An analysis of research priority-setting at the World Health Organization - how mapping to a standard template allows for comparison between research priority-setting approaches.

BACKGROUND: A review of research priorities completed by WHO technical units was undertaken. Results of the mapping were recorded in a database that was used to generate analysis and compare research priorities and the different methodological approaches used in their development. METHODS: A total of 116 documents were reviewed for this study. The documents were published between 2002 and 2017 by the technical programmes of WHO headquarters and deposited in the institutional repository, IRIS. Research priorities were extracted from documents into a standard template and mapped to a five-category research cycle type framework defined in the WHO Strategy on Research for Health covering research to describe the research problem, identifying the cause and risk factors, developing solutions and new interventions, understanding the barriers to implementation, and evaluation of the impact of response. Details of the research priority methods were recorded. A database with user interface was created using Microsoft Excel 2010. RESULTS: A total of 2145 research priorities were extracted from the 116 documents meeting the inclusion criteria. The priorities specifically address 73 diseases/health topics. The document types were 26% Report, 22% WHO Guideline, 26% Research Prioritisation publication and 11% Meeting Notes. The most widely reported method used to identify priorities was expert consultation. Expert consultation was used to identify 86% of the priorities categorised here, with 26% (561) reporting it as the sole method; 52% (1111) explicitly listed a literature review as contributing to the identification of priorities. When the 2145 priorities were categorised across the research cycle framework, the largest portion (43%) addressed implementation challenges. The database is published here under an open access licence. CONCLUSION: Comparing research priorities between diseases/health topics requires standardisation and the research cycle type framework is one approach that can be applied across all the health topics found in public health. There is great variation in the use of research priority-setting methodology at WHO Headquarters. Therefore, a standard reporting approach, linked to established good practice, should be an area for future development by the WHO Global Health R&D Observatory. The database reported here can also be used to quickly access and analyse the research priorities for a specific health topic or to compare across a range of health topics.

Hype, harmony and human factors: applying user-centered design to achieve sustainable telehealth program adoption and growth.

Despite decades of international experience with the use of information and communication technologies in healthcare delivery, widespread telehealth adoption remains limited and progress slow. Escalating health system challenges related to access, cost and quality currently coincide with rapid advancement of affordable and reliable internet based communication technologies creating unprecedented opportunities and incentives for telehealth. In this paper, we will describe how Human Factors Engineering (HFE) and user-centric elements have been incorporated into the establishment of telehealth within a large academic medical center to increase acceptance and sustainability. Through examples and lessons learned we wish to increase awareness of HFE and its importance in the successful implementation, innovation and growth of telehealth programs.

Nevirapine-induced hepatitis: a case series and review of the literature.

Nevirapine, a nonnucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy, can cause mild elevations in transaminase levels. Severe elevations in transaminase levels related to the use of nevirapine developed in 4 patients. Data on these patients were extracted via chart review, and a review of the literature was also completed. Nevirapine-induced hepatitis occurred shortly after drug initiation in patients with and without preexisting liver disease. Significant elevations in liver enzyme levels occurred but resolved promptly in most with discontinuation of the nevirapine. Close monitoring of liver enzyme levels in the early period after starting nevirapine is essential.

Antiretroviral prescribing errors in hospitalized patients.

OBJECTIVE: To quantify error type and frequency and to identify factors associated with antiretroviral prescribing errors in hospitalized HIV-infected patients. DESIGN: Systematic evaluation of all medication prescribing errors involving antiretroviral medications between January 1, 1996, and October 31, 1998. Each error was concurrently evaluated for the potential to result in adverse patient consequences. Each error was retrospectively evaluated by three pharmacists and assigned a "likely related factor." SETTING: A 631-bed tertiary care teaching hospital. PARTICIPANTS: All physicians prescribing antiretroviral medications during the study period and all staff pharmacists involved in the routine review of medication orders. MAIN OUTCOME MEASURES: Type and frequency of prescribing errors involving antiretrovirat medications and frequency of association of likely related factors to errors. RESULTS: A total of 108 clinically significant prescribing errors involving antiretrovirals were detected during the 34-month study period. The most common errors were overdosing and underdosing. Overall, errors occurred in 5.8% of admitted patients prescribed antiretroviral medications. The rate of error increased from 2% of admissions in 1996 to 12% of admissions in 1998. The most common likely related factors associated with errors were confusion/lack of familiarity regarding appropriate dosing frequency (30.3%) or dosage (25.5%), and confusion due to need for multiple dosage units per dose (13%). CONCLUSIONS: Hospitalized patients taking antiretrovirals are at risk for adverse outcomes due to prescribing errors. This risk has increased with the rising complexity of antiretroviral drug regimens. A limited number of factors are associated with a large proportion of antiretroviral prescribing errors. This information should be considered in the development of medication error prevention strategies necessary to prevent adverse patient outcomes resulting from such errors.

Antiretroviral medication errors for patients with HIV infection.

Errors in prescribing antiretroviral agents for patients with HIV infection may lead to treatment failure, drug resistance, or drug toxicity. Several published reports describe such errors, which appear to be related to a lack of knowledge, inexperience, complexities of the antiretroviral regimens, and sound-alike and look-alike names. Clinicians caring for patients with HIV infection should be aware of the potential for prescribing errors and develop strategies to prevent them.

Primary union of ankle arthrodesis: review of a single institution/multiple surgeon experience.

A review of 37 ankle arthrodesis procedures done over a 12-year period by multiple surgeons at a single institution was performed. Six different techniques were used during the study period. The initial success rate, defined as cases achieving a solid union after the index procedure, was 65%. Seven additional patients went on to a solid arthrodesis after subsequent surgical procedures, for an ultimate success rate of 84%. The initial success rate varied considerably depending on the surgical technique used, and ranged from 29% with the RAF fibular strut technique to 100% with T-plate fixation. Although there are many variables that influence the success or failure of ankle arthrodesis, in our hands rigid internal fixation gave the most predictable rate of primary union.

Infection with the human immunodeficiency virus: epidemiology, pathogenesis, transmission, diagnosis, and manifestations.

The epidemiology, pathogenesis, transmission, and manifestations of infection with the human immunodeficiency virus (HIV) are described, along with the development of diagnostic tests and drugs to combat it. Acquired immunodeficiency syndrome (AIDS) is caused by HIV infection. The syndrome was first reported in 1981, and as of March 31, 1989, nearly 90,000 cases had been reported in the United States alone. Most U.S. adults with AIDS are homosexual or bisexual men; intravenous drug abusers, heterosexuals, hemophiliacs, and blood transfusion recipients account for 17%, 4%, 1%, and 2% of AIDS cases, respectively. HIV is transmitted by sexual, blood, and perinatal routes; infection leads to a profound immunosuppression involving both the cellular and humoral immune systems. The hallmark of AIDS is a quantitative deficiency of T4 lymphocytes bearing CD4+ receptors, to which the virus binds. Monocytes are believed to be the major route of infection into the CNS. There has been rapid progress in the development of sensitive and specific diagnostic tests for HIV infection. The enzyme-linked immunosorbent assay and Western blot test are the most widely used; both are used to detect antibodies to the virus. Two major classes of drugs are under development for use against HIV: antiviral agents and immunomodulatory agents. Thus far only one drug, zidovudine (AZT), has decreased mortality and improved quality of life. Infection with HIV encompasses a broad spectrum of clinical manifestations, from seroconversion to AIDS-related complex to full-blown AIDS. AIDS is a clinical diagnosis based on the presence of recurring opportunistic infections, previously rare cancers, and neurologic manifestations. Because of the many people infected and the long incubation periods, AIDS will continue to be a major issue in health care. Continued education of health-care personnel and the public is needed.

Current concepts in clinical therapeutics: immunologic treatment of human immunodeficiency virus infections.

An overview of the immune system is presented, and the pathogenesis, transmission, diagnostic tests, diagnosis, immunotherapy, and vaccine development for human immunodeficiency virus (HIV) are reviewed. More than 42,000 cases of acquired immunodeficiency syndrome (AIDS) have now been reported in the United States, and an additional 250,000 cases are expected by 1991. The immunopathogenesis of HIV infection involves both cellular and humoral components of the immune system, with a characteristic depletion of helper T lymphocytes, impaired delayed hypersensitivity, and polyclonal B-cell activation. Monocytes and macrophages are also infected, and these cells provide a transport mechanism into the central nervous system. HIV is transmitted primarily by sexual, blood, and perinatal mechanisms. Enzyme-linked immunosorbent and Western blot assays are used in diagnostic tests, and diagnosis of AIDS is based on the presence of secondary infection or tumor at least moderately indicative of cellular immune deficiency in the absence of predisposing factors. Three approaches are being tested for treating HIV infection: immunomodulators, vaccines, and antiviral agents. Immunomodulators--including interferons, interleukin-2, immune reconstitution with bone-marrow transplantation and lymphocyte transfusions, transfer factor, granulocyte-macrophage colony-stimulating factor, inosine pranobex (isoprinosine), and naltrexone--are being tested with no great successes. Various approaches to vaccine development, including genetically engineered subunit proteins, synthetic peptides, and infectious recombinant viruses, are being considered. Primary immune responses do result from at least one vaccine. Future studies will evaluate combination approaches to therapy. HIV infections confront the health-care system with a serious challenge. It is too early to assess the effectiveness of the various therapeutic strategies for immune deficiencies caused by HIV.

Regulation of acylcoenzyme A. Cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by lipoproteins in the intestine of parabiont rats.

Parabiont rats were used to study the regulation of intestinal cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase activity) and esterification (acylcoenzyme A/cholesterol acyltransferase [ACAT] activity) by lipoproteins and micellar cholesterol. The parabiont rat model offers a unique way to observe changes in cholesterol metabolism in the intestine, independently of luminal factors. In one group of six surgically joined pairs, one animal was fed rat chow and 0.1% propylthiouracil (PTU). Its joined mate was fed rat chow, 0.1% PTU, 5% lard, and 0.3% taurocholic acid. In another group of five pairs, one rat was fed rat chow, 0.1% PTU, 5% lard, 0.3% taurocholic acid, plus 1% cholesterol. Its joined mate was fed the same diet except the cholesterol was deleted. Serum cholesterol changes were equal between members of a given pair, attesting to their common circulation. The administration of PTU itself caused a significant elevation of serum cholesterol. When one parabiont ingested cholesterol, serum cholesterol concentrations increased significantly for both pair members compared with control pairs not ingesting cholesterol. Hepatic and intestinal HMG-CoA reductase activities were significantly decreased in rats fed the diet containing cholesterol. ACAT activities in both organs were markedly increased. This supports previous data that suggest that dietary or luminal cholesterol affects both HMG-CoA reductase and ACAT activity in the small intestine. Moreover, in rats that were hypercholesterolemic but not ingesting dietary cholesterol, hepatic and intestinal reductase activities were decreased and ACAT activities were increased compared with the control animals. Intestinal microsomal cholesterol content was increased only in rats fed cholesterol. No changes in intestinal microsomal cholesterol were observed in the other animals. The data suggest that intestinal HMG-CoA reductase and ACAT activities are regulated by plasma lipoproteins independently of luminal factors. This nonluminal regulatory effect occurs without a measurable contribution to the intestinal microsomal cholesterol pool.

Desensitization for sulfasalazine skin rash.

Thirteen patients with inflammatory bowel disease and a documented allergy to sulfasalazine, manifested by skin rash with or without fever, were enrolled in a sulfasalazine-desensitization protocol. Twelve patients were successfully desensitized by using two concentrations of a liquid suspension of sulfasalazine. Four of thirteen patients developed a rash during the protocol. Although one patient refused further attempts at desensitization, the remainder completed the regimen successfully, despite recurrence of the rash on two occasions in one patient. No predilection to either fast or slow acetylator phenotype was found. This simple and convenient tolerance induction regimen may be used safely to desensitize most patients with sulfasalazine allergy manifested by skin rash with or without fever, despite recurrence of the rash during tolerance induction. Patients with serious reactions to sulfasalazine, such as agranulocytosis, toxic epidermal necrolysis, or fibrosing alveolitis, are not candidates for desensitization.

Thermal alteration of silica minerals: an archeological approach.

Extensive experiments indicate that the application of heat to flint materials may have conferred an advantage to primitive man in the manufacture of chipped-stone implements. When Florida cherts are slowly heated to between 350 degrees and 400 degrees C and maintained at this temperature for sustained periods, a desirable change occurs in the fracture properties. This alteration takes place when the melting point of the impurities within the intercrystalline spaces is reached; thus the microcrystals of quartz are fitted closer together when materials other than quartz serve as fluxes.