Polymorphism of Apolipoproteine E in Relation with Alzheimer and Vascular Dementia

Summary 1. The epsilon 4 allele of the apolipoprotein E gene increases the risk of late onset familial and sporadic Alzheimer disease. Relation of epsilon 4 allele of the apolipoprotein E gene to various types of dementia and the onset of dementia were analyzed in the present study.2. The study comprised 139 patients (50 men and 89 women) with dementia, mean age 73.61 years (range 47–98). The diagnosis of dementia was made according to Diagnostic and Statistical Manual of Mental Disorders, and subtypes diagnoses were made according to NINCDS-ADRDA and NINDS-AIREN criteria. Minimental State Examination (MMSE) was used for the screening of dementia. Apolipoprotein E polymorphism was determined by the PCR-RFLP technique-polymerase chain reaction and subsequent digestion with specific restriction endonuclease. For statistical analyses chi-square test and the crude Gart′s odds ratio (OR) and 95% confidence intervals (CI) were used.3. From 139 dementia patients (MMSE ≤24 points) in 61 (45%) Alzheimer disease (AD) was present, in 44 patients (31%) vascular dementia (VD), and in 34 (24%) mixed dementia (MD) were revealed. In comparison with control group the presence of at least one ApoE-ɛ4 allele was significantly higher only in the group with AD (p < 0.001), (OR=2.76; 95%: 1.42–5.36). The frequency of ɛ4 allele carriers was significantly overrepresented in AD group compared with VD (χ²=5.94; p=0.0148). Differences between AD and MD or VD and MD were not confirmed.     

Sleep Apnea and the Risk of Dementia: A Population-Based 5-Year Follow-Up Study in Taiwan

Background

Sleep apnea (SA) has been associated with cognitive impairment. However, no data regarding the risk of dementia in patients with SA has been reported in the general population. This retrospective matched-control cohort study was designed to estimate and compare the risk of dementia in SA and non-SA patients among persons aged 40 and above over a 5-year period follow-up.

Methods

We conducted a nationwide 5-year population-based study using data retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan. The study cohort comprised 1414 patients with SA aged 40 years who had at least 1 inpatient service claim or 1 ambulatory care claim. The comparison cohort comprised 7070 randomly selected patients who were matched with the study group according to sex, age, and index year. We performed Cox proportional-hazards regressions to compute the 5-year dementia-free survival rates after adjusting for potentially confounding factors.

Results

The SA patients in this study had a 1.70-times greater risk of developing dementia within 5 years of diagnosis compared to non-SA age- and sex-matched patients, after adjusting for other risk factors (95% confidence interval (CI) = 1.26-2.31; P < .01). For the gender-dependent effect, only females with SA were more likely to develop dementia (adjust HR: 2.38, 95% CI =1.51–3.74; P < .001). For the age-dependent effect of different genders, males with SA aged 50-59 years had a 6.08 times greater risk for developing dementia (95% CI = 1.96-18.90), and females with SA aged ≥ 70 years had a 3.20 times greater risk of developing dementia (95% CI =1.71–6.00). For the time-dependent effect, dementia may be most likely to occur in the first 2.5 years of follow-up (adjusted HR:2.04, 95% CI =1.35-3.07).

Conclusions

SA may be a gender-dependent, age-dependent, and time-dependent risk factor for dementia.     

The Effects of Anti-Dementia and Nootropic Treatments on the Mortality of Patients with Dementia: A Population-Based Cohort Study in Taiwan

Background

Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study.

Objective

To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study.

Methods

12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated.

Results

The median survival time was 3.39 years (95% confidence interval [CI]: 2.88–3.79) for VaD without medication, 6.62 years (95% CI: 6.24–7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85–3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30–8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73–6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02–9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55–2.83) without medication, 1.46 (95% CI: 1.39–1.54) with nootropics, 1.05 (95% CI: 0.82–1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80–1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15–1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22–2.72).

Conclusion

Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.     

The psychometric properties of the Dutch version of the Telephone Interview Cognitive Status (TICS)

The Telephone Interview Cognitive Status (TICS) is an instrument to screen for dementia in older persons by telephone. Although the psychometric properties of the TICS have been studied in various countries, the quality of the Dutch version of the TICS was yet unknown. This paper presents the Dutch version of the TICS and reports on its reliability and validity among 51 patients of Maastricht University Hospital, The Netherlands. The Pearson and intra-class correlations for test-retest reliability were 0.93 and 0.92, respectively. The Pearson and intra-class correlations for inter-rater reliability were 0.91 and 0.90, respectively. Sensitivity and specificity were studied in relation to the Mini Mental State Examination (MMSE, cut-off point 23/ 24) and the diagnosis of dementia as assessed according to DSM-IV criteria. When using the TICS cut-off point of 26/27, the coefficients for sensitivity and specificity were at least 0.80. The percentages ROC under the curve were 90% and 93% with the MMSE and the diagnosis dementia as criterion, respectively. We conclude that the Dutch version of the TICS is an acceptable instrument for screening for dementia in older persons, particularly when face-to-face contact is not possible.     

Diagnostic Value of Circulating Chromogranin A for Neuroendocrine Tumors: A Systematic Review and Meta-Analysis

Background

In previous decades, chromogranin A (CgA) has been demonstrated to be the most promising biomarker for the diagnosis of neuroendocrine tumors (NETs), but its diagnostic value is still controversial. This meta-analysis aimed to estimate the potential diagnostic value of circulating CgA for NETs.

Methods

We collected relevant studies from several electronic databases as well as from reference lists. Diagnostic indices of CgA were pooled with random effects models. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) curves for the diagnosis of NETs were used to estimate the overall diagnostic efficiency.

Results

Through a search strategy, 13 studies met the inclusion criteria and were included. These studies contained 1260 patients with NETs and 967 healthy controls in the total sample. As a result, the overall sensitivity, specificity and diagnostic odds ratio (DOR) were 0.73 (95% CI: 0.71 to 0.76), 0.95 (95% CI: 0.93 to 0.96) and 56.29 (95% CI: 25.27 to 125.38), respectively, while the summary positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 14.56 (95% CI: 6.62 to 32.02) and 0.26 (95% CI: 0.18 to 0.38), respectively. In addition, the area under the curve (AUC) of the circulating CgA in the diagnosis of NETs was 0.8962.

Conclusions

These data demonstrate that circulating CgA is an efficient biomarker for the diagnosis of NETs with high sensitivity and specificity, which indicates that it may be helpful for the clinical management of NETs. However, further studies are needed to clarify this issue.     

Current Practice in the Referral of Individuals with Suspected Dementia for Neuroimaging by General Practitioners in Ireland and Wales

Objectives

While early diagnosis of dementia is important, the question arises whether general practitioners (GPs) should engage in direct referrals. The current study investigated current referral practices for neuroimaging in dementia, access to imaging modalities and investigated related GP training in Ireland and North Wales.

Methods

A questionnaire was distributed to GPs in the programme regions which included approximately two thirds of all GPs in the Republic of Ireland and all general practitioners in North Wales. A total of 2,093 questionnaires were issued.

Results

48.6% of Irish respondents and 24.3% of Welsh respondents directly referred patients with suspected dementia for neuroimaging. Irish GPs reported greater direct access to neuroimaging than their Welsh counterparts. A very small percentage of Irish and Welsh GPs (4.7% and 10% respectively) had received training in neuroimaging and the majority who referred patients for neuroimaging were not aware of any dementia-specific protocols for referrals (93.1% and 95% respectively).

Conclusions

The benefits of direct GP access to neuroimaging investigations for dementia have yet to be established. Our findings suggest that current GP speciality training in Ireland and Wales is deficient in dementia-specific and neuroimaging training with the concern being that inadequate training will lead to inadequate referrals. Further training would complement guidelines and provide a greater understanding of the role and appropriateness of neuroimaging techniques in the diagnosis of dementia.     

Lack of Pupil Reflex and Loss of Consciousness Predict 30-Day Neurological Sequelae in Patients with Carbon Monoxide Poisoning

Background

Predicting the neurological sequelae of carbon monoxide poisoning (COP) has not been well studied. We investigated the independent predictors of neurological sequelae in patients with COP and combined these predictors to predict the prognosis.

Methods

This study was conducted at four hospitals in Shandong Province, China. Data were retrospectively collected from 258 patients with COP between November 1990 and October 2011. Thirty-day neurological sequelae were the primary endpoints.

Results

A lack of pupil reflex and a loss of consciousness appear to be independent predictors for neurological sequelae in patients with COP. The presence of either one had a sensitivity of 77.0% (95% confidence interval [CI]: 69.3–83.2), a specificity of 47.1% (95% CI: 38.3–56.0), positive predictive value (PPV) of 62.9% (95% CI: 55.2–70.1), and a negative predictive value (NPV) of 63.6% (95% CI: 52.6–73.4). With both predictors present, the sensitivity was 11.5% (95% CI: 6.9 to 18.3), the specificity was 99.2 (95% CI: 94.7–100.0), the PPV was 94.1% (95% CI: 69.2–99.7), and the NPV was 49.0% (95% CI: 42.5–55.5).

Conclusions

The risk for neurological sequelae apparently increased with the number of independent predictors. In patients with both predictors, the risk for neurological sequelae was 94.1%. Almost all (99.2%) patients with neither predictor had no neurological sequelae. This finding may help physicians make decisions about and dispositions for patients with COP. For patients with a higher risk, earlier treatment and more appropriate utilization of health care services, including hyperbaric oxygen, should be considered.     

The Value of BISAP Score for Predicting Mortality and Severity in Acute Pancreatitis: A Systematic Review and Meta-Analysis

Purpose

The Bedside Index for Severity in Acute Pancreatitis (BISAP) score has been developed to identify patients at high risk for mortality or severe disease early during the course of acute pancreatitis. We aimed to undertake a meta-analysis to quantify the accuracy of BISAP score for predicting mortality and severe acute pancreatitis (SAP).

Materials and Methods

We searched the databases of Pubmed, Embase, and the Cochrane Library to identify studies using the BISAP score to predict mortality or SAP. The pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were calculated from each study and were compared with the traditional scoring systems.

Results

Twelve cohorts from 10 studies were included. The overall sensitivity of a BISAP score of ≥3 for mortality was 56% (95% CI, 53%-60%), with a specificity of 91% (95% CI, 90%-91%). The positive and negative likelihood ratios were 5.65 (95% CI, 4.23-7.55) and 0.48 (95% CI, 0.41-0.56), respectively. Regarding the outcome of SAP, the pooled sensitivity was 51% (43%-60%), and the specificity was 91% (89%-92%). The pooled positive and negative likelihood ratios were 7.23 (4.21-12.42) and 0.56 (0.44-0.71), respectively. Compared with BISAP score, the Ranson criteria and APACHEⅡscore showed higher sensitivity and lower specificity for both outcomes.

Conclusions

The BISAP score was a reliable tool to identify AP patients at high risk for unfavorable outcomes. Compared with the Ranson criteria and APACHEⅡscore, BISAP score outperformed in specificity, but having a suboptimal sensitivity for mortality as well as SAP.     

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

Background

Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection.

Methods

We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I² statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity.

Results

In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00).

Conclusion

SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.     

Two factors that can increase the length of hospital stay of patients with dementia

ObjectivesPatients with dementia are at greater risk of a long hospital stay and this is associated with adverse outcomes. The aim of this service evaluation was to identify variables most predictive of increased length of hospital stay amongst patients with dementia.Methods/DesignWe conducted a retrospective analysis on a cross-sectional hospital dataset for the period January–December 2016. Excluding length of stay less than 24 h and readmissions, the sample comprised of 1133 patients who had a dementia diagnosis on record.ResultsThe highest incidence rate ratio for length of stay in the dementia sample was: (a) discharge to a care home (IRR: 2.443, 95% CI 1.778–3.357), (b) falls without harm (IRR: 2.486, 95% CI 2.029–3.045).ConclusionsBased on this dataset, we conclude that improvements made to falls prevention strategies in hospitals and discharge planning procedures can help to reduce the length of stay for patients with dementia.     

Bruikbaarheid en validiteit van de Nederlandse versie van de Montreal Cognitive Assessment (MoCA-D) bij het diagnosticeren van Mild Cognitive Impairment

Objective: The MoCA is a new screening test to detect Mild Cognitive Impairment (MCI). Purpose of this study is validating the Dutch version (MoCA-D). Method: We administered the MoCA-D to healthy control subjects and to elderly with MCI or dementia from a memory disorder outpatient clinic and a geriatric (outpatient) clinic (n=30, 32, 37 respectively, age≥60). Neuropsychological testing was part of the standard procedure for patients to diagnose MCI. Sensitivity, specificity and predictive values (positive: PPV and negative: NPV) of the MoCA-D were assessed. Results: A significant effect of group was found on MoCA-D total score (F(2,95)=67,9; p<0,01). With a cutoff score of d25, sensitivity and specificity to detect MCI in relation to healthy controls were 72% and 73%, respectively. PPV and NPV were 84% and 56%, respectively. With a cut-off score of d20, sensitivity to detect dementia in relation to MCI was 100% for severe dementia and 75% for mild dementia. Specificity for dementia was 81%, PPV 94% and NPV 55%. Conclusion: The MoCA-D distinguishes between healthy elderly, MCI patients and dementia patients. However, in this study, insufficient sensitivity and poor specificity were found. For the present, applying a broader and flexible screening procedure in order to detect MCI seems a more useful method than the interpretation of one test result in particular.     

Diagnostic Value of Mutation-Specific Antibodies for Immunohistochemical Detection of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis

Background

Various studies have assessed the diagnostic accuracy of EGFR mutation-specific antibodies in non-small cell lung cancer (NSCLC). We performed a meta-analysis of existing data to investigate the diagnostic value of mutation-specific antibodies for detection of EGFR mutations in NSCLC.

Methods

We systematically retrieved relevant studies from PubMed, Web of Knowledge, and Google Scholar. Data from studies that met the inclusion criteria were extracted for further exploration of heterogeneity, including calculation of the average sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and analysis of SROC(summary receiver operating characteristic) curves.

Results

Fifteen studies met our inclusion criteria. A summary of the meta-analysis of the efficacy of the anti-E746-A750 antibody was as follows: sensitivity, 0.60 (95% CI, 0.55–0.64); specificity, 0.98 (95% CI, 0.97–0.98); PLR, 33.50 (95% CI, 13.96–80.39); NLR, 0.39 (95% CI, 0.30–0.51) and DOR, 111.17 (95% CI, 62.22–198.63). A similar meta-analysis was performed for the anti-L858R antibody with results as follows: sensitivity, 0.76 (95% CI, 0.71–0.79); specificity, 0.96 (95% CI, 0.95–0.97); PLR, 24.42 (95% CI, 11.66–51.17); NLR, 0.22 (95% CI, 0.12–0.39) and DOR, 126.66 (95% CI, 54.60–293.82).

Conclusion

Immunohistochemistry alone is sufficient for the detection of EGFR mutations if the result is positive. Molecular-based analyses are necessary only if the anti-E746-A750 antibody results are negative. Immunohistochemistry seems more suitable for clinical screening for EGFR mutations prior to molecular-based analysis.     

Diagnostic value of the thin-layer, liquid-based Pap test in endometrial cancer: a retrospective study with emphasis on cytomorphologic features

OBJECTIVE: To examine the diagnostic value (sensitivity and specificity of the ThinPrep Pap test in the detection of endometrial cancer and assess the morphologic features of endometrial cancer in ThinPrep tests. STUDY DESIGN: In a retrospective, case-controlled study, we identified 60 Pap slides performed within 12 months of the tissue diagnosis of endometrial carcinoma and 56 comparison slides from patients without known carcinoma. The slides were blindly reviewed by the authors without knowledge of the surgical diagnosis. An independent diagnosis was given for the tests based on 14 diagnostic criteria from the 2001 Bethesda System and 6 additional criteria proposed by the authors. RESULTS: The sensitivity of detecting endometrial carcinoma was 88.3% (95% CI 77.8-94.2%) and specificity was 87.5% (95% CI 76.4-93.8%). The positive likelihood ratio was 7.067 (95% CI 3.513-14.217) and negative likelihood ratio was 0.133 (95% CI 0.066-0.269). Enlarged nuclei and the presence of nucleoli in endometrial cells were the most reliable indicators of endometrial cancer or atypical endometrial cells. CONCLUSION: The ThinPrep Pap test has high sensitivity and specificity in detecting or suggesting the presence of endometrial cancer. Certain cytomorphologic features are helpful in distinguishing benign and malignant endometrial lesions.     

A cluster-randomised trial of staff education to improve the quality of life of people with dementia living in residential care: the DIRECT study

Background

The Dementia In Residential care: EduCation intervention Trial (DIRECT) was conducted to determine if delivery of education designed to meet the perceived need of GPs and care staff improves the quality of life of participants with dementia living in residential care.

Methodology/Principal Findings

This cluster-randomised controlled trial was conducted in 39 residential aged care facilities in the metropolitan area of Perth, Western Australia. 351 care facility residents aged 65 years and older with Mini-Mental State Examination ≤24, their GPs and facility staff participated. Flexible education designed to meet the perceived needs of learners was delivered to GPs and care facility staff in intervention groups. The primary outcome of the study was self-rated quality of life of participants with dementia, measured using the QOL-Alzheimer''s Disease Scale (QOL-AD) at 4 weeks and 6 months after the conclusion of the intervention. Analysis accounted for the effect of clustering by using multi-level regression analysis. Education of GPs or care facility staff did not affect the primary outcome at either 4 weeks or 6 months. In a post hoc analysis excluding facilities in which fewer than 50% of staff attended an education session, self-rated QOL-AD scores were 6.14 points (adjusted 95%CI 1.14, 11.15) higher at four-week follow-up among residents in facilities randomly assigned to the education intervention.

Conclusion

The education intervention directed at care facilities or GPs did not improve the quality of life ratings of participants with dementia as a group. This may be explained by the poor adherence to the intervention programme, as participants with dementia living in facilities where staff participated at least minimally seemed to benefit.

Trial Registration

ANZCTR.org.au ACTRN12607000417482     

Implementing Direct Access to Low-Dose Computed Tomography in General Practice—Method,Adaption and Outcome

Background

Early detection of lung cancer is crucial as the prognosis depends on the disease stage. Chest radiographs has been the principal diagnostic tool for general practitioners (GPs), but implies a potential risk of false negative results, while computed tomography (CT) has a higher sensitivity. The aim of this study was to describe the implementation of direct access to low-dose CT (LDCT) from general practice.

Methods

We conducted a cohort study nested in a randomised study. A total of 119 general practices with 266 GPs were randomised into two groups. Intervention GPs were offered direct access to chest LDCT combined with a Continuing Medical Education (CME) meeting on lung cancer diagnosis.

Results

During a 19-month period, 648 patients were referred to LDCT (0.18/1000 adults on GP list/month). Half of the patients needed further diagnostic work-up, and 15 (2.3%, 95% CI: 1.3–3.8%) of the patients had lung cancer; 60% (95% CI: 32.3–83.7%) in a localised stage. The GP referral rate was 61% higher for CME participants compared to non-participants.

Conclusion

Of all patients referred to LDCT, 2.3% were diagnosed with lung cancer with a favourable stage distribution. Half of the referred patients needed additional diagnostic work-up. There was an association between participation in CME and use of CT scan. The proportion of cancers diagnosed through the usual fast-track evaluation was 2.2 times higher in the group of CME-participating GPs. The question remains if primary care case-finding with LDCT is a better option for patients having signs and symptoms indicating lung cancer than a screening program. Whether open access to LDCT may provide earlier diagnosis of lung cancer is yet unknown and a randomised trial is required to assess any effect on outcome.

Trial Registration

Clinicaltrials.gov NCT01527214     

Diagnosis of early stage ovarian cancer by 1H NMR metabonomics of serum explored by use of a microflow NMR probe

We show that (1)H NMR based metabonomicsof serum allows the diagnosis of early stage I/II epithelial ovarian cancer (EOC) required for successful treatment. Because patient specimens are highly precious, we conducted an exploratory study using a microflow probe requiring only 20 μL of serum. By use of logistic regression on principal components (PCs) of the NMR profiles, we built a 4-variable model for early stage EOC prediction (training set: 69 EOC specimens, 84 healthy controls; test set: 40 EOC, 44 controls) with operating characteristics estimated for the test set at 80% specificity [95% confidence interval (CI): 65-90%], 63% sensitivity (95% CI: 46-77%), and an area under the Receiver Operator Characteristic Curve (AUC) of 0.796. Independent validation (50 EOC, 50 controls) of the model yielded 95% specificity (95% CI: 86-99.5%), 68% sensitivity (95% CI: 53-80%) and an AUC of 0.949. A test on cancer type specificity showed that women diseased with renal cell carcinoma were not incorrectly diagnosed with EOC, indicating that metabonomics bears significant potential for cancer type-specific diagnosis. Our model can potentially be applied for women at high risk for EOC, and our study promises to contribute to developing a screening protocol for the general population.     

Behavioural and psychological symptoms of dementia in primary care: a survey of general practitioners in Ireland

Background Management of neuropsychiatric symptoms is a challenging task in primary care. Aims To assess self-reported confidence and knowledge of general practitioners (GPs) regarding the identification and management of behavioural and psychological symptoms of dementia (BPSD).Methods A self-designed two-page paper questionnaire was sent to a random sample of 160 GPs practising in north Dublin. They were asked to evaluate their confidence and knowledge on several aspects of diagnosis and management of BPSD.Results Completed questionnaires were returned from 109 GPs (response rate = 68%), of which 106 were usable. In general, GPs were somewhat critical of their self-reported skills in diagnosing (76.4%) and managing (77.4%) BPSD, as well as in discriminating BPSD from other behavioural disturbances (71.7%). Many of them (67.9%) also encountered difficulty accessing specialist services. There was no correlation between demographic characteristics of GPs or patient caseload with respect to their responses to questionnaire items. Although many GPs (92.5%) highly valued the important role of non-pharmacological interventions in BPSD, none of them reported recommending these in their daily practice.Conclusions Despite the fact that GPs have a wealth of knowledge about BPSD, they are largely critical of their knowledge and management skills of these symptoms. Efforts should be focused on supporting GPs by means of educational interventions that consider all aspects of dementia, but additionally highlight the more challenging neuropsychiatric components of the illness. Health services need to be structured in a way that promotes collaboration between GPs and mental health professionals for a seamless delivery of care.     

Capacity and Adaptations of General Practice during an Influenza Pandemic

Background

GPs play a major role in influenza epidemics, and most patients with influenza-like-illness (ILI) are treated in general practice or by primary care doctors on duty in out-of-hours services (OOH). Little is known about the surge capacity in primary care services during an influenza pandemic, and how the relationship between them changes.

Aim

To investigate how general practice and OOH services were used by patients during the 2009 pandemic in Norway and the impact of the pandemic on primary care services in comparison to a normal influenza season.

Materials

Data from electronic remuneration claims from all OOH doctors and regular GPs for 2009.

Methods

We conducted a registry-based study of all ILI consultations in the 2009 pandemic with the 2008/09 influenza season (normal season) as baseline for comparison.

Results

The majority (82.2%) of ILI consultations during the 2009 pandemic took place in general practice. The corresponding number in the 2008/09 season was 89.3%. Compared with general practice, the adjusted odds ratio for ILI with all other diagnoses as reference in OOH services was 1.23 (95% CI, 1.18, 1.27) for the 2008/2009 season and 1.87 (95% CI, 1.84, 1.91) for the pandemic influenza season. In total there was a 3.3-fold increase in ILI consultations during the pandemic compared to the 2008/09 season. A 5.5-fold increase of ILI consultations were observed in OOH services in comparison to the 2008/09 season. Children and young adults with ILI were the most frequent users of OOH services during influenza periods.

Conclusions

The autumn pandemic wave resulted in a significantly increased demand on primary care services. However, GPs in primary care services in Norway showed the ability to increase capacity in a situation with increased patient demand.