Education and employment among patients with childhood-onset epilepsy in adulthood: A population-based cohort study.

OBJECTIVE: This study explored the association of childhood-onset epilepsy (COE) with educational attainment, adulthood employment, and income. METHODS: A population-based cohort of 312 children with COE was identified from Tampere University Hospital, Finland. Population Register Center formed a matched random population sample of 1248 children without COE as a reference cohort. The two cohorts were linked to the Statistics Finland database to obtain information on educational attainment, employment status, and income. Fisher's exact test was used to compare employment and graduation. Independent samples t-test was used for analyzing graduation grades and the Mann-Whitney test was used for analyzing yearly income. Results were stratified by sex and disability. RESULTS: During a follow-up of 25 years, a substantially higher proportion of the patients never entered the workforce, 37 % (109/312) compared with 4 % (44/1248) for the referents without COE (p < 0.001). A two-fold difference was observed for COE patients without other disabilities (7.7 %, 13/169, p = 0.01). No clear difference was found in long-term employment between the COE without disabilities and the referents (67 %, 114/169 versus 74 %, 920/1248, p = 0.087). The patients with COE had worse lower secondary school graduation grade averages (7.36 vs 7.6, p = 0.004) and graduation rates (64 % vs 98 %, p < 0.001), the patients without disabilities had similar results to referents (7.43, p = 0.07, 98 %). Of the patients with COE, 18 % graduated from college compared to 38 % of the referents (p < 0.001). The median income was lower in males and females with COE of all ages compared to the referents. The COE patients without additional mental or physical disabilities had income comparable to the healthy referents. 143 patients (46 %) had additional disabilities. SIGNIFICANCE: Patients with COE have lower educational attainment, stable employment, and income. Patients without disabilities also have an increased risk of unemployment, but those capable of entering the workforce have stable careers with earnings comparable to the rest of the population.

Short- and long-term effects of imatinib in hospitalized COVID-19 patients: A randomized trial.

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. METHODS: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. RESULTS: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.

Reporting of costs and economic impacts in randomized trials of de-implementation interventions for low-value care: a systematic scoping review.

BACKGROUND: De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. METHODS: We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. RESULTS: We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). CONCLUSION: De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. TRIAL REGISTRATION: OSF (Open Science Framework): https://osf.io/ueq32 .

Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials.

BACKGROUND: Interpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane COVID-19 trial registry, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and preprint servers from Jan 1, 2020, until April 11, 2022, for RCTs of remdesivir in adult patients hospitalised with COVID-19, and contacted the authors of eligible trials to request individual patient data. The primary outcome was all-cause mortality at day 28 after randomisation. We used multivariable hierarchical regression-adjusting for respiratory support, age, and enrollment period-to investigate effect modifiers. This study was registered with PROSPERO, CRD42021257134. FINDINGS: Our search identified 857 records, yielding nine RCTs eligible for inclusion. Of these nine eligible RCTs, individual data were provided for eight, covering 10 480 patients hospitalised with COVID-19 (99% of such patients included in such RCTs worldwide) recruited between Feb 6, 2020, and April 1, 2021. Within 28 days of randomisation, 662 (12·5%) of 5317 patients assigned to remdesivir and 706 (14·1%) of 5005 patients assigned to no remdesivir died (adjusted odds ratio [aOR] 0·88, 95% CI 0·78-1·00, p=0·045). We found evidence for a credible subgroup effect according to respiratory support at baseline (pinteraction=0·019). Of patients who were ventilated-including those who received high-flow oxygen-253 (30·0%) of 844 patients assigned to remdesivir died compared with 241 (28·5%) of 846 patients assigned to no remdesivir (aOR 1·10 [0·88-1·38]; low-certainty evidence). Of patients who received no oxygen or low-flow oxygen, 409 (9·1%) of 4473 patients assigned to remdesivir died compared with 465 (11·2%) of 4159 patients assigned to no remdesivir (0·80 [0·70-0·93]; high-certainty evidence). No credible subgroup effect was found for time to start of remdesivir after symptom onset, age, presence of comorbidities, enrolment period, or corticosteroid use. Remdesivir did not increase the frequency of severe or serious adverse events. INTERPRETATION: This individual patient data meta-analysis showed that remdesivir reduced mortality in patients hospitalised with COVID-19 who required no or conventional oxygen support, but was underpowered to evaluate patients who were ventilated when receiving remdesivir. The effect size of remdesivir in patients with more respiratory support or acquired immunity and the cost-effectiveness of remdesivir remain to be further elucidated. FUNDING: EU-RESPONSE.

Psychiatric medications and the risk of autoimmune and immune-mediated inflammatory diseases: A systematic review and meta-analysis of observational studies.

BACKGROUND: Pharmacovigilance reports have suggested that certain commonly used medications may trigger autoimmune diseases (ADs) and immune-mediated inflammatory diseases (IMIDs). We systematically reviewed the literature to evaluate whether psychiatric medication use is associated with ADs and IMIDs. METHODS: The protocol was registered in PROSPERO (CRD42022296524) before the start of the study. We searched Medline Ovid and Scopus up to November 28th, 2021, for comparative studies, with any psychiatric medication as exposure and ADs and IMIDs as outcomes. Meta-analysis was performed using DerSimonian-Laird random-effects modeling. The PRISMA 2020 guidelines were followed in reporting. Study-level risk of bias was assessed using the Newcastle-Ottawa Scale, and the overall certainty of evidence using GRADE. RESULTS: There were 7,265 citations from which 31 studies were eligible, all from high-income countries, covering 15 distinct immune diseases. The evidence for the association between selective serotonin reuptake inhibitor (SSRI) use and higher risk of microscopic colitis (meta-OR 2.60, 95% CI 1.05-6.39, I2 97.5%, 6 studies) was of low certainty. A subgroup analysis by the histological type of microscopic colitis showed a statistically significant association only with lymphocytic colitis (meta-OR 2.88, 95% CI 2.60-3.18, I2 00.00%, three studies). In two case-control studies, SSRI use had no significant association with psoriasis (meta-OR 0.80, 95% CI 0.58-1.10, I2 82.4%). The risk of acute pancreatitis was slightly increased with exposure to SSRIs (meta-OR 1.13, 95% CI 1.01-1.26, I2 00.0%), as was the risk of bullous pemphigoid after exposure to antipsychotics (meta-OR 1.79, 95% CI 1.17-2.73, I2 0%). CONCLUSIONS: We reviewed the literature on whether psychiatric medications associate with the risk of ADs and IMIDs and concluded that, despite several signals, the credibility of evidence remains low at best. Prospective cohort studies would be needed as the next step to confirm the suggestions of increased risk.

Autoimmune and immune-mediated inflammatory diseases after exposure to acid-suppressive medication: A systematic review and meta-analysis.

BACKGROUND: Pharmacovigilance risk signals have proposed a relationship between the use of acid-suppressive medications and the development of certain autoimmune and immune-mediated inflammatory diseases. OBJECTIVE: A systematic review and a meta-analysis was performed. METHODS: We reviewed MEDLINE (Ovid) and Scopus for comparative observational studies between these diseases and previous exposure to proton-pump inhibitors (PPI), H2-receptor antagonists (H2RA), and antacids. The protocol was registered on the PROSPERO database (CRD42020192715). RESULTS: From 3,191 citations, 25 articles were eligible and covered 16 diseases. Microscopic colitis (MC) was studied the most (7 studies). In a random-effects meta-analysis, there was low certainty evidence (GRADE approach) of a non-significant relationship between exposure to any PPIs and MC (meta-OR 3.28, 95% CI 0.98-11.0, I2 98.2%, six studies, 4,436 PPI-exposed MC patients). Moderate certainty evidence pointed towards large odds of collagenous colitis after exposure to lansoprazole (meta-OR 14.5, 95% CI 9.37-22.3, I2 10.2%, three studies, 1,725 lansoprazole-exposed patients). After PPI exposure, the risk of rheumatoid arthritis was slightly increased based on low certainty evidence from two cohort studies totaling 475 diagnoses (meta-RR 1.62, 95% CI 1.12-2.34, I2 34.5%). CONCLUSIONS: In patients with MC, it would be reasonable to carefully review the indication of PPI, especially in CC patients using lansoprazole.

Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial.

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.

Randomized controlled trials in de-implementation research: a systematic scoping review.

BACKGROUND: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. METHODS: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. RESULTS: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). CONCLUSIONS: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. REGISTRATION: OSF Open Science Framework hk4b2.

Chronic unilateral groin pain in a young patient who injects drugs: a case report of needle fragment retentions.

BACKGROUND: Subcutaneously retained needle fragments in people who inject drugs (PWIDs) are a possible cause of local symptoms, most commonly pain and infections. It remains unknown how common retained needle fragments are among PWIDs. CASE PRESENTATION: A young PWID consulted a primary care physician due to chronic left-sided groin pain. The patient suspected retention of a broken needle as the cause. She had used a re-used needle 3 months earlier. A plain pelvic radiograph confirmed a needle fragment in the patient's left groin, and a computed tomography scan located it adjacent to the femoral artery and vein. Another asymptomatic needle fragment was found in the right groin. CONCLUSION: Needle fragments are possible causes of local symptoms among PWIDs. The clinical examination presents a potential risk of needlestick injury to the examiner, especially because patients may not be aware of all needle fragments as some are asymptomatic.

Fertility and marital status in adults with childhood onset epilepsy: A population-based cohort study.

OBJECTIVE: Our objective was to explore the association of childhood onset epilepsy (COE) and clinical factors on marital status and fertility in adulthood. METHODS: We identified a population-based cohort of 307 individuals with COE treated in the Tampere University Hospital district with an inception date of December 31, 1992. A matched reference cohort of 1244 individuals without COE was established as a random sample of the population in the study area through the Population Register Center (PRC). The PRC also provided data on marriages and offspring up to 2018. Fertility and marriage analysis was done by calculating the time until first child and marriage. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with Cox regression for follow-up spanning up to January 2018. RESULTS: Patients with COE had lower fertility rates (32.2% vs 57.3% any offspring, HR = 0.47, 95% CI = 0.38-0.58) and fewer marriages (28.3% vs 49.7% ever married, HR = 0.49, 95% CI = 0.39-0.61) than the referents without COE during 25-year follow-up. The largest impact was in patients with COE who had any disability (10.1% any offspring, HR = 0.20, 95% CI = 0.10-0.41; 6.5% ever married, HR = 0.11, 95% CI = 0.06-0.21), symptomatic etiology of epilepsy (13.1%, HR = 0.18, 95% CI = 0.11-0.31; 12.1%, HR = 0.21, 95% CI = 0.12-0.36), onset of epilepsy before 2 years of age (HR = 0.20, 95% CI = 0.12-0.31; HR = 0.29, 95% CI = 0.18-0.46), and high seizure frequency after start of treatment (HR = 0.13, 95% CI = 0.06-0.28; HR = 0.20, 95% CI = 0.10-0.41). Patients with COE without any disabilities had only slightly lowered fertility (HR = 0.76, 95% CI = 0.61-0.95) and a nonsignificant reduction in marriages (HR = 0.80, 95% CI = 0.64-1.02). SIGNIFICANCE: COE was associated with a lower chance of finding a partner at adulthood and having fewer children. The extent of such effect varied between patient subgroups.

Direct Reflectance Measurements from Drones: Sensor Absolute Radiometric Calibration and System Tests for Forest Reflectance Characterization.

Drone-based remote sensing has evolved rapidly in recent years. Miniaturized hyperspectral imaging sensors are becoming more common as they provide more abundant information of the object compared to traditional cameras. Reflectance is a physically defined object property and therefore often preferred output of the remote sensing data capture to be used in the further processes. Absolute calibration of the sensor provides a possibility for physical modelling of the imaging process and enables efficient procedures for reflectance correction. Our objective is to develop a method for direct reflectance measurements for drone-based remote sensing. It is based on an imaging spectrometer and irradiance spectrometer. This approach is highly attractive for many practical applications as it does not require in situ reflectance panels for converting the sensor radiance to ground reflectance factors. We performed SI-traceable spectral and radiance calibration of a tuneable Fabry-Pérot Interferometer -based (FPI) hyperspectral camera at the National Physical Laboratory NPL (Teddington, UK). The camera represents novel technology by collecting 2D format hyperspectral image cubes using time sequential spectral scanning principle. The radiance accuracy of different channels varied between ±4% when evaluated using independent test data, and linearity of the camera response was on average 0.9994. The spectral response calibration showed side peaks on several channels that were due to the multiple orders of interference of the FPI. The drone-based direct reflectance measurement system showed promising results with imagery collected over Wytham Forest (Oxford, UK).

Uncertainty in multispectral lidar signals caused by incidence angle effects.

Multispectral terrestrial laser scanning (TLS) is an emerging technology. Several manufacturers already offer commercial dual or three wavelength airborne laser scanners, while multispectral TLS is still carried out mainly with research instruments. Many of these research efforts have focused on the study of vegetation. The aim of this paper is to study the uncertainty of the measurement of spectral indices of vegetation with multispectral lidar. Using two spectral indices as examples, we find that the uncertainty is due to systematic errors caused by the wavelength dependency of laser incidence angle effects. This finding is empirical, and the error cannot be removed by modelling or instrument modification. The discovery and study of these effects has been enabled by hyperspectral and multispectral TLS, and it has become a subject of active research within the past few years. We summarize the most recent studies on multi-wavelength incidence angle effects and present new results on the effect of specular reflection from the leaf surface, and the surface structure, which have been suggested to play a key role. We also discuss the consequences to the measurement of spectral indices with multispectral TLS, and a possible correction scheme using a synthetic laser footprint.

Epilepsy, excess deaths and years of life lost from external causes.

We systematically quantified excess mortality in epilepsy patients by cause of death using the population-attributable fraction and epilepsy-attributable years of potential life lost (YPLL) by age 75 years at ages 15 and over. We updated and undertook a re-review of mortality studies from our previous systematic review following PRISMA guidelines to identify cohort studies of general epilepsy populations reporting a relative risk (RR) of death by cause relative to the background rates in the population. Studies on epilepsy prevalence were identified through published reviews. Country-specific mortality figures were obtained from the WHO World Mortality Database. We performed a pooled analysis with the DerSimonian-Laird random effects method. In countries with very high Human Development Indices, epilepsy contributed to 0.5-1.1 % of all deaths in the total population. Among external causes, suicides (RR 2.9, 95 % confidence interval 2.2-3.8; I(2) 52 %) were the major contributor to YPLL, corresponding to 6.7 % and 4.2 % of excess YPLL due to epilepsy in the United States (US) and in the United Kingdom (UK) in 2010, with 541 (346-792) and 44 (28-65) excess suicide cases, respectively. Fatal accidental falls were more common, with 813 (610-1064) and 95 (71-125) excess deaths in the US and in the UK, but these caused only 2.0 % of excess YPLL as they occurred in older age groups. Suicides were the most important external cause of death in epilepsy patients in terms of excess YPLL, whereas other external causes were either more common in older ages or caused less excess deaths.

Using Peptide-Level Proteomics Data for Detecting Differentially Expressed Proteins.

The expression of proteins can be quantified in high-throughput means using different types of mass spectrometers. In recent years, there have emerged label-free methods for determining protein abundance. Although the expression is initially measured at the peptide level, a common approach is to combine the peptide-level measurements into protein-level values before differential expression analysis. However, this simple combination is prone to inconsistencies between peptides and may lose valuable information. To this end, we introduce here a method for detecting differentially expressed proteins by combining peptide-level expression-change statistics. Using controlled spike-in experiments, we show that the approach of averaging peptide-level expression changes yields more accurate lists of differentially expressed proteins than does the conventional protein-level approach. This is particularly true when there are only few replicate samples or the differences between the sample groups are small. The proposed technique is implemented in the Bioconductor package PECA, and it can be downloaded from http://www.bioconductor.org.

Epilepsy-related clinical characteristics and mortality: a systematic review and meta-analysis.

OBJECTIVE: We systematically synthesized the epidemiologic literature on mortality in patients with epilepsy (PWE) by epilepsy-related clinical characteristics with an aggregate data meta-analysis. METHODS: We systematically searched 15 electronic databases, browsed reference lists of pertinent publications, and contacted authors in the field. We were interested in cohort studies that reported the relative risk of death in representative epilepsy populations relative to the general population, with exclusion of highly selected subpopulations of PWE, such as patients with intellectual disabilities or epilepsy surgery series. Search, data abstraction, and study quality assessment with the Newcastle-Ottawa Scale were all performed in duplicate. RESULTS: Pooled mortality was threefold (relative risk 3.33, 95% confidence interval 2.83-3.92) in 38 epilepsy cohorts including 165,879 patients (79.6% from Nordic countries). Among incident cases, idiopathic epilepsies did not associate with materially increased mortality (1.29, 0.75-2.20; 4 studies), whereas mortality was almost twofold in cryptogenic epilepsy (1.75, 1.20-2.54; 5 studies), and highly elevated in patients with symptomatic epilepsy (4.73, 3.27-6.83; 12 studies) and especially in epilepsies due to congenital or developmental causes (10.3, 4.03-26.2; 2 studies). Newly diagnosed patients who attained seizure freedom did not have elevated mortality (0.97, 0.73-1.30; 2 studies). CONCLUSION: Excess mortality was highly related to the etiology of epilepsy in all ages. In adult patients without neuroradiologic abnormalities or other identifiable cause of epilepsy, only patients with cryptogenic epilepsy exhibited excess mortality. Risk of premature death was lowest in idiopathic epilepsy and in PWE who attained seizure freedom.

Autoimmunity-related immunological serum markers and survival in a tertiary care cohort of adult patients with epilepsy.

We evaluated mortality in relation to a panel of autoimmunity-related immunological serum markers in adult patients with epilepsy (PWE), seen in 1996-1997 at the Department of Neurology, Oulu University Hospital in Finland. Blood samples were drawn from 968 volunteers, and baseline measurements included serum immunoglobulins (IgG, IgA, and IgM), and the following antibodies: anticardiolipin, antinuclear, antimitochondrial, antigliadin (IgA and IgG classes), IgA tissue transglutaminase, and IgA endomysial. Hazard ratios (HR) for all-cause mortality in PWE with abnormal immunological markers relative to 413 patients with normal findings were evaluated with adjustment for confounders during a follow-up of nine years. Borderline statistically significant associations were found only for elevated IgA (HR 2.09, 95% CI 0.99-4.42) and for having two or more abnormal antibody titers (HR 1.58, 95% CI 0.98-2.56). The findings of this exploratory study suggested that elevated serum IgA might be associated with excess mortality in PWE.

Cross-correlation of spectral count ranking to validate quantitative proteome measurements.

The measurement of change in biological systems through protein quantification is a central theme in modern biosciences and medicine. Label-free MS-based methods have greatly increased the ease and throughput in performing this task. Spectral counting is one such method that uses detected MS2 peptide fragmentation ions as a measure of the protein amount. The method is straightforward to use and has gained widespread interest. Additionally reports on new statistical methods for analyzing spectral count data appear at regular intervals, but a systematic evaluation of these is rarely seen. In this work, we studied how similar the results are from different spectral count data analysis methods, given the same biological input data. For this, we chose the algorithms Beta Binomial, PLGEM, QSpec, and PepC to analyze three biological data sets of varying complexity. For analyzing the capability of the methods to detect differences in protein abundance, we also performed controlled experiments by spiking a mixture of 48 human proteins in varying concentrations into a yeast protein digest to mimic biological fold changes. In general, the agreement of the analysis methods was not particularly good on the proteome-wide scale, as considerable differences were found between the different algorithms. However, we observed good agreements between the methods for the top abundance changed proteins, indicating that for a smaller fraction of the proteome changes are measurable, and the methods may be used as valuable tools in the discovery-validation pipeline when applying a cross-validation approach as described here. Performance ranking of the algorithms using samples of known composition showed PLGEM to be superior, followed by Beta Binomial, PepC, and QSpec. Similarly, the normalized versions of the same method, when available, generally outperformed the standard ones. Statistical detection of protein abundance differences was strongly influenced by the number of spectra acquired for the protein and, correspondingly, its molecular mass.

Long-term mortality risk by cause of death in newly diagnosed patients with epilepsy in Finland: a nationwide register-based study.

To estimate long-term mortality by cause of death in a nationwide, register-based cohort of newly diagnosed patients with epilepsy (PWE). All noninstitutionalized Finnish PWE aged 10-74 years (n = 10,818) eligible for reimbursement for antiepileptic medication for the first time between 1990 and 1994 were identified in the database of Social Insurance Institution of Finland. Mortality was compared against a population-based reference cohort (n = 43,894). Hazard ratios (HR) and their 95 % confidence intervals (95 % CI) during a follow-up of 18 years were estimated using proportional hazards modeling. Potential years of life lost (PYLL) and excess fraction of causes of death attributable to epilepsy were estimated. PWE contributed 137,610 person-years of observation and there were 3,558 deaths. Mortality remained elevated up to 18 years post-diagnosis (HR 3.21, 95 % CI 3.07-3.35). Ischemic heart disease mortality in PWE was two-fold (HR 2.31, 95 % CI 2.09-2.54), and remained constantly elevated during entire follow-up in both men and women. Most premature mortality in terms of PYLL was attributable to brain cancer (17 %), other cancers (15 %), ischemic heart disease (11 %), as well as cerebrovascular diseases (10 %). The percentage of deaths in PWE statistically attributable to epilepsy was 3.9 % for accidents, 3.4 % for alcohol-related diseases, and 1.6 % for suicides. PWE had substantial excess mortality from non-communicable diseases, which did not disappear by 18 years. Diseases of the circulatory system and cancers, especially brain cancer, were the most important causes of death almost regardless of the mortality indicator.