Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008-2018.

OBJECTIVES: World Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process. STUDY DESIGN: We did a systematic, retrospective analysis of research questions identified in the published guidelines. METHODS: We analyzed guidelines published between January 1, 2008, and December 31, 2018, by the Communicable Diseases Cluster in five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs). Research questions were extracted independently by two researchers. We analyzed the distribution of research questions by disease and by topic category and did a qualitative assessment of optimum practice for research question generation during the guideline development process. RESULTS: A total of 48 guidelines were included: 26 on HIV, 1 on malaria, 11 on TB, 5 on TB/HIV, and 5 on NTDs. Overall, 36 (75%) guidelines encompassed a total of 360 explicit research questions; the remainder did not contain specific research questions. The number of research questions that focused on TB was 49, TB/HIV was 38, HIV was 250, and NTDs was 23. The number of research questions that focused on diagnosis was 43 (11.9%) of 360, prevention was 62 (17.2%), treatment was 103 (28.6%), good practice was 12 (3.3%), service delivery was 86 (23.8%), and other areas was 54 (15%). Research questions were often not formulated in a specific or actionable way and were hard to identify in the guideline. Examples of good practice identified by the review team involved the generation of specific and narrowly defined research questions, with accompanying recommendations for appropriate study design. CONCLUSIONS: The WHO must strengthen its approach to identifying and presenting research questions during the guideline development process. Ensuring access to research questions is a key next step in adding value to the guideline development process.

Role of carbonate burial in Blue Carbon budgets.

Calcium carbonates (CaCO3) often accumulate in mangrove and seagrass sediments. As CaCO3 production emits CO2, there is concern that this may partially offset the role of Blue Carbon ecosystems as CO2 sinks through the burial of organic carbon (Corg). A global collection of data on inorganic carbon burial rates (Cinorg, 12% of CaCO3 mass) revealed global rates of 0.8 TgCinorg yr-1 and 15-62 TgCinorg yr-1 in mangrove and seagrass ecosystems, respectively. In seagrass, CaCO3 burial may correspond to an offset of 30% of the net CO2 sequestration. However, a mass balance assessment highlights that the Cinorg burial is mainly supported by inputs from adjacent ecosystems rather than by local calcification, and that Blue Carbon ecosystems are sites of net CaCO3 dissolution. Hence, CaCO3 burial in Blue Carbon ecosystems contribute to seabed elevation and therefore buffers sea-level rise, without undermining their role as CO2 sinks.

Corrigendum to "Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2α Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes".

[This corrects the article DOI: 10.1155/2016/9354937.].

Comparison of the learning of two notations: A pilot study.

INTRODUCTION: MICAP is a new notation in which the teeth are indicated by letters (I-incisor, C-canine, P-premolar, M-molar) and numbers [1,2,3] which are written superscript and subscript on the relevant letters. FDI tooth notation is a two digit system where one digit shows quadrant and the second one shows the tooth of the quadrant. This study aimed to compare the short term retention of knowledge of two notation systems (FDI two digit system and MICAP notation) by lecture method. METHODS: Undergraduate students [N=80] of three schools participated in a cross-over study. Two theory-driven classroom based lectures on MICAP notation and FDI notation were delivered separately. Data were collected using eight randomly selected permanent teeth to be written in MICAP format and FDI format at pretest (before the lecture), post-test I (immediately after lecture) and post-test II (one week after the lecture). Analysis was done by SPSS version 20.0 using repeated measures ANCOVA and independent t-test. RESULTS: The results of pre-test and post-test I were similar for FDI education. Similar results were found between post-test I and post-test II for MICAP and FDI notations. CONCLUSION: The study findings indicated that the two notations (FDI and MICAP) were equally mind cognitive. However, the sample size used in this study may not reflect the global scenario. Therefore, we suggest more studies to be performed for prospective adaptation of MICAP in dental curriculum.

Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2α Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Background. Our aim was to evaluate the protective effect of lipoic acid (LA) on fetal outcome of diabetic mothers. Methods. Diabetes was induced in female rats using streptozotocin and rats were made pregnant. Pregnant control (group 1; n = 9; and group 2; n = 7) or pregnant diabetic (group 3; n = 10; and group 4; n = 8) rats were treated daily with either LA (groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the fetuses, placentas, and membranes were dissected, examined morphologically, and then homogenized, to measure cyclooxygenase (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2α (PGFM) levels. The level of total glutathione was measured in the maternal liver and plasma and in all fetuses. Results. Supplementation of diabetic rats with LA was found to significantly (p < 0.05) reduce resorption rates in diabetic rats and led to a significant (p < 0.05) increase in liver, plasma, and fetuses total glutathione from LA-TD rats as compared to those from V-TD. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas, and membranes were characteristic of experimental diabetic gestation associated with malformation. The levels of PGEM in malformed fetuses from LA-TD mothers was significantly (p < 0.05) higher than those in malformed fetuses from V-TD rats. Conclusions. LA treatment did not completely prevent the occurrence of malformations. Thus, other factors may be involved in the pathogenesis of the diabetes-induced congenital malformations.

Knowledge, Attitudes and Beliefs Related To Drugs among Pahang Matriculation Students in Malaysia

​Drug abuse has been a global threat not only in Malaysia but worldwide, especially among adolescents. This is alarming issue had been a serious public health problem worldwide. The aim of the study is to access the knowledge and attitude on drug abuse among Pahang Matriculation students in 2016. A cross¬-sectional study was conducted involving 217 matriculation students. A self-determined questionnaire was distributed among the students regarding knowledge and attitude about drugs. The prevalence of good knowledge on drug abuse was (82.03%). The prevalence of students’ attitude on drug abuse has higher number of good attitude with the sum of 182 (83.9 %). Only gender showed a significant association with students’ knowledge (P= 0.046). The knowledge, attitude, and practice of drug abuse among Pahang Matriculation students are good.​

Identifying factors affecting age at first semen freezing and age at first semen use in Sahiwal bulls.

AIM: The objective of the study was to evaluate the effects of non-genetic factors on reproduction traits viz. age at first semen freezing and age at first semen use of breeding bulls in Sahiwal bulls by fitting least-squares analysis. MATERIALS AND METHODS: The information on reproduction traits of 43 Sahiwal breeding bulls belonging to 8 sets of Sahiwal breeding program at Indian Council of Agricultural Research-National Dairy Research Institute (ICAR-NDRI), Karnal (Haryana), India during 27 years (1987-2013) were analyzed using fixed linear model. The information was collected from AI records, reproduction sheets, and bull AI register maintained at different sections of Institute viz. record room of Dairy Cattle Breeding Division (DCB), Cattle Yard, Artificial Breeding Research Centre, ICAR-NDRI, Karnal. RESULTS: The average age at first semen freezing and age at first semen use of Sahiwal breeding bulls was estimated as 3.17±0.01 years and 5.35±0.01 years, with the coefficient of variation 18.93% and 20%, respectively. The overall least-squares mean for age at first semen freezing and age at first semen use was estimated as 3.14±0.09 years and 5.25±0.02 years, respectively, in Sahiwal breeding bulls. Period of freezing/use had significant effects on reproductive traits (p<0.01). Season had no significant effect on any of the traits considered in this study. CONCLUSION: It can be concluded that management inputs such as nutrition, breeding, and optimum environment should be taken care of to optimize age at first semen freezing and age at first semen use for better utilization of superior germplasm.

Knowledge, Attitude And Practice Of Dengue Fever And Heath Education Programme Among Students Of Alam Shah Science School, Cheras, Malaysia

Dengue Fever is a major public health issue in Malaysia. This study aimed to assess knowledge, attitude and practice regarding dengue fever and effectiveness of health education programme among 204 students of Alam Shah Science School, Cheras/Kuala Lumpur. Study design was a cross sectional study followed by an interventional (pre-post) Study. The self-administered questionnaire included questions on sociodemographic factors, knowledge, attitude and practice regarding dengue fever. Majority of respondents were Malays (96.6%), monthly family income more than RM 3000 (64.6%) and lives in urban area (64.6%). There was no significant association between knowledge status and socio-demographic factors (p-value>0.05). Most of the respondents had good knowledge (63.2%) good attitudes (79.9%) regarding dengue fever. However, practices to prevent dengue was poor (74.0%). Only about one-fifth of the respondents (18.2%) believed that dengue fever is a flu-like illness. Knowledge score was significantly increased after health education programme (p value <0.001). There is a need to increase health education activities through campaigns and mass media to increase knowledge regarding dengue fever. This would help to inculcate positive attitudes and cultivate better preventive practices among the public to eliminate dengue fever in the country.

Association of increased postoperative opioid administration with non-small-cell lung cancer recurrence: a retrospective analysis.

BACKGROUND: Evidence suggests that opioid-sparing anaesthetic techniques might be associated with increased cancer-free postoperative survival. This could be related to suppression of natural killer cells by opioid analgesics in the perioperative period. This retrospective analysis tested the hypothesis that greater opioid use in the postoperative period is associated with a higher incidence of recurrences after surgery for lung cancer. METHODS: The medical records of 99 consecutive patients who underwent video-assisted thoracoscopic surgery with lobectomy for Stage I or IIa biopsy-proven non-small-cell lung cancer (NSCLC) were reviewed. Perioperative information including patient characteristics, laboratory data, and surgical, anaesthetic, nursing, and pharmacy reports were collected. Doses of opioids administered intra-operatively and for the first 96 h after operation were converted into equianalgesic doses of oral morphine using a standard conversion table. Data were then compared with the National Cancer Registry's incidence of disease-free survival for 5 yr. RESULTS: A total of 99 patients with similar characteristics were included in the final analysis, 73 of whom were NSCLC recurrence-free at 5 yr and 26 had NSCLC recurrence within 5 yr. Total opioid dose during the 96 h postoperative period was 124 (101) mg of morphine equivalents in the cancer-free group and 232 mg (355) mg in the recurrence group (P=0.02). CONCLUSIONS: This retrospective analysis suggests an association between increased doses of opioids during the initial 96 h postoperative period with a higher recurrence rate of NSCLC within 5 yr.

Open access for operational research publications from low- and middle-income countries: who pays?

Open-access journal publications aim to ensure that new knowledge is widely disseminated and made freely accessible in a timely manner so that it can be used to improve people's health, particularly those in low- and middle-income countries. In this paper, we briefly explain the differences between closed- and open-access journals, including the evolving idea of the 'open-access spectrum'. We highlight the potential benefits of supporting open access for operational research, and discuss the conundrum and ways forward as regards who pays for open access.

Les articles de journaux en accès libre visent à assurer la dissémination large de nouvelles connaissances et de rendre leur accès libre de façon à pouvoir être utilisées rapidement pour améliorer la santé des populations, surtout dans les pays à revenu faible ou moyen. Dans cet article, nous expliquons briêvement les différences entre les publications à accès limité et à accès libre, notamment l'idée en gestation de « spectre d'accès libre ¼. Nous soulignons les bénéfices potentiels du soutien à l'accès libre pour la recherche opérationnelle et ensuite discutons la question de qui paye pour cet accès et la recherche de solutions.

El propósito de las publicaciones en las revistas de acceso libre es lograr una amplia difusión de los nuevos conocimientos mediante el acceso libre y oportuno, de manera que los avances se puedan aplicar a fin de mejorar la salud de las personas, sobre todo en los países de bajos y medianos ingresos. En el presente artículo se explican brevemente las diferencias entre las revistas de acceso libre y acceso restringido y se analiza además la idea evolutiva del 'espectro del acceso libre'. Se destacan las ventajas que puede ofrecer el respaldo al libre acceso a la investigación operativa y se analiza luego el dilema y las opciones que pueden permitir progresar con respecto a la fuente de financiamiento del libre acceso.

Pharmacokinetics and safety of Intragam 10 NF, the next generation 10% liquid intravenous immunoglobulin, in patients with primary antibody deficiencies.

BACKGROUND AND AIMS: Intragam® 10 NF is the next generation 10% intravenous immunoglobulin with three pathogen reduction steps and a noncarbohydrate stabiliser. This open label, cross-over study in patients with primary immunodeficiency was designed to evaluate whether Intragam 10 NF differed in its pharmacokinetics (PK) compared with Intragam P and to assess Intragam 10 NF safety and tolerability. METHODS: Nineteen primary immunodeficiency patients were administered one cycle of their existing Intragam P dose (0.2-0.8 g/kg 3-4 weekly), followed by seven cycles of Intragam 10 NF administered at the same dosing schedule as Intragam P. The primary objective was to compare serum immunoglobulin G (IgG) trough levels. Secondary endpoints were PK variables, safety and tolerability. RESULTS: There was no significant within-patient difference in the average trough immunoglobulin G concentration between Intragam P and Intragam 10 NF (8.76 g/L, 8.55 g/L respectively) (geometrical mean ratio 1.034; 95% confidence interval 0.996-1.073; P = 0.079). Mean PK parameters for both products were similar, with all 95% confidence interval encompassing 1.0 except for time to maximum concentration. Time to maximum concentration occurred earlier with Intragam 10 NF compared with Intragam P, with a shorter infusion time (mean 1.75 h vs 2.52 h respectively; P < 0.05). Headache was the most frequent treatment-related event following both products. There were no study withdrawals, deaths, or notable changes in laboratory values or vital signs. CONCLUSION: Intragam 10 NF was well tolerated and exhibited similar PK to Intragam P, with the advantage of a 45 min shorter infusion time.

The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis.

The prevalence of diabetes mellitus is increasing at a dramatic rate, and countries in Asia, particularly India and China, will bear the brunt of this epidemic. Persons with diabetes have a significantly increased risk of active tuberculosis (TB), which is two to three times higher than in persons without diabetes. In this article, we argue that the epidemiological interactions and the effects on clinical presentation and treatment resulting from the interaction between diabetes and TB are similar to those observed for human immunodeficiency virus (HIV) and TB. The lessons learned from approaches to reduce the dual burden of HIV and TB, and especially the modes of screening for the two diseases, can be adapted and applied to the screening, diagnosis, treatment and prevention of diabetes and TB. The new World Health Organization (WHO) and The Union Collaborative Framework for care and control of TB and diabetes has many similarities to the WHO Policy on Collaborative Activities to reduce the dual burden of TB and HIV, and aims to guide policy makers and implementers on how to move forward and combat this looming dual epidemic. The response to the growing HIV-associated TB epidemic in the 1980s and 1990s was slow and uncoordinated, despite clearly articulated warnings about the scale of the forthcoming problem. We must not make the same mistake with diabetes and TB. The Framework provides a template for action, and it is now up to donors, policy makers and implementers to apply the recommendations in the field and to 'learn by doing'.

Morbidity in HIV-1-infected individuals before and after the introduction of antiretroviral therapy: a longitudinal study of a population-based cohort in Uganda.

BACKGROUND: We compared morbidities in HIV-1-infected patients before and after the introduction of antiretroviral therapy (ART) in a rural Ugandan cohort followed from 1990 to 2008. ART was introduced in 2004. METHODS: Random-effects Poisson regression models were used to estimate incidence rates of World Health Organization (WHO) stage-defining diseases in HIV-infected individuals aged 13 years or older with known seroconversion dates, and in an age-stratified sample of HIV-negative individuals. RESULTS: The most common morbid event was bacterial pneumonia, with an incidence of 7.4/100 person-years (pyr) among 309 HIV seroconverters and 1.3/100 pyr among 348 HIV-negative participants [hazard ratio (HR) 5.64; 95% confidence interval (CI) 3.6-8.8]. Among seroconverters, the incidence of the acquisition of any WHO stage-defining disease rose from 14.4/100 pyr (95% CI 11.1-18.6) in 1990-1998 to 46.0/100 pyr (95% CI 37.7-56.0) in 1999-2003. Following the introduction of ART, the incidence among seroconverters declined to 36.4/100 pyr (95% CI 27.1-48.9) in 2004-2005 and to 28.3/100 pyr (95% CI 21.2-37.8) in 2006-2008. At the individual level, a higher rate of acquiring any WHO stage-defining disease was independently associated with lower CD4 cell count, longer duration of HIV infection and older age. In addition, individuals who had been on ART for longer than 12 months had a substantially lower rate of any WHO stage disease than those not yet on ART (adjusted HR 0.35; 95% CI 0.2-0.6). CONCLUSION: Morbidity in HIV-positive participants decreased following the introduction of ART, and this decline was more marked with increasing duration on ART. The benefits of decreased HIV-related morbidity from ART lend support to urgent efforts to ensure universal access to early diagnosis of HIV infection and to ART, especially in rural Africa.

Coming of age: reconstruction of heterosexual HIV-1 transmission in human ex vivo organ culture systems.

Heterosexual transmission of human immunodeficiency virus-1 (HIV-1), from men to women, involves exposure to infectious HIV-1 in semen. Therefore, the cellular and molecular processes that underlie HIV-1 transmission are closely interconnected with fundamental principles of human reproductive biology. Human ex vivo organ culture systems allow experimental reconstruction of HIV-1 transmission, using human semen and premenopausal cervicovaginal mucosal tissue, with specific emphasis on the progression from exposure to development of primary HIV-1 infection. Clearly, an isolated piece of human tissue cannot duplicate the full complexity of events in natural infections, but with correct observation of conventional medical and ethical standards, there is no opportunity to study HIV-1 exposure and primary infection in young women. Human mucosal organ cultures allow direct study of HIV-1 infection in a reproducible format while retaining major elements of complexity and variability that typify community-based HIV-1 transmission. Experimental manipulation of human mucosal tissue both allows and requires acquisition of new insights into basic processes of human mucosal immunology. Expanding from the current foundations, we believe that human organ cultures will become increasingly prominent in experimental studies of HIV-1 transmission and continuing efforts to prevent HIV-1 infection at human mucosal surfaces.

On/off luminescence vapochromic selective sensing of benzene and its methylated derivatives by a trinuclear silver(I) pyrazolate sensor.

{[3,5-(CF(3))(2)Pz]Ag}(3) (1) films exhibit selective/reversible sensing of small-organic-molecule (SAM) vapors, which readily switch-on bright-green (benzene or toluene) or bright-blue (mesitylene) luminescence that switches-off upon vapor removal. Vapors of electron-deficient SAMs or non-aromatic solvents did not attain luminescence switching and were not adsorbed.

Health transition in Africa: practical policy proposals for primary care.

Sub-Saharan Africa is undergoing health transition as increased globalization and accompanying urbanization are causing a double burden of communicable and noncommunicable diseases. Rates of communicable diseases such as HIV/AIDS, tuberculosis and malaria in Africa are the highest in the world. The impact of noncommunicable diseases is also increasing. For example, age-standardized mortality from cardiovascular disease may be up to three times higher in some African than in some European countries. As the entry point into the health service for most people, primary care plays a key role in delivering communicable disease prevention and care interventions. This role could be extended to focus on noncommunicable diseases as well, within the context of efforts to strengthen health systems by improving primary-care delivery. We put forward practical policy proposals to improve the primary-care response to the problems posed by health transition: (i) improving data on communicable and noncommunicable diseases; (ii) implementing a structured approach to the improved delivery of primary care; (iii) putting the spotlight on quality of clinical care; (iv) aligning the response to health transition with health system strengthening; and (v) capitalizing on a favourable global policy environment. Although these proposals are aimed at primary care in sub-Saharan Africa, they may well be relevant to other regions also facing the challenges of health transition. Implementing these proposals requires action by national and international alliances in mobilizing the necessary investments for improved health of people in developing countries in Africa undergoing health transition.