CI, 2.19–33.60). Readmission within 30 days was associated with group (in-hospital ED application of NIV) (OR, 3.24; 95% CI, 2.62–6.45) and prior dependence (OR, 2.08; 95% CI, 1.02–4.22). [...]

Reflexiones sobre la pandemia COVID-19 en el estudio VentilaMadrid / The VentilaMadrid study and the COVID-19 pandemic: reflections

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Hundred Days of Teleconsultations and Their Usefulness in the Management of COVID-19: Experience of the COVID-19 National Call Center in Bolivia.

Background: There is currently little scientific evidence on the usefulness of implementing strategies against COVID-19 remotely with the help of telemedicine. Objective: Evaluate whether teleconsultation is helpful as an instrument of mediated care in the monitoring and follow-up of individuals with high suspicion of COVID-19 through early detection by the Call Center COVID-19 of the Ministry of Health and Sports, Bolivia. Methodology: Descriptive and cross-sectional observational study of patients captured by the Call Center-COVID-19, who were monitored and followed up in their homes through teleconsultations carried out by the National TeleHealth Program, remotely through information and communication technologies throughout the Bolivian territory during the first 100 days of its implementation. Results: A total of 3,278 patients were studied, recruited between March 16 and June 23, 2020; 49.4% were women, with an overall mean age of 37.5 years (standard deviation [SD] 15.2). The mean detection time was 7.6 days (SD 6.92); 93.8% required home isolation, and only 6.2% were transferred for hospitalization. The mean follow-up time for all patients was 6.7 days (SD 4.87; range 2-38). A total of 75.6% were discharged as recovered patients, and 1.9% died. Conclusions: Early detection of individuals with suspected COVID-19 was achieved, knowing their clinical evolution until their recovery or death. Teleconsultations showed good outcomes at discharge and low fatal outcomes. From these results, it can be inferred that teleconsultation is a valuable tool in the monitoring, evaluation, and follow-up of patients. The Ministry of Health and Sports through Call Center-COVID-19 reinforced the Epidemiological Surveillance System as a passive search tool for possible suspected cases at the national level and decongesting other services in charge of this task.

Overlapping of Independent SARS-CoV-2 Nosocomial Transmissions in a Complex Outbreak.

SARS-CoV-2 nosocomial outbreaks in the first COVID-19 wave were likely associated with a shortage of personal protective equipment and scarce indications on control measures. Having covered these limitations, updates on current SARS-CoV-2 nosocomial outbreaks are required. We carried out an in-depth analysis of a 27-day nosocomial outbreak in a gastroenterology ward in our hospital, potentially involving 15 patients and 3 health care workers. Patients had stayed in one of three neighboring rooms in the ward. The severity of the infections in six of the cases and a high fatality rate made the clinicians suspect the possible involvement of a single virulent strain persisting in those rooms. Whole-genome sequencing (WGS) of the strains from 12 patients and 1 health care worker revealed an unexpected complexity. Five different SARS-CoV-2 strains were identified, two infecting a single patient each, ruling out their relationship with the outbreak; the remaining three strains were involved in three independent, overlapping, limited transmission clusters with three, three, and five cases. Whole-genome sequencing was key to understand the complexity of this outbreak. IMPORTANCE We report a complex epidemiological scenario of a nosocomial COVID-19 outbreak in the second wave, based on WGS analysis. Initially, standard epidemiological findings led to the assumption of a homogeneous outbreak caused by a single SARS-CoV-2 strain. The discriminatory power of WGS offered a strikingly different perspective consisting of five introductions of different strains, with only half of them causing secondary cases in three independent overlapping clusters. Our study exemplifies how complex the SARS-CoV-2 transmission in the nosocomial setting during the second COVID-19 wave occurred and leads to extending the analysis of outbreaks beyond the initial epidemiological assumptions.

Imported cases of malaria in Spain: observational study using nationally reported statistics and surveillance data, 2002-2015.

BACKGROUND: Malaria was eliminated in Spain in 1964. Since then, more than 10,000 cases of malaria have been reported, mostly in travellers and migrants, making it the most frequently imported disease into this country. In order to improve knowledge on imported malaria cases characteristics, the two main malaria data sources were assessed: the national surveillance system and the hospital discharge database (CMBD). METHODS: Observational study using prospectively gathered surveillance data and CMBD records between 2002 and 2015. The average number of hospitalizations per year was calculated to assess temporal patterns. Socio-demographic, clinical and travel background information were analysed. Bivariate and multivariable statistical methods were employed to evaluate hospitalization risk, fatal outcome, continent of infection and chemoprophylaxis failure and their association with different factors. RESULTS: A total of 9513 malaria hospital discharges and 7421 reported malaria cases were identified. The number of reported cases was below the number of hospitalizations during the whole study period, with a steady increase trend in both databases since 2008. Males aged 25-44 were the most represented in both data sources. Most frequent related co-diagnoses were anaemia (20.2%) and thrombocytopaenia (15.4%). The risks of fatal outcome increased with age and were associated with the parasite species (Plasmodium falciparum). The main place of infection was Africa (88.9%), particularly Equatorial Guinea (33.2%). Most reported cases were visiting friends and relatives (VFRs) and immigrants (70.2%). A significant increased likelihood of hospitalization was observed for children under 10 years (aOR:2.7; 95% CI 1.9-3.9), those infected by Plasmodium vivax (4.3; 95% CI 2.1-8.7) and travellers VFRs (1.4; 95% CI 1.1-1.7). Only 4% of cases reported a correct regime of chemoprophylaxis. Being male, over 15 years, VFRs, migrant and born in an endemic country were associated to increased risk of failure in preventive chemotherapy. CONCLUSIONS: The joint analysis of two data sources allowed for better characterization of imported malaria profile in Spain. Despite the availability of highly effective preventive measures, the preventable burden from malaria is high in Spain. Pre-travel advice and appropriately delivered preventive messages needs to be improved, particularly in migrants and VFRs.

Identification of Proliferative and Apoptotic Sertoli Cells Using Fluorescence and Confocal Microscopy.

Sertoli cells, the testicular somatic cells of the seminiferous epithelium, are vital for the survival of the epithelium. They undergo proliferation and apoptosis during fetal, neonatal, and prepubertal development. Apoptosis is increased in certain situations such as exposure to many substances, for example, toxics, or short photoperiod in the non-breeding season of some mammals. Therefore, it has always been considered that Sertoli cells that reach adulthood are quiescent cells, that is to say, nonproliferative, do not die, are terminally differentiated, and whose numbers remain constant. Recently, a degree of both proliferation and apoptosis has been observed in normal adult conditions, suggesting that consideration of this cell as quiescent may be subject to change. All this make it necessary to use histochemical techniques to demonstrate whether Sertoli cells are undergoing proliferation or apoptosis in histological sections and to allow the qualitative and quantitative study of these. In this chapter, we present two double-staining techniques that can be used for identifying Sertoli cells in proliferation or apoptosis by fluorescence microscopy. In both, the Sertoli cells are identified by an immunohistochemistry for vimentin followed by an immunohistochemistry for PCNA or a TUNEL histochemistry.