Funding agencies in low- and middle-income countries: support for knowledge translation

OBJECTIVE: The aim was to describe how selected health research funding agencies active in low- and middle-income countries promote the translation of their funded research into policy and practice. METHODS: We conducted inductive analysis of semi-structured interviews with key informants from a purposive sample of 23 national and international funding agencies that fund health research in Brazil, Colombia, India, the Philippines, South Africa and Thailand. We also surveyed web sites. FINDINGS: We found a commitment to knowledge translation in the mandate of 18 of 23 agencies. However, there was a lack of common terminology. Most of the activities were traditional efforts to disseminate to a broad audience, for example using web sites and publications. In addition, more than half (13 of 23) of the agencies encouraged linkage/exchange between researchers and potential users, and 6 of 23 agencies described "pull" activities to generate interest in research from decision-makers. One-third (9 of 23) of funding agencies described a mandate to enhance health equity through improving knowledge translation. Only 3 of 23 agencies were able to describe evaluation of knowledge translation activities. Furthermore, we found national funding agencies made greater knowledge translation efforts when compared to international agencies. CONCLUSION: Funding agencies are engaged in a wide range of creative knowledge translation activities. They might consider their role as knowledge brokers, with an ability to promote research syntheses and a focus on health equity. There is an urgent need to evaluate the knowledge translation activities of funding agencies.     

Clinical evaluation of two strategies for improving patient recall of prior drug therapy

The ability to recall details of current and prior drug therapy was evaluated in two studies employing a total of 94 patients with inflammatory polyarthritis. Ten per cent of patients were unable to completely recall the names of their current anti-inflammatory drugs and eighty-three per cent of patients to completely recall the details of prior anti-inflammatory drug therapy. Prompting firstly with the proprietary names of drugs and thereafter with a pill board substantially enhanced recall particularly for prior NSAID therapy. Nineteen per cent of responses obtained with verbal prompting were inaccurate. No such problems were encountered in responses obtained using the pill board. These findings indicate that a complete and accurate drug history can only be obtained in the majority of patients using recall enhancement strategies.     

Modeling of main characteristics of bullous pemphigoid antigen-2 (BPAG2) peptide structure in serological recognition by autoantibodies

The serum level of autoantibodies against autoantigens of the bullous pemphigoid peptides 1 and 2 (BPAG1 and BPAG2) is a relevant diagnostic marker. Twelve representative sera of BP were tested against the RSILPYGDSMDRIEKDRLQMAP amino acid sequence that is an epitope fragment of the NC16A domain of BPAG2 (AC Q02802; 507–528) to find the most suitable antigenic form for specific detection of autoantibodies of BP patients’ sera by quantitative ELISA system. The antigenic epitope sequence was presented as an antigen in a carrier free form of dimeric peptide (BP22), dimeric peptide fused to glutathione S-transf erase (GST-BP22) or dimeric peptide chemically conjugated to polyLys(Ser-DL-Ala_m) (SAK-BP22). The intensity of ELISA reaction was highest against the recombinant fusion antigen GST-BP22; the chemically conjugated SAK-BP22 performed less well than the free dimeric form of the peptide. In the case of the GST-BP22 antigen, the (GST-BP22)-(GST)_492nm optical density values were determined. There was no significant difference between the mean ODs of the GST-BP22 and the SAK-BP22 (0.888 vs. 0.892, p= 0.9726). Conjugating the epitope peptide with the synthetic carrier SAK was advantageous, as it abrogated cross-reactivity with GST carrier protein. Consequently, the SAK-BP22 conjugate appears to be the most reliable assay component, avoiding cross-reactivity with GST and simplifying the detection and evaluation of BP autoantibodies in routine ELISA diagnostic system.     

Phase I trial of the antifolate ZD9331 in combination with cisplatin in patients with refractory solid malignancies

Purpose To determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of ZD9331 in combination with cisplatin in patients with refractory solid tumors and to describe any preliminary antitumor activity associated with this regimen.Materials and methods Patients received combination therapy with ZD9331 as a 30-min infusion on days 1 and 8 of a 21-day cycle at doses of 100 or 130 mg/m², followed by cisplatin at 50 or 75 mg/m² as a 30- to 60-min infusion on day 1 only.Results A total of 16 patients received 59 cycles of ZD9331 and cisplatin. Patients were enrolled at three dose levels: ZD9331/cisplatin 100/50 (n=3), 130/50 (n=9), 130/75 (n=4). DLTs at 130/75 included thrombocytopenia, neutropenia, fatigue, nausea, vomiting and stomatitis. Among 15 evaluable patients, 2 showed a partial response (patients with mesothelioma and head and neck cancer) and 6 showed stable disease (for a median of 5.5 cycles).Conclusions ZD9331 in combination with cisplatin was well tolerated at a dose of 130/50 mg/m² after establishing the principal DLTs of neutropenia and thrombocytopenia. The combination shows evidence of antitumor activity in a pretreated population.This work was supported by a grant from AstraZeneca.     

Preoperative hypoalbuminemia is an independent risk factor for increased high-grade morbidity after elective rectal cancer resection

Purpose

This study investigated the association of preoperative hypoalbuminemia and postoperative complications after elective resection for rectal cancer.

Methods

From September 2009 to December 2014, all patients who underwent elective rectal resection for adenocarcinoma of the rectum were identified using a prospective colorectal cancer database. Hypoalbuminemia was defined as a serum albumin < 35 g/L. Characteristics and outcomes of hypoalbuminemic patients were compared to those of patients with normal albumin levels. Potential risk factors for postoperative major morbidity, defined as Clavien-Dindo ≥ grade 3, were analyzed by both univariate and multivariate analyses.

Results

Three hundred seventy patients met the inclusion criteria. Hypoalbuminemic patients (67/370 (18%)) were significantly older and had more advanced tumor stages and more comorbidities (more ASA III, higher percentage of diabetics). Furthermore, they were more likely to undergo abdominoperineal resection instead of low anterior resection and less likely to be operated laparoscopically. On univariate analysis, a higher BMI, advanced tumor stages, diabetes, open procedures, pre- and postoperative hypoalbuminemia, a higher decrease in albumin (? preop-postop), and conversion were significantly associated with postoperative high-grade morbidity. On multivariate analysis, diabetes, advanced tumor stages, a higher decrease in the albumin level, as well as preoperative hypoalbuminemia turned out to be independent risk factors for postoperative high-grade morbidity.

Conclusions

Hypoalbuminemia is an independent risk factor for postoperative high-grade morbidity. As a low-cost and easy accessible test, serum albumin should be used as a prognostic tool to detect patients at risk for adverse outcomes after resection for rectal cancer.