Unexplained Symptoms Research Articles

Conversive and Factitious disorders: Differential diagnosis based on a case report

IntroductionConversive disorder is characterised by the presence of one or more involuntary neurological symptoms that are not due to a clear medical pathology. On the other hand, consciously simulated illnesses fall into two diagnostic categories: factitious disorders and malingering, which are differentiated by both the motivation for the behaviour and the awareness of that motivation. Factitious disorder behaviours are motivated by an unconscious need to assume the sick role, whereas malingering behaviours are consciously driven to achieve external secondary gains.ObjectivesStudy of the differences between conversion disorder and factitious disorder and their repercussions from a case of difficult diagnosis.MethodsBibliographic review of scientific literature based on a relevant clinical case.ResultsWe present the case of a 14-year-old male patient. Adoptive parents. Studying in high school. Social difficulties since childhood. He comes to the emergency department on several occasions referring stereotyped movements and motor tics in the four extremities with left cervical lateralization. Increase of these symptoms in the last month, so it was decided to admit him to the pediatric hospital. After observation and study of the patient’s movements with normal complementary tests he should return home. The following day he returned to the emergency department after an episode of dizziness, mutism and emotional block. It was decided to admit him to Psychiatry for behavioral observation and differential diagnosis.ConclusionsIn the assessment of patients it is essential to make an appropriate diagnosis taking into account the patient’s symptomatology and the patient’s background and life context. Conversion disorder is the unintentional production of neurological symptom, whereas malingering and factitious disorder represent the voluntary production of symptoms with internal or external incentives. They have a close history and this has been frequently confounded. Practitioners are often confronted to medically unexplained symptoms; they represent almost 30% of neurologist’s consultation. The first challenge is to detect them, and recent studies have confirmed the importance of “positive” clinical bedside signs based on incoherence and discordance. Multidisciplinary therapy is recommended with behavioral cognitive therapy, antidepressant to treat frequent comorbid anxiety or depression, and physiotherapy. Factitious disorder and malingering should be clearly delineated from conversion disorder. Factitious disorder should be considered as a mental illness and more research on its physiopathology and treatment is needed, when malingering is a non-medical condition encountered in medico-legal cases.Disclosure of InterestNone Declared

INTERNET-BASED COGNITIVE BEHAVIORAL THERAPY FOR SOMATIC SYMPTOM DISORDER

Introduction – Somatic symptom disorder (SSD), before known as somatoform disorder (SD), is characterized by a preoccupation that is nondelusional and general with fears of having, or the idea that the body has a serious disease based on his or her misinterpretation of bodily symptoms in six or more months. In SSD management there is a multifaceted approach that is tailored to each patient. Psychological interventions specifically cognitive behavioral therapy reported can improve the symptoms and reduce the healthcare cost significantly. Internet-delivered cognitive behavior therapy (ICBT) has an accepted evidence base for a range of psychiatric problems, especially for SSD treatment also has been suggested as one possible approach that could adapted to this situation. Methods – In this article, researchers used the review method by collecting several kinds of literature from 2011-2021 that discuss somatic symptom disorder, cognitive behavioral therapy, and internet-based cognitive behavioral therapy for somatic symptom disorder. Results – A referral system for patients with SSD to a mental health expert is needed if they do not find any progress when handled by the physician in primary care. Proven therapies for SSD such as CBT and mindfulness-based therapy. ICBT was approved and increased usage within the pandemic of COVID-19 and brought some highly standardized courses consistent across patients. Discuss – The effectiveness of ICBT has been evaluated in the management of generalized anxiety disorder (GAD), depression, panic disorder, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), adjustment disorder, chronic pain, bipolar disorder, and phobias. CBT in multicenter randomized controlled trials reported effectiveness in the treatment of SSD and medically unexplained symptoms, “Health anxious” patients get over two years of sustained symptomatic benefit, without any different impact on total costs, and also decreased the physical symptoms, disability, and psychological distress. Conclusion – Internet-based Cognitive Behavioral Therapy (ICBT) can be highly effective in the treatment of somatic symptom disorder (SSD). ICBT can provided in therapist-guided, unguided, or as a bibliotherapy. This tool is already recommended as a treatment of choice during the pandemic. Although wider RCT on the use of ICBT in clinical practice, particularly in SSD therapy, with a variety of demographic characteristics to provide additional evidence of the effectiveness of this technique, as well as increased awareness among clinicians and the general public. Keywords: SSD, somatic, CBT.

Post molar choriocarcinoma with solitary renal metastasis in the absence of primary uterine tumor: a case report and review of the literature

BackgroundChoriocarcinoma is a rare and highly malignant form of gestational trophoblastic disease that may develop following pregnancy, abortion, or a hydatiform mole. Renal metastatic involvement by post molar choriocarcinoma is even rarer. In this case report, we describe a unique case of post molar choriocarcinoma with a solitary renal metastasis in the absence of a primary uterine tumor and metastases in other sites, which presented with urological symptoms and spontaneous renal hemorrhage.Case presentationA 41-year-old Persian woman with history of complete hydatiform mole presented with severe flank pain, nausea, vomiting, gross hematuria, and vaginal bleeding. Laboratory tests demonstrated a serum beta human chorionic gonadotropin hormone level of 60,000 mIU/mL. Imaging studies showed a lesion at the lower pole of the left kidney with active bleeding surrounded by hematoma, as well as an empty uterine cavity. Additionally, bilateral pleural effusion was detected without any lesion within the lungs. Subsequently, the patient underwent laparotomy, partial nephrectomy, and left para-ovarian cystectomy. Endometrial curettage was also carried out. The histopathology report revealed choriocarcinoma renal metastasis with high expression of beta human chorionic gonadotropin, cytokeratin 7, and Ki 67. Moreover, there were no malignant cells in the endometrial curettage specimens, and a corpus luteum cyst was found within the para-ovarian cyst. Further investigations revealed that the pleural effusion was free of malignant cells, and there was no evidence of metastatic lesions in the brain. As a result, the patient was referred to the oncology department to receive chemotherapy, and the beta human chorionic gonadotropin levels dropped to 5 mIU/mL after receiving courses of a standard regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine/oncovin over 3 weeks. Finally, monthly measurements of beta human chorionic gonadotropin levels for 6 months indicated that levels have constantly remained within normal ranges, showing no evidence of recurrence or new metastasis.ConclusionsUrological symptoms such as hematuria or spontaneous renal hemorrhage might be the only presentation of post molar choriocarcinoma with renal involvement. Thus, it can be beneficial to measure serum beta human chorionic gonadotropin levels among females of childbearing age who present with unexplained urological symptoms, especially if there is a history of prior hydatiform mole.

Intensive short-term dynamic psychotherapy for irritable bowel syndrome: a randomized controlled trial examining improvements in emotion regulation, defense mechanisms, quality of life, and IBS symptoms.

Studies have provided evidence for the effectiveness of intensive short-term dynamic psychotherapy (ISTDP) in treating medically unexplained symptoms (MUS). This study aimed to examine the effectiveness of ISTDP on individuals living with irritable bowel syndrome (IBS) in terms of, emotion regulation (ER) abilities, defense mechanisms, quality of life (QOL), and IBS symptoms. A total of 30 patients diagnosed with IBS were recruited and randomly assigned to either the intervention (n = 15) or control (n = 15) group. Pre- and post-treatment assessments were conducted, along with a follow-up assessment after ten weeks. Repeated measures analyses of variance were employed to analyze the data. The findings revealed that ISTDP led to significant improvements in ER, defense mechanisms, and QOL, as well as a reduction in the severity and frequency of IBS symptoms. These results provide further support for the efficacy of ISTDP as a treatment modality for individuals with IBS.

Lyme borreliosis and medical wandering: what do patients think about multidisciplinary management? A qualitative study in the context of scientific and social controversy

IntroductionTo answer to patients’ medical wandering, often due to “unexplained symptoms” of “unexplained diseases” and to misinformation, multidisciplinary care centers for suspected Lyme borreliosis (LB), such as the 5 Tick-Borne Diseases (TBDs) Reference Centers (TBD-RC), were created a few years ago in France, the Netherlands and Denmark. Our study consisted of a comprehensive analysis of the satisfaction of the patients managed at a TBD-RC for suspected LB in the context of scientific and social controversy.MethodsWe included all adults who were admitted to one of the TBD-RC from 2017 to 2020. A telephone satisfaction survey was conducted 12 months after their first consultation. It consisted of 5 domains, including 2 free-text items: “What points did you enjoy?” and “What would you like us to change or to improve?”. In the current study, the 2 free-items were analyzed with a qualitative method called reflexive thematic analysis within a semantic and latent approach.ResultsThe answer rate was 61.3% (349/569) and 97 distinctive codes from the 2-free-text items were identified and classified into five themes: (1) multidisciplinarity makes it possible to set up quality time dedicated to patients; (2) multidisciplinarity enables seamless carepaths despite the public hospital crisis compounded by the COVID-19 pandemic; (3) multidisciplinarity is defined as trust in the team’s competences; (4) an ambivalent opinion and uncertainty are barriers to acceptance of the diagnosis, reflecting the strong influence of the controversy around LB; and (5) a lack of adapted communication about TBDs, their management, and ongoing research is present.ConclusionThe multidisciplinary management for suspected LB seemed an answer to medical wandering for the majority of patients and helped avoid misinformation, enabling better patient-centered shared information and satisfaction, despite the context of controversy.

Evaluation of Tools to Assess Symptoms and Symptom Severity in Patients With Medically Unexplained Physical Symptoms: A Systematic Review and Narrative Synthesis.

A substantial portion of patients presenting to healthcare settings exhibit physical symptoms lacking clear, demonstrable organic causes. Accurate assessment of symptom severity is crucial for documenting outcomes and establishing treatment efficacy. This systematic review and narrative synthesis aims to provide researchers with insights into available and validated tools for assessing medically unexplained physical symptoms (MUPS). It involved comprehensive searches across electronic databases, including PubMed, Wiley, and Cochrane, adhering to PRISMA and COSMIN guidelines. The study comprised two phases: Phase 1 systematically reviewed tools for assessing MUPS symptoms and severity, while Phase 2 conducted a narrative synthesis of their measurement properties, focusing on validity and reliability. Out of 14,459 records, 191 articles were identified, leading to the recognition of 16 validated tools for assessing MUPS symptoms and severity. Most tools demonstrated excellent internal consistency and structural validity. However, the majority lacked cross-cultural validity. The choice of tools for the assessment of MUPS will assist clinicians and researchers in determining the severity of MUPS and developing a tailored treatment plan to improve the physical and psychological functioning of these patients.

Development and Validation of a Symptom Scale for Indian Patients With Medically Unexplained Physical Symptoms.

Introduction Patients with medically unexplained physical symptoms (MUPS) account for a substantial proportion of patients visiting the outpatient department. Diagnosis of MUPS is a challenge for most physicians. An accurate diagnosis relies on obtaining a detailed history from patients regarding the nature of their symptoms, their onset, and any associated aggravating or relieving factors. This study aims to develop a symptom scale for Indian patients with MUPS. Methods The study had a mixed-method study design. Phase 1 involved designing the questionnaire using qualitative techniques, such as literature reviews, focus-group discussions, expert evaluation, and pre-testing of a Hindi and English language Likert-rated interviewer-administered scale. In phase 2, the construct validity of the questionnaire was established using quantitative approaches among 116 patients diagnosed with MUPS. Results The final questionnaire consists of 38 items, with good internal consistency (Cronbach 𝛂 = 0.916). Confirmationsampling adequacy for factor analysis was done using the Kaiser-Meyer-Olkin test (KMO value = 0.792) and Bartlett's test of sphericity (p < 0.001). The newly developed scale showed a Pearsoncorrelation coefficient of 0.568 (p < 0.001) with Patient Health Questionnaire (PHQ)-15 scores. Conclusion A reliable and valid tool has been developed to assess patients' symptoms with MUPS in English and Hindi languages. This questionnaire can be used for assessment, screening, and diagnostic purposes as well as to chart longitudinal changes in patients with MUPS.

Representing Human Ethical Requirements in Hybrid Machine Learning Models: Technical Opportunities and Fundamental Challenges

Hybrid machine learning encompasses predefinition of rules and ongoing learning from data. Human organizations can implement hybrid machine learning (HML) to automate some of their operations. Human organizations need to ensure that their HML implementations are aligned with human ethical requirements as defined in laws, regulations, standards, etc. The purpose of the study reported here was to investigate technical opportunities for representing human ethical requirements in HML. The study sought to represent two types of human ethical requirements in HML: locally simple and locally complex. The locally simple case is road traffic regulations. This can be considered to be a relatively simple case because human ethical requirements for road safety, such as stopping at red traffic lights, are defined clearly and have limited scope for personal interpretation. The locally complex case is diagnosis procedures for functional disorders, which can include medically unexplained symptoms. This case can be considered to be locally complex because human ethical requirements for functional disorder healthcare are less well defined and are more subject to personal interpretation. Representations were made in a type of HML called Algebraic Machine Learning. Our findings indicate that there are technical opportunities to represent human ethical requirements in HML because of its combination of human-defined top down rules and bottom up data-driven learning. However, our findings also indicate that there are limitations to representing human ethical requirements: irrespective of what type of machine learning is used. These limitations arise from fundamental challenges in defining complex ethical requirements, and from potential for opposing interpretations of their implementation. Furthermore, locally simple ethical requirements can contribute to wider ethical complexity.

Medically unexplained symptoms are common in women in tertiary neurological healthcare center: A survey cohort study of persons investigated for suspected multiple sclerosis.

A significant proportion of individuals with suspicious onset of multiple sclerosis (MS) does not fulfill the diagnostic criteria. Although some receive other diagnoses, many remain undiagnosed and lack healthcare follow-up. This study aimed to characterize persons with undetermined diagnosis (PwUD) through a questionnaire. Incident cases with suspected MS were consecutively admitted to a tertiary neurological healthcare center in a prospective cohort study. Those who remained undiagnosed after 40 months (mean, range 31-52) were considered PwUD. They completed a modified questionnaire, previously used in a population-based case-control study of incident MS cases. Their responses were compared with two control cohorts, persons with MS (PwMS) and healthy controls, randomly selected from national registries, matched by age, gender, and area of residence. Out of 271 patients with suspected MS onset, 72 (20.3%) were PwUD with a female majority (79%). The response rate was 83% and 39% reported persisting MS-like symptoms. Compared to controls (n=548) and PwMS (n=277), fewer PwUD were currently smoking (p=.4 and p=.03), consumed less alcohol (p=.04 and p=.01), and had children (p=.02 and p=.002). PwUD reported occurrence of other autoimmune disease in 29%, higher compared to PwMS and controls (p<.001 and p<.001). UD is common among persons investigated for suspected MS, in particular among female parents. Our data suggest that PwUD can be characterized as nonsmokers with low alcohol consumption and a higher prevalence of autoimmune disease, in particular thyroid disease.

Negative expectations (nocebo phenomenon) in clinical interventions: A scoping review.

Unpredictable, undesirable, and confusing reactions in the face of psychological or medical interventions make the clinical presentation more complicated and may represent clinically unexplained symptoms and also disturbed the doctor-patients relationship and decrease patients' benefits of treatment. It seems that negative expectations from the treatment (nocebo phenomenon) can explain such reactions. The aim of the current study is a scoping review and investigate different aspects of the nocebo phenomenon (negative expectations) in clinical interventions. This paper follows a scoping review of the existence, importance, and multidimensions of the nocebo phenomenon in medical and psychological interventions. Data sources include literature databases (ProQuest, PubMed, Google Scholar, and Scopus) reviewed from inception dates to 2023, and the terms negative expectations, nocebo effect, placebo effect, negative placebo, and clinical interventions were searched. The review of the available articles showed that negative expectations play an important role in the process and effectiveness of clinical interventions. Negative expectations (here named nocebo effect) can significantly interfere with rapport and treatment processes. Some underlying components of the nocebo effect include negative expectancies, conditioning, social learning, memory, cognitive distortions, meaning, motivation, somatic focus, negative reinforcements, personality, anxiety, and neurophysiological factors such as CCK, dopamine, and cortisol are proposed for development and presence of nocebo phenomenon in clinical practice. Negative expectations with its biopsychosocial aspects play an important and amazing role in disorganizing medical and psychological interventions. Using appropriate methods to reduce nocebo effects in therapeutic interventions may increase treatment compliance and adherence and increase the effectiveness of interventions.

The role of high-resolution impedance manometry to identify rumination syndrome in children with unexplained foregut symptoms.

Diagnosis of rumination syndrome (RS) relies on Rome IV criteria. Oesophageal high-resolution impedance manometry (HRIM) can objectively demonstrate the episodes of rumination, but its role in the diagnostic pathway is not yet established. We aimed to demonstrate the clinical contribution of this tool for the timely diagnosis of RS and diagnostic work-up of children with unexplained foregut symptoms deemed to be due to other conditions. HRIMs performed between 2012 and 2021 were searched to retrieve all diagnoses of RS. Medical records were reviewed for clinical data. Out of 461 HRIMs performed, 76 children had manometric diagnosis of RS (35 male, median age: 13 years). Of them, 47% were not clinically suspected as the symptoms did not fulfil clinical criteria for RS. The indications for HRIM in these cases were investigation of unexplained foregut symptoms (37%), suspected refractory gastroesophageal reflux disease (8%) and dysphagia (2%). Among all HRIMs performed for investigations of unexplained foregut symptoms (n = 80), 35% demonstrated rumination episodes. Identification of characteristic patterns of rumination on HRIM in children with unexplained foregut symptoms enables the immediate diagnosis of RS. Thus, in situations of diagnostic uncertainty, the use of HRIM at early stages of the diagnostic pathway would reduce unnecessary investigations and treatments.

Transcatheter Arterial Embolization for Atraumatic Splenic Rupture in TEE-negative Endocarditis: A Case Report.

Spontaneous splenic rupture is an extremely rare complication of infective endocarditis. We present a case of a 56-year-old immunocompetent female with porcine bioprosthetic mitral valve replacement, automated implanted cardioverter-defibrillator, and atrial fibrillation on apixaban who was found to have in-hospital atraumatic splenic rupture complicating infective endocarditis with Haemophilus parainfluenza. The rupture was treated successfully by endovascular embolization. Usual treatment with six weeks of antibiotics provided durable cure without further complication, and no surgical intervention was needed for either the valve or spleen. Transcatheter arterial embolization should be considered early in atraumatic splenic rupture. Relevant abdominal and cerebral imaging should be considered in all cases of suspected or confirmed infective endocarditis where unexplained symptoms are present.

When the Stomach Pain Is Literally “In Your Head”

Abdominal epilepsy (AE) is an extremely rare condition, classified as temporal lobe epilepsy, and is usually a diagnosis of exclusion. Temporal lobe epilepsy often has no clear cause, although it may be associated with diseases such as temporal lobe sclerosis, dysembryoplastic neuroepithelial tumours, and other benign tumours, as well as arterio-venous malformations, gliomas, defects in neuronal migration, or lesions of the cortex caused by encephalitis. AE is more common in children but has been reported in adults. AEs are characterised by recurrent and unexplained gastrointestinal symptoms such as seizure pain, nausea, bloating and diarrhoea, which improve with antiepileptic treatment. Given the vague nature of these symptoms, patients are at high risk of misdiagnosis. An electroencephalogram and neuroimaging of the brain are needed to confirm the diagnosis.&#x0D; We present the clinical case of a 67-year-old female patient who was investigated at the Gastroenterology Department for a sharp pain in the left side of the abdomen, frequent abdominal distension and gurgles, diarrhoeal episodes, weight loss, paroxysmal hallucinations, and headaches. After a thorough gastroenterological examination, consultations with a psychiatrist and a neurologist, an MRI and an EEG were performed and the patient was diagnosed with focal temporal lobe epilepsy.

Mental health treatment utilization among Gulf War era veterans with probable alcohol use disorder

IntroductionAlcohol use disorder (AUD) is prevalent among veterans, and excessive alcohol use is associated with significant mental and physical health consequences. Currently, the largest cohort of veterans seeking services at the VA are those from the 1990s Gulf War Era. This cohort of veterans is unique due to the nature of their deployment resulting in a myriad of unexplained symptoms collectively known as “Gulf War Illness” and higher rates of mental health problems. The present study sought to examine the association between probable AUD and mental health treatment utilization in a sample of 1126 (882 male) Gulf War-era veterans. MethodsVeterans completed a self-report survey including the AUDIT-C, questions about mental health treatment engagement, and demographic questions. ResultsResults demonstrated that approximately 20 % of the sample screened positive for probable AUD, determined by standard AUDIT-C cutoff scores. Among those screening positive for AUD, 25 % reported engaging in mental health treatment in the past year. Veterans with probable AUD who use VA care had 3.8 times the odds of receiving mental health services than veterans not using VA care. Use of mental health services was associated with mental health comorbidity and identifying as Black/African American. ConclusionsThe results of the present study highlight a significant unmet need for mental health treatment among Gulf War-era veterans with AUD.

The role of the brainstem in sleep disturbances and chronic pain of Gulf War and Iraq/Afghanistan veterans.

Gulf War Illness is a type of chronic multisymptom illness, that affects about 30% of veterans deployed to the 1990-91 Persian Gulf War. Veterans deployed to Iraq/Afghanistan after 2000 are reported to have a similar prevalence of chronic multisymptom illness. More than 30 years after the Persian Gulf War, Gulf War Illness still has an unexplained symptom complex, unknown etiology and lacks definitive diagnostic criteria and effective treatments. Our recent studies have found that substantially smaller brainstem volumes and lower fiber integrity are associated with increased sleep difficulty and pain intensity in 1990-91 Persian Gulf War veterans. This study was conducted to investigate whether veterans deployed to Iraq/Afghanistan present similar brainstem damage, and whether such brainstem structural differences are associated with major symptoms as in Gulf War Illness. Here, we used structural magnetic resonance imaging and diffusion tensor imaging to measure the volumes of subcortices, brainstem subregions and white matter integrity of brainstem fiber tracts in 188 veterans including 98 Persian Gulf War veterans and 90 Iraq/Afghanistan veterans. We found that compared to healthy controls, veterans of both campaigns presented with substantially smaller volumes in brainstem subregions, accompanied by greater periaqueductal gray matter volumes. We also found that all veterans had reduced integrity in the brainstem-spinal cord tracts and the brainstem-subcortical tracts. In veterans deployed during the 1990-91 Persian Gulf War, we found that brainstem structural deficits significantly correlated with increased sleep difficulties and pain intensities, but in veterans deployed to Iraq/Afghanistan, no such effect was observed. These structural differences in the brainstem neurons and tracts may reflect autonomic dysregulation corresponding to the symptom constellation, which is characteristic of Gulf War Illness. Understanding these neuroimaging and neuropathological relationships in Gulf War and Iraq/Afghanistan veterans may improve clinical management and treatment strategies for modern war related chronic multisymptom illness.

Vaccine and antiviral drug promise for preventing post-acute sequelae of COVID-19, and their combination for its treatment.

Most healthy individuals recover from acute SARS-CoV-2 infection, whereas a remarkable number continues to suffer from unexplained symptoms, known as Long COVID or post-acute COVID-19 syndrome (PACS). It is therefore imperative that methods for preventing and treating the onset of PASC be investigated with the utmost urgency. A mathematical model of the immune response to vaccination and viral infection with SARS-CoV-2, incorporating immune memory cells, was developed. Similar to our previous model, persistent infection was observed by the residual virus in the host, implying the possibility of chronic inflammation and delayed recovery from tissue injury. Pre-infectious vaccination and antiviral medication administered during onset can reduce the acute viral load; however, they show no beneficial effects in preventing persistent infection. Therefore, the impact of these treatments on the PASC, which has been clinically observed, is mainly attributed to their role in preventing severe tissue damage caused by acute viral infections. For PASC patients with persistent infection, vaccination was observed to cause an immediate rapid increase in viral load, followed by a temporary decrease over approximately one year. The former was effectively suppressed by the coadministration of antiviral medications, indicating that this combination is a promising treatment for PASC.

Unraveling the mystery: congenital absence of the portal vein and its cardiac implications.

A 25-year-old male with tachycardia and right heart enlargement was diagnosed with atrial-ventricular nodal reentrant tachycardia (AVNRT) and successfully treated with radiofrequency ablation. Cardiac MRI confirmed right heart enlargement but ruled out cardiomyopathy. Further imaging revealed a rare congenital absence of the portal vein (CAPV) with an associated portosystemic shunt. This case highlights the importance of considering CAPV in unexplained cardiac symptoms and structural heart changes.

Comparing the Physiological Responses to the 6-Minute Walk Test, Timed Up and Go Test, and Treadmill Cardiopulmonary Exercise Test.

Purpose: To compare physiological responses during a treadmill cardiopulmonary exercise test (CPX), 6-minute walk test (6MWT), and timed up and go test (TUGT) in individuals referred for unexplained breathlessness and symptom limited treadmill exercise testing. Methods: Heart rate (HR), oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), respiratory exchange ratio (RER), minute ventilation (V̇E), systolic blood pressure (SBP), and rating of perceived exertion (RPE) were recorded throughout each test. Results: Each test demonstrated a significant increase (p < 0.01) in the cardiopulmonary (V̇O2, V̇CO2 and V̇E, RPE, SBP, and HR) and perceptual (RPE) responses from rest to end exercise. The increase in cardiopulmonary and perceptual responses was greatest for the CPX with significantly smaller responses demonstrated during the 6MWT (p < 0.01) and even smaller responses for the TUGT (p < 0.01 vs CPX and 6MWT). Conclusion: Not surprisingly, the treadmill CPX results is the greatest physiological response in our group. Despite being of short duration, the TUGT results in an increased physiological response.

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC): A Cross-sectional Study from Malaysia

Introduction: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare genetic disorder. There are few descriptions of phenotype and genotype in pediatric patients, especially from Asia. Methods: We retrospectively reviewed the records of 11 patients who were diagnosed with FHHNC due to a common homozygous mutation in CLDN19, the gene encoding claudin-19, in the state of Sarawak, Malaysia. Results: Eleven patients from eight families, predominantly of Iban descent, were diagnosed with FHHNC at a median age of 7 years. These patients had an identical novel homozygous pathogenic variant in CLDN19, c427del. Seven patients (63.7%) had ocular abnormalities. All patients had nephrocalcinosis; hypomagnesemia and hypocalcemia were seen in 10 and 6 cases, respectively. One patient was asymptomatic at diagnosis. Progression to kidney failure was seen in two patients, at 7 and 15 years of age. Conclusions: The finding of a common novel mutation in non-consanguineous families from the Iban population across different regions in the Sarawak state suggests a founder effect, underscoring the importance of genetic screening in children from this region presenting with unexplained ocular symptoms or electrolyte abnormalities associated with nephrocalcinosis, to facilitate early diagnosis and management of FHHNC.

Difficulty Falling Asleep, Nocturnal Awakening, Sleep Dissatisfaction, and Irritability in the General Population.

Sleep disturbance is characterized by problems with sleep quantity and quality. However, the exact mechanisms and factors underlying sleep dissatisfaction in the general population remains unclear. This cross-sectional study collected sleep data and irritability level from individuals who visited hospitals for medical checkups or with unexplained physical symptoms using self-report questionnaires. This study included 328 individuals (157 males and 171 females). Bivariate correlation analyses revealed that irritability (ρ = 0.420; p < 0.0001), short sleep length (ρ = 0.405; p < 0.0001), difficulty falling asleep (ρ = 0.443; p < 0.0001), and nocturnal awakening (ρ = 0.528; p < 0.0001) were strongly correlated with sleep dissatisfaction. Multiple linear regression analyses among the overall individuals, following bivariate correlation analyses, indicated that stress at home (β = 0.245; p < 0.0001), irritability ( β= 0.172; p = 0.0021), difficulty falling asleep (β = 0.215; p < 0.0001), later bedtime (β = 0.140; p = 0.0331), and nocturnal awakening (β = 0.386; p < 0.0001) were independently correlated with sleep dissatisfaction, whilst short sleep length was not (β = 0.107; p = 0.1024). Further multivariable analyses revealed that difficulty falling asleep and nocturnal awakening were independently associated with each other. The obtained results were reproduced in the subgroup analyses among the 151 individuals taking medical checkups. In summary, major factors underlying sleep dissatisfaction in the general population included difficulty falling asleep and nocturnal awakening. Irritability was associated with difficulty falling asleep and sleep dissatisfaction. Carefully evaluating each of these sleep-related subscales and irritability may be beneficial in managing individuals with sleep problems.