Statistical process control of manufacturing tablets for antiretroviral therapy

Abstract In this study, the manufacturing process of lamivudine (3TC) and zidovudine (AZT) tablets (150+300 mg respectively) was evaluated using statistical process control (SPC) tools. These medicines are manufactured by the Fundação para o Remédio Popular "Chopin Tavares de Lima" (FURP) laboratory, and are distributed free of charge to patients infected with HIV by the Ministry of Health DST/AIDS national program. Data of 529 batches manufactured from 2012 to 2015 were collected. The critical quality attributes of weight variation, uniformity of dosage units, and dissolution were evaluated. Process stability was assessed using control charts, and the capability indices Cp, Cpk, Pp, and Ppk (process capability; process capability adjusted for non-centered distribution; potential or global capability of the process; and potential process capability adjusted for non-centered distribution, respectively) were evaluated. 3TC dissolution data from 2013 revealed a non-centered process and lack of consistency compared to the other years, showing Cpk and Ppk lower than 1.0 and the chance of failure of 2,483 in 1,000,000 tablets. Dissolution data from 2015 showed process improvement, revealed by Cpk and Ppk equal to 2.19 and 1.99, respectively. Overall, the control charts and capability indices showed the variability of the process and special causes. Additionally, it was possible to point out the opportunities for process changes, which are fundamental for understanding and supporting a continuous improvement environment.

Proteomics provides insights into the inhibition of Chinese hamster V79 cell proliferation in the deep underground environment.

As resources in the shallow depths of the earth exhausted, people will spend extended periods of time in the deep underground space. However, little is known about the deep underground environment affecting the health of organisms. Hence, we established both deep underground laboratory (DUGL) and above ground laboratory (AGL) to investigate the effect of environmental factors on organisms. Six environmental parameters were monitored in the DUGL and AGL. Growth curves were recorded and tandem mass tag (TMT) proteomics analysis were performed to explore the proliferative ability and differentially abundant proteins (DAPs) in V79 cells (a cell line widely used in biological study in DUGLs) cultured in the DUGL and AGL. Parallel Reaction Monitoring was conducted to verify the TMT results. γ ray dose rate showed the most detectable difference between the two laboratories, whereby γ ray dose rate was significantly lower in the DUGL compared to the AGL. V79 cell proliferation was slower in the DUGL. Quantitative proteomics detected 980 DAPs (absolute fold change ≥ 1.2, p < 0.05) between V79 cells cultured in the DUGL and AGL. Of these, 576 proteins were up-regulated and 404 proteins were down-regulated in V79 cells cultured in the DUGL. KEGG pathway analysis revealed that seven pathways (e.g. ribosome, RNA transport and oxidative phosphorylation) were significantly enriched. These data suggest that proliferation of V79 cells was inhibited in the DUGL, likely because cells were exposed to reduced background radiation. The apparent changes in the proteome profile may have induced cellular changes that delayed proliferation but enhanced survival, rendering V79 cells adaptable to the changing environment.

Evaluation of Malaria Blood Smears Sent to National Malaria Reference Laboratory

Objective: Although the disease has been eliminated in Turkey malaria continues to be a threat due to increase in the number of people coming from or going to countries where the disease is endemic. In this study, we aimed to evaluate blood smears sent to the National Malaria Reference Laboratory within the malaria surveillance system. Methods: From March 2016 to July 2018 a retrospective study was conducted to compare the results of Malaria Reference Laboratory and Public Health Laboratories. A total of 16.827 blood stains were sent to our laboratory for approval. Results: In Public Health Laboratories, 315 (1.88%) of the smears were positive, 16.510 (98.12%) were negative, and in the National Malaria Reference Laboratory 252 (1.50%) were positive, 16.466 were negative. In the Public Health Laboratories, one of the two samples considered to be malaria suspected was positive in the National Malaria Reference Laboratory and one was negative. In Public Health Laboratories 35.88% of smears were P. falciparum, 27.30% were Plasmodium spp., 20.96% were P. vivax, 14.92% were mixed infection, 0.63% were P. malariae, 0.31% were P. ovale, and in the Reference Laboratory 49.60% were Plasmodium spp., 29.37% were P. falciparum, 16.27% were P. vivax, 4.36% were mixed infection, 0.40% were P. malariae. Conclusion: In order to malaria surveillance system to be maintained in a healthy manner, preparation, staining, coding, packaging, transportation of blood slides is very important. Also if necessary, continuing training of laboratory staff working in malaria diagnosis is crucial.

Survey of Suspected Laboratory-Acquired Infections and Biosafety Practices in Research, Clinical, and Veterinary Laboratories in Karachi, Pakistan.

Laboratory-acquired infections (LAIs), an occupational illness, are defined as all infections acquired through laboratory or laboratory-related activities. A report published in 1898 described an LAI resulting from Corynebacterium diphtheriae being transmitted through mouth pipetting. Despite all efforts, LAIs continue, especially in developing countries like Pakistan, which has been fighting to curb many infectious diseases. As reflected in the published literature, the biosafety culture is severely lacking in many laboratories, and there are no data available from Pakistan on LAIs. Our objective was to ascertain the frequency and rate of LAIs in various labs with versatile portfolios in relation to biosafety and biosecurity practices in Karachi. Ours is a descriptive multicenter cross-sectional study conducted in 30 laboratories located in Karachi from November 2017 to April 2018. Data were collected from laboratories including the university hospital labs, research labs, animal labs, and biomedical labs. Out of 30 facilities, half (n = 15) were clinical/biomedical laboratories, 16.6% (n = 5) were university hospital laboratories, 26.6% (n = 8) were R&D laboratories, and 6.6% (n = 2) were animal laboratories. Needle stick was found to be the most common injury, followed by animal bite/scratch, cut on mucous membrane, falling of personnel, and burn injury.

Quality evaluation of malaria diagnosis in the local laboratories network and in intermediate laboratories in a setting towards the disease elimination in Ecuador / Evaluación de la calidad del diagnóstico de malaria en la red local de laboratorios y en los laboratorios intermedios en el contexto de la eliminación de la enfermedad en Ecuador

Introduction: To reach the goal of malaria elimination in Ecuador for the year 2020, it is necessary to have a laboratory network with the capacity to perform microscopic diagnosis according to the WHO/PAHO quality standards and to provide the adequate treatment of cases. Objective: To determine the level of competence for parasitological diagnosis of the microscopists from the local public network and the performance of intermediate reference laboratories. Materials and methods: We conducted a cross-sectional study based on the information collected in workshops carried out to appraise the competence for microscopic diagnosis of the local laboratory network (zonal health coordinating offices 1 to 8) using a slide panel to evaluate diagnosis agreement, as well as the diagnostic performance of the intermediate laboratories using an external quality assessment program. The results were compared against the reference standards of the supranational laboratory in Perú. Results: We evaluated the competencies of 191 microscopists in 11 workshops and 153 (80.1%) of them were approved. The medians of the indicators were the following: concordance for parasite detection, 100% (Q1- Q3: 96-100), concordance for species identification, 100% (Q1- Q3: 93-100), and concordances for stage identification, 93.0% (Q1- Q3: 86-95) and parasite counting, 77.0% (Q1- Q3: 71-82). In the external quality assessment, the three intermediate laboratories obtained 100% in parasite detection concordance and 96% for species detection concordance. Conclusions: The results for the primary network and the performance indicators for the intermediate laboratories showed the high-quality standards of the training program implemented in the country.

Introducción. El cumplimiento de la meta de eliminación de la malaria en Ecuador en el 2020 exige contar con la capacidad requerida para el diagnóstico microscópico ajustado a los estándares de calidad de la Organización Mundial de la Salud (OMS) y de la Organización Panamericana de la Salud (OPS) y proveer el tratamiento adecuado a los pacientes. Objetivo. Conocer la idoneidad o competencia de los microscopistas de la red pública local para el diagnóstico parasitológico de la malaria y el desempeño de los laboratorios intermedios de referencia. Materiales y métodos. Se hizo un estudio descriptivo de corte transversal a partir de la información obtenida en los talleres de evaluación de idoneidad en el diagnóstico microscópico de la red de laboratorios en las coordinaciones zonales de salud utilizando un panel de láminas para evaluar la concordancia del diagnóstico. Además, se calificó el desempeño de los laboratorios intermedios en el diagnóstico en el marco del programa de evaluación externa del desempeño. Los resultados se compararon con los obtenidos por el laboratorio supranacional de Perú. Resultados. En los 11 talleres realizados, se evaluó la idoneidad de 191 microscopistas, de los cuales 153 (80,1 %) aprobaron las pruebas. Las medianas de los indicadores fueron las siguientes: concordancia entre la detección y el resultado, 100 % (Q1- Q3: 96-100); concordancia en la especie, 100 % (Q1- Q3: 93-100); concordancia en el estadio, 93,0 % (Q1- Q3: 86-95) y concordancia en el recuento, 77 % (Q1- Q3: 71-82). En el programa de evaluación externa de desempeño, los tres laboratorios intermedios obtuvieron una concordancia del 100 % en el resultado y una del 96 % en la especie. Conclusiones. Los indicadores de competencia de la red local y de desempeño de los laboratorios intermedios alcanzaron altos estándares de calidad acordes con el proceso de entrenamiento implementado en el país.

Evaluación de la calidad del diagnóstico de malaria en la red local de laboratorios y en los laboratorios intermedios en el contexto de la eliminación de la enfermedad en Ecuador / Quality evaluation of malaria diagnosis in the local laboratories network and in intermediate laboratories in a setting towards the disease elimination in Ecuador

Resumen Introducción. El cumplimiento de la meta de eliminación de la malaria en Ecuador en el 2020 exige contar con la capacidad requerida para el diagnóstico microscópico ajustado a los estándares de calidad de la Organización Mundial de la Salud (OMS) y de la Organización Panamericana de la Salud (OPS) y proveer el tratamiento adecuado a los pacientes. Objetivo. Conocer la idoneidad o competencia de los microscopistas de la red pública local para el diagnóstico parasitológico de la malaria y el desempeño de los laboratorios intermedios de referencia. Materiales y métodos. Se hizo un estudio descriptivo de corte transversal a partir de la información obtenida en los talleres de evaluación de idoneidad en el diagnóstico microscópico de la red de laboratorios en las coordinaciones zonales de salud utilizando un panel de láminas para evaluar la concordancia del diagnóstico. Además, se calificó el desempeño de los laboratorios intermedios en el diagnóstico en el marco del programa de evaluación externa del desempeño. Los resultados se compararon con los obtenidos por el laboratorio supranacional de Perú. Resultados. En los 11 talleres realizados, se evaluó la idoneidad de 191 microscopistas, de los cuales 153 (80,1 %) aprobaron las pruebas. Las medianas de los indicadores fueron las siguientes: concordancia entre la detección y el resultado, 100 % (Q1- Q3: 96-100); concordancia en la especie, 100 % (Q1- Q3: 93-100); concordancia en el estadio, 93,0 % (Q1- Q3: 86-95) y concordancia en el recuento, 77 % (Q1- Q3: 71-82). En el programa de evaluación externa de desempeño, los tres laboratorios intermedios obtuvieron una concordancia del 100 % en el resultado y una del 96 % en la especie. Conclusiones. Los indicadores de competencia de la red local y de desempeño de los laboratorios intermedios alcanzaron altos estándares de calidad acordes con el proceso de entrenamiento implementado en el país.

Abstract Introduction: To reach the goal of malaria elimination in Ecuador for the year 2020, it is necessary to have a laboratory network with the capacity to perform microscopic diagnosis according to the WHO/PAHO quality standards and to provide the adequate treatment of cases. Objective: To determine the level of competence for parasitological diagnosis of the microscopists from the local public network and the performance of intermediate reference laboratories. Materials and methods: We conducted a cross-sectional study based on the information collected in workshops carried out to appraise the competence for microscopic diagnosis of the local laboratory network (zonal health coordinating offices 1 to 8) using a slide panel to evaluate diagnosis agreement, as well as the diagnostic performance of the intermediate laboratories using an external quality assessment program. The results were compared against the reference standards of the supranational laboratory in Perú. Results: We evaluated the competencies of 191 microscopists in 11 workshops and 153 (80.1%) of them were approved. The medians of the indicators were the following: concordance for parasite detection, 100% (Q1- Q3: 96-100), concordance for species identification, 100% (Q1- Q3: 93-100), and concordances for stage identification, 93.0% (Q1- Q3: 86-95) and parasite counting, 77.0% (Q1- Q3: 71-82). In the external quality assessment, the three intermediate laboratories obtained 100% in parasite detection concordance and 96% for species detection concordance. Conclusions: The results for the primary network and the performance indicators for the intermediate laboratories showed the high-quality standards of the training program implemented in the country.

Challenges and perspectives on the use of mobile laboratories during outbreaks and their use for vaccine evaluation.

Mobile laboratories provide diagnostic capabilities for routine surveillance and patient identification during an outbreak. In either situation, they face many challenges including identification of the appropriate assay(s) to employ, logistical arrangements, and providing for the health and safety of the laboratory staff. Great strides have been made over the last decade in the development of mobile laboratories with assays that require minimal infrastructure and technical experience. This knowledge and expertise have been developed in partnership with many researchers and public health officials who live in regions prone to infectious disease outbreaks. Mobile laboratories should now also be used in the evaluation of novel vaccines and therapeutics in remote locations. Clinical mobile laboratories will include similar diagnostic capabilities as outbreak response mobile labs, but will also include additional point-of-care instruments operated under Good Clinical Practice guidelines. They will also operate rigorous data management plans so that the data collected will satisfy regulatory agencies during the licensure process. Failure to deploy an adequate clinical mobile laboratory when administering a novel biological product in a remote location is a significant limitation to any collected scientific data that could ultimately undermine clinical development and availability of life-saving interventions.

Why pesticides with mutagenic, carcinogenic and reproductive risks are registered in Brazil.

Brazil is the biggest market for pesticides in the world. In the registration process, a pesticide must be authorized by the Institute of the Environment, Health Surveillance Agency and Ministry of Agriculture. Evaluations follow a package of toxicological studies submitted by the companies and also based on the Brazilian law regarding pesticides. We confronted data produced by private laboratories, submitted to the Institute of the Environment for registration, with data obtained from scientific databases, corresponding to mutagenicity, carcinogenicity and teratogenicity of pesticides. All studies submitted by the companies were carried out by private laboratories. From 247 pesticide formulations analyzed, none showed positive results for mutagenicity, carcinogenicity or teratogenicity. From 574 articles in the scientific literature, 84% published by public laboratories showed positive results, while 79% of those showing negative results came from private laboratories. There is an ethical concern about a conflict of interest between public/independent laboratories and private laboratories that produce data for registering pesticides. We demonstrated that there is a clear contradiction between public and private laboratories. Brazilian regulatory authorities have approved the registration of pesticides based almost exclusively on the monographs provided by the pesticide industry, because the use of scientific articles or information from the independent literature is strongly belittled by the industry. Pesticide companies argue that scientific articles cannot be trusted. Also, according to the industry, pesticide registration cannot be refused based on results from scientific articles. Thus, the registration of pesticides with mutagenic, carcinogenic and teratogenic risks has been approved in Brazil.

Malaria Diagnostic Practices in U.S. Laboratories in 2017.

In the United States, the gold standard for malaria diagnosis is microscopic blood smear examination. Because malaria is not endemic in the United States, diagnostic capabilities may be limited, causing delays in diagnosis and increased morbidity and mortality. A survey of the malaria diagnostic practices of U.S. laboratories was conducted from June to July 2017; members of the American Society for Microbiology's listserv received a questionnaire inquiring about malaria diagnostic test availability, techniques, and reporting. Results were assessed using the Clinical and Laboratory Standards Institute (CLSI) guidelines for malaria diagnostics. After excluding incomplete and duplicate responses, responses representing 175 laboratories were included. Most labs (99%) received at least one specimen annually for malaria diagnosis, and 31% reported receiving only 1 to 10 specimens. The majority (74%) diagnosed five or fewer cases of malaria per year. Most (90%) performed blood smears on-site. Two-thirds (70%) provided initial blood smear results within 4 h. Although diagnostic testing for malaria was available 24/7 at 74% (141) of responding laboratories, only 12% (17) met criteria for analysis and reporting of malaria testing, significantly more than reported in a similar survey in 2010 (3%; P < 0.05). The majority of laboratories surveyed had the capability for timely diagnosis of malaria; few comply with CLSI guidelines. Inexperience may factor into this noncompliance; many laboratories see few to no cases of malaria per year. Although reported adherence to CLSI guidelines was higher than in 2010, there is a need to further improve laboratory compliance with recommendations.

Prior high-risk HPV testing and Pap test results for 427 invasive cervical cancers in China's largest CAP-certified laboratory.

BACKGROUND: Cervical cancer and its precursor lesions are caused by a persistent high-risk human papillomavirus (hrHPV) infection. hrHPV testing has been reported to have higher sensitivity than Papanicolaou (Pap) testing for the detection of cervical precursor lesions. However, limited data are available for prior human papillomavirus (HPV) testing results for patients later diagnosed with invasive cervical cancer, especially in countries lacking a national cervical cancer screening program such as China. This study investigated prior hrHPV testing results for patients with invasive cervical cancer in China. METHODS: Cases with a histologic diagnosis of invasive cervical carcinoma were retrieved from Guangzhou KingMed Diagnostics (the largest independent pathology laboratory in China); prior hrHPV and Pap test results obtained within the year before the cancer diagnosis were recorded. RESULTS: HPV testing was negative in 7.5% of 427 cases of invasive cervical carcinoma, including squamous cell carcinoma (5%) and adenocarcinoma (25%). In 155 cervical cancer cases with prior hrHPV and Pap testing, the negative rate for Pap testing was 1.9%, and the negative rate for HPV was 9.7%. Furthermore, when only cases of adenocarcinoma (n = 18) were examined, both the hrHPV-negative rate and the Pap-negative rate were higher at 33% and 5.6%, respectively. CONCLUSIONS: These data demonstrate a considerable prior hrHPV-negative rate and a lower prior Pap-negative rate in patients with invasive cervical carcinoma (especially adenocarcinoma) from a population of women without access to an established screening program.

Serological diagnosis of paracoccidioidomycosis: high rate of inter-laboratorial variability among medical mycology reference centers.

BACKGROUND: Serological tests have long been established as rapid, simple and inexpensive tools for the diagnosis and follow-up of PCM. However, different protocols and antigen preparations are used and the few attempts to standardize the routine serological methods have not succeeded. METHODOLOGY/PRINCIPAL FINDINGS: We compared the performance of six Brazilian reference centers for serological diagnosis of PCM. Each center provided 30 sera of PCM patients, with positive high, intermediate and low titers, which were defined as the "reference" titers. Each center then applied its own antigen preparation and serological routine test, either semiquantitative double immunodifusion or counterimmmunoelectrophoresis, in the 150 sera from the other five centers blindly as regard to the "reference" titers. Titers were transformed into scores: 0 (negative), 1 (healing titers), 2 (active disease, low titers) and 3 (active disease, high titers) according to each center's criteria. Major discordances were considered between scores indicating active disease and scores indicating negative or healing titers; such discordance when associated with proper clinical and other laboratorial data, may correspond to different approaches to the patient's treatment. Surprisingly, all centers exhibited a high rate of "major" discordances with a mean of 31 (20%) discordant scores. Alternatively, when the scores given by one center to their own sera were compared with the scores given to their sera by the remaining five other centers, a high rate of major discordances was also found, with a mean number of 14.8 sera in 30 presenting a discordance with at least one other center. The data also suggest that centers that used CIE and pool of isolates for antigen preparation performed better. CONCLUSION: There are inconsistencies among the laboratories that are strong enough to result in conflicting information regarding the patients' treatment. Renewed efforts should be promoted to improve standardization of the serological diagnosis of PCM.

Semi-automated unidirectional sequence analysis for mutation detection in a clinical diagnostic setting.

BACKGROUND: The past 10 years have seen an improvement in sequence data quality due to the introduction of capillary sequencers and new sequencing chemistries. In parallel, new software programs for automated mutation detection have been developed. We evaluated the sensitivity of semiautomated unidirectional sequence analysis for the detection of heterozygous base substitutions using the Mutation Surveyor software package. METHODS: Detection rates for heterozygous base substitutions in 29 genes by automated and visual inspection were compared. Examples of heterozygous bases not detected in one direction during bidirectional analysis were also sought through a national survey of United Kingdom (UK) genetics laboratories. Sequence quality was assessed in a consecutive cohort of 50 patients for whom the 39 exons of the ABCC8 gene had been sequenced in one direction. RESULTS: A total of 701 different heterozygous base substitutions were detected by the software with no false negatives (sensitivity >or=99.57%). Four examples of heterozygous bases missed in one direction during bidirectional analysis were reported. Two were detected using unidirectional analysis settings, and the other two bases had low-quality scores. Of the 1950 amplicons examined, 97.2% had a quality score >or=30 and an average PHRED-like score >or=50 for the defined region of interest, and 98.1% of the 323,650 bases had a PHRED score >40. CONCLUSIONS: We found no evidence to support a requirement for bidirectional sequencing. Semiautomated analysis of good quality unidirectional sequence data has high sensitivity and is suitable for heterozygote mutation scanning in clinical diagnostic laboratories. Further work is required to determine minimum quality parameters for semiautomated analysis.

[Glossary of the acronyms for the institutions concerned by metrology]. / Glossaire des acronymes d'institutions relevant de la métrologie.

Metrology and one of its contributions, metrological traceability represent two fundamental developments for the clinical laboratories. Several international and national institutions take part in these developments. They elaborate recommendations going from concepts to implementation in the clinical laboratories. These activities are helpful for accrediting clinical laboratories.

Índice de qualidade laboratorial (IQL): uma proposta para laboratórios de controle ambiental / Laboratorial quality index (IQL) a purpose for environmental laboratories

A abordagem sobre a elaboração de índices representativos da qualidade constitui recurso cada vez mais utilizado para o monitoramento ou comparação de uma ou mais situações, permitindo expressar de forma simplificada as condições avaliadas. Na área de meio ambiente, os resultados fornecidos pelos laboratórios de controle ambiental assumem um importante papel, proporcionando situações de julgamento e decisão por parte de quem utiliza esses resultados, pois o mérito dessas decisões pode ser influenciado pela qualidade desses resultados. Para tanto, objetivou-se propor um índice de qualidade aplicável a laboratórios de controle ambiental, avaliando a sua representatividade, a realidade do laboratório com base no seu histórico de qualidade e aplicabilidade do índice no acompanhamento de condições gerais de desempenho. A pesquisa, de caráter exploratório, foi constituída a partir da seleção de dez especialistas em laboratórios de controle ambiental, representantes dos setores público, privado e academia, entrevistados nas sucessivas etapas de proposição do índice. A primeira etapa constituiu entrevista aos especialistas com uso da técnica de Brainstorming que culminou com a seleção de vinte parâmetros de consulta. Nas etapas seguintes, seguiram-se os preceitos da técnica DELPHI para extrair e refinar os julgamentos do grupo, bem como, selecionar os parâmetros finais de avaliação do IQL, critérios de pontuação e as três faixas de enquadramento dos laboratórios (inadequada, em fase de adequação ou adequada). Foram realizados experimentos de aplicação do IQL em seis laboratórios de controle ambiental, também representantes dos setores público, privado e da academia, a razão de duas unidades por setor, dentre os quais se encontravam laboratórios acreditados pelo INMETRO, conforme a norma ISO IEC 17.025. A experiência na prática laboratorial revelou que o IQL poderá ser utilizado como ferramenta de apoio a pré-qualificação de laboratórios ambientais prestadores de serv...

[Identification and generalization of classes of public health laboratory detection activities].

OBJECTIVE: To identify and generalize classes of public health laboratory detection activities and to discuss the method of identification and generalization of classes of Public Health Conceptual Information Model. METHODS: At first, materials should be collected from consulting literatures and experts, referring to the existing system. Then, identification and generalization of classes are got for business process analysis, writing description documents, summing up important conceptions and activities, By use-case analysis, use-case diagram and tabulation of important conception and activities and reference to PHCDM, a structural diagram of classes is constructed. RESULTS: A structure diagram of classes of public health laboratory detection activity is given. CONCLUSIONS: This is a feasible method in identification and generalization of classes of public health laboratory detection activities.

[HIV infection under laboratory conditions]. / Ekspozycja na HIV w warunkach pracy laboratorium.

Laboratory workers are at a particularly high risk of acquiring HIV. Based on the medical literature, selected cases of occupational HIV infections among laboratory workers are presented. Having analyzed specific circumstances connected with occupational exposures, risk factors of such incidents are discussed. The importance of continuing education in the areas of infection control procedures and compliance with universal precautions as well as reporting on occupational exposures to any infectious material in the context of post-exposure prophylaxis are pointed as the best ways to achieve a successful outcome in the HIV infection prevention under laboratory conditions. The lack of efficient, multifaceted legislation covering all aspects of occupational exposure to blood-borne pathogens, still observed in Poland, is stressed.

Time to pregnancy among Danish laboratory technicians who were a part of the National Birth Cohort.

OBJECTIVES: The Danish National Birth Cohort was used to examine whether laboratory work was associated with reduced fecundity. METHODS: Self-reported data on laboratory work and waiting time to pregnancy (0-2, 3-5, 6-12 and > 12 months) were used for 829 female laboratory technicians interviewed in 1997-2003. Altogether 6250 female teachers formed the reference group. A discrete-time survival analysis with a complementary log-log link was applied to estimate the fecundability ratio between the exposed and unexposed women, with adjustment for maternal age, gravidity, smoking, prepregnancy body mass index, and paternal job. RESULTS: No difference in time to pregnancy was found between the laboratory technicians and teachers or between the laboratory technicians with different exposures. The adjusted fecundability ratio for the laboratory technicians was 0.94 [95% confidence interval (95% CI) 0.86-1.02] for all pregnancies and 0.98 (95% CI 0.86-1.13) for first pregnancies. A healthy worker effect was found for the laboratory technicians working with the work processes under study. CONCLUSIONS: The results do not suggest that laboratory work in Denmark at present impairs female fecundity.