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Background The gold standard for assessment and diagnosis of significant proteinuria in pregnancy has been by 24-hour urine collection and analysis. Determining fast, accurate methods to identify clinically significant proteinuria would aid diagnosis of pre-eclampsia. The objective of this study was to determine the accuracy of spot protein-creatinine ratio (PCR) and albumin-creatinine ratio (ACR) measurements compared with 24-hour urine collection for the identification of clinically significant proteinuria in women with hypertensive disorders of pregnancy. Methods Search strategies were developed for electronic databases from inception to 1st October 2020. Data were assessed for methodological quality using the QUADAS-II checklist for risk of bias and quality of the evidence using GRADE. Meta-analysis was performed where there were at least four studies presenting data for the same comparison (test and threshold). This is an update of the review for NICE guideline NG133 (published June 2019) and includes additional data. Results Twenty-nine studies were included. PCR measurements (28 studies) showed high sensitivity (91%) and specificity (89%) at a threshold of 30 mg/mmol (n = 3577). Higher thresholds (>60 mg/mmol) increased specificity, but reduced sensitivity. At a threshold of PCR 30 mg/mmol, diagnostic accuracy improved for sensitivity and specificity (93% for both) in studies where the first morning void was excluded (n = 1868). Data available (4 studies) for ACR supports ruling out of significant proteinuria at less than 2 mg/mmol, though evidence was limited by paucity of data and wide confidence intervals around the result. Conclusions PCR and ACR have high accuracy compared to the gold standard 24-hour urine collection.

Background and aim: Colorectal cancer [CRC] is highly prevalent worldwide, with dietary habits being a major risk factor. We systematically reviewed and meta-analysed the observational evidence on the association between CRC and dietary patterns [DP] derived from Principal Component Analysis. Design: PRISMA guidelines were followed. Web of Science, Medline/PubMed, EMBASE, and The Cochrane Library were searched to identify all eligible papers published up to July 2017. Any pre-defined cancer in the colon was included, namely colon-rectal cancer (CRC), colon cancer (CC), rectal cancer (RC), or proximal and distal CC, if available. Western (WDP) and prudent (PDP) dietary patterns were compared as a proxy to estimate ‘unhealthy’ (Rich in meat and processed foods) and ‘healthy’ diets (containing fruits or vegetables), respectively. Meta-analyses were carried out using random effects model to calculate overall risk estimates. Relative risks (RR) and 95% confidence intervals were estimated comparing the highest versus the lowest categories of dietary patterns for any of the forms of colon cancer studied. Results: 28 studies were meta-analysed. A WDP was associated with increased risk of CRC (RR 1.25; 95% CI 1.11, 1.40), and of CC (RR 1.30; 95% CI 1.11, 1.52). A PDP was negatively associated with CRC (RR 0.81; 95% CI 0.73, 0.91). Sensitivity analyses showed that individuals from North- and South- American countries had a significantly higher risk of CRC than those from other continents. Conclusion: A PDP might reduce the risk of CRC. Conversely, a WDP is associated with a higher risk of disease.

Prefilled syringes, pen injectors, inhalers, auto-injectors, and transdermal patches are all examples of products that combine a drug or biologic with a delivery device. These combination products are increasing in popularity and promise to reduce the cost of healthcare delivery while improving patients’ quality of life. As with other medical devices, makers of combination products are required by regulators to validate that their products can be used safely and effectively by intended users in intended use environments. This typically includes conducting human factors validation testing. While conceptually similar, there are differences in the design of human factors validation tests of combination products. These differences stem from the fact that combination products include use-related risks related to the drug itself, as well as to nuanced differences in how the centers of the FDA who lead the review of combination products and medical device submissions view human factors. In this chapter, we review additional considerations for the design of human factors validation tests for combination products relative to tests for other medical devices. We also discuss a related type of human factors test, that may be used in lieu of a human factors validation test of a combination product involving a generic or biosimilar. For companies that wish to establish that their combination products are substitutable or interchangeable, a comparative use human factors test may be needed.

To make medical devices safer and to optimize their designs, manufacturers need to understand when users are likely to have difficulties using devices and the factors that contribute to or cause errors. This isn't just good practice. Regulators require that manufacturers conduct root cause analysis of use issues that arise during validation testing in order to determine the residual risk and priorities for implementing additional risk management measures (Food and Drug Administration, 2016). This chapter outlines a framework for understanding the causes of errors people make when using a medical device. It begins by exploring differing views of error, including a discussion of differing taxonomies that have been proposed for characterizing the causes of use errors. It describes the objective of Root Cause Analysis and reviews methods for conducting that are found helpful in practice. It describes how these methods can be applied to understanding the causes of errors with medical devices. Finally, this chapter discusses pitfalls in conducting Root Cause Analysis with examples of good and bad descriptions of root causes.

Importance Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively synthesized.\ud \ud Objective To systematically review and meta-analyze evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease.\ud \ud Data Sources MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS databases were searched between January 1946 and March 2016.\ud \ud Study Selection Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization were included.\ud \ud Data Extraction and Synthesis Data were extracted in duplicate and synthesized for meta-analysis using generic inverse variance or Mantel-Haenszel methods with a random-effects model. GRADE was used to assess the certainty of evidence.\ud \ud Main Outcomes and Measures Wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization, type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, autoimmune thyroid disease, and juvenile rheumatoid arthritis.\ud \ud Results Of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. There was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95% CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95% CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95% CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95% CI, 6-22 cases) per 1000 population. Certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Timing of egg or peanut introduction was not associated with risk of allergy to other foods. There was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes.\ud \ud Conclusions and Relevance In this systematic review, early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies.

Objective To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. Design Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. Data Sources Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. Eligibility Criteria For Selecting Studies Prospective intervention trials of hydrolysed cows’ milk formula compared with another hydrolysed formula, human breast milk, or a standard cows’ milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. Results 37 eligible intervention trials of hydrolysed formula were identified, including over 19 000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows’ milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I2=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I2 =74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I2=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could allergy to cows’ milk. COnclusion These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants.

Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, anti-allergic and anti-inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score >=32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma.

Objectives.This study evaluated the delivery characteristics and vascular response to placement of a novel balloon-expandable stent in swine with experimentally induced atherosclerosis.Background.The Multi-Link stent is a balloon-expandable stainless steel stent with an interconnected ring structure designed to provide a high degree of compressive resistance while preserving longitudinal flexibility. The placement characteristics and vascular response to this stent in atherosclerotic coronary arteries have not been characterized.Methods.We tested the delivery characteristics and vascular response to the Multi-Link stent in 19 miniature swine with experimentally induced coronary atherosclerosis created in 37 coronary artery segments by overstretch balloon injury and high cholesterol diet. Quantitative coronary angiography was used to define stent performance characteristics, such as lesion dilation and compressive resistance. Pathologic assessment of the stented arteries was used to evaluate the immediate and long-term vascular response to stent placement.Results.Nineteen (95%) of 20 stents were successfully implanted in the left anterior descending (n = 11), left circumflex (n = 7) or right (n = 1) coronary artery. The baseline angiographic minimal lumen diameter of the stented coronary segment was 2.48 ± 0.09 mm (reference diameter 2.87 ± 0.06 mm, mean ± SE) and increased to 2.82 ± 0.05 mm (p < 0.001) after stent placement. The ballooninflated stent diameter was 2.98 ± 0.06 mm with minimal recoil to a final minimal lumen diameter of 2.82 ± 0.06 mm at 15 min after implantation (p = 0.001). Angiographic and histologic follow-up at 72 h (n = 7), 14 days (n = 4) and 56 days (n = 8) demonstrated that all stents were patent, without evidence of migration, intraluminal filling defects or side branch occlusion. At 56 days, mean neointimal thickness was significantly greater at the stent wire sites in the region of the plaque where the media was absent than the stent wire sites, where the internal elastic lamina was intact with underlying normal media (0.48 ± 0.01 vs. 0.27 ± 0.02 mm, p < 0.0001). Compared with the nonstented atherosclerotic lesions, after 56 days the stented vessels had a mildly reduced lumen area when normalized to the proximal reference vessel (2.81 ± 0.27 vs. 2.68 ± 0.30 mm2, p = 0.07). The mean change in the area within the external elastic lamina relative to a normal proximal reference segment was significantly greater in stented vessels (1.45 ± 0.34 mm2) than nonstented atherosclerotic vessels (0.44 ± 0.28 mm2, p = 0.033).Conclusions.Morphologic data confirm that the principal beneficial effect of stent placement is vessel expansion and attenuation of constrictive remodeling. In vessels with eccentric atherosclerotic fibrocellular plaques, the presence of normal media underlying the stent determines the degree of neointimal formation. These data may be useful in understanding the mechanism of stent restenosis in patients with prior percutaneous transluminal coronary angioplasty.

Four experiments examined differences in probabilistic reasoning as a function of whether problems were presented in a frequentist or case-specific form. The experiments demonstrated that these different forms influence the likelihood of Ss committing the conjunction and disjunction fallacies. The authors contend that these 2 forms elicit different approaches to probability. Frequency problems, it is argued, elicit a distributional approach in which probabilities are equated with relative frequencies, whereas case-specific problems elicit a singular approach in which probabilities are equated with the propensities or causal forces operating in an individual case

A newly designed flow support catheter with a supporting wire mesh cage which can be expanded into a tubular configuration and then readily reduced was evaluated in mongrel dogs. Regional myocardial blood flow (RMBF) was measured using the radioactive microsphere technique in the area of both balloon-denuded instrumented and control non-instrumented coronary arteries following placement of either a fixed-wire or a higher profile rapid exchange flow support catheter. At 5, 20, and 180 min following delivery and expansion of either device, RMBF was not significantly different in left ventricular subepicardium and subendocardium perfused by the instrumented vs. the control coronary arteries. Angiography demonstrated widely patent instrumented arteries in 15/18 dogs; in no dog was side branch occlusion observed. Significant cage thrombus deposition was seen angiographically in 3 animals causing temporary total coronary occlusion in 1. Following reduction and removal of the flow support catheter, vessel patency was present in all dogs. The flow support catheter is an effective endovascular stenting device capable of providing structural arterial support, while simultaneously maintaining distal coronary blood flow. It is envisioned that the primary application of this catheter will be to enable primary salvage of vessels acutely injured during coronary angioplasty, by "tacking up" intimal flaps for an extended period. It may also provide a bridge to emergency surgical revascularization.