Somatic Causes Research Articles

Diagnostic and psychopharmacotherapy in the general practictioner practice

IntroductionDue to the often long-standing and extensive doctor-patient relationship, family doctors have special access to the mental state of their patients. They are often the first point of contact, and consequently the treatment of depression often begins in the GP’s practice or even takes place entirely there. This requires dedicated knowledge on the part of the general practitioner, especially with regard to diagnostic criteria and treatment.Objectives The aim of this article is to describe the basic diagnostic process for the general practitioner’s practice, to give advice on the indication and implementation of psychopharmacological interventions, and to present the results. This overview summarises the most relevant connections to the diagnosis, assessment of the severity and psychopharmacotherapy of depression in general practice.MethodsThe following therapy algorithms and remarks are essentially based on the treatment recommendations of the Swiss Society for Psychiatry and Psychotherapy (SGPP) and the Swiss Society for Anxiety and Depression (SGAD) as well as the German S3 guideline of the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN).Results Family doctors play a central role in the treatment of depressive disorders. They are often the first point of contact for patients with depression and in about 40 percent of cases even the only contact point. The likelihood of developing a depressive episode in the course of a lifetime is 10 to 15 percent globally. Evaluations by the World Health Organisation WHO show that 9 to 23 percent of people with chronic illnesses have depression as a concomitant illness. A cross-sectional epidemiological study in Germany showed that 60 percent of patients in general medical care were not treated with antidepressants and/or psychotherapy in accordance with guidelines. In Switzerland, about half of the antidepressants are currently prescribed by general practitioners. Image 1 shows a detailled overview (in German) of the current medication.Image:ConclusionsSpecialists in general internal medicine have a central role in recognition and treatment of depressive syndromes. Somatic causes can be ruled out by means of physical examination, laboratory and ECG/EEG/imaging. Mild and moderate depressive episodes can be treated by psychoeducation, counselling and medication. If the symptoms are mild, psychosocial support or psychotherapy alone can be considered. If acute suicidal tendencies or psychotic symptoms are identified, emergency symptoms, emergency admission to a psychiatric hospital should be considered.The presence of other psychiatric comorbidities, resistance to therapy or complex psychiatric medication necessitate referral to outpatient specialists. Metabolic and cardiovascular side effects and interactions between psychopharmacological and internal medicine must be considered.Disclosure of InterestNone Declared

Functional Constipation and Nonretentive Fecal Incontinence in Children and Adolescents: Clinical Guideline for Assessment and Treatment

Functional Constipation and Nonretentive Fecal Incontinence in Children and Adolescents: Clinical Guideline for Assessment and Treatment Abstract. Objective: Constipation and fecal incontinence are common disorders in children and adolescents and are associated with incapacitation and a high rate of comorbid psychological disorders. Functional constipation and nonretentive fecal incontinence can be differentiated according to the current Rome-IV classification systems. This interdisciplinary guideline aims to summarize the current state of knowledge regarding somatic and psychiatric assessment and treatment. It formulates consensus-based, practical recommendations. Methods: The members of the Guideline Commission consisted of 11 professional associations and a parental organization. The guideline was based on current literature searches, several online surveys, and consensus conferences based on standard procedures. Results: Functional constipation is much more common than nonretentive fecal incontinence. Constipation requires a detailed medical assessment to exclude somatic causes, especially in young children. Red flags are useful indicators of organic causes to be considered. Most cases of constipation are functional (approximately 95 %). Counseling, toilet training, disimpaction, and long-term oral laxatives, combined with cognitive-behavioral interventions, are most effective. The assessment and treatment of nonretentive fecal incontinence are similar. The rate of somatic factors is much lower (approximately 1 %). Laxatives can worsen outcomes and should be avoided. Comorbid psychological disorders are common (approximately 30 % to 50 %). They should be assessed and treated additionally according to evidence-based guidelines. Conclusions: The recommendations of this guideline were approved with a high consensus. Interdisciplinary cooperation is especially important, as somatic factors and comorbid psychological disorders and symptoms need to be considered. More research is required, especially regarding nonretentive fecal incontinence.

The need of having a plan in excessive infant crying - A qualitative study of parents' experiences of healthcare support.

Excessive infant crying increases parents' concerns regarding their infant's health and the burden of parenting. We aimed to gain insight into the healthcare support needs of parents with excessively crying infants. An exploratory qualitative study was conducted in the Netherlands. We performed semi-structured interviews with parents of 12 infants between June and December 2020, followed by inductive and deductive thematic analysis. Parents described what their needs were with regard to the assessment of infant crying and support by professionals. Long-lasting crying made parents feel that there must be a somatic cause. If they could soothe their infant, they gained more confidence that their infant was healthy. We identified four interrelated themes: (i) confidence in the professional; (ii) seeking a somatic cause for the crying; (iii) seeking acknowledgment; and (iv) exhaustion of parents and feelings of failure. Parental support needs were best fulfilled by professionals who took them seriously, demonstrated medical expertise, and offered a practical plan. Perinatal parental education on normal infant behaviour and infant soothing techniques might improve parental self-efficacy at an early stage and prevent medicalization of excessive crying.

THE ROLE OF MICROSATELLITE INSTABILITY IN COLORECTAL CANCER:
 LITERATURE REVIEW

Relevance: According to Globocan 2020, colorectal cancer (CRC) incidence in Kazakhstan is lower than in all OECD countries except
 Mexico. However, the CRC incidence in Kazakhstan is steadily growing. In the structure of cancer incidence, CRC went up from 5th place in 2006
 to 3rd place in 2021. More than 80% of tumors associated with Lynch syndrome were found to have microsatellite instability (MSI). Thus, MSI is
 detected in 12% of sporadic colon tumors. At that, MSI in the tumor is caused by a decreased activity of DNA repair genes that can be due to both
 hereditary and somatic causes.
 The study aimed to systematize the current literature data to consider the need and adequacy of pre-scribing preventive chemotherapy, personalizing the treatment of patients, and predicting the course of the disease in CRC.
 Methods: A review was made of the published results of scientific and clinical studies for 2006-2021 from the PubMed, MedLine, and Cancer
 Observe database for the keywords “colon cancer,” “microsatellite resistance,” “adjuvant chemotherapy,” “PCR study,” “IGH-study.”
 Results: The value and adequacy of determining the IHC characteristics of the MSI status. The prognostic and predictive value of MSI in CRC
 has been proven. The optimal treatment options were determined depending on the status of MSI.
 Conclusion: Tumors with certain MSI status should be classified as a separate group of malignancies. Instability status determination is
 preferred in case of suspected Lynch syndrome, in patients with stage II CRC, as well as in clinical and histological features characteristic of MSI
 (proximal localization of the primary tumor, mucinous histotype, poorly differentiated tumors, lymphocytic infiltration of the tumor). Further determination of these tumors’ molecular characteristics will help stratify patients who may respond differently to chemotherapy. Also, the MSI status
 determination can be an importnant prognostic marker in patients whose tumors have a somatic mutation in the BRAF gene

THE ROLE OF MICROSATELLITE INSTABILITY IN COLORECTAL CANCER: A LITERATURE REVIEW

Relevance: According to Globocan 2020, colorectal cancer (CRC) incidence in Kazakhstan is lower than in all OECD countries except Mexico. However, the CRC incidence in Kazakhstan is steadily growing. In the structure of cancer incidence, CRC went up from 5th
 place in 2006 to 3rd place in 2021. More than 80% of tumors associated with Lynch syndrome were found to have microsatellite instability
 (MSI). Thus, MSI is detected in 12% of sporadic colon tumors., MSI in cancer is caused by a decreased activity of DNA repair genes due
 to hereditary and somatic causes.
 The study aimed to systematize the current literature data to consider the need and adequacy of prescribing preventive chemotherapy,
 personalizing the treatment of patients, and predicting the course of the disease in CRC.
 Methods: A review was made of the published results of scientific and clinical studies for 2006-2021 from the PubMed, MedLine,
 and Cancer Observe databases for the keywords “colon cancer,” “microsatellite resistance,” “adjuvant chemotherapy,” “PCR study,”
 “IGH-study.”
 Results: The value and adequacy of determining the IHC characteristics of the MSI status. The prognostic and predictive value of MSI
 in CRC has been proven. The optimal treatment options were selected depending on the status of MSI.
 Conclusion: Tumors with certain MSI status should be classified as a separate group of malignancies. Instability status determination is preferred in case of suspected Lynch syndrome in patients with stage II CRC, as well as in clinical and histological features
 characteristic of MSI (proximal localization of the primary tumor, mucinous histotype, poorly differentiated tumors, lymphocytic infiltration of the tumor). Further determination of these tumors’ molecular characteristics will help stratify patients who may respond
 differently to chemotherapy. Also, the MSI status determination can be an important prognostic marker in patients whose tumors have
 a somatic mutation in the BRAF gene.

Intérêt de l’évaluation somatique systématique chez les patients adultes à présentation psychiatrique en structure des urgences

IntroductionDuring a consultation with a psychiatric presentation in emergency departments (EDs), a somatic examination is often performed. However, the value of systematic somatic assessment remains debated. Materials and methodsMulticenter study in three EDs, retrospective, over two months, including all major patients consulting in an ED for psychiatric reason, without associated intoxication. The primary objective was to evaluate the rate of consultations in which a somatic etiology was found on admission and at D7. The secondary objective was to look for initial clinical features predicting the risk of an underlying somatic problem in ED. ResultsIn all, 638 consultations were included. Main reasons were anxiety (35.7%) and depression (35.7%). Psychiatric history was found in 60.7% of cases. No abnormalities in the vitals parameters were found in 412 cases (64.6%) during the nurse screening. A somatic etiology related to the reason for consultation was found in ED on day 0 for 38 (6.0%) consultations. The hospitalization rate was 47.3%, mainly in psychiatry (87.4%). Analysis of the files revealed 63 (10.9%) somatic adverse events at D7, which may have created or increased psychiatric symptoms. The somatic cause found (55.6% of new pathologies) was neurological in 34.9% of cases, metabolic in 30.1%, and infectious in 12.6%. Factors correlated with a somatic etiology at admission were (P<0.001 for all): older age: 64.5 [46.5–83.8] vs. 37 [25–54] years; the presence of behavioral disorders: 68.4% vs. 29.3% or delusions: 36.8% vs. 9.8%; the existence of a history of cardiological, neurological, renal or metabolic disorders; the presence of at least one abnormal parameter at the time of the nurse triage: 63.2% vs. 33.7%. In young patients (≤45 years), with no history other than psychiatric, no delusions or behavioral problems, and no abnormalities on the nurse triage, we found a significant somatic etiology in 1% of cases on admission and 3.2% of cases at D7. ConclusionThe prevalence of somatic problems in patients with a psychiatric presentation is low in our study but somatic examination remains desirable for certain categories of patients where the incidence of somatic pathology is higher.

Mortality, Causes of Death, and Predictors of Death among Patients On and Off Opioid Agonist Treatment: Results from a 19-Year Cohort Study

Background: Mortality is increased among people with opioid use disorder but reduced while on opioid agonist treatment (OAT). However, the impact of patient and treatment characteristics on mortality and causes of death is insufficiently studied. Objectives: The objective of this study was to explore mortality and causes of death and examine the impact of patient and treatment characteristics on mortality in an OAT cohort with high retention in treatment. Methods: Design: longitudinal cohort study. Setting: Norway. Observation period: time from OAT start as of 1998 until death or end of 2016, 2,508 person-years (PY) in total. Sample: 200 persons starting OAT 1998–2007. Data sources: hospital records, interviews, the Norwegian Cause of Death Registry, Statistics Norway. Results: Retention: 86.4% of the observation period was on OAT, 9.0% off, 4.6% unknown OAT status. All-cause crude mortality rate per 100 PY during the whole observation period was 1.64 (95% CI: 1.19–2.20), for deaths of somatic cause 0.88 (0.56–1.31), for drug-induced deaths 0.44 (0.23–0.76), and traumatic deaths 0.24 (0.10–0.50). Off-versus-on-OAT all-cause mortality ratio was 2.31 (1.00–4.85). On OAT, 58% of the deaths were of somatic cause and 21% drug-induced; off OAT, 38% of somatic cause and 50% drug-induced. Increasing baseline age and rate of somatic hospital treatment episodes were independently associated with increased all-cause mortality risk, while increasing rate of in-patient psychiatric treatment episodes was associated with reduced risk. Increasing duration of nicotine and cannabis use and alcohol dependence as well as increasing severity of polydrug use were associated with increased all-cause and somatic mortality adjusted for age and sex. Conclusion: The long observation period made it possible to demonstrate the importance of long-term retention in OAT to reduce mortality. Further, the preponderance of somatic and reduction of drug-induced causes of death during OAT underlines the need for follow-up of chronic diseases and health-promoting lifestyle changes. These findings add to the knowledge about long-term OAT effects, not least in ageing OAT populations.

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

Nucleic acid damage from oxidative stress (NA-OXS) may be a molecular mechanism driving the severely increased morbidity and mortality from somatic causes in adults with psychiatric disorders. To systematically retrieve and analyze data on NA-OXS across the psychiatric disorder diagnostic spectrum. The PubMed, Embase, and PsycINFO databases were searched from inception to November 16, 2021. A hand search of reference lists of relevant articles was also performed. Key study inclusion criteria in this meta-analysis were as follows: adult human study population, measurement of any marker of DNA or RNA damage from oxidative stress, and either a (1) cross-sectional design comparing patients with psychiatric disorders (any diagnosis) with a control group or (2) prospective intervention. Two authors screened the studies, and 2 senior authors read the relevant articles in full and assessed them for eligibility. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two authors performed data extraction independently, and a senior coauthor was consulted in cases of disagreement. Data were synthesized with random-effects and multilevel meta-analyses. The predefined hypothesis was that individuals with psychiatric disorders have increased NA-OXS levels. The main outcome was the standardized mean differences (SMDs) among patients and controls in nucleic acid oxidation markers compared across diagnostic groups. Analyses were divided into combinations of biological matrices and nucleic acids. Eighty-two studies fulfilled the inclusion criteria, comprising 205 patient vs control group comparisons and a total of 10 151 patient and 10 532 control observations. Overall, the data showed that patients with psychiatric disorders had higher NA-OXS levels vs controls across matrices and molecules. Pooled effect sizes ranged from moderate for urinary DNA markers (SMD = 0.44 [95% CI, 0.20-0.68]; P < .001) to very large for blood cell DNA markers (SMD = 1.12 [95% CI, 0.69-1.55; P < .001). Higher NA-OXS levels were observed among patients with dementias followed by psychotic and bipolar disorders. Sensitivity analyses excluding low-quality studies did not materially alter the results. Intervention studies were few and too heterogenous for meaningful meta-analysis. The results of this meta-analysis suggest that there is an association with increased NA-OXS levels in individuals across the psychiatric disorder diagnostic spectrum. NA-OXS may play a role in the somatic morbidity and mortality observed among individuals with psychiatric disorders.

Tinnitus as a comorbidity to depression and transcranial magnetic stimulation as a treatment for both - case report

IntroductionDepressive symptoms are common in individuals with tinnitus, however, the mechanisms of their interaction are not fully understood. There is neurobiological evidence that might help understanding the interplay between tinnitus and depression which, in turn, helps in making the right choice for treating both conditions.ObjectivesThis case report describes a 70-year old female patient that presented with tinnitus and depressive symptoms lasting for the past 5 years.MethodsThe patient showed limited treatment results with different antidepressants. The otorhinolaryngologist ruled out any possible somatic causes of her tinnitus. Tinnitus was causing her sleep disturbances, which worsened her everyday functioning that was already quite poor even further.ResultsAfter being administered with 30 rounds of TMS, her symptoms either completely resolved or at least reached a level that was adequate for her to start functioning normally on a day-to-day basis.ConclusionsTMS is a technique that provides non-invasive cortical stimulation, more specifically, when used for depression treatment it stimulates the left dorsolateral prefrontal cortex, a brain region synaptically connected to the limbic system involved in mood regulation that is proven to be hypoactive in depression. The limbic system is where tinnitus-related brain networks and regions involved in the pathophysiology of depression overlap. Further research is needed to deepen the understanding of this topic.DisclosureNo significant relationships.

Regression in Young Adults with Down-Syndrome: A Case Series

Regression in young adults with Down syndrome can present itself with an acute loss of acquired skills and change in behavior. The aim of our case series was to describe the heterogeneous clinical presentation of this syndrome as well as accompanying diagnostic and therapeutic challenges and consequences. All three patients were assessed with the CAMDEX-DS (Cambridge Examination for Mental Disorders of Older People with Down Syndrome and Others with Intellectual Disabilities) and the criteria published by the DSMIG-USA (Down-Syndrome Medical Interest Group USA). After ruling out somatic or other psychiatric causes, the application of the DSMIG-USA criteria resulted in diagnosing at least a probable unexplained regression in all three patients. The thorough diagnostic investigation of unexplained acute regression in young adults with Down syndrome allows for quick initiation of therapeutic and supportive measures. Using the DMSIG-USA criteria facilitates the assessment of the underlying diffuse and heterogenous pathology.

What Predicts Improvement of Dizziness after Multimodal and Interdisciplinary Day Care Treatment?

Background: Vertigo and dizziness are common in community-dwelling people and can be treated in specialized multidisciplinary settings. To develop tailored interventions, however, we have to explore risk factors for favorable and unfavorable outcomes. Methods: We prospectively investigated patients with chronic vertigo and dizziness subjected to our 5-day multimodal and interdisciplinary day care treatment in the Center for Vertigo and Dizziness of Jena University Hospital, Germany. The Vertigo Severity Scale (VSS), the Body Sensations Questionnaire (BSQ), the Hospital Anxiety and Depression Scale (HADS), the Agoraphobic Cognitions Questionnaire (ACQ), the Mobility Inventory (MI), and the burden and intensity of dizziness (using a visual analogue scale) were assessed at baseline (n = 754) and after 6 months (n = 444). In addition, 14 Likert-scaled questions were used to quantify the change in personal attitude and behavior towards the complaints after 6 months. Results: Dizziness-related burden and intensity improved with a large effect size. The largest improvement was seen in the attitudes towards dizziness, the understanding of somatic causes, and the perceived ability to influence dizziness. However, the ability to work and to carry out professional activity was improved to a lesser extent. The overall improvement of dizziness was associated with the absence of a depressive mood, a short duration of vertigo, a lower VSS, a lower perceived intensity of vertigo, and distinct vertigo diagnoses, namely Meniere’s disease, vestibular migraine, vestibular neuritis, vestibular paroxysmia, and vestibular schwannoma. Worsening of dizziness/vertigo was associated with depressive symptoms, permanent vertigo, distinct vertigo diagnoses (central vertigo, multisensory deficit), and a higher perceived burden due to vertigo. Conclusion: The six-month outcome of patients with dizziness presented to a specialized outpatient clinic appears to be favorable. Nevertheless, people with the abovementioned risk factors at baseline have less benefit and probably need adapted and tailored vertigo interventions to improve long-term outcome.

Multidisciplinary treatment for functional urological disorders with psychosomatic comorbidity in a tertiary pelvic care center-A retrospective cohort study.

BackgroundFunctional urological disorders are highly prevalent, frequently interrelated, and characterized by a chronic course and considerable treatment resistance. From our point of view, poor treatment outcomes are often attributable to underlying but undetected mental disorders.ObjectiveTo investigate the effect of integrated outpatient care by a urologist and a psychiatrist on the symptomatology of patients with functional urological disorders in a tertiary referral Pelvic Care Centre.SettingRetrospective observational cohort study in functional urological disorders in combination with psychosomatic co‐morbidity. When treatment by a urologist alone was not sufficient, the suitability for a multidisciplinary approach was considered i) if there was a susceptibility for psychiatric comorbidity, ii) if diagnostic procedures did not reveal a treatable somatic cause, or iii) if multiple failed somatic treatments did not relieve complaints. Patients underwent urological treatments before, without reduction of complaints, no treatable somatic cause could be found after diagnostic procedures; or patients suffered from psychiatric comorbidity.MethodOutcome was measured using patient global impression of improvement, hospitality anxiety and depression scale (HADS), global assessment of functioning (GAF), and a health consumption questionnaire.ResultsA significant reduction in HADS‐depression score was found (p = 0.001) after multidisciplinary treatment. The GAF score increased from 61 to 80, leading to no more than slight impairment in social, occupational, or school functioning. Patients reported their situation as better in comparison with before multidisciplinary treatment. An association was found between pelvic pain and anxiety (p = 0.032) and panic disorder (p = 0.040). Psychological trauma was found to be associated with depression (p = 0.044), with an odds ratio of 2.93 (1.01–8.50). Psychological trauma coincided in 62.3% of patients with urological pain syndromes and in 83.3% with pelvic pain.ConclusionOverall results indicate that functional urological patients, previously refractory to urological treatment, benefit from an integrated care approach by urologists and psychiatrists. Explanation about the bladder–brain axis and the alarm falsification model enlightens understanding of urological and psychological contributions to functional syndromes and creates an opportunity for integrated care.

A Comparison of Regional Brain Volumes in Older Adults With and Without History of COVID-19: Региональные объемы мозга у пожилых людей с наличием и отсутствием COVID-19 в анамнезе.

Recent studies have shown that SARS-CoV-2 can have neuropsychiatric consequences and has the ability to penetrate the blood-brain barrier. If SARS-CoV-2 has a specific route of entry into the brain, it may leave imprints in the form of specific changes in brain morphology. Older individuals are most vulnerable to the neuropsychiatric COVID-19 complications. This study aims to compare regional brain volumes in older adults individuals with and without COVID-19 history (COVID+ and COVID-, respectively). Individuals over 65 years old who applied for treatment to the Memory Clinic (Mental-Health Clinic No. 1 named after N.A. Alexeev, Moscow, Russia) were assessed between October 2020 and April 2021. Their COVID-19 history was determined by the self-report and COVID-19 certificate. Individuals with severe neuropsychiatric or acute or severe chronic somatic or infectious disease and those taking medications potentially affecting cognitive functioning were excluded. All participants underwent MRI examinations followed by image segmentation and morphometric quantitative analysis. Regional brain volumes were compared in COVID+ and COVID- people. 207 participants were included in the study. The COVID+ group consisted of 24 participants. The comparison between groups revealed statistically significant differences in left amygdala area (median 1199.3 mm3 in COVID+ vs. 1263.7 mm3 in COVID-) and right postcentral gyrus volumes (median 8055.5 mm3 in COVID+ vs. 8434.0 mm3 in COVID-). Then case-control analysis was performed in individuals matched for gender, age and common somatic causes of structural brain changes (hypertension and/or diabetes mellitus type 2) for 22 subjects in each group. Statistically significant differences in regional brain volumes between groups were absent. We did not find strong evidence for any regional brain volumes changes in people older than 65 years with a history of COVID-19 in comparison to those without history of COVID-19. Though, given study limitations, these results cannot be generalized to other people who recovered from COVID-19.

Management of Psychiatric Disorders with HIV and Dermatological Disorders.

Management of Psychiatric Disorders with HIV and Dermatological Disorders.

Clinical "Experience" as aCriterion of Evidence? Psychiatric Contributions to aPost-War Debate on a"Reform of Medicine" and the Development of Jürg Zutt's "Understanding Anthropology"

At the Wiesbaden Internist Congress of 1949, Alexander Mitscherlich and Viktor von Weizsäcker called for an expansion of the scientific concept of causality to include the search for the meaning of illness in one's personal history. This called into question atraditional psychiatric paradigm which presumed somatic causes of mental illness. Additionally, common psychiatric evidence practices were put to the test. In the first part of this article, three psychiatric positions that were presented at the 1949 congress are reconstructed. In the second part, the development of one of the psychiatrists involved, Jürg Zutt, is examined by focusing on the question of the possible effects of the Wiesbaden debate on his scientific reorientation as well as its consequences for his view of psychiatric evidence.

Characterization of deceased drug users in Denmark based on treatment status: A nationwide retrospective autopsy study

BackgroundMany drug users are not receiving treatment for their drug use. Little is known about drug users not receiving treatment, as they are difficult to identify and recruit for research. MethodsWe identified 479 autopsied decedents with illegal/unmarketed drug or opioid agonist treatment positive toxicological screenings from 2015 to 2016 in Denmark. Toxicological screenings from autopsy, and information on treatment status at time of death, health care utilization, educational attainment, employment status and prescription drug use from Danish national health registers were used for comparison between groups. ResultsDrug users not in treatment constituted 63.3% of the study population and died at a younger age than those in treatment (41 vs. 44 years). Fatal overdose was the most common cause of death in both groups. Nearly thrice as many drug users not in treatment died from somatic causes compared with drug users in treatment (18.2% vs. 6.8%). On average, drug users not in treatment received fewer prescriptions prior to their deaths than those in treatment, but non-prescribed medications were equally prevalent among both groups (74.3% vs. 81.3%) except for non-prescribed methadone which was significantly less prevalent among drug users not in treatment (33.3% vs. 42.6%). ConclusionTwo-thirds of decedents were not in treatment at time of death. Drug users not in treatment died more often from somatic causes compared to those in treatment. Decedents had equal amounts of non-prescribed psychotropic medication in the blood, but non-prescribed methadone was more common among those in treatment at the time of death.

Fatigue as the Chief Complaint–Epidemiology, Causes, Diagnosis, and Treatment.

Fatigue is a main or secondary reason for 10-20% of all consultations with a primary care physician. This review is based on pertinent publications retrieved by a comprehensive, selective literature search on the epidemiology, etiology, and diagnostic evaluation of fatigue as a leading symptom of disease, as well as on the treatment of its common causes. Information was also included from the literature search we conducted for the German clinical practice guideline on fatigue that was issued by the German College of General Practitioners and Family Physicians (Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin, DEGAM). Fatigue can be due to any of a broad spectrum of diseases, including decompensation of already known conditions. Sleep disorders and sleep-related disorders of breathing, depression (18.5%), and excessive psychosocial stress are the most common causes of persistent fatigue. Previously undiagnosed cancer is a rare cause, accounting for only 0.6% of cases (95% confidence interval [0.3; 1.3]). Anemia and other organic causes are rare as well (4.3% [2.7; 6.7]). Investigations beyond the history, physical examination, and simple laboratory tests are needed only in the presence of additional symptoms or findings. If the diagnosis remains unclear, watchful waiting and regularly scheduled follow-up help prevent an excessive focus on somatic causes, leading to overdiagnosis. Irrespective of specific causes, psychoeducative and psychotherapeutic approaches should be discussed with the patient, as well as an individually adapted exercise program. The work-up of fatigue as a chief complaint should be guided by investigating common and/or potentially dangerous disorders. Since the latter are rare, an exclusively somatic focus should be avoided in order to prevent overdiagnosis.

Adoption of universal next generation sequencing for Lynch syndrome screening in endometrial cancer

<h3>Objectives:</h3> To assess implementation of a novel microsatellite instability (MSI) screen using next generation sequencing (NGS) in endometrial cancer (EC) through comparison to prior Lynch syndrome screening strategies, as well as to compare characteristics of patients with microsatellite stable (MSS) and microsatellite unstable endometrial cancer. <h3>Methods:</h3> Retrospective review was performed of patients with newly diagnosed endometrial cancer at a single academic institution during three time periods and using different screening strategies: 1) 01/2010 - 01/2013 with provider-directed mismatch repair immunohistochemistry (MMR IHC) in women ≤60, 2) 01/2013 - 01/2016 with universal MMR IHC in all women ≤60, and 3) 10/2018 - 10/2019 with universal screening for MSI using NGS regardless of age. In cohorts 1 and 2, women with abnormal MMR IHC were referred to a genetic counselor who ordered MLH1 promoter methylation or germline genetic testing as indicated. In cohort 3, reflexive MLH1 promoter methylation was performed for patients with MSI and no MMR germline or somatic mutations, with referral to genetic counseling for suspected germline MMR mutation or unexplained MSI. Statistical analysis was performed using a t-test for continuous variables and Fisher's exact test for categorical variables. ≤60, 2) 01/2013 - 01/2016 with universal MMR IHC in all women ≤60, and 3) 10/2018 - 10/2019 with universal screening for MSI using NGS regardless of age. In cohorts 1 and 2, women with abnormal MMR IHC were referred to a genetic counselor who ordered MLH1 promoter methylation or germline genetic testing as indicated. In cohort 3, reflexive MLH1 promoter methylation was performed for patients with MSI and no MMR germline or somatic mutations, with referral to genetic counseling for suspected germline MMR mutation or unexplained MSI. Statistical analysis was performed using a t-test for continuous variables and Fisher's exact test for categorical variables. <h3>Results:</h3> There were 133 subjects in cohort 1, 135 subjects in cohort 2, and 140 subjects in cohort 3. The proportion of patients screened for Lynch syndrome increased over time (39%, 94%, and 100% of intended screening population). The proportion of positive screens was similar between the 3 cohorts (27%, 21%, and 27%). The proportion with positive screens who underwent confirmatory testing with germline genetic testing or MLH1 promoter methylation was 50% in cohort 1 and 59% in cohort 2. Following implementation of reflexive MLH1 promoter methylation testing when indicated, the proportion increased to 89% (p=0.001). Attendance at genetic counseling appointments following referral was 50%, 59%, and 61% in each cohort. Eleven patients were diagnosed with Lynch syndrome across the 3 cohorts (4%, 3%, and 1% respectively). In cohort 3, subjects with MSI EC had similar clinicopathologic characteristics compared with MSS cancers, and over half of MSI cancers were identified in subjects over the age of 60 (71%). Eight subjects had incidental somatic mutations identified through NGS, including 6 <i>POLE</i> mutations, 1 <i>BRIP1</i> mutation, and a subject with mutations in <i>TP53, AKT1,</i> and <i>FBXW7.</i> At our institution, MSI testing by NGS was billed at $905 versus $1200 for MMR IHC screening. <h3>Conclusions:</h3> Transition to universal screening using NGS with reflexive MLH1 promoter methylation testing increased the number of subjects completing genetic assessment for Lynch syndrome after a positive screen, likely as somatic causes of MSI were ruled out, allowing more focused genetics referrals. Similar characteristics between subjects with MSI and MSS EC supports universal screening regardless of clinical characteristics. In addition to identifying Lynch syndrome, detection of MSI through NGS can identify somatic alterations with therapeutic implications, and can be performed at a lower cost than MMR IHC.

P 29. Age-associated characteristics in chronic vertigo patients: A survey of a specialized center for vertigo and dizziness

Introduction. Dizziness and vertigo are among the most important leading symptoms in everyday medical practice. They often become chronic and regularly lead to significant distress with a considerably limited quality of life. Considering the demographic change, the already increased prevalence of vertigo/dizziness in older people will continue to increase progressively in the near future. Therefore, it is necessary to optimize diagnosis and therapy of chronic vertigo patients. Methods. The study included 1.752 patients with chronic vertigo/dizziness who were undergoing treatment at our specialized center for dizziness and vertigo in the period from January 2013 to November 2017. The data was collected based on a questionnaire and analysis of associated patient records. Information concerning age, gender, vertigo-appearance, diagnosis, diagnostics and therapies of all patients are included. Furthermore, the Dizziness Handicap Inventory (DHI) was used to quantitatively measure the level of vertigo and dizziness impairment. Using descriptive statistics, the collected data was finally analyzed and interpreted concerning to three different age groups (age group I < 41, age group II = 41–65, age group III > 65 years of age). Results. In participants of older age, primarily somatic deficits determined the genesis of vertigo, whereas disorders in younger participants were mostly due to psychological processes. For instance, more than 80% of patients over 65 years of age had vertigo of somatic cause and in more than 50% of those under 41 years of age vertigo was based on psychological reasons (Fig. 1). Furthermore, a steady increase in vertigo impairment with advancing age was shown, which couldn“t be reasonably justified by pathogenesis or the symptomatic manifestation of the disease. Therefore, it is more likely that age-related physiological degeneration of the vestibular system as well as cognitive restrictions limit the possibilities of compensation and thus increase the level of suffering from vertigo. In addition, older patients surprisingly were less frequently affected by accompanying symptoms such as nausea/vomiting, headache, ear pressure, tinnitus and visual impairment than younger patients. Conclusion. For the interdisciplinary day care approach a combination of physiotherapy, occupational therapy as well as cognitive-based behavioral therapy is recommended. Our data suggest the assignment of patients to age-specific therapy groups. Further, because of its more frequent occurrence, symptomatic therapy of accompanying symptoms should be intensified in younger patients. Moreover, the recruitment of potential vertigo patients based on the DHI has proven to be convincing. Fig. 1. Classification and distribution of vertigo/dizziness according to somatic, psychogenic or unspecific origin in different age groups.

Diagnostic Overshadowing in Psychiatric-Somatic Comorbidity: A Case for Structural Testimonial Injustice

People with mental illnesses have higher prevalence and mortality rates with regard to common somatic diseases and causes of death, such as cardio-vascular conditions or cancer. One factor contributing to this excess morbidity and mortality is the sub-standard level of physical healthcare offered to the mentally ill. In particular, they are often subject to diagnostic overshadowing: a tendency to attribute physical symptoms to a pre-existing diagnosis of mental illness. This might be seen as an unfortunate instance of epistemic bad luck, where particular features of a group of patients make a timely and correct diagnosis unlikely. While this can explain some cases of diagnostic overshadowing, I argue that in other cases, epistemic injustice is involved. Analyzing the case of diagnostic overshadowing, I distinguish two kinds of testimonial injustice. For one, there are classic cases of transactional testimonial injustice resulting from prejudices against the mentally ill. In addition, there are cases of structural testimonial injustice resulting from features of health care systems. To overcome diagnostic overshadowing, remedies on the individual as well as structural level are thus needed.