Multimorbidity impacts cardiovascular disease risk following percutaneous coronary intervention: latent class analysis of the Melbourne Interventional Group (MIG) registry.

BACKGROUND: Multimorbidity is strongly associated with disability or functional decline, poor quality of life and high consumption of health care services. This study aimed (1) To identify patterns of multimorbidity among patients undergoing first recorded percutaneous coronary intervention (PCI); (2) To explore the association between the identified patterns of multimorbidity on length of hospital stay, 30-day and 12- month risk of major adverse cardiac and cerebrovascular events (MACCE) after PCI. METHODS: A retrospective cohort study of the Melbourne Interventional Group (MIG) registry. This study included 14,025 participants who underwent their first PCI from 2005 to 2015 in Victoria, Australia. Based on a probabilistic modelling approach, Latent class analysis was adopted to classify clusters of people who shared similar combinations and magnitude of the comorbidity of interest. Logistic regression models were used to estimate odd ratios and 95% confidence interval (CI) for the 30-day and 12-month MACCE. RESULTS: More than two-thirds of patients had multimorbidity, with the most prevalent conditions being hypertension (59%) and dyslipidaemia (60%). Four distinctive multimorbidity clusters were identified each with significant associations for higher risk of 30-day and 12-month MACCE. The cluster B had the highest risk of 30-day MACCE event that was characterised by a high prevalence of reduced estimated glomerular filtration rate (92%), hypertension (73%) and reduced ejection fraction (EF) (57%). The cluster C, characterised by a high prevalence of hypertension (94%), dyslipidaemia (88%), reduced eGFR (87%), diabetes (73%) and reduced EF (65%) had the highest risk of 12-month MACCE and highest length of hospital stay. CONCLUSION: Hypertension and dyslipidaemia are prevalent in at least four in ten patients undergoing coronary angioplasty. This study showed that clusters of patients with multimorbidity had significantly different risk of 30-day and 12-month MACCE after PCI. This suggests the necessity for treatment approaches that are more personalised and customised to enhance patient outcomes and the quality of care delivered to patients in various comorbidity clusters. These results should be validated in a prospective cohort and to evaluate the potential impacts of these clusters on the prevention of MACCE after PCI.

Prevalence and risk factors of peripheral artery disease in a population with chronic kidney disease in Australia: A systematic review and meta-analysis.

There is a lack of clarity and guidance for screening peripheral artery disease (PAD) in persons with chronic kidney disease (CKD) and end stage kidney disease (ESKD) despite this group being at excess risk of cardiovascular disease (CVD). In this current study, we performed a systematic review and meta-analysis to examine the prevalence and risk factors for PAD in persons with CKD in Australian cohorts. We used the inverse variance heterogeneity meta-analysis with double arcsine transformation to summarize the prevalence of PAD (with 95% CIs). Nine studies and 18 reports from the Australia and New Zealand dialysis and transplant registry with 36 cohorts were included in the review. We found a substantially higher PAD prevalence in cohorts based on an ankle-brachial index (ABI) or toe systolic pressure (TBI) than cohorts based on self-reported history. Higher PAD prevalence was observed in ESKD persons than CKD persons without dialysis (PAD diagnosis based on ABI or TBI: 31% in ESKD persons and 23% in CKD persons, PAD diagnosis based on self-reported history: 17% in ESKD persons and 10% in CKD persons). Older age, Caucasian race, cerebrovascular disease and haemodialysis were associated with the presence of PAD in ESKD persons. Our findings indicated a considerable proportion of PAD in CKD and ESKD persons particularly in those with ESKD. To develop and provide an adequate plan to clinically manage CKD patients with PAD, evidence of cost-effectiveness and clinical benefit of early detection of PAD in persons with CKD in Australia is recommended for future studies.

Contrast-Enhanced Ultrasound Algorithms (CEUS-LIRADS/ESCULAP) for the Noninvasive Diagnosis of Hepatocellular Carcinoma - A Prospective Multicenter DEGUM Study.

BACKGROUND: This prospective multicenter study funded by the DEGUM assesses the diagnostic accuracy of standardized contrast-enhanced ultrasound (CEUS) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. METHODS: Patients at high risk for HCC with a histologically proven focal liver lesion on B-mode ultrasound were recruited prospectively in a multicenter approach. Clinical and imaging data were entered via online entry forms. The diagnostic accuracies for the noninvasive diagnosis of HCC were compared for the conventional interpretation of standardized CEUS at the time of the examination (= CEUS on-site) and the two CEUS algorithms ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) and CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System). RESULTS: 321 patients were recruited in 43 centers; 299 (93.1 %) had liver cirrhosis. The diagnosis according to histology was HCC in 256 cases, and intrahepatic cholangiocarcinoma (iCCA) in 23 cases. In the subgroup of cirrhotic patients (n = 299), the highest sensitivity for the diagnosis of HCC was achieved with the CEUS algorithm ESCULAP (94.2 %) and CEUS on-site (90.9 %). The lowest sensitivity was reached with the CEUS LI-RADS algorithm (64 %; p < 0.001). However, the specificity of CEUS LI-RADS (78.9 %) was superior to that of ESCULAP (50.9 %) and CEUS on-site (64.9 %; p < 0.001). At the same time, the negative predictive value (NPV) of CEUS LI-RADS was significantly inferior to that of ESCULAP (34.1 % vs. 67.4 %; p < 0.001) and CEUS on-site (62.7 %; p < 0.001). The positive predictive values of all modalities were high (around 90 %), with the best results seen for CEUS LI-RADS and CEUS on-site. CONCLUSION: This is the first multicenter, prospective comparison of standardized CEUS and the recently developed CEUS-based algorithms in histologically proven liver lesions in cirrhotic patients. Our results reaffirm the excellent diagnostic accuracy of CEUS for the noninvasive diagnosis of HCC in high-risk patients. However, on-site diagnosis by an experienced examiner achieves an almost equal diagnostic accuracy compared to CEUS-based diagnostic algorithms.

CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells.

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) system is a highly efficient and powerful tool for RNA-guided editing of the cellular genome. Whether CRISPR/Cas9 can also cleave the genome of DNA viruses such as Epstein-Barr virus (EBV), which undergo episomal replication in human cells, remains to be established. Here, we reported on CRISPR/Cas9-mediated editing of the EBV genome in human cells. Two guide RNAs (gRNAs) were used to direct a targeted deletion of 558 bp in the promoter region of BART (BamHI A rightward transcript) which encodes viral microRNAs (miRNAs). Targeted editing was achieved in several human epithelial cell lines latently infected with EBV, including nasopharyngeal carcinoma C666-1 cells. CRISPR/Cas9-mediated editing of the EBV genome was efficient. A recombinant virus with the desired deletion was obtained after puromycin selection of cells expressing Cas9 and gRNAs. No off-target cleavage was found by deep sequencing. The loss of BART miRNA expression and activity was verified, supporting the BART promoter as the major promoter of BART RNA. Although CRISPR/Cas9-mediated editing of the multicopy episome of EBV in infected HEK293 cells was mostly incomplete, viruses could be recovered and introduced into other cells at low m.o.i. Recombinant viruses with an edited genome could be further isolated through single-cell sorting. Finally, a DsRed selectable marker was successfully introduced into the EBV genome during the course of CRISPR/Cas9-mediated editing. Taken together, our work provided not only the first genetic evidence that the BART promoter drives the expression of the BART transcript, but also a new and efficient method for targeted editing of EBV genome in human cells.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol.

INTRODUCTION: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management. METHODS AND ANALYSIS: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used. ETHICS AND DISSEMINATION: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings. TRIAL REGISTRATION NUMBER: NCT05972785.

Historical overview of Taenia asiatica in Taiwan.

An overview of the epidemiological, biological, and clinical studies of Taenia and taeniasis in Taiwan for the past century is presented. The phenomenal observations that led to the discovery of Taenia asiatica as a new species, which differ from Taenia solium and Taenia saginata, are described. Parasitological surveys of the aborigines in Taiwan revealed a high prevalence of taeniasis, which might be due to the culture of eating raw liver of hunted wild boars. Chemotherapeutic deworming trials involving many patients with taeniasis were discussed. Praziquantel was found to be very effective, but sometimes complete worms could not be recovered from the feces after treatment, probably due to the dissolution of the proglottids. Atabrine, despite some side effects, can still be used, in properly controlled dosages, as the drug of choice for human T. asiatica infection if we need to recover the expelled worms for morphological examinations. Research results on the infection of T. asiatica eggs from Taiwan aborigines in experimental animals were also noted. Since the pig serve as the natural intermediate host of T. asiatica and the predilection site is the liver, a differential comparison of other parasitic pathogens that might cause apparently similar lesions is also presented.

Association between ambient temperature and stroke risk in high-risk populations: a systematic review.

Background: Significant associations exist between ambient temperature and stroke risk, but results in high cardiovascular risk populations are lacking. This systemic review summarised current evidence on ambient temperature and overall stroke risk in a high cardiovascular risk population. Methods: We performed a systematic literature search across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and GEOBASE, from inception to 3 July 2023, to identify all population-based studies. Eligible studies screened by independent reviewers recruited individuals aged 18 years and over, where minimum 80% of participants had a high cerebral vascular disease (CVD) risk profile. The primary outcomes are stroke morbidity and mortality, while the secondary outcomes are morbidity and mortality of ischaemic stroke (IS), intracranial cerebral haemorrhage (ICH), and subarachnoid haemorrhage (SH). Results: The database searches identified 9,025 articles. After removing duplicates, 7,647 articles were screened in title and abstract to identify 380 articles for full-text screening. After the full-text screening of 380 articles by two independent reviewers, 23 articles were included in the review. Conclusion: The evidence for an association between ambient temperature and stroke incidence is that lower temperatures were more likely to increase morbidity and mortality risk of both haemorrhagic and ischaemic stroke in older people. Conversely, higher ambient temperature is significantly associated with intracranial haemorrhage risk, but decreased risk with IS. Higher and lower ambient temperatures consistently increase stroke risks in patients with comorbidities of congestive heart failure and dyslipidaemia. This evidence implies the need to establish clinical guidelines for preventive intervention in patients with high stroke risks during extreme ambient temperatures.

Use of CT, ED presentation and hospitalisations 12 months before and after a diagnosis of cancer in Western Australia: a population-based retrospective cohort study.

OBJECTIVE: To examine the use of CT, emergency department (ED)-presentation and hospitalisation and in 12 months before and after a diagnosis of cancer. DESIGN: Population-based retrospective cohort study. SETTING: West Australian linked administrative records at individual level. PARTICIPANTS: 104 009 adults newly diagnosed with cancer in 2004-2014. MAIN OUTCOME MEASURES: CT use, ED presentations, hospitalisations. RESULTS: As compared with the rates in the 12th month before diagnosis, the rate of CT scans started to increase from 2 months before diagnosis with an increase in both ED presentations and hospitalisation from 1 month before the diagnosis. These rates peaked in the month of diagnosis for CT scans (477 (95% CI 471 to 482) per 1000 patients), and for hospitalisations (910 (95% CI 902 to 919) per 1000 patients), and the month prior to diagnosis for ED (181 (95% CI 178 to 184) per 1000 patients) then rapidly reduced after diagnosis but remained high for the next 12 months. While the patterns of the health services used were similar between 2004 and 2014, the rate of the health services used during after diagnosis was higher in 2014 versus 2004 except for CT use in patients with lymphohaematopoietic cancer with a significant reduction. CONCLUSION: Our results showed an increase in demand for health services from 2 months before diagnosis of cancer. Increasing use of health services during and post cancer diagnosis may warrant further investigation to identify factors driving this change.

Potential Roles of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs) in Nondiabetic Populations.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been observed in several large cardiovascular outcome trials to significantly reduce the incidence of major cardiovascular event (MACE) with type 2 diabetic patients. The clinical trials of GLP-1 RAs, including lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, and dulaglutide, are associated with a significantly 14% lower risk of MACE in patients with T2DM and a history of CV disease, and with a nonsignificantly 6% lower risk in patients without history of CV disease. Some of the interpretation with GLP-1 RA trials suggested the possible role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in primary prevention of cardiovascular diseases in nondiabetic individual, echoed by a recent editorial redefining the role of GLP-1 RAs being beyond glycaemic control. The narrative review provides an in-depth insight into GLP-1 RA use guideline in different countries and regions of the world and examines the safety and concern of GLP-1 RA use. The narrative review draws the comparison of GLP-1 RA use between diabetic and nondiabetic individual in terms of cardiovascular and metabolic benefits and points out the direction of future clinical trials of GLP-1 RAs in nondiabetic individuals. The focus of the review is on GLP-1 RAs' preventive roles in nondiabetic individuals with cardiovascular disease, chronic kidney diseases, obesity, dyslipidaemia, hypertension, nonalcoholic fatty liver diseases, polycystic ovarian syndrome (PCOS), and perioperative complications of bariatric surgery, albeit in small studies and subset analysis of clinical trials of diabetic patients.

Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway.

Ling Zhi-8 (LZ-8), an immunomodulatory protein, is derived from and has been cloned from the medicinal mushroom Ganoderma lucidum (Reishi or Ling Zhi); this protein exhibits immunomodulating and antitumor properties. We investigated the effects of recombinant LZ-8 protein (rLZ-8) on the proliferation of A549 human lung cancer cells. Here, we showed that rLZ-8 inhibits cell growth and that this is correlated with increased G(1) arrest. The treatment of A549 cells with rLZ-8 activated p53 and p21 expression, and both the G(1) arrest and the antigrowth effect were found to be p53 dependent. It was further demonstrated that rLZ-8 inhibited tumor growth in mice transplanted with Lewis lung carcinoma cells. Interestingly, rLZ-8 treatment was found to lead to nucleolar stress (or ribosomal stress) as evidenced by inhibition of precursor ribosomal RNA synthesis and reduced polysome formation in A549 cells. These changes resulted in an increasing binding of ribosomal protein S7 to MDM2 and a decreased interaction between MDM2 and p53. Taking these results together, we have identified a novel rLZ-8 antitumor function that positively modulates p53 via ribosomal stress and inhibits lung cancer cell growth in vitro and in vivo. Our current results suggest that rLZ-8 may have potential as a therapeutic intervention for the treatment of cancers that contain wild-type p53 and high expression of MDM2.

The effect of taking blood pressure lowering medication at night on cardiovascular disease risk. A systematic review.

To investigate the effect of night-time BP-lowering drug treatment on the risk of major CVD and mortality, we systematically reviewed randomized controlled trials comparing night-time versus morning dosing. Two studies were found relevant to the clinical question (the MAPEC and Hygia trials). They were similar in study design and population and were conducted by the same study group. As the Hygia trial had more power with a significantly larger sample size, we did not perform a meta-analysis. Both studies reported a reduction of ~50% in major CVD events and all-cause mortality with night-time dosing and a reduction of 60% in CVD mortality. The results from these studies support the implementation of night-time BP-lowering drug treatment in the prevention of CVD and mortality. However there is an on-going discussion on the validity and methodology of MAPEC and Hygia trials, the interpretation of the results should be cautious. Stronger evidence is needed prior to changing clinical practice. Questions that remain to be answered relate to the generalisability of the results across different populations at different levels of BP related risk and the importance of morning versus evening timing of medication on CVD prevention as determined though a well-designed randomised controlled trial.

Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively novel class of drug for treating type 2 diabetes mellitus (T2DM) that inhibits glucose reabsorption in the renal proximal tubule to promote glycosuria and reduce blood glucose levels. SGLT2i has been clinically indicated for treating T2DM, with numerous recent publications focussing on both primary and secondary prevention of cardiovascular and renal events in Type 2 diabetic patients. The most recent clinical trials showed that SGLT2i have moderately significant beneficial effects on atherosclerotic major adverse cardiovascular events (MACE) in patients with histories of atherosclerotic cardiovascular disease. In this review and analysis, SGLT2i have however demonstrated clinically significant benefits in reducing hospitalisation for heart failure and worsening of chronic kidney disease (CKD) irrespective of pre-existing atherosclerotic cardiovascular disease or previous heart failure history. A meta-analysis suggests that all SGLT2 inhibitors demonstrated the therapeutic benefit on all-cause and cardiovascular mortality, as shown in EMPAREG OUTCOME study with a significant decrease in myocardial infarction, without increased stroke risk. All the above clinical trial recruited type 2 diabetic patients. This article aims to postulate and review the possible primary prevention role of SGLT2i in healthy individuals by reviewing the current literature and provide a prospective overview. The emphasis will include primary prevention of Type 2 Diabetes, Heart Failure, CKD, Hypertension, Obesity and Dyslipidaemia in healthy individuals, whom are defined as healthy, low or intermediate risks patients.

Dermatophagoides pteronyssinus and Tyrophagus putrescentiae allergy in allergic rhinitis caused by cross-reactivity not dual-sensitization.

Tyrophagus putrescentiae and Dermatophagoides pteronyssinus are causative factors for the development of airway hypersensitivity. The main objective in this study was to identify the cross-reactive allergens between T. putrescentiae and D. pteronyssinus and investigate their sensitization in patients with allergic rhinitis. The prevalence of sensitization to mites was determined by skin prick tests and histamine release assays. Both immunoblot and ELISA inhibition assays were performed by using the recombinant allergens of T. putrescentiae and D. pteronyssinus. The cross-reactive allergens were identified by using IgE-binding inhibition analysis. The correlations of specific IgE between T. putrescentiae and D. pteronyssinus to group 2 and group 3 mite allergens were compared. A total of 117 allergic rhinitis patients, aged between 16 and 40 years old were recruited to be included in this study. The results showed that 70% (82/117) of allergic rhinitis subjects had skin test positive reactions to D. pteronyssinus or T. putrescentiae. Among these mite-sensitive subjects, there were 81 subjects (81/82) sensitive to D. pteronyssinus and 34 subjects (34/82) sensitive to T. putrescentiae. Among the T. putrescentiae hypersensitive subjects, 97% (33/34) were also sensitized to D. pteronyssinus. In the IgE-binding inhibition analysis, 59% (13/22) subjects had IgE-binding activity of T. putrescentiae that was completely absorbed by D. pteronyssinus, especially components with MW at 16 kDa. In ELISA inhibition testing, 69% of IgE-binding was inhibited by rTyr p 2, and 45% inhibited by rTyr p 3. The titers of IgE antibodies to rTyr p 2 and rDer p 2 were well correlated, but not rTyr p 3 and rDer p 3. In conclusion, most T. putrescentiae sensitized subjects were also sensitized to D. pteronyssinus in young adult allergic rhinitis patients. The complete absorption of IgE binding activity by D. pteronyssinus indicates that T. putrescentiae hypersensitivity might be due to the cross-reactivity, not dual-sensitization of D. pteronyssinus and T. putrescentiae. The IgE-binding titers of group 2 allergens were well correlated and the binding activity of Tyr p 2 could be absorbed by Der p 2, suggesting that group 2 allergens are the major cross-reactive allergen of D. pteronyssinus and T. putrescentiae.

Prevalence of Tyrophagus putrescentiae hypersensitivity in subjects over 70 years of age in a veterans' nursing home in Taiwan.

BACKGROUND: Domestic mites are present in house dust samples throughout the world. Reports have shown a high prevalence of Tyrophagus putrescentiae (Tp) sensitization in Europe and Asia, and its importance and clinical relevance in elderly subjects have grown rapidly. The main objective of this study was to investigate the prevalence of Tp sensitization in elderly subjects in a veterans' nursing home using mite allergen extracts and recombinant allergens. METHODS: A total of 199 subjects were enrolled in this study: 112 elderly subjects from a nursing home and 87 healthy young adults from the hospital staff as controls. The prevalence of Tp hypersensitivity was determined by specific IgE measurements and basophil histamine release. Immunoblotting with or without inhibition with Dermatophagoides pteronyssinus (Dp) was performed to identify the major allergens and species-specific allergen to Tp. RESULTS: It was determined that 39.3% (44/112) of the elderly population were sensitized to Tp and 17.9% (20/112) to Tp alone. There was a significantly higher prevalence of Tp hypersensitivity in elderly subjects in comparison with the young adult population. In the age association study of Tp and Dp sensitization, the elderly subjects were more sensitized to Tp than to Dp (p = 0.02). Among the elderly subjects with chronic obstructive pulmonary disease (COPD) 45.8% (11/24) were Tp sensitive. The major allergens, Tyr p 2 and Tyr p 3, were identified with molecular weights of 16 kDa (53%) and 26 kDa (50%) as determined by ELISA and immunoblot inhibition analyses. CONCLUSION: The prevalence of Tp sensitization was higher in elderly subjects, especially in patients with COPD. The high percentage of IgE-binding components to the allergens Tyr p 2 and Tyr p 3 indicated that both allergens may play a role in the pathogenesis of IgE-mediated allergic diseases in elderly populations.

Legacy effect of delayed blood pressure lowering drug treatment in middle-aged adults with mildly elevated blood pressure: systematic review and meta-analysis.

To investigate if there is evidence for a 'legacy effect' for blood pressure (BP) lowering treatment, that is, worse health outcomes from not initiating drug treatment at a systolic BP threshold of 140 mmHg in middle-age adults. We systematically reviewed studies comparing the effects of delayed BP treatment (placebo/untreated during the trial or no previous treatment at trial entry) vs. early treatment (actively treated during the trial or previous BP treatment at trial entry) on mortality in the short term (5-year in-trial period) and long term (≥10 years in total period). The data were pooled using Peto ORs. A subgroup analysis by 10-year Framingham risk score was performed. Three studies (ALLHAT, Oslo and PREVEND-IT) involving 4746 participants were included. The results were heavily influenced by the ALLHAT trial. We found no significant difference in all-cause mortality between 'delayed BP' and 'early treatment' in the short-term OR 0.95 (95% CI 0.68-1.32) or long-term OR 0.90 (95% CI 0.78-1.04), with similar results for mortality from cardiovascular disease (CVD). The effects of delayed BP lowering treatment on long-term all-cause and CVD mortality did not vary with baseline risk of CVD. The review showed no clinically adverse 'legacy effect' on mortality or major CVD event from not treating middle-aged adults at a systolic BP threshold of 140 mmHg or over. The results were consistent for all CVD risk subgroups. Although these studies are non-randomised post-hoc analyses, they may allay concerns that early treatment of elevated systolic BP is necessary to prevent CVD events in primary prevention populations.

Lack of a significant legacy effect of baseline blood pressure 'treatment naivety' on all-cause and cardiovascular mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

OBJECTIVES: To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in 'treatment-naive' or 'previous treatment' groups based on blood pressure (BP)-lowering treatment status at baseline. METHODS: A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed. RESULTS: In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80-1.09) and hazard ratio 0.95 (0.88-1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72-1.23) and hazard ratio 0.93 (0.80-1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups. CONCLUSION: Physicians are concerned about 'legacy effects' of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP 'treatment naivety' was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution.

Immunologic characterization and allergenicity of recombinant Tyr p 3 allergen from the storage mite Tyrophagus putrescentiae.

BACKGROUND: The involvement of the storage mite Tyrophagus putrescentiae in allergies has been increasingly reported in many countries. Molecular analysis has shown that group 3 mite allergens are homologous to trypsin. Similar allergens have not been identified in T. putrescentiae. Our aims were to characterize group 3 allergens in T. putrescentiae and to investigate their significance in allergenicity. METHODS: cDNAs of PreTyr p 3 and rTyr p 3 from T. putrescentiae were cloned and expressed in Escherichia coli. Native Tyr p 3 (nTyr p 3) was purified from spent growth medium with an affinity column coupling of antibody. Biological activities of rTyr p 3 were compared with nTyr p 3 in terms of IgE activity, enzymatic activity and histamine release. RESULTS: Full-length cDNA of PreTyr p 3 encodes a 285-amino acid trypsin-like protease and acquires enzymatic activity after removing the pre- and pro-sequences. rTyr p 3 is a 26-kDa protein with equivalent IgE reactivity but weaker enzymatic activity than that of nTyr p 3. A limited level of cross-reactivity has been found between rTyr p 3, Der p 3 and Blomia. Eight of 10 T. putrescentiae-sensitized individuals showed >50% histamine release after triggering with rTyr p 3. CONCLUSIONS: Our studies demonstrate that Tyr p 3 is a frequent allergen (58%) in T. putrescentiae-sensitized patients. Since rTyr p 3 displays equivalent biological activities as nTyr p 3, the role of group 3 allergens can be studied using rTyr p 3 to elucidate the pathogenic effects and diagnostic applications of Tyr p 3.

Toxic chemical releases, health effects, and productivity losses in the United States.

In this paper we examine the impacts of toxic chemical releases on labor productivity. The hypothesis is that exposure to releases results in chronic or acute illnesses, which increases number of work days lost. To test the hypothesis we combine data from the National Health Interview Survey with data from US Environmental Protection Agency's Toxic Release Inventory, using an instrumental variable approach to control for endogeneity of subjective binary health status. We find that the survey respondents are significantly more likely to have increased work days lost as their exposure to toxic releases increases and that work days lost increase at an increasing rate with diminished health status.

Short- and long-term association of lipid-lowering drug treatment and cardiovascular disease by estimated absolute risk in the Second Australian National Blood Pressure study.

BACKGROUND: There is currently insufficient evidence to support the use of lipid-lowering drug treatment (LLT) for primary prevention of cardiovascular disease (CVD) in the elderly. OBJECTIVES: We examined the relationship of early initiation of LLT with short- and long-term all-cause and CVD mortality in persons older than 65 years in this post hoc study from the Second Australian National Blood Pressure study (ANBP2). METHODS: This was an in- and post-trial observational study. About 4257 hypertensive participants aged 65 to 84 years within Australian family practices were randomized to an angiotensin-converting enzyme inhibitor or a diuretic treatment group. After excluding participants with a prior history of CVD, the cohort was stratified into "LLT" and "no LLT" subgroups based on LLT status at randomization. RESULTS: At randomization, the participants had a mean age of 72 years, average blood pressure of 168/91 mm Hg and estimated 5-year CVD risk of 18.7 ± 8.3%. In the overall study population, the association of LLT with long-term (11-years) all-cause and non-CVD mortality was significant (hazard ratio [HR] 0.78 [95% confidence interval {CI} 0.66-0.92, P = .003] and HR 0.70 [95% CI 0.54-0.90, P = .006], respectively). Magnitudes of the association of LLT with long-term mortality and the association with short-term mortality were similar; however, no statistically significant association with short-term mortality was observed. In the subgroup analysis by baseline 5-year CVD risk, LLT participants in the highest risk tertile had a substantially lower relative risk for short-term all-cause mortality (HR 0.31, 95% CI 0.13-0.71, P for interaction .02) compared to those with lower estimated CVD risk. All analyses were adjusted for baseline and in-trial characteristics. CONCLUSION: Our study showed a strong association between LLT and reduced long-term all-cause mortality. Thus, our findings support recommendations of the use of LLT in patients over 65 years, particularly those with high CVD risk who were more likely to obtain additional benefits in the short term. The findings also suggested that mortality benefits of LLT for the elderly may take longer to become evident.