Concordance

Non-motor symptoms (NMS) of Parkinson's disease (PD) affect virtually every patient, yet they are under-recognized and under-treated. The NMS Questionnaire (NMSQuest) is a validated 30-item self-assessment instrument useful for NMS screening in clinic. Development of a straight forward grading classification of the burden of non-motor symptoms in PD based on the number of NMS as assessed by the NMS Questionnaire. In an observational, cross-sectional, international study of 383 consecutive patients distribution of the declared NMS as per NMSQuest was analyzed according to previously published levels based on the Non-Motor Symptoms Scale and also the median and interquartile range (IR, percentiles 25 and 75) of the total NMSQuest scores. After post hoc checking, these values were proposed as cut-off points for estimating NMS burden based only on the accumulation of symptoms. Burden and number of NMS correlate closely (r ≥ 0.80). On the basis of this finding, five levels (0 = No NM...

The cagA gene, alleles of the vacA gene,random amplified polymorphic DNA (RAPD), and neutrophil activating capacity (HpNAC) were used to examine paired H. pylori isolates from 10 noneradicated individuals 9 years apart. Paired isolates from each patient were indistinguishable with regard to vacA alleles, RAPD, and HpNAC. Isolates from nine patients showed concordance for the cagA gene, which was not detected in the recent isolate of the tenth patient. Antibodies to CagA were, however, demonstrated in the serum specimens 9 years apart and were also present in two other patients whose paired isolates were cagA-, indicating the existence of both cagA+ and cagA− organisms, with the latter predominating in some patients. The present study suggests a greater stability of phenotypic and genotypic markers of H. pylori than previously regarded. This might be true for a community with low infection and transmission rates. Complementary techniques like microarrays might, however, disclose evolutionary changes not identified here.

Objective-Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk

Although autopsy diagnosis includes routinely, a thorough evaluation of all available pathological results and also of any available clinical data, the contribution of this clinical information to the diagnostic yield of the autopsy has not been analyzed. We aimed to determine to which degree the use of clinical data improves the diagnostic accuracy of the complete diagnostic autopsy (CDA) and the minimally invasive autopsy (MIA), a simplified pathological postmortem procedure designed for low-income sites. A total of 264 coupled MIA and CDA procedures (112 adults, 57 maternal deaths, 54 children, and 41 neonates) were performed at the Maputo Hospital, Mozambique. We compared the diagnoses obtained by the MIA blind to clinical data (MIAb), the MIA adding the clinical information (MIAc), and the CDA blind to clinical information (CDAb), with the results of the gold standard, the CDA with clinical data, by comparing the International Classification of Diseases, Tenth Revision codes and the main diagnostic classes obtained with each evaluation strategy (MIAb, MIAc, CDAb, CDAc). The clinical data increased diagnostic coincidence to the MIAb with the gold standard in 30 (11%) of 264 cases and modified the CDAb diagnosis in 20 (8%) of 264 cases. The increase in concordance between MIAb and MIAc with the gold standard was significant in neonatal deaths (κ increasing from 0.404 to 0.618, P = .0271), adult deaths (κ increasing from 0.732 to 0.813, P = .0221), and maternal deaths (κ increasing from 0.485 to 0.836, 0.;P b .0001). In conclusion, the use of clinical information increases the precision of MIA and CDA and may strengthen the performance of the MIA in resource-limited settings.

In recent decades, the world has witnessed unprecedented progress in child survival. However, our knowledge of what is killing nearly 6 million children annually in low- and middle-income countries remains poor, partly because of the inadequacy and reduced precision of the methods currently utilized in these settings to investigate causes of death (CoDs). The study objective was to validate the use of a minimally invasive autopsy (MIA) approach as an adequate and more acceptable substitute for the complete diagnostic autopsy (CDA) for pediatric CoD investigation in a poor setting. In this observational study, the validity of the MIA approach in determining the CoD was assessed in 54 post-neonatal pediatric deaths (age range: ≥1 mo to 15 y) in a referral hospital of Mozambique by comparing the results of the MIA with those of the CDA. Concordance in the category of disease obtained by the two methods was evaluated by the Kappa statistic, and the sensitivity, specificity, and positive...

In recent decades, the world has witnessed unprecedented progress in child survival. However, our knowledge of what is killing nearly 6 million children annually in low- and middle-income countries remains poor, partly because of the inadequacy and reduced precision of the methods currently utilized in these settings to investigate causes of death (CoDs). The study objective was to validate the use of a minimally invasive autopsy (MIA) approach as an adequate and more acceptable substitute for the complete diagnostic autopsy (CDA) for pediatric CoD investigation in a poor setting. In this observational study, the validity of the MIA approach in determining the CoD was assessed in 54 post-neonatal pediatric deaths (age range: ≥1 mo to 15 y) in a referral hospital of Mozambique by comparing the results of the MIA with those of the CDA. Concordance in the category of disease obtained by the two methods was evaluated by the Kappa statistic, and the sensitivity, specificity, and positive...

Background There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique.

BackgroundThe recent COVID-19 pandemic has posed an unprecedented challenge to laboratory diagnosis, based on the amplification of SARS-CoV-2 RNA. With global contagion figures exceeding 4 million persons, the shortage of reagents for RNA extraction represents a bottleneck for testing globally. We present the validation results for a RT-qPCR protocol without prior RNA extraction. Because of its simplicity, this protocol is suitable for widespread application in resource-limited settings.MethodsOptimal protocol was selected by comparing RT-qPCR performance under a set of thermal (65°, 70°, and 95° for 5, 10, and 30 minutes) and amplification conditions (3 or 3,5 uL loading volume; 2 commercial RT-qPCR kits with limit of detection below 10 copies/sample) in nasopharyngeal swabs stored at 4°C in sterile Weise’s buffer pH 7.2. The selected protocol was evaluated for classification concordance with the standard protocol (automated RNA extraction) in 130 routine samples and in 50 historic...

Background: Adrenal insufficiency is a common occurrence in the critically ill and it is essential that intensivists and endocrinologists involved in the care of these patients have a good understanding of the concepts related to this condition. Objectives: To assess the knowledge, attitudes and practices about adrenal insufficiency in the critically ill among the endocrinologists and intensivists practicing in the city of Chennai. Materials and Methods: Questionnaires containing ten questions pertaining to adrenal insufficiency in the critically ill were sent to a total of six endocrinologists and 52 intensivists practicing in Chennai. Results: About 77% of all the respondents agreed to the fact that adrenal insufficiency is a frequent occurrence in critical illness. But 57% of them felt that there is no need for routine evaluation of critically ill patients for adrenal insufficiency. Random serum cortisol was selected by 62% of the responders as the method for evaluating adrenal function in the critically ill. There is clearly no agreement among the endocrinologists or the intensivists on the various cut off levels for diagnosis. Neither is there a clear consensus on the method followed for treatment of patients with adrenal insufficiency in the critical care unit. Conclusion: There is no concordance in the knowledge, attitudes or practices on adrenal insufficiency in the critically ill among the endocrinologists and intensivists in Chennai. There is a need for developing standard diagnostic and treatment guidelines and making it available for all the practicing endocrinologists and intensivists.

Objective: To evaluate the effect of amyloid imaging on clinical decision making. Methods: We conducted a retrospective analysis of 140 cognitively impaired patients (mean age 65.0 years, 46% primary b-amyloid (Ab) diagnosis, mean Mini-Mental State Examination 22.3) who underwent amyloid (Pittsburgh compound B [PiB]) PET as part of observational research studies and were evaluated clinically before and after the scan. One hundred thirty-four concurrently underwent fluorodeoxyglucose (FDG)-PET. We assessed for changes between the pre-and post-PET clinical diagnosis (from Ab to non-Ab diagnosis or vice versa) and Alzheimer disease treatment plan. The association between PiB/FDG results and changes in management was evaluated using x 2 and multivariate logistic regression. Postmortem diagnosis was available for 24 patients (17%). Results: Concordance between scan results and baseline diagnosis was high (PiB 84%, FDG 82%). The primary diagnosis changed after PET in 13/140 patients (9%) overall but in 5/13 (38%) patients considered pre-PET diagnostic dilemmas. When examined independently, discordant PiB and discordant FDG were both associated with diagnostic change (unadjusted p , 0.0001). However, when examined together in a multivariate logistic regression, only discordant PiB remained significant (adjusted p 5 0.00013). Changes in treatment were associated with discordant PiB in patients with non-Ab diagnoses (adjusted p 5 0.028), while FDG had no effect on therapy. Both PiB (96%) and FDG (91%) showed high agreement with autopsy diagnosis. Conclusions: PET had a moderate effect on clinical outcomes. Discordant PiB had a greater effect than discordant FDG, and influence on diagnosis was greater than on treatment. Prospective studies are needed to better characterize the clinical role of amyloid PET. Neurology ® 2014;82:230-238 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; AUC 5 appropriate use criteria; CBS 5 corticobasal syndrome; CDR 5 Clinical Dementia Rating; Che-I 5 cholinesterase inhibitor; CMS 5 Centers for Medicare & Medicaid Services; DLB 5 dementia with Lewy bodies; FDG 5 fluorodeoxyglucose; FTD 5 frontotemporal dementia; MCI 5 mild cognitive impairment; PiB 5 Pittsburgh compound B; UCSF

Background. Understanding the hospital impact of influenza requires enriching epidemiological surveillance registries with other sources of information. The aim of this study was to determine the validity of the Hospital Care Activity Record – Minimum Basic Data Set (RAE-CMBD) in the analysis of the outcomes of patients hospitalised with this infection. Methods. Observational and retrospective study of adults admitted with influenza in a tertiary hospital during the 2017/2018 and 2018/2019 seasons. We calculated the concordance of the RAE-CMBD with the influenza epidemiological surveillance registry (gold standard), as well as the main parameters of internal and external validity. Logistic regression models were used for risk adjustment of in-hospital mortality and length of stay. Results. A total of 907 (97.74%) unique matches were achieved, with high inter-observer agreement (ƙ=0.828). The RAE-CMBD showed a 79.87% sensitivity, 99.72% specificity, 86.71% positive predictive value a...

Background Assessment of KRAS, NRAS (RAS) and BRAF mutations is a standard in the management of patients with metastatic colorectal cancer (mCRC). Mutations could be assessed using next-generation sequencing (NGS) or real-time PCR-based assays. Times to results are 1 to 2 weeks for NGS and 1 to 3 days for real-time PCR-based assays. Using NGS can delay first-line treatment commencement and using PCR-based assays is limited by the number of possible analysed targets. The Idylla system is a real-time PCR cartridge-based assay, able to analyse hotspots mutations using one section of FFPE tumour tissue sample. To combine short delays and analysis of a large gene-panel, we propose here a laboratory workflow combining the Idylla system and NGS and compatible with FFPE samples with low tissue quantity. In this study we evaluated and validated the Idylla system for the analysis of RAS and BRAF mutations by pipetting directly DNA in the cartridge instead of FFPE section as recommended by the manufacturer. Materials and methods DNA extracted from 29 FFPE samples from mCRC patients with NGS-characterized RAS and BRAF mutations were tested with the Idylla KRAS and the Idylla NRAS-BRAF mutation tests to assess sensitivity, specificity, reproducibility and limit of detection of each test.

Familial concordance of nutritional status is an emerging field of study that may guide the development of interventions that operate beyond the individual and within the family context. Little published data exist for concordance of nutritional status within Pakistani households. We assessed the associations between weight status of mothers and their children in a nationally representative sample of households in Pakistan using Demographic and Health Survey data. Our analysis included 3465 mother-child dyads, restricting to children under-five years of age with body mass index (BMI) information on their mothers. We used linear regression models to assess the associations between maternal BMI category (underweight, normal weight, overweight, obese) and child’s weight-for-height z-score (WHZ), accounting for socio-demographic characteristics of mothers and children. We assessed these relationships in all children under-five and also stratified by age of children (younger than 2 years...

We aimed to determine diagnostic accuracy of CT-guided bone lesion biopsy for the confirmation of bone metastases in patients with breast cancer and assessment of hormone receptor status in metastatic tissue. A total of 56 female patients with breast cancer that underwent CT-guided biopsy of suspected bone metastasis were enrolled in this retrospective study. Three different techniques were employed to obtain samples from various sites of skeleton. Collectively, 11 true negative and 3 false negative findings were revealed. The sensitivity of CT-guided biopsy for diagnosing bone metastases was 93.6%, specificity was 100% and accuracy was 94.8%. Discordance in progesterone receptor status and complete concordance in estrogen receptor status was observed. Based on our single-center experience, bone metastasis biopsy should be routinely performed in patients with breast cancer and suspicious bone lesions, due to the impact on further treatment.

Objective This study aims to assess the use of Semmes-Weinstein monofilaments (SWMs) and of the Chemotherapy-Induced Neurotoxicity Questionnaire (CINQ) in the detection of chemotherapy-induced peripheral neuropathy (CIPN). Method It is a comparative and cross-sectional study performed in a philanthropic general hospital, located in the state of Minas Gerais, Brazil. One hundred seventeen individuals have participated in this study; they were divided into two groups: patients (n=87) treated with oxaliplatin, paclitaxel, or docetaxel and controls (n=30) without malignant disease. Results There were statistically significant differences between groups for all symptoms assessed by means of the CINQ. Lower limbs were more severely affected. Patients had increased frequency and severity of changes in all points assessed with SWM compared with controls. In the analyses of concordance between CINQ and SWM, kappa=0.320 (p<0.001) was obtained, and there was a moderate and positive correlation (ρ=0.357; p<0.001). Conclusion CINQ and SWM may be valid tools for diagnosing CIPN in oncology practice. SWM may identify subclinical CIPN.

Background The burden of Parkinson’s disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson’s disease (APD) and suboptimal medication control. The 5–2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5–2-1 screening criteria. Methods Data were drawn from the Adelphi Parkinson’s Disease Specific Program (DSP™), a multi-country point-in-time survey (2017–2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5–2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) “off” symptoms for ≥2 h of waking da...

BACKGROUND AND PURPOSE: The ketogenic diet, including both classic and modified forms, is an alternative to antiepileptic medications used in the treatment of drug-resistant epilepsy. We sought to evaluate the utility of proton MR spectroscopy for the detection of ␤-hydroxybutyrate in a cohort of children with epilepsy treated with the ketogenic diet and to correlate brain parenchymal metabolite ratios obtained from spectroscopy with ␤-hydroxybutyrate serum concentrations. MATERIALS AND METHODS: Twenty-three spectroscopic datasets acquired at a TE of 288 ms in children on the ketogenic diet were analyzed with LCModel using a modified basis set that included a simulated ␤-hydroxybutyrate resonance. Brain parenchymal metabolite ratios were calculated. Metabolite ratios were compared with serum ␤-hydroxybutyrate concentrations, and partial correlation coefficients were calculated using patient age as a covariate. RESULTS: ␤-hydroxybutyrate blood levels were highly correlated to brain ␤-hydroxybutyrate levels, referenced as either choline, creatine, or N-acetylaspartate. They were inversely but more weakly associated with N-acetylaspartate, regardless of the ratio denominator. No strong concordance with lactate was demonstrated. CONCLUSIONS: Clinical MR spectroscopy in pediatric patients on the ketogenic diet demonstrated measurable ␤-hydroxybutyrate, with a strong correlation to ␤-hydroxybutyrate blood levels. These findings may serve as an effective tool for noninvasive monitoring of ketosis in this population. An inverse correlation between serum ␤-hydroxybutyrate levels and brain tissue N-acetylaspartate suggests that altered amino acid handling contributes to the antiepileptogenic effect of the ketogenic diet. ABBREVIATIONS: BHB ϭ ␤-hydroxybutyrate; GABA ϭ gamma-aminobutyric acid; KD ϭ ketogenic diet; MAD ϭ modified Atkins diet

(1) Background: The authors developed a new non-invasive dermatological infrared macroimaging analysis technique (MacroIR) that evaluates microvascular, inflammatory, and metabolic changes that may be dermoscopy complimentary, by analyzing different skin and mucosal lesions in a combined way-naked eye, polarized light dermatoscopy (PLD), and MacroIR-and comparing results; (2) Methods: ten cases were evaluated using a smartphone coupled with a dermatoscope and a macro lens integrated far-infrared transducer into specific software to capture and organize high-resolution images in different electromagnetic spectra, and then analyzed by a dermatologist; (3) Results: It was possible to identify and compare structures found in two dermoscopic forms. Visual anatomical changes were correlated with MacroIR and aided skin surface dermatological analysis, presenting studied area microvascular, inflammatory, and metabolic data. All Ma-croIR images correlated with PLD, naked eye examination, and histopathological findings; (4) Conclusion: MacroIR and clinic dermatologist concordance rates were comparable for all dermatological conditions in this study. MacroIR imaging is a promising method that can improve dermatological diseases diagnosis. The observations are preliminary and require further evaluation in larger studies.

ObjectiveTo determine the diagnostic accuracy and clinical utility of electromagnetic source imaging (EMSI) in presurgical evaluation of patients with epilepsy.MethodsWe prospectively recorded magnetoencephalography (MEG) simultaneously with EEG and performed EMSI, comprising electric source imaging, magnetic source imaging, and analysis of combined MEG-EEG datasets, using 2 different software packages. As reference standard for irritative zone (IZ) and seizure onset zone (SOZ), we used intracranial recordings and for localization accuracy, outcome 1 year after operation.ResultsWe included 141 consecutive patients. EMSI showed localized epileptiform discharges in 94 patients (67%). Most of the epileptiform discharge clusters (72%) were identified by both modalities, 15% only by EEG, and 14% only by MEG. Agreement was substantial between inverse solutions and moderate between software packages. EMSI provided new information that changed the management plan in 34% of the patients, and...

We conducted a secondary analysis of data from the Prevention of Recurrent Episodes of Depression With Venlafaxine Extended Release (ER) for Two Years (PREVENT) trial to evaluate whether discrepancies between clinician and patient ratings of depression severity were predictive of response, remission, and recurrence during treatment for a depressive episode. Patients who self-rated depression severity in concordance with the clinician ("concordant patients") were defined as having a standardized patient-rated Inventory of Depressive Symptoms-Self Report (IDS-SR30) score minus standardized clinician-rated Hamilton Rating Scale for Depression (HAM-D 17) score <1 SD from mean. Non-concordant patients ("underrating patients" [−1 SD], "overrating patients" [+1 SD]) were identified. Cohorts were compared for remission and response on the HAM-D 17 , Clinician Global Impression-Severity (CGI-S), and IDS-SR 30 during acute and continuation therapy and time to recurrence during maintenance therapy. During acute treatment female patients were more likely to overrate their depression severity compared to the clinician; older age predicted overrating during continuation treatment. Overrating patients had a slower onset of response on the HAM-D 17 during acute treatment (P = 0.004). There were no differences between cohorts for remission or response on the HAM-D 17 or CGI-S. Overrating patients at week 10 had lower remission and response rates on the IDS-SR30 during continuation therapy (32% and 50%, respectively; P ≤ 0.001) compared with underrating patients (76%, 77%) or concordant patients (64%, 78%). Patient concordance at the end of continuation therapy did not predict recurrence during maintenance therapy, indicating that patient rating scales may be useful in tracking recurrence during maintenance therapy. Poor agreement between patient-and clinicianratings of depression severity is primarily a state phenomenon, although it is trait-like for some patients.

Loss of hemodynamic reserve in intracranial cerebrovascular disease reduces blood oxygenation level-dependent activation by fMRI and increases asymmetry in MTT measured by provocative DSC perfusion MR imaging before and after vasodilation with intravenous acetazolamide. The concordance for detecting hemodynamic reserve integrity has been compared. Patients (n = 40) with intracranial cerebrovascular disease and technically adequate DSA, fMRI and provocative DSC perfusion studies were retrospectively grouped into single vessels proximal to and distal from the circle of Willis, multiple vessels, and Moyamoya disease. The vascular territories were classified as having compromised hemodynamic reserve if the expected fMRI blood oxygenation level-dependent activation was absent or if MTT showed increased asymmetry following vasodilation. Concordance was examined in compromised and uncompromised vascular territories of each group with the Fischer exact test and proportions of agreement. Ext...

Background: Evidence-based recommendations have the potential to improve the quality of health care by promoting interventions of proven benefit and discouraging unnecessary, ineffective, or harmful interventions. Osteoarthritis (OA) treatment recommendations are generally addressing strength training and training to increase aerobic capacity together with referral to, or treatment by, physiotherapists. Previous research has revealed that treatment of patients with OA by medical doctors show low adherence with recommendations (1). Little is not known about the treatment provided by physiotherapists in Norway and whether the treatment provided is in concordance with general recommendations for OA treatment. Objectives: To investigate knee OA treatment performed by physiotherapists in Norway and its concordance with EULAR recommendations for nonpharmacological treatment modalities. Methods: Patient records in the hospital region of middle Norway were searched to identify patients with knee OA. A letter was sent to the identified patients (N=87) asking for information about which physiotherapist they had seen for treatment. A letter was sent to the physiotherapists asking for the discharge summary, in which they are obliged to send to the referring doctor. A survey of the discharge summaries was conducted independently by 3 health professionals (two physiotherapists, one physician) to categorise and group the treatment given. Results: Response rate from patients was 93% (N=81). Of the 81, 13 (15%) had not been referred to physiotherapy treatment. Response rate from physiotherapists (N=68) was 38 (56%). Of the treatment described in the discharge summaries 7 (10%) was partly in line with EULAR recommendations; of these, all 7 used strengthening exercises and 0 used improvement of aerobic capacity as their choice of therapeutic modality. Conclusions: According to our findings it may seem that physiotherapy treatments are not always in line with recommendations for knee OA treatment. The incidence of total knee replacement is increasing, raising costs personal and societal. Physiotherapy treatment in line with recommendations may help prevent OA from progression and prevent prosthesis operations to further increase. There seems to be a need for further work to make physiotherapists implement the EULAR guidelines in their day to day work with knee OA patients. References: [1] Østerås N, Garratt A, Grotle M, Natvig B, Kjeken I, Kvien TK, Hagen KB. Patient-reported quality of care for osteoarthritis: development and testing of the osteoarthritis quality indicator questionnaire. Arthritis Care Res (Hoboken).

Background: Emergence of more autonomous roles for physiotherapists warrants more evidence regarding their diagnostic capabilities. Therefore, we aimed to evaluate diagnostic and surgical triage concordance between a physiotherapist and expert physicians and to assess the diagnostic validity of the physiotherapist's musculoskeletal examination (ME) without imaging. Methods: This is a prospective diagnostic study where 179 consecutive participants consulting for any knee complaint were independently diagnosed and triaged by two evaluators: a physiotherapist and one expert physician (orthopaedic surgeons or sport medicine physicians). The physiotherapist completed only a ME, while the physicians also had access to imaging to make their diagnosis. Raw agreement proportions and Cohen's kappa (k) were calculated to assess inter-rater agreement. Sensitivity (Se) and specificity (Sp), as well as positive and negative likelihood ratios (LR+/−) were calculated to assess the validity of the ME compared to the physicians' composite diagnosis. Results: Primary knee diagnoses included anterior cruciate ligament injury (n = 8), meniscal injury (n = 36), patellofemoral pain (n = 45) and osteoarthritis (n = 79). Diagnostic inter-rater agreement between the physiotherapist and physicians was high (k = 0.89; 95% CI:0.83-0.94). Inter-rater agreement for triage recommendations of surgical candidates was good (k = 0.73; 95% CI:0.60-0.86). Se and Sp of the physiotherapist's ME ranged from 82.0 to 100.0% and 96.0 to 100.0% respectively and LR+/− ranged from 23.2 to 30.5 and from 0.03 to 0.09 respectively. Conclusions: There was high diagnostic agreement and good triage concordance between the physiotherapist and physicians. The ME without imaging may be sufficient to diagnose or exclude common knee disorders for a large proportion of patients. Replication in a larger study will be required as well as further assessment of innovative multidisciplinary care trajectories to improve care of patients with common musculoskeletal disorders.

Background-Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. Methods-Twin pairs (N = 177; 150 selected for intrapair concordance/ discordance for alcoholrelated problems at age 18½) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ∼25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent "standards" and to ignore occasional "novel" sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intrapair differences in alcohol variables. Results-Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between-and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. Conclusions-Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors.

Background Pharmacogenetic-based dosing support tools have been developed to personalize antidepressantprescribing practice. However, the clinical validity of these tools has not been adequately tested, particularly for specific antidepressants. Objective To examine the concordance between the actual dose and a polygene pharmacogenetic predicted dose of desvenlafaxine needed to achieve symptom remission. Materials and methods A 10-week, open-label, prospective trial of desvenlafaxine among Caucasian adults with major depressive disorder (n = 119) was conducted. Dose was clinically adjusted and at the completion of the trial, the clinical dose needed to achieve remission was compared with the predicted dose needed to achieve remission. Results Among remitters (n = 95), there was a strong concordance (Kendall's τ-b = 0.84, P = 0.0001; Cohen's κ = 0.82, P = 0.0001) between the actual and the predicted dose need to achieve symptom remission, showing high sensitivity (≥85%), specificity (≥86%), and accuracy (≥89%) of the tool. Conclusion Findings provide initial evidence for the clinical validity of a polygene pharmacogenetic-based tool for desvenlafaxine dosing. Pharmacogenetics and Genomics

RATIONALE: To compare the rate, triggers and management of anaphylaxis between adult emergency departments (ED) in Western and Eastern Canada. METHODS: As part of the Cross-Canada Anaphylaxis Registry (C-CARE), we conducted a chart review of adults presenting with allergyrelated ICD-10 codes to a tertiary care centre ED in Western Canada (Edmonton, Alberta) between March 1, 2011 and February 28, 2012. Anaphylaxis cases were defined as those that fulfilled the published consensus definition for anaphylaxis. Clinical and management data were collected and compared to published data from an ED in Eastern Canada (Montreal, Quebec). RESULTS: Among 59,195 presentations to the Edmonton ED, 0.22% (95% CI 0.19%, 0.27%) were due to anaphylaxis. Food was the trigger in 57.1% (48.3%, 65.7%), mainly tree nut (21.0% (12.5%, 31.9%) of foodtriggered cases). Epinephrine was used in 54.9% (46.0%, 63.5%) and 41.3% (32.9%, 50.2%) were prescribed an auto-injector. In Montreal, 0.26% (0.21%, 0.32%) of ED presentations were due to anaphylaxis, and 63.3% (52.9%, 72.6%) were triggered by food, primarily shellfish (12.9% (6.1%, 24.4%) of food-triggered cases). Epinephrine was used to treat 49.0% (38.8%, 59.2%) of patients and 67.1% (55.3%, 77.2%) were prescribed an auto-injector. CONCLUSIONS: In Western and Eastern Canada, anaphylaxis accounted for over 0.2% of adult ED visits and was mainly due to foods. Tree nuts rather than shellfish were the main food triggers in Western Canada. Given the poor adherence to guidelines stipulating epinephrine use in all anaphylaxis cases, education programs promoting early epinephrine use are required across the country.

Background: Esophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms. Methods: In this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson's correlation or Spearman's rank coefficients. Results: 70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= −0.5 to −0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms. Conclusions: Concordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/ proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights  Developmental changes in depressive symptoms were tested  Depression rates increase sharply during early adolescence  They declined as individuals moved into young adulthood  Significant heritability was found for initial levels of depression  Heritability and non-shared environment affected linear and quadratic change

In this study we aim to compare UX2000 (Sysmex Corp, Japan) and SediMAX/AutionMax (Arkray Factory Inc., Japan), totally automatized analyzers, against Fuchs-Rosenthal counting chamber, the gold standard technique for sediment analysis. Design and methods: Urine samples of 1454 patients from three Spanish hospitals were assessed for red and white blood cells (RBC; WBC) using three different techniques: flow cytometry, image-based method and Fuchs-Rosenthal counting chamber. Test strip results were subjected to concordance evaluation. Agreement was assessed by Cohen's weighted kappa for multinomial results. Sensitivity (SE) and specificity (SP) were calculated. Results: The categorization of the results showed that UX-2000 had higher concordance over SediMAX for WBC (0.819 vs. 0.546) and similar for RBC (0.573 vs. 0.630). For RBC, UX-2000 had higher SE (92.7% vs. 80.3%) but lower SP (77.1% vs. 87.4%), and showed higher both SE (94.3% vs. 76.7%) and SP (94.7% vs. 88.2%) for WBC. Inter-devices test strip agreement was substantial (kappa N 0.600) for all variables except for bilirubin (kappa: 0.598). Intra-device test strip agreement was similar for UX2000 and SediMAX with regard to RBC (kappa: 0.553 vs. 0.482) but better for UX2000 with regard to WBC (0.688 vs. 0.465). Conclusions: Both analyzers studied are acceptable for daily routine lab work, even though SediMAX is easier to use in laboratories thanks to its lower maintenance procedure. UX-2000 has shown to have better concordance with the gold standard method. However, it needs some improvements such as an image module in order to decrease manual microscopy review for urine samples.

ObjectiveThe majority of patients with lung cancer are treated on the basis of a diagnosis made from the analysis of a small tumour biopsy or a cytological sample and histotype is becoming a critical variable in clinical workup as it has led to the introduction of newer biologically targeted therapies. Consequently, simply classifying cancers as small cell lung cancers or non‐small cell lung cancers is no longer sufficient.MethodsFrom 2009 to 2011, a review of the histo‐cytological database was conducted to identify all small biopsy and cytology specimens collected for diagnostic purposes in patients with a thoracic lesion. In total, 941 patients were studied by examining exfoliative and/or aspirative cytological samples. To establish the accuracy of these methods, cytological and biopsy diagnoses were compared with each other and with subsequent resection specimens when available. Moreover, during the diagnostic workup, we examined a validated panel of immunohistochemical markers.R...

High resolution electroencephalography (HR-EEG) combined with source localization methods has mainly been used to study interictal spikes and there have been few studies comparing source localization of scalp ictal patterns with depth EEG. To address this issue, 10 patients with four different scalp ictal patterns (ictal spikes, rhythmic activity, paroxysmal fast activity, obscured) were investigated by both HR-EEG and stereoelectroencephalography (SEEG). Sixty-four scalp-EEG sensors and a sampling rate of 1 kHz were used to record scalp ictal patterns. Five different source models (moving dipole, rotating dipole, MUSIC, LORETA, and sLORETA) were used in order to perform source localization. Seven to 10 intracerebral electrodes were implanted during SEEG investigations. For each source model, the concordance between ictal source localization and epileptogenic zone defined by SEEG was assessed. Results were considered to agree if they localized in the same sublobar area as defined by a trained epileptologist. Across the study population, the best concordance between source localization methods and SEEG (9/10) was obtained with equivalent current dipole modeling. MUSIC and LORETA had a concordance of 7/10 whereas sLORETA had a concordance of only 5/10. Four of our patients classified into different groups (ictal spikes, paroxysmal fast activity, obscured) had complete concordance between source localization methods and SEEG. A high signal to noise ratio, a short time window of analysis (b 1 s) and bandpass filtering around the frequency of rhythmic activity allowed improvement of the source localization results. A high level of agreement between source localization methods and SEEG can be obtained for ictal spike patterns and for scalp-EEG paroxysmal fact activities whereas scalp rhythmic discharges can be accurately localized but originated from seizure propagation network.

Murray law-based quantitative flow ratio (µQFR) assesses fractional flow reserve (FFR) in bifurcation lesions using a single angiographic view, enhancing the feasibility of analysis; however, accuracy may be compromised in suboptimal angiographic projections. FFRCT is a well-validated non-invasive method measuring FFR from coronary computed tomographic angiography (CCTA). We evaluated the feasibility of µQFR in left main (LM) bifurcations, the impact of the optimal/suboptimal fluoroscopic view with respect to CCTA, and its diagnostic concordance with FFRCT. In 300 patients with three-vessel disease, the values of FFRCT and µQFR were compared at distal LM, proximal left anterior descending artery (pLAD) and circumflex artery (pLCX). The optimal viewing angle of LM bifurcation was defined on CCTA by 3-dimensional coordinates and converted into a 2-dimensional fluoroscopic view. The best fluoroscopic projection was considered the closest angulation to the optimal viewing angle on CCTA....

The Quick Dementia Rating System (QDRS) and Clinical Dementia Rating Scale (CDR) assess global cognitive and functional decline. We evaluated whether the shorter QDRS was a valid screen for problems identified by the CDR in individuals with minimal clinical abnormalities. Agreement between QDRS-Global and CDR-Global was assessed for 54 participants from the Wisconsin Registry for Alzheimer's Prevention. Resource-savings achieved by adopting an "administer CDR-only-if-QDRS-Global>0" approach were estimated based on 238 subsequent participants. Agreement statistics (concordance = 88.9%) supported use of the QDRS as an initial informant report and modifying center protocol to administer CDRs only when QDRS>0 reduced CDR assessments by 79.8%.

Objectives: to describe the stages of developing and validating two educational brochures to promote breastfeeding and the infant's complementary food. Methods: an observational descriptive study was performed with eight health professionals and 60 caregiver of children under two years old divided into two groups of 30 (one for each brochure) in a Pediatric Outpatient Clinic at a Maternal and Child Reference Hospital. The research was developed in four stages: bibliographical survey, development of the brochures, validation by specialists and target audience and adequacy of the materials. The validation method used was the Índice de Validade de Conteúdo (Content Validity Index) calculation. Results: two nutritional orientation brochures for infants were developed. Experts validated the breastfeeding brochure on its relevance and the brochure on complementary food regarding its relevance and goal. The other items were validated after suggested modifications. In relation to the target audience, the concordance index found in brochures 1 and 2 was higher than 75%.

Background: Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we developed modified eGFR equations for Taiwanese adults. Methods: This cross-sectional study compared the Taiwanese eGFR equations, the MDRD study, and the CKD-EPI equations with inulin clearance (C in). A total of 695 adults including 259 healthy volunteers and 436 CKD patients were recruited. Participants from the Kaohsiung Medical University Hospital were used as the development set (N = 556) to develop the Taiwanese eGFR equations, whereas participants from the National Taiwan University Hospital were used as the validation set (N = 139) for external validation. Results: The Taiwanese eGFR equations were developed by using the extended Bland-Altman plot in the development set. The Taiwanese MDRD equation was 1.3096MDRD 0.912 , Taiwanese CKD-EPI was 1.2626CKD-EPI 0.914 and Taiwanese four-level CKD-EPI was 1.2056four-level CKD-EPI 0.914. In the validation set, the Taiwanese equations had the lowest bias, the Taiwanese equations and the Japanese CKD-EPI equation had the lowest RMSE, whereas the Taiwanese and the Japanese equations had the best precision and the highest P 30 among all equations. However, the Taiwanese MDRD equation had higher concordance correlation than did the Taiwanese CKD-EPI, the Taiwanese four-level CKD-EPI and the Japanese equations. Moreover, only the Taiwanese equations had no proportional bias among all of the equations. Finally, the Taiwanese MDRD equation had the best diagnostic performance in terms of ordinal logistic regression among all of the equations. Conclusion: The Taiwanese MDRD equation is better than the MDRD, CKD-EPI, Japanese, Asian, Thai, Taiwanese CKD-EPI, and Taiwanese four-level CKD-EPI equations for Taiwanese adults.

Clinical heterogeneity in cystic fibrosis (CF) often causes diagnostic uncertainty in infants without symptoms and in older patients with milder phenotypes. We performed a cross-sectional evaluation of a comprehensive set of clinical and laboratory descriptors in a physician-defined cohort (N = 376; Children's Hospital of Wisconsin and the American Family Children's Hospital CF centers in Milwaukee and Madison, WI, USA) to determine the robustness of categorizing CF (N = 300), cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (N = 19),

Angiosarcoma is a rare malignancy of vascular endothelial origin. We describe a case of angiosarcoma of the hand initially histopathologically diagnosed as a pseudoaneurysm, emphasizing the diagnostic importance of radiological pathologic concordance. Here we highlight the distinctive imaging and the histopathologic features of angiosarcoma, invaluable to its accurate and timely diagnosis.

Long-term video-EEG monitoring (LTM) is the gold standard for initial lateralization and localization of seizures in the workup for neurosurgical treatment of medically intractable epilepsy. Previous studies have yielded contradictory results as to whether seizures that occur in clusters tend to arise from the same brain region and may lead to the incorrect conclusion that seizures arise from a single focus. To determine whether seizure clustering affects localization in an LTM setting, the authors performed an observational study over 6 years at a large regional epilepsy center on those undergoing LTM for seizure diagnosis, characterization, or presurgical workup. Excluding repeat studies and LTMs with generalized or nonepileptic seizures resulted in 479 monitorings with 2774 focal seizures for analysis. Sequential pairs of consecutive focal seizures were classed as ''concordant'', ''discordant,'' or ''other,'' based on EEG localization. ANOVA analysis on the logarithm of the interseizure interval (LISI) among the three seizure pair groups showed no significant difference, p = 0.47, nor did analysis defining concordance as lateralization to the same hemisphere (p = 0.34). Analyses on subgroups with multifocal seizures, bilateral seizures, and extratemporal seizures all failed to show a significant difference. In conclusion, seizures have the same localizing value whether occurring in a cluster over a few hours or sporadically over a few days. This could potentially lead to shorter monitoring times.

BackgroundThe Literature is no report support material on Shared Decision-making applied to breast cancer screening that is intended for Spanish health professionals. The researcher created both a handbook and a guide for this topic using an adaption of the Three-talk model.ObjectiveA Delphi method will be used to reach an agreement among experts on the contents and design of a manual and guide, designed by the research team, and to be used by health professionals in the application of SDM in breast cancer screening.DesignA qualitative study. The content and design of the handbook and the guide was discussed by 20 experts. The Delphi techniques was in an online mode between July and October 2020 and researchers used Google forms in three rounds with open and closed questions. The criterion established for consensus was a coefficient of concordance (Cc) above 75, for questions using a Likert scale of 1–6—in which 1 meant ‘completely disagree’ and 6 ‘completely agree’—with a cut-off p...

PALABRAS CLAVE Concordancia; Atención primaria; Atención hospitalaria; Enfermedades crónicas Resumen Objetivos: Medir la concordancia respecto a las enfermedades crónicas registradas en atención primaria (AP) y hospitalaria, y valorar la utilidad de sus registros asistenciales con fines de investigación. Emplazamiento: Estudio transversal retrospectivo integrando información diagnóstica de AP y hospitalaria de la población de Aragón ingresada en 2010. Participantes: Se analizó a 75.176 pacientes Intervenciones: Se analizaron coincidencias, divergencias e índice kappa de los diagnósticos registrados en AP y hospital, estratificando por grupos de edad y sexo. Mediciones principales: Enfermedades estudiadas: EPOC, diabetes, hipertensión, enfermedad cerebrovascular, cardiopatía isquémica, asma, epilepsia e insuficiencia cardiaca. Resultados: La concordancia fue mayor en hombres y entre los 45-64 años. Diabetes fue el diagnóstico más concordante (índice kappa: 0,75) mientras que asma obtuvo los valores más bajos (índice kappa: 0,34). Conclusiones: La baja concordancia de la información diagnóstica contenida en AP y hospital obliga a adoptar medidas que permitan a los profesionales sanitarios a conocer el conjunto de problemas de salud que presenta un paciente.

Circulating tumour cell (CTC) clusters have been proposed to be major players in the metastatic spread of breast cancer, particularly during advanced disease stages. Yet, it is unclear whether or not they manifest in early breast cancer, as their occurrence in patients with metastasis-free primary disease has not been thoroughly evaluated. In this study, exploiting nanostructured titanium oxide-coated slides for shear-free CTC identification, we detect clustered CTCs in the curative setting of multiple patients with early breast cancer prior to surgical treatment, highlighting their presence already at early disease stages. These results spotlight an important aspect of metastasis biology and the possibility to intervene with anti-cluster therapeutics already during the early manifestation of breast cancer.

Multimorbidity remains an underexplored domain in Indian primary care. We undertook a study to assess the prevalence, correlates, and outcomes of multimorbidity in primary care settings in India. This paper describes the process of development and validation of our data collection tool "Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC)." An iterative process comprising desk review, chart review, and expert consultations was undertaken to generate the questionnaire. The MAQ-PC contained items on chronic conditions, health care utilization, health related quality of life, disease severity, and sociodemographics. It was first tested with twelve adults for comprehensibility followed by test-retest reliability with 103 patients from four primary care practices. For interrater reliability, two interviewers separately administered the questionnaire to sixteen patients. MAQ-PC displayed strong internal consistency (Cronbach's alpha: 0.69), interrater reliability (Cohen's Kappa: 0.78-1), and test-retest reliability (ICC: 0.970-0.741). Substantial concordance between self-report and physician diagnosis (Scott Kappa: 0.59-1.0) was observed for listed chronic conditions indicating strong concurrent validity. Nearly 54% had one chronic condition and 23.3% had multimorbidity. Our findings demonstrate MAQ-PC to be a valid and reliable measure of multimorbidity in primary care practice and suggest its potential utility in multimorbidity research in India.