General Clinical Practice Research Articles

Chapter 15 - Psychopharmacology of traumatic brain injury

The pathophysiology of traumatic brain injury (TBI) can be highly variable, involving functional and/or structural damage to multiple neuroanatomical networks and neurotransmitter systems. This wide-ranging potential for physiologic injury is reflected in the diversity of neurobehavioral and neurocognitive symptoms following TBI. Here, we aim to provide a succinct, clinically relevant, up-to-date review on psychopharmacology for the most common sequelae of TBI in the postacute to chronic period. Specifically, treatment for neurobehavioral symptoms (depression, mania, anxiety, agitation/irritability, psychosis, pseudobulbar affect, and apathy) and neurocognitive symptoms (processing speed, attention, memory, executive dysfunction) will be discussed. Treatment recommendations will reflect general clinical practice patterns and the research literature.

In Hospital outcome of Prediction of Peripheral Arterial disease In Diabetic Tobacco User Patients

Background: Peripheral artery disease (PAD) is a distinct atherosclerotic disorder marked by stenosis of the arteries common in tobacco users. Here we investigate prediction of unknown peripheral arterial disease (PAD) amongst patients with diabetic tobacco user and diabetic without tobacco user.Methodology: This prospective observational study was conducted in the Department of Cardiology, Ibrahim Cardiac Hospital and Research Institute, Dhaka, Bangladesh. A total of 60 patients were enrolled in this study who were presented with chest pain associated with lower limb claudication. They were diabetic population, constituted tobacco user in group-I and without tobacco user in group-II.Results: Hypertension was the leading risk factor in both groups (76.7% vs. 80%). 80% of patients of group I and 46.7% of patients of group II had mild form of ABI value. 3.3% of patient of group II had severe form of ABI value. There was no statistical significant difference between two group of patients (p=0.053). 93.3% patients of group I and 96.7% patients of group II had coronary artery disease. Twenty three patients of tobacco user group (n=30) had peripheral artery disease, whereas ten patients of without tobacco user group (n=30) had peripheral artery disease which was statistically significant (p=0.003). Three quarters (76.7%) of group I developed PVD as compared to 33.3% of group II. The risk of developing PVD in diabetic smokers was observed to be more than 6 fold (95% CI: 2.109-20.479) higher than that in non tobacco user were diabetics. 16.7% patients of group I atherosclerosis in femoral artery and the value is 10% in case of group-II, which is statistically in significant(p=0.433).Conclusion: The awareness and implementation of ABI in general clinical practice is poor. A simple, inexpensive test like ABI can improve the diagnosis of PAD in clinical practice and thus help in preventing CAD and consequent death by a range of medical therapies.Anwer Khan Modern Medical College Journal Vol. 9, No. 2: Jul 2018, P 102-109

Health Outcomes for Definite Concurrent Chemoradiation in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

Background: In patients with locally advanced lung cancer treated with concurrent chemoradiation, outcome measurements have been mostly limited to survival. Objectives: We aimed to measure outcomes that matter to these patients beyond survival in a general clinical practice. Methods: In a prospective single-centre study, consecutive patients with locally advanced non-small cell lung cancer reported their own outcomes using the EORTC Quality of Life Questionnaire Core 30 at baseline, during therapy, at therapy stop and till 1 year after therapy end every 3 months. Survival, complications, quality of death and case-mix variables were measured. Results: There were 32 consecutive patients included prospectively from June 2013 until September 2016. Median overall survival was 24.3 months (95% CI 12.7–35.9). Severe toxicity (grade III–IV) was frequent (haematologic toxicity III–IV in 59%). Patient-reported outcomes (PROs) documented the burden on global health status and on functional domains (physical, role, social, emotional and cognitive functioning). Deterioration was pronounced during and after treatment with drops over 20 up to 40% points from baseline for physical, role and social functioning. Clinically meaningful negative effects did persist up to 6 and 9 months for physical and role functioning. Fifty-six percent of the deceased patients died in hospital. Conclusions: The assault on health-related quality of life during concurrent chemoradiation for locally advanced lung cancer is considerable. Loss of physical and role functioning persists up to 6 and 9 months after therapy end, respectively. Measuring PROs can help to identify issues for improvement of the value of care delivered.

Impact of the Affordable Care Act on elective general surgery clinical practice

BackgroundThe Affordable Care Act (ACA) dramatically changed the healthcare system in the United States. This study aims to analyze the impact of the ACA on general surgery clinic visits and resultant procedures. MethodsA retrospective review was conducted on new patients who presented to the elective general surgery clinic at an academic medical center between Jan. 1, 2012 and Dec. 31, 2015. Based on the open enrollment start date of Jan.1, 2014 patients were divided into pre-ACA and post-ACA periods. Data on demographics, type of insurance, missed appointments, and elective surgical procedures performed were collected. ResultsMedi-Cal insurance coverage increased post-ACA from 20.9% to 56.7%, p < 0.001; self-pay status went from 9.8% to 0%. There were 296 (35.4%) surgical procedures performed pre-ACA and 347 (37.1%) post-ACA (p = 0.445). Missed clinic visits decreased after implementation of the ACA, with 26.8% no-shows pre-ACA and 20.7% no-shows post-ACA (p = 0.003). ConclusionThe ACA had a profound impact on the general surgery clinic with fewer uninsured patients, fewer no-shows and a modest increase in the number of procedures performed. SummaryIn 2014 the Affordable Care Act mandate was implemented. This legislation impacted healthcare by significantly decreasing the number of uninsured patients and increasing overall volume in one general surgery clinic.

Assessment of surgical outcomes of femtosecond laser-assisted in situ keratomileusis in patients with low compliance to postoperative follow-up: a retrospective observational study in a tertiary hospital in China

ObjectivesPoor follow-up after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) is common in general clinical practice. We aimed to assess the surgical outcomes of patients with poor compliance to FS-LASIK follow-up...

274P - Real-world experience of olaparib maintenance in high grade serous recurrent ovarian cancer patients with BRCA 1/2 mutation

Objective: Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, maintenance therapy has shown efficacy with tolerability in phase 3 trial of patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). However, real-world effectiveness could be different from result of clinical trials because treatment is used in unselected, general clinical practice populations. We aimed to present real-world experience of olaparib in Korea. Methods: We included HSROC patients with BRCAm treated with olaparib maintenance at 4 institutions (Samsung Medical Center, National Cancer Center, Yonsei University Severence Hospital, and Seoul National University Hospital) in Korea between 2016 and 2018. Their medical records were reviewed retrospectively for objective response, survival outcomes and safety. Results: One hundred HSROC patients with BRCAm were treated with olaparib maintenance therapy. BRCA1 mutation was shown in 66 patients (66.0%), and BRCA2 mutation was shown in 22 patients (22.0%). Number of chemotherapy regimen before olaparib was mostly two (n=63, 63.0%) and three (n=26, 26.0%). Time to progression to chemotherapy before olaparib was median 12.8 months (range 1.0 ~86.4). For objective response to most recent chemotherapy, complete response was shown in 46 patients (46.0%), and partial response in 53 (53.0%). For best objective response with olaparib maintenance, no evidence of disease was shown in 40 patients (40.0%), partial remission in eight (8.0%) and, stable disease in 44 patients (44.0%). During follow-up period (median 10.2 month (range 1.0 ~35.7), 37 recurrences (37.0%), and five death events (5.0%) were observed. Grade 3 or more adverse events were shown in 14 patients (14.0%) with anemia, seven patients with neutropenia (7.0%), two patients with thrombocytopenia (2.0%), one patients with oral mucositis (1.0%) and soft tissue infection (1.0%). Conclusions: Safety and effectiveness of olaparib maintenance treatment in this study was consistent with the results of previous studies with tolerable toxicity profiles.

Somatosensory and transcranial motor evoked potential monitoring in a porcine model for experimental procedures

Evoked potential monitoring has evolved as an essential tool not only for elaborate neurological diagnostics, but also for general clinical practice. Moreover, it is increasingly used to guide surgical procedures and prognosticate neurological outcome in the critical care unit, e.g. after cardiac arrest. Experimental animal models aim to simulate a human-like scenario to deduct relevant clinical information for patient treatment and to test novel therapeutic opportunities. Porcine models are particularly ideal due to a comparable cardiovascular system and size. However, certain anatomic disparities have to be taken into consideration when evoked potential monitoring is used in animal models. We describe a non-invasive and reproducible set-up useful for different modalities in porcine models. We further illustrate hints to overcome multi-faceted problems commonly occurring while using this sophisticated technique. Our descriptions can be used to answer a plethora of experimental questions, and help to further facilitate experimental therapeutic innovation.

P20.01: Low‐set ear detected by three‐dimensional ultrasound in the first trimester and genetic cause

To investigate relationship between fetal low-set ear in the first trimester and congenital abnormality. Between October of 2013 and December of 2017, a total of 12, 671 cases visited our institute for first trimester scan (FTS) were enrolled in this study. Fetal profile was demonstrated by 3D ultrasound and the ear position was confirmed. Low-set ear was defined the upper end of external ear is located below the line between the centre of eye lens and the end of hyaloid, demonstrated by 3D silhouette ultrasound. In low-set ear group, ratios of genetic abnormalities and morphological abnormalities were retrospectively investigated. Low-set ear was detected in 948 cases (7.5%). In a group of low-set ear, genetic tests were done in 791 cases (83.4%). Results of genetic test, abnormal G-banding karyotype was found in 292 cases, including 281 aneuploidy and 11 chromosomal structural abnormality. SNP microarray was done in 123 cases out of negative G-band group, and abnormal CNVs was found in 12 cases including 9 pathogenic CNVs and 3 likely-pathogenic CNVs. In 499 cases of normal genetic test with low-set ear, morphological abnormalities were confirmed by ultrasound in 49 cases (10.1%). From our data in this study, congenital diseases including genetic and morphological abnormalities were confirmed in a total of 45 % of low-set ear group. Furthermore, cases of low-set ear with micrognathia had significantly higher incidence of abnormal genetic result than cases of low-set ear without micrognathia. In this study, it was obvious fetal low-set ear in the first trimester should be strongly associated with congenital abnormalities therefore it can become one of useful ultrasound markers for screening fetal diseases. We have discovered the new method of using silhouette ultrasound for detecting landmarks of exact line for assessment of ear position. However it may be difficult to utilize this new marker because it is a machine-depending method therefore not utilised in general clinical practice. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Development of a quality improvement audit tool for the primary care of children with chronic wet cough using a modified Delphi consensus approach.

In the absence of quality indicators (QIs) for the management of chronic wet cough, our study's aim was to determine whether consensus on QIs reflecting good primary health care, prior to referral for children with chronic wet cough, can be achieved. A questionnaire consisting of 10 QIs was developed by a clinical working group based on current evidence and guidelines on the management of chronic wet cough in children. Each indicator reflected the quality of care provided to children with chronic wet cough in primary care prior to referral. A modified Delphi consensus questionnaire was undertaken involving expert paediatric respiratory clinicians and general paediatricians who graded the importance of each indicator for the purposes above. We a priori defined that consensus was considered achieved if >75% agreed on the indicator. Twenty-two specialists (from Brisbane, Melbourne, Perth and Canberra) participated in the survey. The cumulative number of years of their respiratory experience was 324 and that of general clinical practice was 504. Consensus was achieved in all 10 QIs, with 6 reaching 100% agreement. Mean agreement for the 10 items was 97%. As complete consensus was achieved on these QIs, it can be used as a provisional clinical audit tool and can guide the development of a robust audit tool for primary care clinical practice to assist with quality improvement initiatives.

Classification accuracy of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Effort Index (EI) and Effort Scale (ES) relative to the Test Of Memory Malingering (TOMM) in a mixed clinical sample

Performance Validity Testing has become an integral part of neuropsychological assessment, and a variety of embedded screening measures for performance validity have been proposed. Several performance validity indexes have been developed for the Repeatable Battery for the Assessment of Neuropsychological Status. Although the RBANS Effort Index (EI) and Effort Scale (ES) have garnered some empirical support, other research has raised questions regarding their accuracy in a number of assessment contexts. We evaluated the classification accuracy of the EI and ES against a standalone performance validity measure (Test of Memory Malingering; TOMM) in a mixed clinical patient sample. Our results showed limited utility for the ES in a mixed sample and modest classification accuracy for the EI, raising concerns about the appropriate scope of use for these scales in general clinical practice, which suggested that an alternate EI cutoff score of >0 may be most appropriate.

Variations in Australian dental therapy practice by practitioner and workplace characteristics

Understanding dental therapy practice across clinical settings is useful for education and service planning. This study assessed if dental therapy service provision varied according to practitioner and workplace characteristics. Members of professional associations representing dental therapists (DT) and oral health therapists (OHT) were posted a self-complete survey collecting practitioner and workplace characteristics, together with clinical activity on a self-selected typical day of practice. Differences in service provision according to characteristics were assessed by comparing mean services per patient visit. Negative binomial regression models estimated adjusted ratios (R) of mean services per patient. The response rate was 60.6%. Of practitioners registered as an OHT or a DT, 80.0% (n = 500) were employed in general clinical practice. Nearly one-third of OHT and nearly two-thirds of DT worked in public sector dental services. Patterns of service provision varied significantly according to practice sector and other characteristics. After adjusting for characteristics, relative to private sector, public sector practitioners had higher provision rates of fissure sealants (R = 3.79, 95% confidence interval [95% CI]: 2.84-5.06), restorations (R = 3.78, 95% CI: 2.94-4.86) and deciduous tooth extractions (R = 3.58, 95% CI: 2.60-4.93) per patient visit, and lower provision rates of oral health instruction (R = 0.86, 95% CI: 0.76-0.98), fluoride applications (R = 0.43, 95% CI: 0.33-0.56), scale and cleans (R = 0.39, 95% CI: 0.34-0.45) and periodontal services (R = 0.20, 95% CI: 0.14-0.28) per patient visit. Differences in service provision according to sector indicate that OHT and DT adapt to differing patient groups and models of care. Variations may also indicate that barriers to utilising the full scope of practice exist in some settings.

Reliability and validity of arm function assessment for the Fugl–Meyer assessment with a Japanese guideline

The Fugl–Meyer Assessment (FMA) is widely used in stroke research as a gold standard. However, the FMA has not been used in general clinical practice in Japan, which may be related to that the FMA was not translated in the standardized way (including forward translation and back translation). Against the background of linguistic and cultural differences, we translated the standardized FMA into Japanese and adapted it for use in Japan. The aim of the present study is to assess its reliability and validity for the FMA with a Japanese guideline. A prospective single-center study involving 30 patients with mild-to-severe hemiparesis was conducted. This study was registered in 2016 as a pre-initiation condition. A standardized guidebook for the FMA test administration and scoring was used. The FMA and the Action Research Arm Test, the Box-and-Block Test, and the Motor Activity Log were employed. The simultaneous/non-simultaneous inter-rater reliability and the criterion-referenced validity were assessed in the following ways: the intraclass correlation coefficient (ICC) and the Spearman's rank-order correlation coefficient (Spearman's rho). The ICC for the simultaneous and the non-simultaneous reliability in the motor section were 0.999 (0.997–0.999, P < 0.001) and 0.983 (0.928–0.994, P < 0.001). The Spearman's rho for the validity in the motor section ranged from 0.93 to 0.95 (P < 0.05). The FMA with a Japanese guideline reliably assesses the affected upper extremities in patients with hemiparesis after stroke.

Predictors of dental plaque and gingivitis in patients receiving integrated dental treatment-a longitudinal retrospective study.

The identification of predictors of supragingival biofilm accumulation may improve the results of therapeutic strategies for dental caries and periodontal diseases in general clinical practice. This study aimed to determine predictors of changes in visible plaque (VP) and gingival bleeding (GB) during integrated dental care. A retrospective longitudinal study was conducted by a census of patients receiving integrated dental care in a general clinical practice ambulatory at the Federal University of Rio Grande do Sul (Brazil). The sample comprised 91 charts of patients attended over a 6-months period. Gender, age, patient's main complaint, oral hygiene pattern, and clinical data were recorded from charts for the last two dental visits in the ambulatory. Changes in VP and GB were modeled by multiple linear regression and beta coefficients (b) were reported. The mean follow-up time was 13months. Significant reductions in VP (32.8 ± 27.9 to 17.4 ± 19.4%; p < 0.001) and GB (27.1 ± 23.8 to 18.5 ± 17.3%; p < 0.001) were observed. Higher plaque reductions were predicted by higher baseline VP levels (p = 0.02), shorter time (< 12months) elapsed between VP recordings (b = 14.1%, p = 0.02), interproximal cleansing (b = 11.9%, p = 0.03), lower number of sessions for oral hygiene instruction (b = 13.7%, p = 0.02), and presence of pockets ≥ 6mm (b = - 12.4%, p = 0.02). GB was predicted by time of follow-up > 12months and baseline VP. Plaque and gingivitis improved in patients under integrated dental care. Factors related to motivation, oral hygiene practices, and baseline periodontal status might be used as predictors of VP and GB changes. Visible plaque and gingivitis reduced in a sample of patients treated under integrated dental care. Some predictors may determine for which patients the treatment may be maximize and those who will need greater efforts to achieve the therapeutic goal for oral hygiene.

Obesity Education in Medical School Curricula in Korea.

Obesity is one of the three most common diseases, affecting about one-third of adults. Obesity also increases vulnerability to metabolic disorders, psychological disorders, and various cancers and decreases quality of life. Therefore, obesity must be adequately addressed in medical school. Here, I will review how obesity education is implemented in medical school curricula in Korea. Many studies have shown that students who are well educated about obesity through various educational methods reduce their prejudice toward obese patients. The Korean Society for the Study of Obesity is an interdisciplinary academy, including experts from fields such as general research, clinical practice, nutrition, nursing, exercise, and rehabilitation. They aim to identify the core competencies of obesity education necessary for medical students, develop curricula of obesity education, and present examples of lectures and discussions. In the future, health professionals who receive such education will be able to take better care of obese patients without bias.

Nursing and midwifery use, perceptions and barriers to evidence-based practice: a cross-sectional survey.

The study aimed to explore how nurses and midwives obtain, use and embed evidence in everyday practice. The study design was cross-sectional survey method. The setting was one local health district in metropolitan Sydney, Australia. All nurses and midwives working within the local health district, with access to an email account, were invited to participate in the study. An online survey questionnaire was distributed to explore how evidence is obtained, used and embedded within the clinical setting. The data were analysed using descriptive statistics (frequency and percentages). Pearson's Chi-square tests were used for comparison between groups. There were 204 survey respondents. The findings identified that the majority (n = 157; 76.96%) of respondents obtained evidence primarily from clinical practice guidelines. The majority (n = 149; 73.04%) of respondents reportedly searched databases and used evidence related to general clinical practice. There was a statistical difference (χ = 17.069; df = 8; P = 0.029) when comparing leadership positions and other registered practitioner groups in the frequency of searching for evidence. Most respondents (n = 138; 67.65%) were confident in their ability to change practice on the basis of available evidence. Thematic analysis identified four barriers to sustaining evidence-based practice, which included: the need for time; the need for organizational and management support; the need for educational opportunities and challenges to accessing evidence. The study provided an understanding of how nurses and midwives obtain, use and embed evidence into everyday practice. More importantly, the role of leadership is significant to support a process of knowledge generation, research translation and the implementation of evidence into clinical settings.

Abstract OT3-05-04: A randomized, open-label, multi-center phase IV study evaluating palbociclib plus endocrine treatment versus a chemotherapy-based treatment strategy in patients with hormone receptor-positive, HER2-negative metastatic breast cancer in a real world setting (PADMA)

Abstract Background: Although endocrine therapy (ET) is recommended as first-line therapy for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC) up to 50% of patients receive chemotherapy in this setting. Meanwhile new targeted treatment options for combination with ET have been developed and endocrine-based therapy with the CDK4/6 inhibitor Palbociclib (P) improves the progression free survival (PFS) of ET alone by about 50%. So far, there is no data comparing chemotherapy with or without maintenance ET and ET in combination with P as first-line therapy. Patients included in clinical trials are often criticized not to mirror the general breast cancer population and every-day clinical practice due to rigid inclusion and exclusion criteria, limited number of treatment options, strict monitoring intervals and study assessments. Methods: PADMA trial is a so called low intervention trial with no rigid inclusion and exclusion criteria, and study assessments.Patients with first-line HR+/HER2- MBC who are candidate for mono-chemotherapy will be eligible to receive either P plus ET per label or mono-chemotherapy per investigator´s choice with or without maintenance ET (1:1 randomization). Primary objective is to compare the time-to-treatment failure (TTF) for patients randomized to receive the mono-chemotherapy treatment strategy versus those randomized to receive P and ET. TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient's preference, or death. Main secondary objectives are progression free survival, overall survival at 36 months, amongst other time to event endpoints as well as toxicity and compliance. All patients receive a specific mobile device (PADMA-Phone) and a validated wearable device (ActiWatch) in order to collect data regarding sleep and activity levels, patient well-being and health care utilization (number and duration of phone calls, and patient visits to investigator site) for assessment of daily monitoring treatment impact (DMTI). Results: Overall, 360 patients will be accrued to show an improved TTF for P in combination with ET compared to mono-chemotherapy of investigator´s choice with or without maintenance ET. Recruitment will start in QIII/2017 and is planned for approximately 18 months in 100 sites in Germany, Spain, Poland, Italy, France, UK and Canada. Conclusions: The aim of PADMA is to demonstrate that an endocrine-based strategy consisting of ET plus P is superior to a chemotherapy-based strategy as first-line therapy in women with HR+/HER2- MBC in a real world setting. Assessment of patient-reported outcome, health care utilization, and sleep and activity levels will deliver important information on the differences between endocrine-based and chemotherapy-based treatment. Citation Format: Loibl S, Barinoff J, Seiler S, Decker T, Denkert C, Hardy-Bessard A-C, Senkus-Konefka E, Cognetti F, Palmieri C, Gelmon K, Luebbe K, Furlanetto J, Mueller V, Mundhenke C, Schmidt M, von Minckwitz G, Uhlig M, Burchardi N, Thill M. A randomized, open-label, multi-center phase IV study evaluating palbociclib plus endocrine treatment versus a chemotherapy-based treatment strategy in patients with hormone receptor-positive, HER2-negative metastatic breast cancer in a real world setting (PADMA) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-05-04.

Circulating tumor cells as predictors of prognosis in metastatic breast cancer: clinical application outside a clinical trial.

Circulating tumor cells have a prognostic role in metastatic breast cancer. The aim of the study was to confirm the ability of circulating tumor cells, detected by the US Food and Drug Administration approved Cell Search assay, to predict the outcome of patients treated in a community general hospital. A prospective mono-institutional study was conducted at the Department of Medical Oncology at Spedali Civili, Brescia, Italy, from January 2009 to September 2010. A total of 93 consecutive patients with metastatic breast cancer were enrolled. Patients underwent a blood sample collection to detect circulating tumor cells at baseline and, subsequently, at the first follow-up examination (after 3-4 weeks from the beginning of a systemic therapy). A third sample was drawn at disease progression (at the beginning of a subsequent new course of therapy). The prognostic cutoff value of circulating tumor cells was fixed at 5 cells/7.5 ml of blood. At baseline, median overall survival and progression-free survival in the subgroup ≥5 circulating tumor cells/7.5 ml of blood were significantly shorter (5 months and 3 months, respectively) than in the subgroup with <5 circulating tumor cells (8 months and 7 months, respectively) (P = 0.003 and P <0.001). At the first follow-up, the subgroup with more than 5 circulating tumor cells/7.5 ml of blood had a median overall survival of 4 months versus 8 months in the subgroup with <5 circulating tumor cells (P <0.001) and a median progression-free survival of 3 months versus 7 months respectively (P <0.001). At multivariate analysis, the level of circulating tumor cells at the first follow-up and at baseline remained significant as a predictor of progression-free and overall survival. The number of metastatic sites was significantly associated with overall and progression-free survival and correlated with the number of circulating tumor cells. Our study confirms the role of circulating tumor cells as predictors of prognosis in metastatic breast cancer patients treated in general clinical practice.

Automation on an Open-Access Platform of Alzheimer's Disease Biomarker Immunoassays.

The lack of (inter-)laboratory standardization has hampered the application of universal cutoff values for Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and their transfer to general clinical practice. The automation of the AD biomarker immunoassays is suggested to generate more robust results than using manual testing. Open-access platforms will facilitate the integration of automation for novel biomarkers, allowing the introduction of the protein profiling concept. A feasibility study was performed on an automated open-access platform of the commercial immunoassays for the 42-amino-acid isoform of amyloid-β (Aβ1-42), Aβ1-40, and total tau in CSF. Automated Aβ1-42, Aβ1-40, and tau immunoassays were performed within predefined acceptance criteria for bias and imprecision. Similar accuracy was obtained for ready-to-use calibrators as for reconstituted lyophilized kit calibrators. When compared with the addition of a standard curve in each test run, the use of a master calibrator curve, determined before and applied to each batch analysis as the standard curve, yielded an acceptable overall bias of -2.6% and -0.9% for Aβ1-42 and Aβ1-40, respectively, with an imprecision profile of 6.2% and 8.4%, respectively. Our findings show that transfer of commercial manual immunoassays to fully automated open-access platforms is feasible, as it performs according to universal acceptance criteria.

A review of functional gastrointestinal disorders: A primer for mental health professionals

Functional gastrointestinal disorders (FGIDs) are chronic, recurrent, frequently debilitating disorders with no identifiable underlying pathology. They occur due to a complex interplay between biological, psychological, and social factors and are some of the most common conditions encountered in general clinical practice as well as the specialist gastroenterological clinic. The top-down regulation of visceral sensations plays an important role in the pathophysiology of the disease, i.e., the central processing of emotions and stressors altering the sensory and motor components of the gut, which increases hypersensitivity and therefore symptom severity. In addition, the core personality traits of the individual play their part in the way symptoms are perceived, further providing proof for the long-prevailing belief that the gut and emotions are linked, the so-called “gut feeling.” The current diagnostic criteria for FGIDs are entirely based on subjective symptoms, challenging in itself due to the varied presentations, and further complicated by the current unavailability of objective laboratory tests which could confirm its presence in the symptomatic individual. The various treatment modalities include psychotherapies ranging from cognitive behavioral therapy to mindfulness, along with appropriate pharmacotherapy to treat physical and psychiatric comorbidities. Addressing all these underlying causes, in addition to weighing in the genetic makeup of the individual, is necessary for delineating accurate prognosis, reducing attending health-care costs, and improving overall outcome of the individual.

Clinical update on central hypersomnias.

The central hypersomnias encompass a range of conditions causing persisting or intermittent excessive daytime sleepiness (EDS). These conditions therefore present not infrequently in general clinical sleep practice, and remain in the differential for patients presenting with sleepiness. Our understanding of the pathophysiology, diagnosis and management of these conditions has progressed significantly over recent years, and in this article we review this group of disorders, focussing in particular on recent changes in classification and diagnosis, pathophysiological advances, and novel treatment options.