Community-based cardiovascular disease prevention programmes and cardiovascular risk factors: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to summarise the effect of community-based intervention programmes on the prevention of cardiovascular disease (CVD) by reducing cardiometabolic risk factors. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: A systematic search in the PubMed database and screening of reference lists aimed to identify community-based CVD prevention programmes from inception up to April 2020. The mean differences and standard deviations for CVD risk factors, including blood pressure, lipid profile, blood glucose and body weight indices, were extracted and pooled using a random effects model. RESULTS: Screening of 11,889 titles/abstracts and full texts resulted in 48 studies being included in this review. The meta-analysis showed that community-based programmes have led to considerable decreases in systolic blood pressure (weighted mean difference [WMD] = -2.90 mm Hg, 95% confidence interval [95% CI]: -3.63, -2.16), diastolic blood pressure (WMD = -2.21 mm Hg, 95% CI: -3.12, -1.29), serum levels of low-density lipoprotein cholesterol (LDL-C; WMD = -8.88 mg/dl, 95% CI: -12.84, -4.92), triglycerides (WMD = -8.40 mg/dl, 95% CI: -12.10, -4.70), total cholesterol (WMD = -2.96 mg/dl, 95% CI: -3.10, -2.81) and fasting blood glucose (WMD = -2.06 mg/dl, 95% CI: -3.02, -1.10). A moderate decrease in body weight was also found with community-based CVD prevention programmes. However, community-based CVD prevention programmes were not associated with any significant changes in serum levels of high-density lipoprotein. CONCLUSIONS: The present study indicates that community-based strategies have successfully led to an improvement in CVD risk factors, particularly by reducing blood pressure, serum levels of LDL-C and triglycerides, obesity indices and blood glucose. The impact of these programmes on CVD is modified by the type of intervention and by different cultural and physical environments.

Diversification across biomes in a continental lizard radiation.

Ecological opportunity is a powerful driver of evolutionary diversification, and predicts rapid lineage and phenotypic diversification following colonization of competitor-free habitats. Alternatively, topographic or environmental heterogeneity could be key to generating and sustaining diversity. We explore these hypotheses in a widespread lineage of Australian lizards: the Gehyra variegata group. This clade occurs across two biomes: the Australian monsoonal tropics (AMT), where it overlaps a separate, larger bodied clade of Gehyra and is largely restricted to rocks; and in the larger Australian arid zone (AAZ) where it has no congeners and occupies trees and rocks. New phylogenomic data and coalescent analyses of AAZ taxa resolve lineages and their relationships and reveal high diversity in the western AAZ (Pilbara region). The AMT and AAZ radiations represent separate radiations with no difference in speciation rates. Most taxa occur on rocks, with small geographic ranges relative to widespread generalist taxa across the vast central AAZ. Rock-dwelling and generalist taxa differ morphologically, but only the lineage-poor central AAZ taxa have accelerated evolution. This accords with increasing evidence that lineage and morphological diversity are poorly correlated, and suggests environmental heterogeneity and refugial dynamics have been more important than ecological release in elevating lineage diversity.

Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis.

Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)-κB signalling pathways have been reported associated with responsiveness to tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis (RA). The present study was undertaken to replicate these findings. In a retrospective case-case study including 1007 Danish anti-TNF-treated RA patients, we genotyped 7 previously reported associated single-nucleotide polymorphisms (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60-0.94, P=0.014) with a negative treatment response. Meta-analyses combining data from previous studies suggested smaller effect sizes of associations between variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative treatment response. In conclusion, this study validates rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response, and suggests true positive associations of previously reported SNPs within genes encoding activators/inhibitors of NF-κB (CHUK, MYD88, NFKBIB, and NLRP3).

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1ß levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFκB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.

Adherence to Healthy Eating Index-2010 is inversely associated with metabolic syndrome and its features among Iranian adult women.

BACKGROUND/OBJECTIVES: Nowadays, metabolic syndrome (MetS) is deemed as a major public health challenge in both developed and developing countries. Therefore, the aim of this study was to determine the association between Healthy Eating Index-2010 (HEI-2010) score and MetS and its features among Iranian female nurses. SUBJECTS/METHODS: This cross-sectional study was performed among 1036 Iranian women. A validated, self-administered, dish-based, semiquantitative food frequency questionnaire was used to assess the habitual intake of participants. HEI-2010 score was used to assess diet quality of participants. MetS was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Multivariate logistic regression adjusted for potential confounders was used to assess the relation between HEI-2010 and MetS. RESULTS: After adjusting for potential confounders, participants in the highest quartile of HEI-2010 had the lowest risk of MetS compared with those in the first quartile (odds ratio: 0.72; 95% confidence interval: 0.50-0.96). Furthermore, the risk of MetS features including abdominal obesity, high blood pressure, high serum triacylglycerol and low serum high-density lipoprotein-cholesterol significantly decreased across HEI-2010 quartiles (P<0.05). CONCLUSIONS: Higher HEI-2010 scores were inversely associated with lower risk of MetS and its components among Iranian women.

Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases.

BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. AIM: To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis. METHODS: We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis. RESULTS: A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis. CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

A validation of the Danish microbiology database (MiBa) and incidence rate of Actinotignum schaalii (Actinobaculum schaalii) bacteraemia in Denmark.

Actinotignum schaalii (former named Actinobaculum schaalii) can cause urinary tract infections (UTIs) and bacteraemia, mainly in the elderly. A. schaalii is difficult to identify with conventional biochemical tests, and it is often overlooked if the urine is only cultured in ambient air. The aim of this study was to validate data from the nationwide Danish microbiology database (MiBa) with data from the laboratory information system (LIS) at the local department of microbiology in Viborg-Herning, and to evaluate the incidence rate of bacteraemia caused by A. schaalii in Denmark by using data from the MiBa. All departments of microbiology in Denmark report data to the MiBa. All microbiological samples with A. schaalii in Denmark were extracted for a period of 5 years from the MiBa and from the local LISs. All data obtained from our local LIS were also found in the MiBa, except for data on real-time PCR, which were not registered, owing to missing ID codes in the MiBa. From 2010 to 2014, there was a significant increase in the incidence rate of blood cultures with A. schaalii, from 1.8 to 6.8 cases per million, which was probably due to coincident implementation of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in routine diagnostics. We found that A. schaalii caused bacteraemia and UTIs mainly in the elderly. In conclusion, the MiBa can be a useful source of nationwide microbiological data in Denmark. Our results suggest that the incidence rate of A. schaalii as a cause of bacteraemia has been underestimated, and that culture of urine in CO2 can improve the detection of A. schaalii.

Cross-sectional scanning thermal microscopy of ErAs/GaAs superlattices grown by molecular beam epitaxy.

Scanning thermal microscopy has been implemented in a cross-sectional geometry, and its application for quantitative, nanoscale analysis of thermal conductivity is demonstrated in studies of an ErAs/GaAs nanocomposite superlattice. Spurious measurement effects, attributable to local thermal transport through air, were observed near large step edges, but could be eliminated by thermocompression bonding to an additional structure. Using this approach, bonding of an ErAs/GaAs superlattice grown on GaAs to a silicon-on-insulator wafer enabled thermal signals to be obtained simultaneously from Si, SiO2, GaAs, and ErAs/GaAs superlattice. When combined with numerical modeling, the thermal conductivity of the ErAs/GaAs superlattice measured using this approach was 11 ± 4 W m(-1) K(-1).

Fusobacterium necrophorum tonsillitis: an important cause of tonsillitis in adolescents and young adults.

The role of Fusobacterium necrophorum in tonsillitis in adolescents and young adults was retrospectively investigated by culture examination. We compared the prevalence of F. necrophorum in 212 subjects with confirmed clinical tonsillitis and in 176 subjects with confirmed no clinical tonsillitis. The prevalence of F. necrophorum was significantly higher (p < 0.001) in subjects with clinical tonsillitis (27%) compared to subjects with no clinical tonsillitis (6%). These results clearly demonstrate the role of F. necrophorum in tonsillitis. By diagnosing and treating F. necrophorum tonsillitis with, for example, penicillin, metronidazole, or both, we might prevent some cases of Lemierre syndrome.

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease.

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1ß, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.

A cost-effectiveness analysis of identifying Fusobacterium necrophorum in throat swabs followed by antibiotic treatment to reduce the incidence of Lemierre's syndrome and peritonsillar abscesses.

The main purpose of this paper was to estimate the cost per quality-adjusted life year (QALY) saved by identifying Fusobacterium necrophorum in throat swabs followed by proper antibiotic treatment, to reduce the incidence of Lemierre's syndrome and peritonsillar abscesses (PTA) originating from a pharyngitis. The second purpose was to estimate the population size required to indicate that antibiotic treatment has an effect. Data from publications and our laboratory were collected. Monte Carlo simulation and one-way sensitivity analysis were used to analyse cost-effectiveness. The cost-effectiveness analysis shows that examining throat swabs from 15- to 24-year-olds for F. necrophorum followed by antibiotic treatment will probably be less costly than most other life-saving medical interventions, with a median cost of US$8,795 per QALY saved. To indicate a reduced incidence of Lemierre's syndrome and PTA in Denmark, the intervention probably has to be followed for up to 5 years. Identifying F. necrophorum in throat swabs from 15- to 24-year-olds followed by proper antibiotic treatment only requires a reduction of 20-25 % in the incidence of Lemierre's syndrome and PTA to be cost-effective. This study warrants further examination of the effect of antibiotic treatment on the outcome of F. necrophorum acute and recurrent pharyngitis, as well as the effect on Lemierre's syndrome and PTA.

Effects of medications on post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIMS: Drug-induced pancreatitis accounts for about 2% of acute pancreatitis. The aim of this study is to determine whether propofol and other medications are associated with increased risk for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS: A retrospective study was conducted at a single tertiary care hospital. All patients who underwent ERCP from 2001 to 2004 were included. Diagnosis of acute post-ERCP pancreatitis was based on a consensus definition. RESULTS: A total of 506 patients underwent ERCP. The total incidence of post-ERCP pancreatitis was 7.1%. There was no significant difference in post-ERCP pancreatitis between patients who received propofol compared to patients who received midazolam and fentanyl (9.0 vs. 5.9%, p = 0.18). Patients receiving an angiotensin receptor blocker were approximately 4 times more likely to develop post-ERCP pancreatitis (OR = 4.1, 95% CI 1.6-10.9). Patients younger than 65 years and smokers also had higher risk of developing acute post-ERCP pancreatitis than those who were older than 65 years (OR = 3.9, 95% CI 1.7-9.1) and non-smokers (OR = 2.8, 95% CI 1.3-6.2). CONCLUSIONS: Propofol is a safe sedative drug for ERCP without additional risk of developing acute post-ERCP pancreatitis. Use of angiotensin receptor blockers, smoking and younger age are independent risk factors for post-ERCP pancreatitis.

Highly spin-polarized room-temperature tunnel injector for semiconductor spintronics using MgO(100).

The spin polarization of current injected into GaAs from a CoFe/MgO(100) tunnel injector is inferred from the electroluminescence polarization from GaAs/AlGaAs quantum well detectors. The polarization reaches 57% at 100 K and 47% at 290 K in a 5 T perpendicular magnetic field. Taking into account the field dependence of the luminescence polarization, the spin injection efficiency is at least 52% at 100 K, and 32% at 290 K. We find a nonmonotonic temperature dependence of the polarization which can be attributed to spin relaxation in the quantum well detectors.

Feasibility and safety of percutaneous endoscopic gastrostomy in patients with subtotal gastrectomy.

BACKGROUND AND STUDY AIMS: We aimed to study the technical feasibility, safety, efficacy and complications of endoscopic feeding tube placement in patients who had previously undergone subtotal gastrectomy. We also investigated whether jejunal feeding tube placement (percutaneous endoscopic jejunostomy [PEJ]) is superior to gastric feeding tube placement (percutaneous endoscopic gastrostomy [PEG]) in the prevention of aspiration pneumonia in patients with subtotal gastrectomy. PATIENTS AND METHODS: A retrospective cohort study was carried out which included 48 patients treated between 1995 and 2001. Participants were selected from 3400 patients who were referred for PEG placement. The study group consisted of 15 consecutive patients with a prior subtotal gastrectomy. The control group comprised 33 randomly selected patients with intact stomachs. The primary end point of the study concerned the safety of PEG placement. The secondary end points included the efficacy and technical difficulty of the procedure. RESULTS: PEG/PEJ placement was successful in 14 of the 15 patients (93 %) who had previously had a subtotal gastrectomy. None of the study patients developed procedure-related complications. Feeding intolerance was more common in patients with gastrectomy compared with patients with an intact stomach, but the difference did not reach statistical significance (10 % vs. 3 %, P>0.05). A significantly higher incidence of pneumonia was observed in patients with gastrectomy compared with patients with an intact stomach (P=0.01). Subgroup analysis showed that the risk was higher with jejunal tube placement compared with gastric tube placement (42 % vs. 12 %, P=0.001). CONCLUSION: PEG/PEJ placement in patients with gastrectomy is a technically safe procedure. These patients are at higher risk of aspiration pneumonia and risk is higher with jejunal tube placement compared with gastric tube placement.

From mental health professional to expert witness: testifying in court.

Our democratic principles rest on the belief that truth is discovered through the fair and open combat of ideas in a court of law. When mental health professionals participate in this adversary process as expert witnesses, it is essential for them to understand that attorneys will attempt to impeach their credibility. Mental health professionals who appreciate the spirit and mechanics of courtroom communication will be best prepared to protect the integrity of their testimony. The courtroom communications model provides experts with a conceptual framework utilizing three components: the speaker is the expert, the message is testimony, and the audience is the judge or jury. Within the structure of this model, communication principles from social psychology can be used to enhance the clarity of testimony and to prevent attorneys from distorting the expert's opinions. First and foremost, expert witness testimony must be formulated on accepted scholarly and ethical standards. To establish credibility, experts must appear knowledgeable and trustworthy to the judge and jury. The expert must come to court prepared for both direct examination and cross-examination, know when to emphasize logic or emotion, tailor speech in order to reach the maximum number of jurors, and remain nondefensive by projecting the same demeanor regardless of which side is conducting the examination. The role of the expert witness is forever changing because the judicial system--like the mental health field--continues to evolve. Although the adversary process has undergone dramatic changes over the past eight hundred years, historical vestiges continue to echo throughout our courtrooms. Today expert witnesses are the champions of both victims and the accused. Legal disputes are increasingly being decided by the battle of the experts, who must undergo the ordeal of cross-examination. When you consider the brutality of ancient ordeals, responding to attorneys armed with questions may not seem so daunting.

Long-term follow-up of twenty patients with adenocarcinoma of the pancreas: resection following combined modality therapy.

Long-term follow-up of 5 or more years in 20 patients with initially unresectable cancer of the pancreas that responded to chemoradiation therapy is detailed in this article. All patients underwent resection. Seven or 18 surgical survivors are alive 50 or more months.