Symptom Categories Research Articles

Cluster analysis of patients with granulomatosis with polyangiitis (GPA) based on clinical presentation symptoms: a UK population-based cohort study

BackgroundGranulomatosis with polyangiitis (GPA) is small vessel vasculitis with heterogeneous clinical presentation. In the present population-based cohort study, we classified patients with GPA based on clinical features at presentation using an unsupervised clustering approach and compared their mortality, infections and frequency of comorbidities.MethodsIn this open cohort study, de-identified primary care data of patients with GPA included in the IQVIA Medical Research Data database between 1 January 1995 and 25 September 2019 was analysed retrospectively. Latent class analysis was performed to create symptom clusters of patients based on 16 categories of symptoms representing various organ involvement. All-cause mortality of resultant clusters was compared after adjusting for age, sex, Townsend deprivation quintile and smoking status at index date using extended Cox proportional hazards models. Prescription of antibiotics, considered as an indirect indicator of recurrent bacterial infection, was compared using a recurrent event model, after adjusting for quarterly use of steroid as a time-dependent covariate. Cumulative frequencies of common comorbidities were compared among the clusters at index visit, 1-year and 3-year follow-up.ResultsAltogether, 649 patients with GPA [median age 60.0 (IQR: 49.6–70.1)] were included. Three clusters were identified: patients with limited disease mainly with involvement of ENT and cough were classified into cluster 1 (n = 426); cluster 2 had generalised non-renal disease (n = 176); while patients in cluster 3 had renal-predominant disease (n = 47). Many patients in cluster 1 developed generalised disease at the end of 1 year. Mortality in clusters 2 and 3 was higher compared with cluster 1. Mortality in cluster 1 itself was 68% higher than the general population without GPA. The duration of antibiotics prescription and frequency of coexisting medical illnesses was also higher in clusters 2 and 3.ConclusionsIn a primary care setting, patients with GPA can be classified into three distinct clusters with different prognosis, susceptibility to recurrent infections and presence of comorbidities. The tendency of cluster 1 to evolve into a more generalised disease raises questions about current immunosuppressive treatment approaches in these patients.

Rare presentation of lower limb weakness, a case report

SUMMARY This is a 53 year old male, who was previously healthy, and who presented to a primary care physician, complaining of from chronic back pain. He was seen multiple times with the same problem, which was treated as Myalgia with pain killers only. After a proper approach and investigation he was found to have ALS Amyotrophic lateral sclerosis. BACKGROUND: Lower limb weakness is a common problem in the primary care setting, with a multiple differential diagnosis. It is defined as loss of muscle strength[1]. The physician should firstly isolate and be sure that the complaint of patient is weakness of the muscle , mainly by investigating other causes that may mimic and overlap with the presentation; the famous and most common cause being fatigue[2]. History and physical examination in addition to investigation will assure that the physician will reach the proper diagnosis and management plan but before that knowing the mechanisms of weakness is the corner stone in approach[3,5], which includes[3,4]: Upper motor neurons, Lower motor neurons, Neuromuscular junction, Muscle. In the primary care setting and because of patient flow, usually common is common, which is exactly what happened to the patient, as he visited the center multiple time because of weakness and mild pain which did not attract the attention of the treating physicians to more serious and complicated disease[6,7]. Amyotrophic lateral sclerosis (ALS), commonly called Lou Gehrig’s disease, is a progressive neurodegenerative disease affecting both upper and lower motor neurons. ALS is a condition characterized by weakness, muscle wasting, fasciculations and increased reflexes[1,2]. The annual incidence rate is one to three cases per 100,000. The disease is mostly diagnosed in middle age and affects more men than women [5]. Over a period of months or years, patients with ALS develop severe, progressive muscular weakness and other symptoms caused by loss of function in both upper and lower motor neurons. Mainly it presents with 2 major categories of symptoms: Upper motor neuron, Lower motor neuron [2]. In the patient’s case it was mainly lower motor neuron symptoms without any symptoms of upper motor which makes the presentation unique and confusing with other differential diagnoses. ALS has a bad prognosis and limited options of treatment. Respiratory failure limits survival to 2-5 years after disease onset. RILUZOLE is the only drug that can affect prognosis [1,7,8,9]. Being rare, difficult to treat and with a bad prognosis, makes us want to share this case with our colleagues as the learning opportunity in this case makes it a valuable one for a case report. Key words: lower limb weakness, case report

Distinct functional brain connectivity patterns associated with specific symptom categories in PTSD

Distinct functional brain connectivity patterns associated with specific symptom categories in PTSD

Application of Artificial Intelligence Algorithm in Image Processing for Cattle Disease Diagnosis

Livestock is a critical socioeconomic asset in developing countries such as Ethiopia, where the economy is significantly based on agriculture and animal husbandry. However, there is an enormous loss of livestock population, which undermines efforts to achieve food security and poverty reduction in the country. The primary reason for this challenge is the lack of a reliable and prompt diagnosis system that identifies livestock diseases in a timely manner. To address some of these issues, the integration of an expert system with deep learning image processing was proposed in this study. Due to the economic significance of cattle in Ethiopia, this study was only focused on cattle disease diagnosis. The cattle disease symptoms that were visible to the naked eye were collected by a cell phone camera. Symptoms that were identified by palpation were collected by text dialogue. The identification of the symptoms category was performed by the image analysis component using a convolutional neural network (CNN) algorithm. The algorithm classified the input symptoms with 95% accuracy. The final diagnosis conclusion was drawn by the reasoner component of the expert system by integrating image classification results, location, and text information obtained from the users. We developed a prototype system that incorporates the image classification algorithms and the reasoner component. The evaluation result of the developed system showed that the new diagnosis system could provide a rapid and effective diagnosis of cattle diseases.

Diglossia Correlates With Prodromal Symptoms of Psychosis Among First-Generation Migrants.

We have previously hypothesized that diglossia may be a risk factor for psychosis, drawing from observations on migration, ethnicity, social adversity, and language disturbances among others. However, empirical data on this association and the tools necessary for its measurement are limited. In a cross-sectional online sample of first-generation migrants residing in majority English-speaking countries, a response-based decision tree was introduced to classify the sociolinguistic profiles of 1497 participants as either with or without diglossia. Using multivariate logistic regression, the association of diglossia with psychosis risk screening outcomes in the Prodromal Questionnaire-16 was calculated, adjusting for demographic and linguistic confounders. Differences in the symptom categories endorsed between the 2 groups were also examined. Diglossia was identified in 18.4% of participants and was associated with an adjusted odds ratio of 2.58 for a positive risk screening outcome. Other significant factors included subjective social status, hearing difficulty, age, sex, country of residence, education level, and cannabis consumption. The effects of ethnicity, age at migration, fluency, relationship, and employment status were no more significant in the multivariate model. Finally, the largest differences in the proportion of positively responding participants between the two groups were found in symptoms relating to thought insertion and thought broadcasting. In a sociolinguistic hierarchical framework, diglossia is correlated with prodromal symptoms of psychosis in first-generation migrants.

Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Treatment of Patients With Concussion

Investigate the efficacy of 3 anti-Calcitonin Gene-Related Peptide monoclonal antibodies (anti-CGRP mAbs), fremanezumab, galcanezumab, and erenumab, in concussion patients with post-traumatic headache (PTH) with a migraine phenotype. A study using monoclonal antibodies in mice with mild traumatic brain injury saw improvements in cutaneous allodynia.1 A study from Denmark using erenumab for PTH found patients had an 82% decrease in the number of headache days. This study also demonstrated that 44% of patients had a reduction in HIT-6 score = 5 after 9-12 weeks of treatment.2. Retrospective chart review of patients diagnosed with PTH (n = 168) evaluated HIT-6, number of reported headache days, and the number of modifiable concussion variables (headache, dizziness, attention/concentration deficit, mood and sleep disturbance) prior to initiation of anti-CGRP mAbs and after at least 3 months of treatment were recorded. Patients saw a decrease in HIT-6 score (p < 0.0001), with a mean difference of -4.26 from pre-treatment to at least 3 months after treatment. When evaluating 5 concussion symptom categories, patients experienced x¯ = 2.35 symptoms prior to anti-CGRP mAbs treatment, and x¯ = 1.67 after at least 3 months of treatment. Patients also experienced a decrease in the number of headache days per month (<0.0001) with a mean difference of -7.25 (range 0-30) headache days per month. Seven patients experienced adverse effects (1 patient had 2 different adverse effects), including injection site rash, fatigue, constipation, and dizziness. Only one patient discontinued medication due to adverse event. Anti-CGRP mAbs used to treat PTH showed improved headache severity and frequency, as well as a decreased number of overall concussion symptoms. There was a subset of patients with a more robust response. Switching anti-CGRP mAbs was beneficial in some patients.

Substance-Induced Psychoses: An Updated Literature Review.

Background: On the current psychopharmacological panorama, the variety of substances able to provoke an episode of acute psychosis is rapidly increasing. Such psychotic episodes are classified according to the major category of symptoms: positive, negative, or cognitive psychotic episodes. On one hand, the abuse of methamphetamines, cannabis, and cocaine plays a big role in increasing the incidence of episodes resembling a psychotic disorder. On the other hand, the progress in terms of pharmacodynamics knowledge has led to the synthesis of new drugs, such as cannabinoids and cathinone's, which have rapidly entered into the common pool of abusers' habits. Regarding these newly synthesized substances of abuse, further clinical studies are needed to understand their psychogenic properties. The topic of this review is complicated due to the frequent abuse of psychotomimetic drugs by patients affected by psychotic disorders, a fact that makes it extremely difficult to distinguish between an induced psychosis and a re-exacerbation of a previously diagnosed disorder.Methods: The present narrative review summarizes results from clinical studies, thus investigating the psychotogenic properties of abused substances and the psychotic symptoms they can give rise to. It also discusses the association between substance abuse and psychosis, especially with regards to the differential diagnosis between a primary vs. a substance-induced psychotic disorder.Findings: Our findings support the theory that psychosis due to substance abuse is commonly observed in clinical practice. The propensity to develop psychosis seems to be a function of the severity of use and addiction. Of note, from a phenomenological point of view, it is possible to identify some elements that may help clinicians involved in differential diagnoses between primary and substance-induced psychoses. There remains a striking paucity of information on the outcomes, treatments, and best practices of substance-induced psychotic episodes.

DETEKSI DINI PENYAKIT BALITA MENGGUNAKAN ALGORITMA SORENSEN BERBOBOT

There are still many parents who do not have sufficient understanding in terms of toddler disease. One way to provide education is the availability of a system that can be used for consultation based on the symptoms of illness experienced by toddlers and the actions needed to overcome them. The system that will be built is an expert system that can relatively provide suggestions for solutions to children's health problems using the Case Based Reasoning (CBR) method. namely an expert system that uses case-based reasoning methods, namely looking for similarities of a disease compared to a disease that has existed before. In this study, the CBR method was combined with a weighting process using the pairwise comparison method which was within the scope of the AHP (Analytic Hierarchy Process) method. In comparing consultations with old diseases that already exist in the system, and looking for similarities from the comparison results, the Sorensen similarity algorithm is used. This study resulted in weights with 3 symptom categories, namely mild symptoms with a weight of 0.09, moderate symptoms with a weight of 0.24 and severe symptoms with a weight of 0.67 and will recommend several diseases with a similarity above 0.5 and diseases with a similarity below 0.5 will be entered into the revise table to find a solution.

The Effect of Povidone-Iodine Nasal Spray on Nasopharyngeal SARS-CoV-2 Viral Load: A Randomized Control Trial.

Objectives/HypothesisTo determine the effect of povidone‐iodine (PVP‐I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold (Ct) on quantitative polymerase chain reaction (qPCR) of SARS‐CoV‐2 in outpatients.Study DesignThree arm, triple blinded, randomized, placebo‐controlled clinical trial.MethodsParticipants were randomized within 5 days of testing positive for COVID‐19 to receive nasal sprays containing placebo (0.9% saline), 0.5% PVP‐I, or 2.0% PVP‐I. NP swabs for qPCR analysis were taken at baseline, 1‐hour post‐PVP‐I spray (two sprays/nostril), and 3 days post‐PVP‐I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30.ResultsMean Ct values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP‐I groups. The 2.0% PVP‐I group showed statistically significant improvement in all symptom categories; however, it also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30 days of study enrollment.ConclusionsSaline and low concentration PVP‐I nasal sprays are well tolerated. Similar reductions in SARS‐CoV‐2 NP viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30 days. These data suggest that dilute versions of PVP‐I nasal spray are safe for topical use in the nasal cavity, but that PVP‐I does not demonstrate virucidal activity in COVID‐19 positive outpatients.Level of EvidenceII Laryngoscope, 2021

Dopamine Circuit Mechanisms of Addiction-Like Behaviors.

Addiction is a complex disease that impacts millions of people around the world. Clinically, addiction is formalized as substance use disorder (SUD), with three primary symptom categories: exaggerated substance use, social or lifestyle impairment, and risky substance use. Considerable efforts have been made to model features of these criteria in non-human animal research subjects, for insight into the underlying neurobiological mechanisms. Here we review evidence from rodent models of SUD-inspired criteria, focusing on the role of the striatal dopamine system. We identify distinct mesostriatal and nigrostriatal dopamine circuit functions in behavioral outcomes that are relevant to addictions and SUDs. This work suggests that striatal dopamine is essential for not only positive symptom features of SUDs, such as elevated intake and craving, but also for impairments in decision making that underlie compulsive behavior, reduced sociality, and risk taking. Understanding the functional heterogeneity of the dopamine system and related networks can offer insight into this complex symptomatology and may lead to more targeted treatments.

Mobility and Muscle Strength in Recipients of Hematopoietic Cell Transplantation for Sickle Cell Disease: A Preliminary Report from Sickle Transplant Evaluation of Longterm and Late Effects Registry (STELLaR)

IntroductionRecipients of Hematopoietic Cell Transplantation (HCT) are at risk for treatment related late effects including cardiovascular disease and diabetes. Physical fitness including mobility and muscle strength are important predictors of cardiovascular health and quality of life. Physical fitness has been described in children and adults who are long term survivors of HCT for malignant disease [1]. Patients with sickle cell disease (SCD) are likely to be subject to unique morbidity post-HCT as a consequence of the pathophysiology of SCD which is characterized by anemia, inflammation, pain, bone infarcts and neurological complications. A systematic assessment of physical fitness is required to understand some of the long-term outcomes HCT for SCD.MethodsWe enrolled patients with SCD ≥ 1-year post-HCT in Sickle Transplantation Evaluating Long Term And Late Effects Registry (STELLaR). We assessed physical fitness including mobility using the timed up and go (TUG) test, and muscle strength using the handgrip strength (HGS) test. TUG scores were compared with published normative data for children (mean 9.2s; SD = 0.8) and young adults (mean 10.5s, SD = 1.1) [2]. TUG scores ≥ mean+ 2SD were considered abnormal (children: ≥10.8s, young adults ≥12.7s). The HGS of each patient was compared to published normative data of children and adults [3,4]. Patients ≤12 years were abnormal if they had a HGS of two standard deviations below the mean. Patients ≥13 years were considered abnormal if they had a HGS lower than the lower limit of the 85% age-sex standard. Additionally, patients were also assessed for chronic graft versus host disease (cGvHD) by means of the Lee Chronic GvHD Symptom Scale [5]. Patients rated their extent of being bothered by cGvHD symptoms on a scale from 1 to 5, with 1 being not at all and 5 being extremely. These scores were then organized into 7 categories of cGVHD symptoms and normalized to a 0-100 scale. We report the results of an interim analysis of physical fitness in these HCT recipients.ResultsOut of 121 patients enrolled in the study, 37 HCT recipients were assessed for mobility using the TUG test, and for muscle strength using the HGS test. Children were defined as being below the age of 18 and young adults between 18 and 40 years of age. Patient demographic and clinical results for TUG and HGS are presented in Table 1. Young adult participants were more likely to have abnormal TUG and HGS results than pediatric study participants. Patient self-reporting of overall (summary) cGvHD symptoms was found to be statistically significant between children and young adults (p=0.037) with young adults iappearing to be slightly more bothered by GvHD symptoms. There was no correlation in length of time in years between a patient's transplant and whether or not there was abnormal physical fitness (TUG and HGS) for both the young adult and children cohorts.ConclusionsThese data suggest the existence of impaired physical fitness in the long term in SCD patients who are HCT recipients. They provide the rationale for systematic evaluation of physical fitness and other risk factors for cardiovascular disease post-HCT.

General and Disease-Specific Factors Associated with Health Related Quality of Life Among Patients With Peripheral Artery Disease to Inform Treatment Selection in the Era of Patient-Reported Outcomes

<h3>Introduction and Objective</h3> Patient-reported outcomes (PRO) have been championed for assessment of peripheral artery disease (PAD) severity and treatment outcomes. Limited evidence exists regarding factors associated with PRO that may affect their sensitivity to change with PAD interventions. We performed a prospective, cross-sectional study to evaluate how patient-level factors are associated with a validated PAD-specific health related quality of life (QOL) instrument, the VascuQol-6. <h3>Methods</h3> Patients were recruited from a diagnostic vascular unit based on referral for ankle brachial index (ABI) testing. All participants were assessed for PAD symptoms using the San Diego Claudication Questionnaire and tested for neuropathy using the Michigan Neuropathy Screening Instrument (MNSI). PAD-specific QOL was assessed using the VascuQol-6. Clinical data was collected from the medical record and patient-self report. Factors associated with QOL were evaluated using ANOVA, confidence intervals, and linear models. <h3>Results</h3> 70 patients were recruited and participated. Mean age was 67.8±11.7 years (Figure 1Figure 1Plot of age versus VascuQOI-6 summary score (P=0.011).Figure 1); 41% of participants were women and 87.1% were white, and 29% were current smokers. Comorbid conditions included diabetes (23.2%) and peripheral neuropathy (44.3%). Mean ABI was 0.77±0.29 and mean TBI was 0.48±0.23. PAD symptoms were classified as claudication in 48.6%, CLTI in 31.4%, and asymptomatic in 20%. Among symptomatic patients, 21 had multi-level symptoms, 13 had calf symptoms only, 4 had buttock symptoms only, and 3 had thigh symptoms (Figure 2Figure 2Distribution of Vascuqol-6 summary scores by anatomic symptom distribution (P=0.025).Figure 2). Symptoms were bilateral in 55 patients (78.6%). Patients with multi-level disease had lower QOL scores (13.8±4.0; 90% CI 12.3-15.3) versus those with no symptoms (17.6±4.8; 90% CI 16.1-19.2), calf symptoms (17.8±3.1; 90% CI 16.2-19.3) (P=0.024). In multivariable models QOL was associated with minimum ABI (P=0.020), symptom anatomic level (P=0.002) and age (P=0.001); a trend was also observed for symptom category (P=0.121). No associations between QOL and smoking status, diabetes, neuropathy, or bilateral versus unilateral symptoms were observed. <h3>Conclusions</h3> PAD-specific QOL assessments are associated with factors related and unrelated to PAD. Higher QOL scores among older participants was unanticipated and may impart ceiling effects that limit potential for improvement through PAD interventions in this subgroup, while patients with multi-level symptoms may have greater potential gains from PAD treatment. Future work following this cohort will explore changes in QOL over time and associations with treatment interventions, adverse events, and patient-level factors.

Joint Associations of Physical Activity and Insomnia Symptoms with Incident Mood Disorder in a population-based cohort study

Background: When examined as separate risk factors, low physical inactivity and insomnia symptoms are both associated with increased risk of mood disorders including depression, however few studies examine these risk factors jointly. The aim of this study was to examine the joint association of physical activity and insomnia symptoms with the incidence of mood disorder in Australian adults. Methods: Data were drawn from the 2013-2018 waves of the annual Household Income and Labour Dynamics in Australia panel study. In 2013, participants completed a survey assessing mood and anxiety disorder, physical activity, insomnia symptoms, lifestyle behaviours (i.e., diet, sleep duration, smoking, alcohol), reported diagnosis of depression/anxiety, and sociodemographic characteristics. Incident mood disorder was assessed using the MHI-5 and defined as mood disorder (MHI-5 score <54) in 2013 and no mood disorder (MHI-5 score >54) in 2014-2018. Physical activity was assessed using the IPAQ-SF and classified as low, moderate, and high using standard scoring protocols. Insomnia symptoms were assessed using three items assessing poor sleep quality and difficulty initiating and/or maintaining sleep and dichotomised as Insomnia symptoms/ No Insomnia. Participants were then classified into one of six groups representing distinct combinations of physical activity and insomnia symptoms. Only participants with complete data on covariates and exposure variables and who were free of mood disorder in 2013, and who had at least one follow-up survey during 2014-2018 were included in the analysis. A discrete-time proportional-hazards model was estimated using a logit-hazard (i.e., logistic) regression model to examine the association between joint categories of physical activity and insomnia symptoms and incident mood disorder between 2014-2018 adjusted for sociodemographics, lifestyle behaviours and prior/current diagnosis of depression/anxiety. Results: There were 11,023 participants with complete data and no mood disorder in 2013. The incidence of mood disorder in 2014-2018 was 21.1%. Relative to participants classified as High PA/No insomnia symptoms, reporting either High PA/Insomnia (OR = 1.87, 95% CI 1.57, 2.23), Moderate PA/Insomnia (OR = 1.94, 95% CI 1.62, 2.32), or Low PA/Insomnia (OR = 2.33, 95% CI 1.96, 2.77) was significantly associated with increased likelihood of incident mood disorder. Discussion: The combination of any level of physical activity and insomnia symptoms was associated with an increased likelihood of reporting mood disorder during the following five years, and this increased as physical activity decreased. These observations highlight the potential benefit of interventions targeting physical activity and insomnia symptoms to promote good mental health. Conflict of Interest Statement: My co-authors and I acknowledge that we have no conflict of interest of relevance to the submission of this abstract

Insomnia symptoms and chronic pain: Outcomes of an interdisciplinary pain rehabilitation program.

Insomnia is a highly prevalent problem among patients with chronic pain. Interdisciplinary pain rehabilitation programs (IPRPs) are a leading treatment option for chronic pain; however, research is limited and existing findings are mixed on the impact of insomnia symptoms on IPRP outcomes and the extent to which insomnia symptoms improve as a result of IPRP treatment. In this study, insomnia and pain-related outcomes following a 10-week IPRP were examined from a relatively large sample (N = 393) of adult patients with varying chronic pain conditions who completed the Insomnia Severity Index (ISI) at program admission and discharge. Both group- and individual-level changes in insomnia severity were examined to evaluate statistically and clinically significant changes in insomnia symptoms, along with the impact of insomnia symptoms on measures of pain, emotional distress, and functioning. Participants were categorized as having no clinically significant insomnia symptoms (NCSI), mild, moderate, or severe insomnia based on ISI scores. Higher levels of insomnia severity were associated with worse pain, functioning, and emotional distress. Most patients reporting mild, moderate, or severe insomnia symptoms at program admission moved to a lower insomnia symptom category at the time of discharge (62%); however, only 33% of these patients reported a meaningful score reduction (i.e., ISI change ≥8 points). In addition, insomnia symptoms had a negative impact on treatment gains related to pain interference and physical health-related quality of life. These findings suggest that usual IPRP care confers overall treatment benefit for individuals with chronic pain and insomnia. However, insomnia symptoms may negatively impact pain treatment outcomes and usual care appears insufficient to address elevated insomnia symptoms for many patients. Additional insomnia-specific treatment may be warranted for patients with comorbid chronic pain.

Biopsychosocial Predictors of Quality of Life in Paediatric Patients With Sickle Cell Disease.

Sickle cell disease (SCD) refers to a group of inherited blood disorders with considerable morbidity that causes severe pain, reduces life expectancy, and requires significant self-management. Acute painful episodes are the hallmark of SCD, but persistent daily pain is also highly prevalent in this population. Characterising the impact and experience of SCD-related morbidity (i.e., sleep disruption, frequent emergency department visits, cognitive dysfunction) on health-related quality of life (HRQOL) requires multiple assessment methods to best capture the underlying mechanisms. To gain a greater understanding of the effect of common symptom categories on HRQOL and to determine potential pain coping targets, the present study investigated whether demographic, socioeconomic, sleepiness, pain burden, frequency of emergency department (ED) visits, and cognition predicted HRQOL in a paediatric sample of patients with SCD. Our study was a secondary analysis of baseline assessment data of children with SCD aged 8–15 years (n = 30) in the Prevention of Morbidity in Sickle Cell Anaemia Phase 2b (POMSb2) randomised controlled clinical trial of auto-adjusting continuous positive airways pressure. Patients completed cognitive testing (IQ, Processing Speed Index, Delis-Kaplan Executive Function Scale (DKEFS) Tower, Conner's Continuous Performance Test), sleepiness (Epworth Sleepiness Scale), and HRQOL (PedsQL Sickle Cell Module) at baseline. Patients reported pain burden (Sickle Cell Pain Burden Inventory-Youth) each month over 8 visits. Caregivers provided demographic information and reported their child's executive function (Behavioural Rating Inventory of Executive Function) at baseline. Data from our analysis demonstrated that demographic factors (i.e., age, gender, level of neighbourhood deprivation) and treatment variables (i.e., hydroxyurea use) did not independently predict HRQOL, and laboratory values (i.e., haemoglobin, haematocrit, mean oxygen saturation) were not significantly correlated with HRQOL (ps > 0.05). However, sleepiness, pain burden, ED visits, and executive dysfunction independently predicted HRQOL (R2 = 0.66) with large effects (η2 = 0.16 to 0.32). These findings identify specific, measurable symptom categories that may serve as targets to improve HRQOL that are responsive to change. This knowledge will be useful for multimodal interventions for paediatric patients with SCD that include sleep management, pain coping strategies, and executive function training.

Differential dopamine release by psychosis-generating and non-psychosis-generating addictive substances in the nucleus accumbens and dorsomedial striatum

Schizophrenia is associated with three main categories of symptoms; positive, negative and cognitive. Of these, only the positive symptoms respond well to treatment with antipsychotics. Due to the lack of effect of antipsychotics on negative symptoms, it has been suggested that while the positive symptoms are related to a hyperdopaminergic state in associative striatum, the negative symptoms may be a result of a reduced dopamine (DA) activity in the nucleus accumbens (nAc). Drug abuse is common in schizophrenia, supposedly alleviating negative symptomatology. Some, but not all, drugs aggravate psychosis, tentatively due to differential effects on DA activity in striatal regions. Here this hypothesis was tested in rats by using a double-probe microdialysis technique to simultaneously assess DA release in the nAc and associative striatum (dorsomedial striatum; DMS) following administration of the psychosis-generating substances amphetamine (0.5 mg/kg), cocaine (15 mg/kg) and Δ9-tetrahydrocannabinol (THC, 3 mg/kg), and the generally non-psychosis-generating substances ethanol (2.5 g/kg), nicotine (0.36 mg/kg) and morphine (5 mg/kg). The data show that amphetamine and cocaine produce identical DA elevations both in the nAc and DMS, whereas nicotine increases DA in nAc only. Ethanol and morphine both increased DMS DA, but weaker and in a qualitatively different way than in nAc, suggesting that the manner in which DA is increased might be important to the triggering of psychosis. THC elevated DA in neither region, indicating that the pro-psychotic effects of THC are not related to DA release. We conclude that psychosis-generating substances affect striatal DA release differently than non-psychosis-generating substances.

FREQUENCY OF CUTANEOUS MANIFESTATIONS IN COVID-19

Objective: To provide an insight into the frequency of cutaneous manifestations in patients with Corona Virus Disease of 2019 COVID-19), along with an association of these findings with the severity of the disease.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Tertiary care hospital, Rawalpindi Pakistan, from May to Jul 2020.&#x0D; Methodology: We collected data from 412 confirmed cases of COVID-19 patients directly who were &gt;12 years of age. The data included names of patients, their genders, ages, dates of admission, severity category, presence or absence of symptoms and cutaneous findings along with description of cutaneous findings if present. The data was evaluated using Statistical Package for the Social Sciences (SPSS) version 23.&#x0D; Results: Eleven out of the total 412 patients with COVID-19 included in our study were found to have cutaneous findings. The frequency of cutaneous manifestations associated with COVID-19 was calculated to be 11 (2.7%). Increasing age proved to be positively correlated with increasing severity of the disease whereas no association was found between gender and severity of the disease.&#x0D; Conclusion: Infection with COVID-19 may result in dermatological manifestations with various clinical presentations, which may aid in better understanding and management of the disease.

International Urogynecology Consultation Chapter 1 Committee 5: relationship of pelvic organ prolapse to associated pelvic floor dysfunction symptoms: lower urinary tract, bowel, sexual dysfunction and abdominopelvic pain.

This article from Chapter 1 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) establishes the prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP. An international group of nine urogynecologists/urologists and one medical student performed a search of the literature using pre-specified search terms in Ovid, MEDLINE, Embase and CINAHL from January 2000 to March 2019. Publications were eliminated if not relevant or they did not include clear definitions of POP or the symptoms associated with POP. Definitions of POP needed to include both a physical examination finding using a validated examination technique and the complaint of a bothersome vaginal bulge. Symptoms were categorized into symptom groups for ease of evaluation. The Specialist Unit for Review Evidence (SURE) was used to evaluate for quality of the included articles. The resulting list of articles was used to determine the prevalence of various symptoms in women with POP. Cohort studies were used to evaluate for possible causation of POP as either causing or worsening the symptom category. The original search yielded over 12,000 references, of which 50 were used. More than 50% of women with POP report lower urinary tract symptoms. Cohort studies suggest that women with POP have more obstructive lower urinary tract symptoms than women without POP. Pain described in various ways is frequently reported in women with POP, with low back pain being the most common pain symptom reported in 45% of women with POP. In cohort studies those with POP had more pain complaints than those without POP. Sexual dysfunction is reported by over half of women with POP and obstructed intercourse in 37-100% of women with POP. Approximately 40% of women have complaints of bowel symptoms. There was no difference in the median prevalence of bowel symptoms in those with and without POP in cohort studies. The prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP are common but inconsistently reported. There are few data on incidence of associated symptoms with POP, and cohort studies evaluating causality are rare or inconsistent. Obstructive voiding, lower abdominal and pelvic pain, and sexual dysfunction are most frequently associated with POP.

Ambient particulate matter, ozone, and neurologic symptoms in U.S. Gulf states adults.

Research on neurologic effects of air pollution has focused on neurodevelopment or later-life neurodegeneration; other effects throughout adulthood have received less attention. We examined air pollution levels and neurologic symptoms among 21,467 adults in US Gulf Coast states. We assigned exposure using Environmental Protection Agency estimates of daily ambient particulate matter 2.5 (PM2.5) and ozone. Gulf Long-term Follow-up Study participants reported neurologic symptoms at enrollment (2011-2013). We estimated cross-sectional associations between each air pollutant and prevalence of "any" neurologic, central nervous system (CNS), or peripheral nervous system (PNS) symptoms. Ambient PM2.5 was consistently associated with prevalence of neurologic symptoms. The highest quartile of 30-day PM2.5 was associated with any neurologic symptom (prevalence ratio [PR] = 1.16; 95% confidence interval [CI] = 1.09, 1.23) and there were increasing monotonic relationships between 30-day PM2.5 and each symptom category (P-trend ≤ 0.01). Associations with PM2.5 were slightly stronger among nonsmokers and during colder seasons. The highest quartile of 7-day ozone was associated with increased prevalence of PNS symptoms (PR = 1.09; 95% CI = 1.00, 1.19; P-trend = 0.03), but not with other outcomes. Ozone concentrations above regulatory levels were suggestively associated with neurologic symptoms (PR = 1.06; 95% CI = 0.99, 1.14). Mutual adjustment in co-pollutant models suggests that PM2.5 is more relevant than ozone in relation to prevalence of neurologic symptoms.

Comorbidities: A Decider of Severe Clinical Outcomes in COVID-19 Patients

Background: Comorbidity is the biggest decider in COVID-19 pandemic whether the infected person will develop the severe clinical outcome or not. It is one of the few conclusions that has widespread acceptance.&#x0D; Summary:After analyzing the case fatalities of COVID-19, many patients were found to be having either one of many conditions which are commonly called as comorbidities due to which they cannot made it to survivors list. Also several COVID-19 patients requiring the sophisticated medical attention like ventilators and oxygen support system have any kind of underlying medical condition. Deteriorated immune system is one of the reasons behind slipping into severe symptoms category.&#x0D; Conclusion: It is established that comorbidities are the major influencer in COVID-19 infected patients. More study is needed to further segregate the data on the basis of each comorbidity.