Characteristics of patients with lung cancer in clinical practice and their potential eligibility for clinical trials evaluating tyrosine kinase inhibitors or immune checkpoint inhibitors

IntroductionIn- and exclusion criteria of randomized clinical trials (RCTs) aim to include a homogeneous study-population. This study compared characteristics of lung cancer patients from phase III RCTs evaluating tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) with characteristics of lung cancer patients in a real world setting in the United Kingdom.MethodsA retrospective study was conducted using the Clinical Practice Research Datalink GOLD. Patients (N = 9239) with a first ever lung cancer registration between 2014 and 2018 were identified. Eligibility for inclusion was assessed for twelve RCTs (evaluating TKIs or ICIs). Reasons for potential exclusion and the number of unmet criteria were assessed for each RCT independently. OS was assessed using Kaplan-Meier and Cox proportional hazards analyses.ResultsThe proportion of potentially eligible patients was 74.3% and 51.9% for TKI and ICI RCTs, respectively. History of another malignancy, renal insufficiency or concomitant drug-use were main reasons for exclusion. OS was considerably longer for potentially eligible patients. Hazards ratios varied from 1.17 (95% confidence interval, 1.11–1.24) to 1.35 (1.20–1.42) across the RCTs.ConclusionThis study showed that a considerable proportion of lung cancer patients in a real-world setting would have been ineligible for participation in phase III RCTs and that potentially ineligible patients experienced a shorter OS.     

Continuous Subcutaneous Infusion of Insulin Lispro in Children and Adolescents with Type 1 Diabetes Mellitus

ObjectiveTo provide a comprehensive review of insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in children and adolescents.MethodsWe performed PubMed literature searches to identify clinical studies of insulin lispro administered via CSII within pediatric and adolescent populations.ResultsTwenty-six studies involving 2521 pediatric patients with type 1 diabetes mellitus met inclusion criteria. Of these, 10 were randomized controlled trials (RCTs), 6 of which compared insulin lispro CSII with multiple daily injection (MDI) therapy. We identified 7 additional prospective, nonrandomized studies and 9 retrospective studies. Within the RCTs, endpoint hemoglobin A_1c levels ranged from 6.3% to 8.5% for insulin lispro CSII therapy and from 6.2% to 8.7% for those trials with MDI comparator arms. In those trials that compared insulin lispro CSII with MDI, the endpoint hemoglobin A_1c achieved with insulin lispro was similar or improved compared with observations in the MDI treatment arm. In the RCTs, severe hypoglycemia rates of 0.1 to 0.3 episodes/patient per year were reported for insulin lispro CSII therapy; those trials with MDI comparator arms reported relatively similar severe hypoglycemia rates (0.1 to 0.5 episodes/patient per year). Events of diabetic ketoacidosis (DKA) were rare. Where reported, insulin lispro CSII and MDI therapy demonstrated a similar occurrence of DKA and incidence of severe hypoglycemia. Prospective and retrospective studies demonstrated results similar to the RCT findings.ConclusionsIn 26 studies of more than 2500 pediatric and adolescent patients with type 1 diabetes, with more than 1000 patients specifically receiving insulin lispro CSII, insulin lispro CSII therapy consistently demonstrated similar or improved efficacy and safety vs studied comparators. (Endocr Pract. 2012;18:418-424)     

Systemic redox imbalance in stable chronic obstructive pulmonary disease

Context: Increased oxidative burden is found in chronic obstructive pulmonary disease (COPD).

Objective: To assess the association of ceruloplasmin, albumin, bilirubin, transferrin, thiols and malondialdehyde (MDA) with stable COPD.

Materials and methods: Oxidative stress markers measured in 106 COPD patients and 45 healthy subjects were evaluated.

Results: Higher ceruloplasmin and MDA, and lower albumin, transferrin and thiols in COPD patients were found. Ceruloplasmin was the strongest single predictor of COPD. The model combining ceruloplasmin, albumin and thiols improved their individual diagnostic performances.

Conclusions: Diagnostic characteristics of ceruloplasmin, albumin, transferrin, thiols and MDA suggest their potential value as additional tools in disease diagnosis.     

Blood and sputum protein biomarkers for chronic obstructive pulmonary disease (COPD)

ABSTRACT

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous set of disorders, characterized by airflow limitation, and reduced lung function. Despite increasing knowledge regarding its pathophysiology, there has been limited advancement in therapeutics and the current treatment strategy is symptom management and prevention of exacerbations.

Areas covered: Biomarkers represent important tools for the implementation of precision medicine. As fundamental molecules of all living processes, proteins could provide crucial information about how genes interact with the environment. Proteomics studies could act as important tools in identifying reliable biomarkers to enable a more precise therapeutic approach. In this review, we will explore the most promising blood and sputum protein biomarkers in COPD that have been consistently reported in the literature.

Expert commentary: Given the complexity of COPD, no single protein biomarker has been able to improve the outcomes of COPD patients. According to preliminary studies, precision medicine in COPD will likely require a combination of different proteins in a biomarker panel for clinical translation. With advancements in current mass spectrometry techniques, an enhancement in the identification of new biomarkers will be observed, and improvements in sequence database search can fill in potential gaps between biomarker discovery and patient care.     

Prevalence of Subthreshold Hypomania and Impact on Internal Validity of RCTs for Major Depressive Disorder: Results from a National Epidemiological Sample

Background

Growing evidence supports the validity of distinguishing major depressive disorder (MDD) plus a lifetime history of subthreshold hypomania (D(m)) from pure MDD in psychiatric classifications. The present study sought to estimate the proportion of individuals with D(m) that would have been included in RCTs for MDD using typical eligibility criteria, and examine the potential impact of including these participants on internal validity.

Methods

Data were derived from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a national representative sample of 43,093 adults of the United States population. We examined the proportion of participants with a current diagnosis of pure MDD and D(m) that would have been eligible in clinical trials for MDD with a traditional set of eligibility criteria, and compared it with that of participants with bipolar 2 disorder if the same set of eligibility criteria was applied. We considered 4 models including different definitions of subthreshold hypomania.

Results

We found that more than 7 out of ten participants with pure MDD and with D(m) would have been excluded by at least one classical eligibility criterion. Prevalence rate of individuals with D(m) in RCTs for MDD with traditional eligibility criteria would have ranged from 7.98% to 22.59%. Overall exclusion rate of individuals with MDD plus at least 4 lifetime concomitant hypomanic probes significantly differ from those with pure MDD, whereas it was not significantly different in those with at least 2 lifetime concomitant hypomanic probes compared to those with bipolar 2 disorder.

Conclusions

The current design of clinical trials for MDD may suffer from impaired external validity and potential impaired internal validity, due to the inclusion of a substantial proportion of individuals with subthreshold hypomania presenting with similar pattern of exclusion rates to those with bipolar 2 disorder, possibly resulting in a selection bias.     

Genetic polymorphism of matrix metalloproteinase 9 and susceptibility to chronic obstructive pulmonary disease: A meta-analysis

BackgroundTo systematically analyze the influence of genetic polymorphisms of matrix metalloproteinase 9 (MMP9) on susceptibility to chronic obstructive pulmonary disease (COPD).MethodsRelevant literatures reporting MMP9 and susceptibility to COPD in PubMed, Web of Science, VIP, Wanfang and CNKI databases were searched using the key words "matrix metalloproteinases 9/MMP9, COPD/chronic obstructive pulmonary disease". Data of eligible literatures were extracted and analyzed for the odds ratio (OR) and corresponding 95% CI.ResultsA total of 16 independent studies reporting MMP9-1562C/T and COPD patients were enrolled and analyzed. None of the genetic models revealed the relationship between MMP9-1562C/T and susceptibility to COPD. Subgroup analyses identified lower risk of COPD in Chinese population carrying the TT genotype for theMMP9 rs3918242 relative to those carrying CT and CC genotypes (P=0.03, OR=0.67, 95% CI=0.46-0.97).ConclusionsChinese population carrying the TT genotype for the MMP-9 rs3918242 present lower susceptibility to COPD relative to those carrying CT and CC genotypes.     

Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials

Background

Recruitment of sufficient participants in an efficient manner is still widely acknowledged to be a major challenge to the mounting and completion of randomised controlled trials (RCTs). Few recruitment interventions have involved staff undertaking recruitment. This study aimed i) to understand the recruitment process from the perspective of recruiters actively recruiting RCT participants in six pragmatic RCTs, and ii) to identify opportunities for interventions to improve recruitment.

Methods

Interviews were undertaken with 72 individuals (32 doctors or RCT Chief investigators (CIs); 40 nurses/other health professionals) who were actively recruiting participants in six RCTs to explore their experiences of recruitment. The RCTs varied in scale, duration, and clinical contexts. Interviews were fully transcribed and analysed using qualitative content and thematic analytic methods derived from grounded theory. For this analysis, data were systematically extracted from each RCT and synthesised across all six RCTs to produce a detailed and nuanced understanding of the recruitment process from the perspectives of the recruiters.

Results

Recruiters readily identified organisational difficulties, fewer than expected eligible patients, and patients’ treatment preferences as the key barriers to recruitment. As they described their experiences of recruitment, several previously hidden issues related to their roles as researchers and clinicians emerged, imbued with discomfort and emotion. The synthesis across the RCTs showed that doctors were uncomfortable about aspects of patient eligibility and the effectiveness of interventions, whereas nurses were anxious about approaching potential RCT participants and conflicts between the research and their clinical responsibilities. Recruiters seemed unaware that their views contributed to recruitment difficulties. Their views were not known to RCT CIs. Training and support needs were identified for both groups of staff.

Conclusions

The synthesis showed that recruitment to these RCTs was a complex and fragile process. Clear obstacles were identified but hidden challenges related to recruiters’ roles undermined recruitment, unbeknown to RCT CIs. Qualitative research can elicit and identify the hidden challenges. Training and support are then needed for recruiters to become more comfortable with the design and principles of RCTs, so that they can engage more openly with potentially eligible participants and create a more resilient recruitment process.     

Comparison of Clinical Efficacy and Safety between Indacaterol and Tiotropium in COPD: Meta-Analysis of Randomized Controlled Trials

Two once-daily inhaled bronchodilators, indacaterol and tiotropium, are widely used as first-line therapy in stable COPD patients. This study was performed to compare the clinical efficacy and safety between indacaterol and tiotropium in patients with moderate-to-severe COPD. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to identify all published randomized controlled trials (RCTs). The primary outcome was trough forced expiratory volume in 1 second (FEV₁) at week 12. Four RCTs were eligible for inclusion (three RCTs with moderate-to-severe COPD patients and one RCT with only severe COPD patients). Trough FEV₁ at weeks 12 and 26 were not significantly different between indacaterol and tiotropium by the standardized mean difference with 0.014 (95% CI, -0.036, 0.063, I²= 23.5%) and with 0.037 (95% CI, -0.059 to 0.133, I²= 0%) along with differences in means of 0.003L and 0.014L, respectively. Indacaterol and tiotropium also showed similar St. George`s Respiratory Questionnaire (SGRQ) total scores and percentages of patients with SGRQ improvement (≥ 4 units) at week 26. The incidences of nasopharyngitis, serious cardiovascular events, and serious adverse events were not different between indacaterol and tiotropium, while those of cough (OR = 1.68, P < 0.001, and RR = 1.63) and COPD worsening (OR = 1.18, P = 0.003, and RR = 1.12) were higher for indacaterol than tiotropium. However, when one study with only severe COPD patients was removed from the meta-analysis, the difference in the incidence of COPD worsening between indacaterol and tiotropium became non-significant (OR = 1.13, P = 0.204, and RR = 1.09). The clinical efficacy and serious adverse events between indacaterol and tiotropium were equivocal in patients with moderate-to-severe COPD. Cough is a common complaint associated with indacaterol, and COPD worsening needs to be carefully monitored in severe COPD patients when treated with indacaterol.     

Metformin increases cancer specific survival in colorectal cancer patients—National cohort study

PurposeWe aimed to assess oncological outcomes in colorectal cancer patients with type 2 diabetes mellitus (T2DM) using metformin.MethodsPatients with colorectal cancer and T2DM during 2000–2012 period were identified form Lithuanian Cancer Registry and the National Health Insurance Fund database. Colorectal cancer-specific survival (CS) was the primary outcome. It was measured from date of colorectal cancer diagnosis to date of death due to colorectal cancer, or last known date alive.Results15,052 people who met eligibility criteria for this analysis, including 1094 (7.27%) with pre-existing type 2 diabetes (271 metformin never users and 823 metformin users) and 13 958 people without diabetes assessed. During follow-up (mean follow-up time was 4.4 years, with range from 1 day to 17 years) there were 10,927 deaths including 8559 from colorectal cancer. Significantly lower risk in CS between diabetic and non-diabetic people with lower risk of cancer-specific mortality (HR 0.87, 95% CI 0.80–0.94) in diabetic patient population was seen. After adjustment for age, stage at diagnosis and metformin usage, significant difference in colorectal CS between metformin users in diabetic patient population compared to non-diabetics and metformin non-users in diabetic patient population was found (0.80 (0.72–0.89) vs 1.00 and vs 1.05 (0.91–1.23)). Overall survival (OS) was better for diabetic patients with significant difference in diabetic metformin users (HR 0.91, 95% CI 0.79–0.94).ConclusionsColorectal cancer patients with T2DM treated with metformin as part of their diabetic therapy appear to have a superior OS and CS. However, prospective controlled studies are still needed to evaluate the efficacy of metformin as an anti-tumor agent.     

Centre Selection for Clinical Trials and the Generalisability of Results: A Mixed Methods Study

Background

The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice.

Methods and Findings

Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists’ views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively.

Conclusions

Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize ‘generalisability’ and incorporate it at the design stage of RCTs so that results are readily transferable to ‘real world’ practice.     

Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential biomarkers for chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs).

Objective: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD.

Methods: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control).

Results: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p?p?p?p?Conclusions: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.     

Multifactorial day hospital intervention to reduce falls in high risk older people in primary care: a multi-centre randomised controlled trial [ISRCTN46584556]

Background

There are many barriers to patient participation in randomised controlled trials of cancer treatments. To increase participation in trials, strategies need to be identified to overcome these barriers. Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in randomised controlled trials (RCTs) of cancer treatments.

Methods

A systematic review was conducted. Published and unpublished studies in any language were searched for in fifteen electronic databases, including MEDLINE, EMBASE, CINAHL and PsycINFO, from inception to the end of 2004. Studies of any interventions to improve cancer patient participation in RCTs, which reported the change in recruitment rates, were eligible for inclusion. RCTs and non-randomised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included. Data were extracted by one reviewer into structured summary tables and checked for accuracy by a second reviewer. Each included study was assessed against a checklist for methodological quality by one reviewer and checked by a second reviewer. A narrative synthesis was conducted.

Results

Eight studies were identified that met the inclusion criteria: three RCTs, two non-randomised controlled trials and three observational studies. Six of the studies had an intervention that had some relevance to the UK. There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs, though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer. Although there was no evidence of an effect in any of the studies, the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work.

Conclusion

There is not a strong evidence-base for interventions that increase cancer patient participation in randomised trials. Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials.     

Familial early puberty: presentation and inheritance pattern in 139 families

Background

To describe common type 2 diabetes treatment intensification regimens, patients’ characteristics and changes in glycated hemoglobin (HbA1c) and body mass index (BMI).

Methods

We constructed a national retrospective cohort of veterans initially treated for diabetes with either metformin or sulfonylurea from 2001 through 2008, using Veterans Health Administration (VHA) and Medicare data. Patients were followed through September, 2011 to identify common diabetes treatment intensification regimens. We evaluated changes in HbA1c and BMI post-intensification for metformin-based regimens.

Results

We identified 323,857 veterans who initiated diabetes treatment. Of these, 55 % initiated metformin, 43 % sulfonylurea and 2 % other regimens. Fifty percent (N = 89,057) of metformin initiators remained on metformin monotherapy over a median follow-up 58 months (interquartile range [IQR] 35, 74). Among 80,725 patients who intensified metformin monotherapy, the four most common regimens were addition of sulfonylurea (79 %), thiazolidinedione [TZD] (6 %), or insulin (8 %), and switch to insulin monotherapy (2 %). Across these regimens, median HbA1c values declined from a range of 7.0–7.8 % (53–62 mmol/mol) at intensification to 6.6–7.0 % (49–53 mmol/mol) at 1 year, and remained stable up to 3 years afterwards. Median BMI ranged between 30.5 and 32 kg/m² at intensification and increased very modestly in those who intensified with oral regimens, but 1–2 kg/m² over 3 years among those who intensified with insulin-based regimens.

Conclusions

By 1 year post-intensification of metformin monotherapy, HbA1c declined in all four common intensification regimens, and remained close to 7 % in subsequent follow-up. BMI increased substantially for those on insulin-based regimens.

     

The effect of CYP3A4 genetic variants on the susceptibility to chronic obstructive pulmonary disease in the Hainan Han population

PurposeGenetic polymorphisms act a crucial role in chronic obstructive pulmonary disease (COPD) progression. This study aimed to investigate the correlation between CYP3A4 variants and COPD risk.MethodsWe carried out a case-control study of 821 individuals (313 patients and 508 healthy subjects) to identify the correlation of CYP3A4 SNPs with COPD risk in the Hainan Han population. The association was evaluated by Odds ratios (OR) and 95% confidence intervals (CI).ResultsOur study showed that rs4646437 polymorphism was related to a significantly increased susceptibility to COPD (OR 1.45, 95% CI = 1.10–1.90, p = 0.008). Stratified analyses indicated that rs4646437 polymorphism was significantly related to an increased risk of COPD in males (OR 1.95, 95% CI = 1.19–3.20, p = 0.008). However, rs4646440 played a protective role in females (OR 0.54, 95% CI = 0.31–0.93, p = 0.024). Rs4646437 was found to significantly improve the risk of COPD in smokers (OR 1.67, 95% CI = 1.12–2.48, p = 0.011). While rs4646440 had a significantly lower susceptibility to COPD in non-smokers (OR 0.64, 95% CI = 0.45–0.90, p = 0.010). Haplotype analysis revealed that A_rs4646440T_rs35564277 haplotype of CYP3A4 was found to increase the risk of COPD in non-smokers (OR 1.71, 95% CI = 1.04–2.82, p = 0.034).ConclusionOur result gives a new understanding of the association between CYP3A4 gene and COPD in the Hainan Han population.     

The efficacy of pharmacotherapy for decreasing the expansion rate of abdominal aortic aneurysms: a systematic review and meta-analysis

Background

Pharmacotherapy may represent a potential means to limit the expansion rate of abdominal aortic aneurysms (AAAs). Studies evaluating the efficacy of different pharmacological agents to slow down human AAA-expansion rates have been performed, but they have never been systematically reviewed or summarized.

Methods and Findings

Two independent reviewers identified studies and selected randomized trials and prospective cohort studies comparing the growth rate of AAA in patients with pharmacotherapy vs. no pharmacotherapy. We extracted information on study interventions, baseline characteristics, methodological quality, and AAA growth rate differences (in mm/year). Fourteen prospective studies met eligibility criteria. Five cohort studies raised the possibility of benefit of beta-blockers [pooled growth rate difference: −0.62 mm/year, (95%CI, −1.00 to −0.24)], but this was not confirmed in three beta-blocker RCTs [pooled RCT growth rate difference: −0.05 mm/year (−0.16 to 0.05)]. Statins have been evaluated in two cohort studies that yield a pooled growth rate difference of −2.97 (−5.83 to −0.11). Doxycycline and roxithromycin have been evaluated in two RCTs that suggest possible benefit [pooled RCT growth rate difference: −1.32 mm/year (−2.89 to 0.25)]. Studies assessing NSAIDs, diuretics, calcium channel blockers and ACE inhibitors, meanwhile, did not find statistically significant differences.

Conclusions

Beta-blockers do not appear to significantly reduce the growth rate of AAAs. Statins and other anti-inflammatory agents appear to hold promise for decreasing the expansion rate of AAA, but need further evaluation before definitive recommendations can be made.     

Effect of arginine on microorganisms involved in dental caries: a systematic literature review of in vitro studies

Abstract

This systematic review aimed to discuss the effects of arginine on caries-related microorganisms in different in vitro biofilm models. The eligibility criteria were in vitro studies that evaluated the effect of arginine at different concentrations on caries-related microorganisms using biofilm models. Eighteen studies published between 2012 and 2019 were included. Different bacterial species were studied. Seventeen studies (94.4%) achieved a low risk of bias and only one showed a medium risk of bias. The studies showed that arginine is a promising approach for the ecological management of dental caries. The focus of this review was to evaluate the effects of arginine on microorganisms involved in the mechanism of dental caries.     

Use of Kampo Diagnosis in Randomized Controlled Trials of Kampo Products in Japan: A Systematic Review

Background

The Committee for Evidence-based Medicine (EBM) of the Japan Society for Oriental Medicine started compiling Evidence Reports of Kampo Treatment (EKAT) in 2007. EKAT is a compilation of structured abstracts of randomized controlled trials (RCTs), along with comments by a third party reviewer. As of 31 December, 2012, there were 378 RCTs of Kampo medicines in Japan. The primary research question of this study is “How frequently is Kampo diagnosis used in RCTs of Kampo medicines?” The secondary research question is “When is Kampo diagnosis used in RCTs?”

Materials and Methods

The structured abstract (SA) of each RCT article was reviewed to examine how Kampo diagnosis was used in RCTs, especially how Kampo diagnosis was used in the randomization process.

Results

Kampo diagnosis was used before randomization in 27 RCTs (7.1%), after randomization in 31 RCTs (8.2%), and not used in 320 RCTs (84.7%). Before randomization, Kampo diagnosis was used as a criterion for inclusion in 10 RCTs, criterion for exclusion in 9 RCTs, and criteria for both inclusion and exclusion in 2 RCTs. Kampo formulas were determined according to Kampo diagnosis in 7 RCTs. After randomization, subgroup analyses according to Kampo diagnosis were done in 27 RCTs, and grade of disease severity at Kampo diagnosis was used for analysis as an endpoint in 4 RCTs.

Conclusions

Kampo diagnosis was used before randomization only in approximately 15% of RCTs, and the number of RCT articles using Kampo diagnosis after randomization was almost the same as that before randomization. Further studies to determine the good RCTs conforming to CONSORT requirements and good systematic reviews conforming to PRISMA requirements are needed to clarify the significance of Kampo diagnosis.     

Epidemiology of Mental Health Attendances at Emergency Departments: Systematic Review and Meta-Analysis

BackgroundThe characteristics of Emergency Department (ED) attendances due to mental or behavioural health disorders need to be described to enable appropriate development of services. We aimed to describe the epidemiology of mental health-related ED attendances within health care systems free at the point of access, including clinical reason for presentation, previous service use, and patient sociodemographic characteristics.MethodSystematic review and meta-analysis of observational studies describing ED attendances by patients with common mental health conditions.Findings18 studies from seven countries met eligibility criteria. Patients attending due to mental or behavioural health disorders accounted for 4% of ED attendances; a third were due to self-harm or suicidal ideation. 58.1% of attendees had a history of psychiatric illness and up to 58% were admitted. The majority of studies were single site and of low quality so results must be interpreted cautiously.ConclusionsPrevalence studies of mental health-related ED attendances are required to enable the development of services to meet specific needs.     

Gastric dilatation and intestinal obstruction mimicking acute coronary syndrome with dynamic electrocardiographic changes

Background

Hyperuricemia may be associated with an increased risk of coronary heart disease (CHD) mortality; however, the results from prospective studies are conflicting. The objective of this study was to assess the association between hyperuricemia and risk of CHD mortality by performing a meta-analysis.

Methods

Pubmed and Embase were searched for relevant prospective cohort studies published until July 2015. Studies were included only if they reported data on CHD mortality related to hyperuricemia in a general population. The pooled adjusted relative risk (RR) was calculated using a random-effects model.

Results

A total of 14 studies involving 341 389 adults were identified. Hyperuricemia was associated with an increased risk of CHD mortality (RR: 1.14; 95 % CI: 1.06–1.23) and all-cause mortality (RR: 1.20; 95 % CI: 1.13–1.28). For each increase of 1 mg/dl of serum uric acid (SUA), the overall risks of CHD and all-cause mortality increased by 20 and 9 %, respectively. According to the gender subgroup analyses, hyperuricemia increased the risk of CHD mortality in women (RR: 1.47; 95 % CI: 1.21–1.73) compared to men (RR: 1.10; 95 % CI: 1.00–1.19). The risk of all-cause mortality was greater in women.

Conclusions

Hyperuricemia may modestly increase the risk of CHD and all-cause mortality. Future research is needed to determine whether urate–lowering therapy has beneficial effects for reducing CHD mortality.