Understanding barriers and facilitators to palliative and end-of-life care research: a mixed method study of generalist and specialist health, social care, and research professionals.

BACKGROUND: Palliative care provision should be driven by high quality research evidence. However, there are barriers to conducting research. Most research attention focuses on potential patient barriers; staff and organisational issues that affect research involvement are underexplored. The aim of this research is to understand professional and organisational facilitators and barriers to conducting palliative care research. METHODS: A mixed methods study, using an open cross-sectional online survey, followed by working groups using nominal group techniques. Participants were professionals interested in palliative care research, working as generalist/specialist palliative care providers, or palliative care research staff across areas of North West England. Recruitment was via local health organisations, personal networks, and social media in 2022. Data were examined using descriptive statistics and content analysis. RESULTS: Participants (survey n = 293, working groups n = 20) were mainly from clinical settings (71%) with 45% nurses and 45% working more than 10 years in palliative care. 75% were not active in research but 73% indicated a desire to increase research involvement. Key barriers included lack of organisational research culture and capacity (including prioritisation and available time); research knowledge (including skills/expertise and funding opportunities); research infrastructure (including collaborative opportunities across multiple organisations and governance challenges); and patient and public perceptions of research (including vulnerabilities and burdens). Key facilitators included dedicated research staff, and active research groups, collaborations, and networking opportunities. CONCLUSIONS: Professionals working in palliative care are keen to be research active, but lack time, skills, and support to build research capabilities and collaborations. A shift in organisational culture is needed to enhance palliative care research capacity and collaborative opportunities across clinical and research settings.

Joint Display of Integrated Data Collection for Mixed Methods Research: An Illustration From a Pediatric Oncology Quality Improvement Study.

PURPOSE: Researchers often struggle to integrate quantitative and qualitative data. Joint displays of data collected using mixed methods provide a framework for supporting integration, yet the literature lacks methodologic articles illustrating in detail the iterative nature of constructing such displays. We demonstrate the process for creating a joint display for integrating the collection of data obtained by qualitative and quantitative methods. METHODS: Within a convergent mixed methods cohort study, the Early Discharge of Febrile Neutropenic Children with Cancer Study, we constructed a joint display to inform integrated collection of 2 forms of data (quantitative and qualitative) from 2 sources (a patient-caregiver mixed methods survey and a manual abstraction of medical records). RESULTS: In a first step, we used a data sources table to align related quantitative and qualitative data. The resulting table consisted of 2 side-by-side columns based on the mixed survey data. After several additional iterative steps, we constructed a final 6-column joint display. This final display delineated the separate data sources, linked constructs to the quantitative and qualitative variables within each source, and integrated the constructs across the separate data sources. CONCLUSIONS: Challenges of integration, though not unique to prospective mixed methods cohort studies, stem from the sheer volume of qualitative and quantitative information and the need to logically organize the data in preparation for integrated data analysis. Tailoring joint displays to specific studies is challenging, but mixed methods researchers who embrace the methodologic malleability can produce effective joint displays to illustrate the mixed data collection linkages and create a preliminary structure ultimately for organizing mixed data findings.

The Evolution of Phenomenology in Korean Nursing Research: A Scoping Review.

PURPOSE: Phenomenological methods are used to capture human experience, and nursing research has long attempted phenomenological approaches in many studies. This study explored the 22-year trends (2001- 2022) in phenomenological research within Korean nursing science and identified the types of journals where research is published, common phenomenological data analysis methods, phenomena of interest, and standards of rigor applied to phenomenological studies. METHODS: This scoping review followed the six stages recommended by Arksey and O'Malley's (2005) and utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) for reporting guidance. A total of 4,354 articles acquired through systematic searches across seven search engines PubMed, CINAHL, Embase, Research Information Sharing Service (RISS), Korea Citation Index (KCI), Korea Institute of Science and Technology Information (KISTI), and Korean studies Information Service System (KISS) were reviewed. Key search terms and inclusion and exclusion criteria were used as strategies to identify relevant articles. RESULTS: In the final review, 568 Korean phenomenological studies were included. Among the phenomenology research, 50.4% of the total work was performed between 2016 and 2020, and the Colaizzi method of study was the most common (62.9%). Most researchers were published in nursing journals (55.8%). Nurses constituted the majority of participants (24.5%), followed by people living with illnesses (23.1%) and people of all ages. The primary focus included participants' experiences: the disease experience of the sick, the job-related experience of the nurses, and the learning-related experience of the nursing students. The median sample size of reviewed papers (i.e., 9) is relevant to phenomenological research saturation. The most rigorous studies applied Lincoln and Guba's criteria (54.0%). CONCLUSIONS: Advancing phenomenological research in nursing entails giving priority to diverse perspectives, rigor, and the foundational essence of phenomenology. Ensuring transparency and reliability requires reinforcing rigor through the integration of phenomenology, philosophy, and effective data analysis methods.

Design and psychometric properties of the acute care quality in trauma emergency units scale.

BACKGROUND: Systematic trauma care scale could be designed and used by nurses to completely and adequately fulfill a complex care to improve trauma care quality. The purpose of this study was to design and evaluate the psychometric property of the Nursing Care Quality in Trauma Emergency Units and trauma care promotion. METHODS: This methodological study was conducted in 2022. The process of designing and psychometric assessment of the scale was performed in two steps such as Generating an Item Pool and Validity and Reliability evaluation (Item reduction). The construct validity was determined using the experimental intervention; for determining the reliability of the scale and internal consistency, we measured the inter-rater reliability (IRR). Data were analyzed using the SPSS software, version 22. RESULTS: Based on our findings, the CVI and CVR of the scale were 1 and 0.83-1, respectively. A significant difference between the pre- and post-intervention scores in group 1 supports the inference that the construct has been appropriately represented, and the instrument has construct validity (p < 0.001). We found that there was a significant difference in the scores of Patient assessment, Planning and Implementations, and Evaluation of the care plan. The inter-rater reliability method allows the optimal reliability assessment of observational instruments, which was used in this study, and the results confirmed excellent reliability of the instrument. CONCLUSIONS: The validity and reliability of the Nursing Care Quality in Trauma Emergency Units Scale were confirmed. The instrument could successfully assess the process of nursing care in the trauma emergency ward. The use of this checklist is recommended as a valid observational tool for other researchers. STUDY TYPE: Therapeutic/care management.

In vivo methods for evaluating human midpalatal suture maturation and ossification: An updated review.

OBJECTIVES: The aim of this study was to perform an updated review of the in vivo methods to evaluate human midpalatal suture maturation and ossification, since this evaluation process remains an unsolved and critical problem in orthodontic treatment. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Scopus and Web of Science databases were searched up to November 30, 2021. Literature selection was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020 Edition) statement and was based on predetermined inclusion criteria. The overall and methodological characteristics of the selected studies were collected. The risk of bias was evaluated mainly through inter- and intra-evaluator agreement outcomes reported in each study. As there was a high heterogeneity among methodological studies, meta-analysis of the included studies was not applicable, and results were analysed descriptively. RESULTS: Nine articles met the inclusion criteria. Maxillary occlusal radiograph and computed tomography (CT), especially cone beam CT (CBCT), were reported. The occlusal radiograph is not adequate for evaluating the status of midpalatal suture maturation, and has been replaced by CBCT. Qualitative and quantitative CBCT evaluation methods provide limited evidence; however, opinions differ regarding the efficacy of these methods. CONCLUSIONS: For midpalatal suture maturation and ossification status evaluation, evidence for the current methods is still limited. Further methodological studies should use image information comprehensively and provide verification evidence on larger samples.

Cross-Cultural Adaptation of the Instrument "Nurse-Physician Relationship Survey: Impact of Disruptive Behavior in Patient Care" to the Spanish Context.

Disruptive behavior in the healthcare context has an impact on patient care, healthcare personnel, and the health organization, and it also influences the therapeutic relationship, communication process, and adverse events. However, there is a lack of instruments that could be used for its analysis in the hospital care environment in the Spanish context. The objective of the study was to culturally adapt and perform a content validation of the tool "Nurse−Physician Relationship Survey: Impact of Disruptive Behavior on Patient Care", to the Spanish content (Spain). An instrumental study was conducted, which included an analysis of conceptual and semantic equivalence. A panel of experts analyzed the translations, by analyzing the Content Validity Index (CVI) of the group of items in the scale through the Relevance Index (RI) and the Pertinence Index (PI). Only a single item obtained an RI value of 0.72, although with PI value of 0.81, with consensus reached for not deleting this item. The CVI of all the items was >0.80 for the mean value of the RI, as well as the PI. The instrument was adapted to the Spanish context and is adequate for evaluating the disruptive behaviors on nurse−physician relationships and its impact on patient care. However, the importance of continuing the analysis of the rest of the psychometric properties in future studies is underlined.

A methodological study on the combination of qualitative and quantitative methods in cognitive interviewing for cross-cultural adaptation.

AIM: The aim of this study is to explore the use of the Questionnaire Appraisal System with a combination of qualitative and quantitative methods in cognitive interviewing for cross-cultural adaptation. DESIGN: This is a descriptive methodological study. METHODS: Using the Mandarin version of the Post-Stroke Checklist as an example, cognitive interviews were conducted with 27 stroke survivors in Guangzhou between November 2020 and February 2021. The Questionnaire Appraisal System was applied as a codebook in focus group discussions to perform quantitative data collections and quantitative content analysis. RESULTS: Thirty-eight problems were proposed in focus group discussions and identified all but four of the 30 questions that emerged in the cognitive interviews. A new item was added to the Questionnaire Appraisal System for better categorization. Four categories and six subcategories of problems in the checklist were revealed.

Validation of a search strategy for randomized clinical trials related to periodontitis.

BACKGROUND: Systematic reviews, considered the gold standard for the assessment of scientific evidence, may present conflicting findings for the same clinical issue, and such dissent may be justified by the forms of elaboration of the electronic search strategy. This paper aims to validate a search strategy to identify randomized clinical trials related to periodontitis. A gold standard reference set was developed to validate the identified clinical trials using the relative recall method. The choice of periodontitis is due to the fact that this disease has a high prevalence among chronic non-communicable diseases, is considered the second most common oral disease in the world, is associated with several health problems, such as cardiovascular diseases and diabetes, and, principally, has not been investigated sufficiently to prevent possible damages resulting from it. METHODS: A validation study was developed in MEDLINE/PubMed. In Stage 1, a methodological filter recommended by the Cochrane Collaboration to identify randomized clinical trials was applied. Stage 2 identified articles related only to periodontitis (gold standard reference set) from among the articles retrieved using the eligibility criteria. In Stage 3, a search statement for the retrieval of periodontitis-related articles was elaborated by experts. Stage 4 defined the proposed search strategy comprising of the combination of the search statement developed with the aforementioned methodological filter and subsequent application in MEDLINE/PubMed. The obtained data were analyzed using the set of articles identified in Stage 2, as the gold standard reference set. The following performance values were calculated - sensitivity, specificity, accuracy, and number needed to read - with their respective 95% confidence interval (95%CI). RESULTS: The search strategy under evaluation compared to the gold-standard showed a sensitivity of 93.2% (95%CI, 83.8-97.3), specificity of 99.9% (95%CI 99.8-99.9), and a precision of 77.5% (95%CI, 66.48-85.63). In addition, the number needed to read was 1.3. CONCLUSION: According to the proposed methodological approach, the search strategy under evaluation performed well in the identification of randomized clinical trials related to periodontitis.

Husserlian phenomenology in Korean nursing research: analysis, problems, and suggestions.

PURPOSE: This paper is a critical review of the descriptive phenomenological methodology in Korean nursing research. We propose constructive suggestions for the improvement of descriptive phenomenological methodology in light of Husserl's phenomenological approaches. METHODS: Using the keywords of 'phenomenology,' 'experience,' and 'nursing,' we identify and analyze 64 Korean empirical phenomenological studies (selected from 282 studies) published in 14 Korean nursing journals from 2005 to 2018. The PubMed and the Korea Citation Index were used to identify the studies. RESULTS: Our analysis shows that all the reviewed articles used Giorgi's or Colaizzi's scientific phenomenological methodology, without critical attention to Husserl's philosophical phenomenological principles. CONCLUSIONS: The use of scientific phenomenology in nursing research, which originated in North America, has become a global phenomenon, and Korean phenomenological nursing research has faithfully followed this scholarly trend. This paper argues that greater integration of Husserlian phenomenological principles into scientific phenomenological methodology in nursing research, such as participant-centered bracketing and eidetic reduction, is needed to ensure that scientific phenomenology lives up to its promise as a research methodology.

Validation of the 30-item nurses' observation scale for inpatient evaluation and mental health-care promotion.

CONTEXT: The 30-item nurses' observation scale for inpatient evaluation (NOSIE-30) developed for the behavioral and observational rating of psychiatric inpatients. AIMS: The purpose of this study was to evaluate the validation of the NOSIE-30 and mental health-care promotion. MATERIALS AND METHODS: The participants with psychiatric disorders were selected from 310 inpatients referred to the military educational hospital in Iran. This study was carried out in two phases: First, translation of the NOSIE-30 into Persian followed the stepwise, iterative procedures developed by the International Quality of Life Assessment project approach. Second, face validity, criterion-related validity and construct validity, and reliability of the Persian version were determined. The concurrent validity was assessed by using the global assessment of functioning (GAF) instrument. Data were analyzed with the SPSS software of version 22. Exploratory factor analysis, the Cronbach's alpha coefficient, and interrater agreement with intraclass correlation coefficient and Pearson's correlation coefficient were used to data analysis. RESULTS: Pearson's correlation coefficient between the NOSIE and GAF was 0.75. The interrater reliability for subscale scores and structure of the NOSIE were ranging from 0.70 to 0.94 and Cohen's kappa = 0.74. Furthermore, the internal consistency of the scale's total scores was estimated by Cronbach's alpha = 0.85. CONCLUSIONS: The finding indicated that NOSIE-30 Persian version scale has the desirable validity and reliability for evaluating the nursing care of inpatients. Thus, nurses can promote mental health care by applying this scale in the psychiatric setting.

The logic of equivalence testing and its use in laboratory medicine.

Hypothesis testing is a methodological paradigm widely popularized outside the field of pure statistics, and nowadays more or less familiar to the largest part of biomedical researchers. Conversely, the equivalence testing is still somehow obscure and misunderstood, although it represents a conceptual mainstay for some biomedical fields like pharmacology. In order to appreciate the way it could suit laboratory medicine, it is necessary to understand the philosophy behind it, and in turn how it stemmed and differentiated along the history of classical hypothesis testing. Here we present the framework of equivalence testing, the various tests used to assess equivalence and discuss their applicability to laboratory medicine research and issues.

Parity and primary liver cancer among young women.

PIP: Researchers from the US National Cancer Institute compared data on 25-49 year old US women who died of primary liver cancer between 1985 and 1986 with data on age matched controls who died of causes other than liver conditions or oral contraceptive (OC) related conditions to determine the association between primary liver cancer and parity. Women who had experienced at least 1 live birth wear 1.9 times more likely to have died of primary liver cancer than were nulliparous women. The association was not significant (p=.22), however. The highest risks were among children with at least 6 children (odds ratio [OR]=2.9) and with 2 children (2.1). Further the risks were greater when the parents or spouse completed the questionnaire and the association almost reached significance (p=.07). This may have been due to parents and spouse providing more complete information than a friend or neighbor. The risks of developing primary liver cancer were higher among women who had never used OCs than they were among those who ever did. For example, the OR for never users past parity 2 was 3.6 compared with 1.3 for ever OC users. There was a higher risk associated with parity among long term OC users (=or 5 years) than with short-term OC users, however. The researchers concluded that since parity was positively associated with increased risk of primary liver cancer in the US (a low risk country), endogenous hormones may contribute to liver cancer development. The following facts add to this plausibility. Estrogen profiles of parous women are different from those of nulliparous women. Estrogen levels rise considerably during pregnancy. Estrogens alter liver metabolism. Pregnancy makes the body more defenseless against hepatitis and its sequelae. In low risk countries, the risk of primary liver cancer rises among women using exogenous hormones.^ieng

Adaptación y validación preliminar de la Escala teoría cultural de cosmovisiones ambientales en población chilena / Preliminary Adaptation and Validation of the Cultural Theory of Environmental Worldviews Scale in Chilean Population

Resumen El presente estudio tuvo como objetivo adaptar y aportar evidencias preliminares de validez de la Escala de teoría cultural de cosmovisiones ambientales en el contexto latinoamericano. Se analizaron evidencias de validez de contenido mediante el juicio de cuatro expertos, validez discriminante y convergente, estructura interna a través de análisis factorial exploratorio y confirmatorio, y consistencia interna a través del coeficiente Omega. Mediante un muestreo no probabilístico por conveniencia, se seleccionaron 500 participantes en edad adulta que residían en la región del Ñuble, Chile. Se obtuvo una versión revisada y adecuada lingüísticamente del instrumento, que presentó coeficientes de concordancia de Kappa que fluctuaron entre considerable y casi perfecto en cuanto a su contenido. Los análisis estadísticos dan cuenta de la idoneidad del instrumento de 15 ítems y un análisis factorial confirmatorio que apoya la estructura interna de cuatro factores (individualismo, igualitarismo, jerarquismo y fatalismo); igual que la versión original. Los coeficientes de consistencia interna fueron aceptables para las cuatro subescalas. Respecto a la validez discriminante se obtuvieron medidas de varianza extraída adecuadas para igualitarismo, jerarquismo y fatalismo (sólo individualismo presentó valores levemente bajo lo esperado), y respecto a la validez convergente se obtuvieron valores adecuados en fiabilidad compuesta para los cuatro factores. Estos hallazgos avalan el uso de la versión en español de la Escala de teoría cultural de cosmovisiones ambientales en población de habla hispana, contribuyendo a la potencial ampliación de estudios socioculturales sobre el medioambiente en Latinoamérica.

Abstract The objective of this study was to adapt and provide preliminary validity evidence of the cultural theory and environmental worldviews scale in the Latin-American context. Content validity evidence was assessed by the judgment of four experts, discriminant and convergent validity, internal structure through exploratory and confirmatory factor analysis, and internal consistency using the omega coefficient. The sample consisted of 500 participants from the Ñuble region, Chile. Regarding the results, a revised and linguistically adapted version of the instrument was obtained, which presented a kappa coefficient ranging from substantial to almost perfect regarding the content. The statistical analysis shown the adequacy of the 15-item instrument and a confirmatory factor analysis which supported the four-factor internal structure (individualism, egalitarianism, hierarchy, and fatalism), as in the original version. The internal consistency assessed using the Omega coefficient was acceptable for the four subscales. Regarding discriminant validity, adequate average variance extracted was obtained for egalitarianism, hierarchy, and fatalism (only individualism presented values slightly lower than expected), while convergent validity showed adequate composite reliability values for the four factors. These findings support the use of the Spanish version of Cultural Theory scale of and Environmental Worldviews in Spanish speaking population, contributing to potential further sociocultural studies about the environment in Latin America.

Panning for the gold in health research: incorporating studies' methodological quality in meta-analysis.

BACKGROUND: Systematic reviews now routinely assess methodological quality to gauge the validity of the included studies and of the synthesis as a whole. Although trends from higher quality studies should be clearer, it is uncertain how often meta-analyses incorporate methodological quality in models of study results either as predictors, or, more interestingly, in interactions with theoretical moderators. OBJECTIVE AND METHODS: We survey 200 meta-analyses in three health promotion domains to examine when and how meta-analyses incorporate methodological quality. RESULTS: Although methodological quality assessments commonly appear in contemporary meta-analyses (usually as scales), they are rarely incorporated in analyses, and still more rarely analysed in interaction with theoretical determinants of the success of health promotions. The few meta-analyses (2.5%) that did include such an interaction analysis showed that moderator results remained significant in higher quality studies or were present only among higher quality studies. We describe how to model quality interactively with theoretically derived moderators and discuss strengths and weaknesses of this approach and in relation to current meta-analytic practice. CONCLUSIONS: In large literatures exhibiting heterogeneous effects, meta-analyses can incorporate methodological quality and generate conclusions that enable greater confidence not only about the substantive phenomenon but also about the role that methodological quality itself plays.

The value of cryptococcal serum antigen screening among HIV-positive/AIDS patients in Kinshasa, Zaire.

Cryptococcal meningitis is a frequently observed opportunistic infection in AIDS patients in Zaire and other countries in Central Africa. The prognosis in those patients is very poor because of the advanced stage of their cryptococcal disease at presentation. To improve the prognosis of cryptococcal meningitis in HIV-infected patients through earlier diagnosis, a routine serum cryptococcal antigen screening was performed on 450 HIV-positive/AIDS patients seen at the Cliniques Universitaires de Kinshasa between 1 January 1988 and 31 August 1988. Cryptococcal antigen was detected in the sera of 55 (12.2%) of them. Cerebrospinal fluid was obtained from 44 of these 55 patients and the presence of Cryptococcus neoformans was demonstrated by direct microscopy and culture in 29 (66%) of them.

PIP: A routine serum cryptococcal antigen screening of 450 human immunodeficiency virus (HIV)-positive/acquired immunodeficiency syndrome (AIDS) patients at the Cliniques Universitaires de Kinshasa, Zaire, revealed that cryptococcal antigen was present in the sera of 55 (12.2%) of them. Health professionals collected cerebrospinal fluid of 44 patients from the positive serum group. The fungus Cryptococcus neoformans was identified by direct microscopy and culture in 29 (66%) of them. 6.6% of the originally screened HIV-positive/AIDS patients, therefore, had cryptococcal meningitis which is an opportunistic infection in these individuals. Serum screening for cryptococcal antigens could improve the prognosis of cryptococcal meningitis in HIV-infected patients by introducing an appropriate antifungal treatment at an early stage.

The affordability of antiretroviral therapy in developing countries: what policymakers need to know.

OBJECTIVE: The objective of this paper is to assist policymakers in developing countries and international donors by providing an outline of economic information needed to make a decision regarding the purchase of drugs to provide highly active antiretroviral therapy (HAART). DESIGN: The following paper: (i) reviews existing experiences of policymakers in developing countries regarding the purchase of drugs needed for HAART, (ii) identifies issues that would need to be addressed and data that would be required to make more informed decisions regarding this issue, (iii) develops a cost-benefit model that could be utilized in designing an economic research project evaluating the economic costs and benefits of HAART, and (iv) performs a preliminary test of this model with data from Costa Rica. RESULTS: A review of experiences with this issue reveals that there are growing political, legal and budgetary pressures for countries to make tenable decisions regarding the purchase of drugs for HAART. An economic model describing the costs and benefits of HAART is proposed, although much of the required data for using such a model is currently neither available or in the process of being collected. CONCLUSIONS: It is imperative that economic data be collected to better inform policymakers in developing countries about their decision regarding the purchase of these drugs. It is recommended that such economic data be collected as organizations such as the United Nations Joint Programme on HIV/ AIDS (UNAIDS) initiate their medical assessments of HAART in developing countries.

PIP: The ideal treatment strategy for people with AIDS (PWAs), involving the use of one or more protease inhibitors and 2 reverse transcriptase inhibitors, is known as highly active antiretroviral therapy (HAART). HAART is greatly helping PWAs, sometimes enabling patients in the final stages of AIDS to regain enough health and strength to again actively and productively participate in society. With such successes in developed countries, policymakers in developing countries are increasingly being pressured to provide HAART for their own populations. The drugs needed for HAART, however, are very expensive and may require administration throughout the remainder of the life of the PWA. Few, if any, similarly expensive drugs are currently available in developing countries. The author reviews existing experiences of policymakers in developing countries on the purchase of drugs needed for HAART, identifies the issues to address and data needed to make more informed decisions on the subject, develops a cost-benefit model which could be used to design an economic research project evaluating the economic costs and benefits of HAART, and tests the model with data from Costa Rica. Political, legal, and budgetary pressures are mounting for countries to make viable decisions on buying drugs for HAART. An economic model describing the costs and benefits of HAART is proposed, although much of the required data for using such a model is currently neither available nor being collected.

Selection of primers of optimal sensitivity for the detection of HIV-1 from Africa and Europe by polymerase chain reaction.

In order to facilitate the detection of integrated HIV-1 proviral DNA from African as well as European patients, four new primer pairs for use in the polymerase chain reaction (PCR), localised in the gag, pol, vif and env genes of HIV-1, were constructed. The primer pairs were compared to all accessible HIV-1 sequences from African and European isolates and to some of the earlier published and most commonly used primer pairs. HIV-1 DNA was detected in blood drawn from 13 out of 13 individuals infected in Africa, in three out of three Tanzanian HIV-1 isolates and in three out of three asymptomatic Swedes infected in Europe. The new selection of primer pairs can be used as an alternative to enhance the detection of HIV-1 of different origins.

PIP: In order to facilitate the detection of integrated HIV-1 proviral DNA from African as well as European patients, 4 new primer pairs for use in the polymerase chain reaction (PCR), localized in the gag, pool, vif, and env genes of HIV-1, were constructed. The primer pairs were compared to all accessible HIV-1 sequences from African and European isolates and to some of the earlier published and most commonly used primer pairs. HIV-1 DNA was detected in blood drawn from 13 infected individuals in Africa, in 3 Tanzanian HIV-1 isolates, and in the 3 asymptomatic Swedes infected in Europe. The new selection of primer parts can be used as an alternative to enhance the detection of HIV-1 of different origins.

The impact of HIV-1 infection on mortality in children under 5 years of age in sub-Saharan Africa: a demographic and epidemiologic analysis.

OBJECTIVE: To estimate the effects of the HIV-1 epidemic on mortality in children under 5 years of age in urban and rural populations in eastern and central, and southern Africa. METHODS: A lifetable method that allows for the effects of competing causes (i.e., mortality due to HIV and other causes) was used to estimate mortality. Our calculations used published and unpublished data on HIV-1 infection in African adults and children (incidence and prevalence, vertical transmissions, transmission by blood transfusion and natural history), and typical baseline fertility and child mortality data. The results were applied to model rural and urban populations to explore the effects of parameters such as mortality in HIV-1-infected children, fertility in infected mothers and overall population growth. RESULTS: We estimate that child mortality will rise substantially because of the prevalence of HIV-1 in urban areas. There will be little difference in the absolute levels of increase in mortality between areas in eastern and central, and southern Africa with similar levels of HIV infection; however, in relative terms the effect will be more noticeable in southern Africa because of the lower baseline mortality. Towns with severe epidemics (30% adult seroprevalence) might experience a rise in child mortality of one-third in eastern and central Africa and three-quarters in southern Africa. This will cancel or reverse existing advantages in urban over rural levels of child mortality and this effect will be more pronounced in southern Africa. The exact impact of HIV-1 will vary according to mortality among HIV-1-infected children and to fertility among infected women. However, changes in age structure and population growth have relatively little impact on mortality. CONCLUSIONS: There are likely to be substantial increases in child mortality in sub-Saharan Africa as a result of HIV-1 infection. The main determinant of childhood infection is the scale of the epidemic among adults. Increases in mortality will depend on local adult seroprevalence but are hard to predict precisely because of possible variation in death rates among HIV-1-infected children. In rural areas with low seroprevalence other diseases will remain the main cause of mortality. However, in urban areas families and health services will have to face considerably increased demands from ill and dying children.

PIP: The objective was to estimate the effects of the HIV-1 epidemic on mortality in children under 5 years of age in urban and rural populations in eastern, central, and southern Africa. Epidemiologic parameters were applied to three populations with different characteristics: a rural population with an HIV-1 prevalence of 3%, an urban population (Town A) with 10% seroprevalence, and a second urban population (Town B) with 30% seroprevalence among women of childbearing age, respectively. The output measures were the absolute increases in and the level of the under-5-years' mortality rate, which represents the probability of a child dying before his or her fifth birthday per 1000 births. It was estimated that child mortality will rise substantially because of the prevalence of HIV-1 in urban areas. There will be little difference in the absolute levels of increase in mortality between areas in eastern, central, and southern Africa with similar levels of HIV infection; however, in relative terms the effect will be more noticeable in southern Africa because of the lower baseline mortality. Towns with severe epidemics (30% adult seroprevalence) might experience a rise in child mortality of 1/3 in eastern and central Africa and 3/4 in southern Africa. This will cancel or reverse existing advantages in urban over rural levels of child mortality with more pronounced effect in southern Africa. The exact impact of HIV-1 will vary according to mortality among HIV-1-infected children and according to fertility among infected women. The main determinant of childhood infection is the scale of the epidemic among adults. The educated urban elite can be expected to suffer from more young adult AIDS-related mortality. In rural areas with low seroprevalence, other diseases will remain the main cause of mortality. In urban areas, health services will have to face considerably increased demands from ill and dying children.

A rapid manual method for CD4+ T-cell quantitation for use in developing countries.

OBJECTIVE: To evaluate a manual method (Cytosphere) for quantifying CD4+ T-cell numbers. DESIGN: Cross-sectional study of HIV-1-seronegative and HIV-1-seropositive individuals evaluated for absolute CD4 counts by both standardized flow cytometric measurements and manual Cytosphere technology using a hemacytometer. SETTING: University research hospitals in both the United States and Africa. PATIENTS, PARTICIPANTS: Blood specimens from 382 patients were evaluated. These were broken down into 294 samples obtained from HIV-1-seropositive patients and 88 samples obtained from HIV-1-seronegative patients. INTERVENTIONS: None. OUTCOME MEASURED: Absolute CD4 cell number. RESULTS: Evaluation of samples obtained from HIV-1 patients in both the United States and Africa demonstrated an overall correlation of the Cytosphere assay with flow cytometry of 0.912 (95% confidence interval, 0.895-0.928; P < 0.001). When samples were stratified based on CD4+ T-cell counts determined by flow cytometry, the Cytosphere assay had a 96% predictive value for correctly identifying individuals with CD4 T-cell counts > 200 x 10(6)/l and a 92% predictive value for correctly identifying individuals with CD4 T-cell counts < 200 x 10(6)/l. CONCLUSIONS: This assay appears to have the potential for the quantitation of CD4 cells in the limited laboratory facilities in developing countries and to have a strong correlation with standard flow cytometric technology.

PIP: Clinicians took blood samples from 294 HIV-1 seropositive patients and 88 HIV-1 seronegative patients at Cornell University Medical College and The New York Hospital in New York City, Rush-Presbyterian-St. Luke's Medical Center in Chicago, and Makerere University Medical school in Kampala, Uganda, to assess a manual method's (Cytosphere) ability to accurately determine the CD4+ T-cell count. The Cytosphere assay uses latex beads coated with CD4 antibody which are combined with anticoagulated whole blood followed by red cell lysis. A hemacytometer then counts the bead-coated cells. The average technologist only needs 1-3 days of training (20 CD4 practice assays/days) in the Cytosphere assay. The minimal equipment required for the assay are a pipette, a hemacytometer, and a light microscope. The lysing agent inactivates HIV-1. The overall correlation between the standard flow cytometry method and the Cytosphere assay stood at 0.912 and was significant (p .001). When the researchers stratified the samples based on CD4+ T-cell counts defined by flow cytometry, the predictive values of the Cytosphere assay for correctly identifying patients with CD4 T-cell counts greater or less than 200 x 1 million/1 were 96% and 92%, respectively. These findings suggested that the Cytosphere assay has the potential to quantify CD4 cells in the limited laboratories in developing countries. Larger longitudinal studies of HIV seropositive people in developing countries are needed to test the reliability and reproducibility of the assay.

Evaluation of two staging systems for HIV infection for use in developing countries.

OBJECTIVE: To evaluate the clinical axis of the World Health Organization (WHO) clinical staging system and the modified WHO staging system proposed by Montaner et al. using the lymphocyte strata > 1500, 1500-1000 and < 1000 cells x 10(6)/l. DESIGN: Cross-sectional study. PATIENTS: Four hundred and fifteen consecutive patients with HIV infection attending three HIV reference centres in Belgium. METHODS: Absolute CD4 lymphocyte counts were compared between stages within the two staging systems. RESULTS: Median CD4 lymphocyte counts decreased with increasing stage of disease in both staging systems. Differences in median CD4 lymphocyte counts between stages of each staging system were statistically significant (Kruskal-Wallis one-way analysis of variance, P < 0.001). The WHO clinical stage 1 and the modified WHO stage I had positive predictive values of 56 and 58%, respectively, for identifying patients with CD4 lymphocyte levels > 500 cells x 10(6)/l. The WHO clinical stage 4 and the modified WHO stage IV had positive predictive values of 79 and 80%, respectively, for identifying patients with CD4 lymphocyte levels < 200 cells x 10(6)/l. CONCLUSIONS: The WHO clinical staging system or a modified version of this system using lymphocytes stratification may be a good alternative in developing countries to the CD4 lymphocyte count-based HIV staging system used in the developed world. Cohort studies in developing countries are needed to assess their prognostic value.

PIP: In 1990, Belgium, physicians enrolled 415 consecutive patients attending HIV reference centers in Antwerp, Brussels, and Ghent in a cross-sectional study designed to evaluate the clinical axis of the WHO staging system with and without the lymphocyte stratification proposed by Montaner el al. (that is, modified WHO staging system) (1500, 1500- 1000, and 1000 cells x 1 million/l). They filled in a standardized questionnaire with all criteria of the WHO staging system. Laboratory personnel used standard hematology and flow cytometry techniques to determine absolute and CD4 lymphocyte counts. 80% of the patients were Caucasians. 46% of all patients were homosexual and 42% were heterosexual; 79.2% were men. Median CD4 lymphocyte counts fell in both staging systems as the stage of HIV infection increased. There were significant differences in median CD4 counts between stages of each staging system (p .001). The modified WHO staging system's stage I was more sensitive at identifying patients with CD4 lymphocyte counts of more than 500 cells x 1 million/l than the WHO clinical stage 1 (83% sensitivity vs. 48% sensitivity). The positive predictive value of WHO clinical stage 4 and of the modified WHO staging system's stage IV for identifying people with CD4 lymphocyte counts of less than 200 cells x 1 million/l was quite high (79% and 80%, respectively). The researchers suggested that clinicians use stages 4 and IV as end-points is clinical trials in developing countries. Clinicians completing the questionnaire knew the patients' earlier CD4 lymphocyte count, which may have introduced a bias in the study. For example, they may have more thoroughly examined patients with low CD4 lymphocyte counts than those with normal counts. Nevertheless, the study's results indicated that either one of these systems may be a good alternative in developing countries to the technical equipment-dependent CD4 lymphocyte count-based HIV staging system used in developed countries. Cohort studies in developing countries would evaluate their prognostic value.