Schedules for Self-monitoring Blood Pressure: A Systematic Review.

BACKGROUND: Self-monitoring of blood pressure better predicts prognosis than clinic measurement, is popular with patients, and endorsed in hypertension guidelines. However, there is uncertainty over the optimal self-monitoring schedule. We therefore aimed to determine the optimum schedule to predict future cardiovascular events and determine "true" underlying blood pressure. METHODS: Six electronic databases were searched from November 2009 (updating a National Institute for Health and Care Excellence [NICE] systematic review) to April 2017. Studies that compared aspects of self-monitoring schedules to either prognosis or reliability/reproducibility in hypertensive adults were included. Data on study and population characteristics, self-monitoring regime, and outcomes were extracted by 2 reviewers independently. RESULTS: From 5,164 unique articles identified, 25 met the inclusion criteria. Twelve studies were included from the original NICE review, making a total of 37 studies. Increasing the number of days of measurement improved prognostic power: 72%-91% of the theoretical maximum predictive value (asymptotic maximum hazard ratio) was reached by 3 days and 86%-96% by 7 days. Increasing beyond 3 days of measurement did not result in better correlation with ambulatory monitoring. There was no convincing evidence that the timing or number of readings per day had an effect, or that ignoring the first day's measurement was necessary. CONCLUSIONS: Home blood pressure should be measured for 3 days, increased to 7 only when mean blood pressure is close to a diagnostic or treatment threshold. Other aspects of a monitoring schedule can be flexible to facilitate patient uptake of and adherence with self-monitoring.

Basal Insulin Regimens for Adults with Type 1 Diabetes Mellitus: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM). METHODS: A systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials comparing two or more basal insulin regimens were conducted. The following basal insulin regimens were included: Neutral Protamine Hagedorn (iNPH) (once [od], twice [bid], and four times daily [qid]), insulin detemir (iDet) (od and bid), insulin glargine 100 IU (iGlarg) (od), and insulin degludec (iDegl) (od). We searched the following databases: MEDLINE via OVID, Embase via OVID, and the Cochrane Library (Wiley). Study quality was appraised using Cochrane risk-of-bias checklist for randomized controlled trials. Two outcomes (change in hemoglobin A1c [HbA1c] and rate of severe/major hypoglycemia [SH]) were analyzed. Network inconsistency was assessed using Bucher and chi-square tests. RESULTS: Thirty studies met the eligibility criteria. Twenty-five were included in the HbA1c network and 16 in the SH network. All studies were of moderate quality. No network inconsistency was evident in the HbA1c network. Of the seven regimens of interest, iDet (bid) had the highest probability of being best (mean change in HbA1c -0.48; 95% credible interval -0.69 to -0.29). In contrast, the SH network demonstrated both considerable uncertainty and significant network inconsistency (χ2 test, P = 0.003). CONCLUSIONS: Of the specified frequency regimens, iDet (bid) had the highest probability of being the best basal insulin regimen in terms of reduction in HbA1c. Ranking of the regimens in terms of the SH rate was highly uncertain and no clear conclusion could be made.

Synopsis of the National Institute for Health and Clinical Excellence guideline for prevention of delirium.

DESCRIPTION: Delirium is common, is often underrecognized, and is associated with poor outcomes and high costs. In July 2010, the National Institute for Health and Clinical Excellence released a guideline that addressed diagnosis, prevention, and management of delirium. This synopsis focuses on the main recommendations about prevention of delirium. METHODS: The National Clinical Guideline Centre developed these guidelines by using standard methodology of the National Institute for Health and Clinical Excellence. A multidisciplinary guideline development group posed review questions, discussed evidence, and formulated the recommendations. To underpin the guideline, a technical team from the National Clinical Guideline Centre systematically reviewed and graded pertinent evidence identified from literature searches of studies published in English to August 2009 and performed health economic modeling. Stakeholder and public comment informed guideline development and modifications. RECOMMENDATIONS: Considering prevention a feasible and cost-effective health strategy, the guideline development group made 13 specific recommendations that addressed the stability of the care environment (both the care team and location) and the provision of a multicomponent intervention package tailored for persons at risk for delirium. The multicomponent intervention package included assessment and modification of key clinical factors that may precipitate delirium, including cognitive impairment or disorientation, dehydration or constipation, hypoxia, infection, immobility or limited mobility, several medications, pain, poor nutrition, sensory impairment, and sleep disturbance.

Piloting the development of a cost-effective evidence-informed clinical pathway: managing hypertension in Jordanian primary care.

OBJECTIVES: The UK's National Institute for Health and Clinical Excellence (NICE) and the Jordan office of the Medicines Transparency Alliance embarked on a pilot project to design an evidence-based guideline for cost-effective pharmacological treatment of essential hypertension in Jordan. The project's objectives were to directly address a major health problem for Jordan by producing a guideline; and to delineate the strengths and weaknesses of Jordan's healthcare process to allow similar future efforts to be planned more efficiently. METHODS: The pilot spanned a period of approximately 8 months. Activities were overseen by local technical and guideline development teams, as well as experts from NICE. NICE's hypertension guidelines and economic model were used as a starting point. Parameters in the economic model were adjusted according to input and feedback from local experts with regards to Jordanian physician and patient practices, resource costs, and quality of life estimates. The results of the economic model were integrated with the updated available clinical trial literature. RESULTS: The outputs of the economic model were used to inform recommendations, in the form of a clinical algorithm. A report of the process and the strengths and weaknesses observed was developed, and recommendations for improvements were made. CONCLUSIONS: The pilot represented the start of what is intended to be a healthcare process change for the country of Jordan. Issues emerged which can inform strategies to ensure a more cohesive and comprehensive approach to the cost-effective use of appropriate drugs in managing chronic disease in Jordan and countries operating in a similarly resource-constrained environment. Furthermore, our pilot highlights how richer countries with relevant experience in evidence-informed healthcare policy making can assist others in strengthening their decision-making methods and processes.

Value of information in the osteoarthritis setting: cost effectiveness of COX-2 selective inhibitors, traditional NSAIDs and proton pump inhibitors.

BACKGROUND: Recent National Institute for Health and Clinical Excellence (NICE) guidance recommended that when traditional NSAIDs or cyclo-oxygenase (COX)-2 selective inhibitors are used by people with osteoarthritis (OA), they should be prescribed along with a proton pump inhibitor (PPI). However, specific recommendations about the type of NSAID or COX-2 could not be made due to high levels of uncertainty in the economic evaluation. OBJECTIVE: To investigate the value of obtaining further evidence to inform the economic evaluation of NSAIDs, COX-2s and PPIs for people with OA. METHODS: An economic evaluation with an expected value of perfect information (EVPI) analysis was conducted, using a Markov model with data identified from a systematic review. The base-case model used adverse event data from the three largest randomized trials of COX-2 inhibitors, and we repeated the analysis using observational adverse event data. The model was run for a hypothetical population of people with OA, and subgroup analyses were conducted for people with raised gastrointestinal (GI) and cardiovascular (CV) risk. The EVPI was based upon the OA population in England - approximately 2.8 million people. Of these, 50% were assumed to use NSAIDs or COX-2 selective inhibitors for 3 months per year and 56% of these were assumed to be patients with raised GI and CV risk. RESULTS: The value of further information for this decision problem was very high. Population-level EVPI was £85.1 million in the low-risk group and £179.5 million in the high-risk group (2007-8 values). Expected value of partial perfect information (EVPPI) analysis showed that the groups of parameters for which further evidence was likely to be of most value were CV adverse event risks and all adverse event rates associated with the specific drugs celecoxib and ibuprofen. The value of perfect information remained high even when observational adverse event data were used. CONCLUSIONS: There is a very high value associated with obtaining further information on uncertain parameters for the economic evaluation of NSAIDs, COX-2 selective inhibitors and PPIs for people with OA. Obtaining further randomized or observational information on CV risks is likely to be particularly cost effective.

Withdrawal of disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a systematic review and meta-analysis.

OBJECTIVE: To define the effects of withdrawing disease-modifying antirheumatic drug (DMARD) treatment from patients with established rheumatoid arthritis (RA) receiving stable, effective long-term DMARD treatment. METHODS: A systematic literature search was conducted. Studies were included that were of high quality and enrolled adults with RA over 2 years' duration. A meta-analysis was performed on the number of disease flares in groups withdrawn from DMARD treatment compared with those who continued to receive DMARD. RESULTS: The randomised controlled trial data were pooled into a meta-analysis and this showed that patients who withdrew from DMARD had a significantly worse risk of disease flare or deterioration than those who continued DMARD treatment. CONCLUSION: In patients who have their disease adequately controlled by DMARD and wish to reduce the dose or withdraw them, this should be done cautiously. Their disease activity should be monitored carefully so that they recommence DMARD therapy in the event of disease flare or deterioration.

A human domain antibody and Lewis b glycoconjugate that inhibit binding of Helicobacter pylori to Lewis b receptor and adhesion to human gastric epithelium.

Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewis(b) antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis(b) and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis(b) oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le(b). The poly-D-lysine-Le(b) hexasaccharide and an Le(b) human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le(b) and sialyl Le(x) or domain antibody 25 and sialyl Le(x) acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Le(b) glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.

Cost effectiveness of COX 2 selective inhibitors and traditional NSAIDs alone or in combination with a proton pump inhibitor for people with osteoarthritis.

OBJECTIVES: To investigate the cost effectiveness of cyclo-oxygenase-2 (COX 2) selective inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs), and the addition of proton pump inhibitors to these treatments, for people with osteoarthritis. DESIGN: An economic evaluation using a Markov model and data from a systematic review was conducted. Estimates of cardiovascular and gastrointestinal adverse events were based on data from three large randomised controlled trials, and observational data were used for sensitivity analyses. Efficacy benefits from treatment were estimated from a meta-analysis of trials reporting total Western Ontario and McMaster Universities (WOMAC) osteoarthritis index score. Other model inputs were obtained from the relevant literature. The model was run for a hypothetical population of people with osteoarthritis. Subgroup analyses were conducted for people at high risk of gastrointestinal or cardiovascular adverse events. Comparators Licensed COX 2 selective inhibitors (celecoxib and etoricoxib) and traditional NSAIDs (diclofenac, ibuprofen, and naproxen) for which suitable data were available were compared. Paracetamol was also included, as was the possibility of adding a proton pump inhibitor (omeprazole) to each treatment. MAIN OUTCOME MEASURES: The main outcome measure was cost effectiveness, which was based on quality adjusted life years gained. Quality adjusted life year scores were calculated from pooled estimates of efficacy and major adverse events (that is, dyspepsia; symptomatic ulcer; complicated gastrointestinal perforation, ulcer, or bleed; myocardial infarction; stroke; and heart failure). RESULTS: Addition of a proton pump inhibitor to both COX 2 selective inhibitors and traditional NSAIDs was highly cost effective for all patient groups considered (incremental cost effectiveness ratio less than pound1000 (euro1175, $1650)). This finding was robust across a wide range of effectiveness estimates if the cheapest proton pump inhibitor was used. In our base case analysis, adding a proton pump inhibitor to a COX 2 selective inhibitor (used at the lowest licensed dose) was a cost effective option, even for patients at low risk of gastrointestinal adverse events (incremental cost effectiveness ratio approximately pound10 000). Uncertainties around relative adverse event rates meant relative cost effectiveness for individual COX 2 selective inhibitors and traditional NSAIDs was difficult to determine. CONCLUSIONS: Prescribing a proton pump inhibitor for people with osteoarthritis who are taking a traditional NSAID or COX 2 selective inhibitor is cost effective. The cost effectiveness analysis was sensitive to adverse event data and the specific choice of COX 2 selective inhibitor or NSAID agent should, therefore, take into account individual cardiovascular and gastrointestinal risks.

Human domain antibodies against virulence traits of Candida albicans inhibit fungus adherence to vaginal epithelium and protect against experimental vaginal candidiasis.

Antibody variable domains (domain antibodies [DAbs]) are genetically engineered antibody fragments that include individual heavy-chain (VH) or kappa-chain (Vkappa) variable domains and lack the Fc region. Human DAbs against the 65-kDa mannoprotein (MP65) or the secretory aspartyl proteinase (SAP)-2 of Candida albicans (monospecific DAbs) or against both fungal antigens (heterodimeric, bispecific DAbs) were generated from phage expression libraries. Both monospecific and bispecific DAbs inhibited fungus adherence to the epithelial cells of rat vagina and accelerated the clearance of vaginal infection with the fungus. When heterodimeric DAbs were used, the clearance of infection was at least equivalent to treatment with fluconazole. The in vivo protective effects of DAbs were demonstrated by both pre- and postchallenge schedules of DAb administration and with both fluconazole-susceptible and fluconazole-resistant strains of C. albicans. This is the first demonstration that human DAbs lacking the Fc constituent can efficiently control an infection and can act largely by inhibiting adherence.

Comparison of image analysis software packages in the assessment of adhesion of microorganisms to mucosal epithelium using confocal laser scanning microscopy.

We have compared current image analysis software packages in order to find the most useful one for assessing microbial adhesion and inhibition of adhesion to tissue sections. We have used organisms of different sizes, the bacterium Helicobacter pylori and the yeast Candida albicans. Adhesion of FITC-labelled H. pylori and C. albicans was assessed by confocal microscopy. Four different Image analysis software packages, NIH-Image, IP Lab, Image Pro+, and Metamorph, were compared for their ability to quantify adhesion of the two organisms and several quantification methods were devised for each package. For both organisms, the dynamic range that could be detected by the software packages was 1x10(6)-1x10(9) cells/ml. Of the four software packages tested, our results showed that Metamorph software, using our 'Region of Interest' method, with the software's 'Standard Area Method' of counting, was the most suitable for quantifying adhesion of both organisms because of its unique ability to separate clumps of microbial cells. Moreover, fewer steps were required. By pre-incubating H. pylori with the glycoconjugate Lewis b-HSA, an inhibition of binding of 48.8% was achieved using 250 mug/ml Lewis b-HSA. The method we have devised using Metamorph software, provides a simple, quick and accurate way of quantifying adhesion and inhibition of adhesion of microbial cells to the epithelial surface of tissue sections. The method can be applied to organisms ranging in size from small bacteria to larger yeast cells.

Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori.

AIM: To investigate the bactericidal and anti-adhesive properties of 25 plants against Helicobacter pylori (H. pylori). METHODS: Twenty-five plants were boiled in water to produce aqueous extracts that simulate the effect of cooking. The bactericidal activity of the extracts was assessed by a standard kill-curve with seven strains of H. pylori. The anti-adhesive property was assessed by the inhibition of binding of four strains of FITC-labeled H. pylori to stomach sections. RESULTS: Of all the plants tested, eight plants, including Bengal quince, nightshade, garlic, dill, black pepper, coriander, fenugreek and black tea, were found to have no bactericidal effect on any of the isolates. Columbo weed, long pepper, parsley, tarragon, nutmeg, yellow-berried nightshade, threadstem carpetweed, sage and cinnamon had bactericidal activities against H. pylori, but total inhibition of growth was not achieved in this study. Among the plants that killed H. pylori, turmeric was the most efficient, followed by cumin, ginger, chilli, borage, black caraway, oregano and liquorice. Moreover, extracts of turmeric, borage and parsley were able to inhibit the adhesion of H. pylori strains to the stomach sections. CONCLUSION: Several plants that were tested in our study had bactericidal and/or anti-adhesive effects on H. pylori. Ingestion of the plants with anti-adhesive properties could therefore provide a potent alternative therapy for H. pylori infection, which overcomes the problem of resistance associated with current antibiotic treatment.

Helicobacter pylori: current status and future prospects.

Helicobacter pylori is a global pathogen that causes severe gastrointestinal diseases leading to a significant morbidity and mortality. There is an effective treatment for peptic ulcer disease, however, this is being compromised by an increase in the prevalence of antibiotic resistance. Although alternative rescue regimens have been advocated, the best strategy would be to prevent disease, especially in the case of gastric cancer for which there is still no treatment. One approach is to inhibit the first step in the pathogenic process - adhesion of the organism to the host tissue. Another and probably a better approach is vaccination, but clinical trials have so far been unsuccessful. There is still a large uncertainty in relation to how H. pylori causes disease. Knowledge from genomics, proteomics, and the relationship between polymorphism of the bacterium and the host, as well as the continuing investigation of the role played by important virulence factors in the outcome of the disease, will help both in understanding pathogenesis of disease and in the design of the best vaccine.

Innate immunity and pathogen-host interaction.

The skin and contiguous mucosal surfaces define the primary locus of interaction between host and micro-organisms. In this review, we focus on the innate immune system in the mucosa, which manages to deal with invading pathogens, the mechanisms that organisms have evolved in order to circumvent this primary defensive barrier and, finally, potential therapeutic manipulation of the innate immune system that was the focus of meeting at a Euroconference/Workshop on "Novel Strategies of Mucosal Immunisation through Exploitation of Mechanisms of Innate Immunity in Pathogen-Host Interaction", which was held in Siena, Italy, November 2002.