Improving Diabetes Care in Rural Areas: A Systematic Review and Meta-Analysis of Quality Improvement Interventions in OECD Countries

Background and Aims

Despite well documented disparities in health and healthcare in rural communities, evidence in relation to quality improvement (QI) interventions in those settings is still lacking. The main goals of this work were to assess the effectiveness of QI strategies designed to improve diabetes care in rural areas, and identify characteristics associated with greater success.

Methods

We conducted a systematic review and meta-analysis. Systematic electronic searches were conducted in MEDLINE, EMBASE, CINAHL, and 12 additional bibliographic sources. Experimental studies carried out in the OECD member countries assessing the effectiveness of QI interventions aiming to improve diabetes care in rural areas were included. The effect of the interventions and their impact on glycated hemoglobin was pooled using a random-effects meta-analysis.

Results

Twenty-six studies assessing the effectiveness of twenty QI interventions were included. Interventions targeted patients (45%), clinicians (5%), the health system (15%), or several targets (35%), and consisted of the implementation of one or multiple QI strategies. Most of the interventions produced a positive impact on processes of care or diabetes self-management, but a lower effect on health outcomes was observed. Interventions with multiple strategies and targeting the health system and/or clinicians were more likely to be effective. Six QI interventions were included in the meta-analysis (1,496 patients), which showed a significant reduction in overall glycated hemoglobin of 0.41 points from baseline in those patients receiving the interventions (95% CI -0.75% to -0.07%).

Conclusions

This work identified several characteristics associated with successful interventions to improve the quality of diabetes care in rural areas. Efforts to improve diabetes care in rural communities should focus on interventions with multiple strategies targeted at clinicians and/or the health system, rather than on traditional patient-oriented interventions.     

Using quantum dots to visualize clathrin associations

Our current understanding of clathrin-mediated endocytosis proposes that the process is initiated at a specialized anatomical structure called a coated pit. Electron microscopy has been required for elucidation of the morphology of coated pits and the vesicles produced therein, and the presence of a bristle coat has been taken as suggestive of clathrin surrounding these vesicles. More recently, immunocytochemical methods have confirmed that endocytic vesicles are surrounded by clathrin and its adaptor proteins, but there is a need to identify precisely and to follow the fate of the cellular organelles seen by fluorescence microscopy. We used quantum immune-electron microscopy to localize clathrin in a human adrenal cortical cell line (SW-13). Clathrin was shown to associate with a variety of vesicle types including the classic clathrin-coated vesicles and pits used in receptor internalization, pentilaminar annular gap junction vesicles, and multivesicular bodies. The images obtained with quantum dot technology allow accurate and specific localization of clathrin and the clathrin adaptor protein, AP-2, with cellular organelles and suggest that some of the structures classified as typical coated vesicles by immunocytochemical light microscopic techniques actually may be membrane bound pits.     

Novel inhibitors of Leishmanial dihydrofolate reductase

The program DOCK3.5 was used to search the Cambridge Structural Database for novel inhibitors of Leishmanial dihydrofolate reductase. A number of compounds were obtained and screened against the enzyme and against the intact parasite Leishmania donovani and the related organisms Trypanosoma brucei and Trypanosoma cruzi. The compounds screened showed weak activity in both the enzyme assays and the in vitro assays.     

Preparation of transition-state analogues of sterol 24-methyl transferase as potential anti-parasitics

There is an urgent need for new drugs to treat leishmaniasis and Chagas disease. One important drug target in these organisms is sterol biosynthesis. In these organisms the main endogenous sterols are ergosta- and stigmata-like compounds in contrast to the situation in mammals, which have cholesterol as the sole sterol. In this paper we discuss the design, synthesis and evaluation of potential transition state analogues of the enzyme Delta24(25)-methyltransferase (24-SMT). This enzyme is essential for the biosynthesis of ergosterol, but not required for the biosynthesis of cholesterol. A series of compounds were successfully synthesised in which mimics of the S-adenosyl methionine co-factor were attached to the sterol nucleus. Compounds were evaluated against recombinant Leishmania major 24-SMT and the parasites L. donovani and Trypanosoma cruzi in vitro, causative organisms of leishmaniasis and Chagas disease, respectively. Some of the compounds showed inhibition of the recombinant Leishmania major 24-SMT and induced growth inhibition of the parasites. Some compounds also showed anti-parasitic activity against L. donovani and T. cruzi, but no inhibition of the enzyme. In addition, some of the compounds had anti-proliferative activity against the bloodstream forms of Trypanosoma brucei rhodesiense, which causes African trypanosomiasis.     

The karyotype of Axarus festivus (Say) and a comparison with species of Lipiniella (Chironomidae: Diptera)

Larvae of Axarus andLipiniella share several apparantly apomorphic features of the mouth-part structure, however adults ofLipiniella show possible relationships toDemeijerea andChironomus. In order to assist in refining the relationships ofAxarus toLipiniella the karyotype ofAxarus festivus was determined and compared to the karyotypes ofLipiniella arenicola andL. moderata. Larvae ofA. festivus from a population in Kansas were monomorphous, with 2n=8, the Ist, IInd and IIIrd chromosomes metacentric, and IVth acrocentric.Axarus festivus therefore differs fromL. arenicola in chromosome number (2n=6), however homologous sections of all chromosomes were identified. Inversions were detected in the Ist, IInd and IIIrd chromosomes ofA. festivus relative toL. arenicola. It was determined that both species have high functional activity, as indicated by the presence of three Balbiani rings, and more than one nucleolus per genome. Differing degrees of polyteny, a feature previously described forL. arenicola, were observed in the salivary glands, with highest degrees of polyteny in cells near the salivary duct. These similarities of chromosome structure indicate close genetic relationships betweenA. festivus andL. arenicola. However, we did not find evidence for similarity ofA. festivus toL. moderata, which supports the previous conclusions byKiknadze et al. (1989) regardingL. arenicola andL. moderata.     

Gel filtration of bacterial cell extract

Так как от остатков гомогенизированных клеток легко отделить растительные вирусы (Steere и Qckers, 1962; ?ech, 1962) и митохондрии (Hjertén, 1962), мы сделали попытку использовать этот простой метод и для отделения рибосом. Надосадок гомогената растущих клеток Bacillus megaterium 110 наносили на столбец 3% гранулированного агара (Polson, 1961) и промывали 66 мл буферного раствора Tris (pH 7,72, 0,005 M с 0,01 M?MgCl₂) в течение часа при комнатной температуре. В элюате определяли абсорбцию при 260 мμ и белки (рис. 1). При ультрацентрифугировании образца были обнаружены рибосомы с S ₂₀ ⁰ 107, 71, 5, 45 и 30S (рис. 2). Ультрацентрифугированием фракции № 10 были с помощью адсорбции в УФ лучах найдены рибосомы с s ₂₀ ⁰ 107 и 44,6S (рис. 3). Группа 100S перекрывалась абсорбцией рибосом 70S, группа 30 не была обнаружена. Отделение рибосом как самостоятельной вершины не было получено. Однако, судя по соотношению нуклеиновых кислот и белков во главе вымываемой плазмы (где присутствует только РНК), здесь имела место концентрация практически чистых рибосом, как подтверждает и седиментация. ДНК удавалось определить только во фракциях второй половины элюата плазмы (рис. 4).     

Sequence variation in the guillemot (Alcidae: Cepphus) mitochondrial control region and its nuclear homolog

We describe sequence variation in the mitochondrial control region and its nuclear homolog in three species and seven subspecies of guillemots (Cepphus spp.). Nuclear homologs of the 5' end of the control region were found in all individuals. Nuclear sequences were approximately 50% divergent from their mitochondrial counterparts and formed a distinct phylogenetic clade; the mitochondrial-nuclear introgression event must have predated the radiation of Cepphus. As in other vertebrates, the guillemot control region has a relatively conserved central block flanked by hypervariable 5' and 3' ends. Mean pairwise interspecific divergence values among control regions were lower than those in other birds. All individuals were heteroplasmic for the number of simple tandem nucleotide repeats (A(n)C) at the 3' end of the control region. Phylogenetic analyses suggest that black guillemots are basal to pigeon and spectacled guillemots, but evolutionary relationships among subspecies remain unresolved, possibly due to incomplete lineage sorting. Describing molecular variation in nuclear homologs of mitochondrial genes is of general interest in phylogenetics because, if undetected, the homologs may confound interpretations of mitochondrial phylogenies.      

Saturation site-directed mutagenesis of thymidylate synthase

We have subjected 12 different codons of a synthetic Lactobacillus casei thymidylate synthase (TS) gene to saturation site-directed mutagenesis to create amino acid "replacement sets" at each of those positions. The target residues were chosen because they are highly conserved and because they are important for the structure and function of the protein as indicated by solution and structural studies. The mutagenesis procedure involved excision of a fragment of the synthetic gene containing the target codon, followed by its replacement with a mixture of oligonucleotides which code for all 20 amino acids and the amber stop codon. TS mutants were identified by DNA sequencing, and catalytically active mutants were identified by genetic complementation using a Thy- strain of Escherichia coli. Only 3 of the 12 target amino acids examined were essential for TS activity; and of the 125 total mutants identified, 57 were catalytically active. These results point to a high degree of plasticity of TS in accommodating function with structural change.     

Implications from predictions of HLA-DRB1 binding peptides in the membrane proteins of Corynebacterium diphtheriae

The aerobic gram positive bacterium Corynebacterium diphtheriae causes diphtheria, a respiratory tract illness characterized by symptoms such as sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity. Therefore, it is important to develop preventive vaccines for diphtheria. The availability of the 2,488,635 bp long complete sequence for the C. diphtheriae genome provides an opportunity to understand cell mediated immune response using Computational Biology tools from the bacterial proteome sequence data. We selected 355 membrane proteins from the C. diphtheriae proteome using annotation data to identify potential HLA-DRB1 binding short peptide using modeling, simulations and predictions. This exercise identified 30 short peptides in membrane proteins showing binding capability to HLA-DRB1 alleles. These peptides serve as outline for the understanding of cell mediated immune response to C. diphtheriae. It should be noted that the predicted data to be verified using binding assays for further consideration.