Insufficient Symptom Control Research Articles

Contagion beyond the virus: A case obsessive-compulsive disorder centered on Covid-19

IntroductionThe Covid-19 pandemic has generated an unprecedented impact on multiple levels (health, occupational, economic, and social) which affected the general population and has been an enormous stress factor for individuals with obsessive-compulsive disorder (OCD), particularly for those with contamination symptoms. Many patients, as well as healthy individuals, experienced new obsessive-compulsive-like symptoms centered on COVID-19 during the pandemic. However, data on this population are still scarce.ObjectivesTo present a case exemplifying the association between the Covid-19 pandemic and the onset of OCD.MethodsCase presentation and non-systematic review of existing literature on Pubmed using the keywords: Covid-19, OCD, pandemic, depression.ResultsWe report a case of a 30-year-old female who presented to the emergency department due to depressive mood and suicidal ideation associated with exacerbation of OCD symptoms, namely intense fear of being infected with Covid-19. These symptoms led to avoidance of touching objects, surfaces or even herself in addition to frequent and long rituals of hand-washing and showers. She was asymptomatic prior to being infected with Covid-19, when she started developing obsessive ideas of contamination. She sought psychiatric support and was medicated with fluoxetine, olanzapine and clonazepam. Due to insufficient symptom control, she was admitted to the psychiatry ward, where treatment was initiated with aripiprazol and fluvoxamine. After dose titration, gradual remission of OCD symptomatology and depressive mood was observed.ConclusionsThe present case illustrates the correlation between Covid-19 and the onset of OCD symptomatology. Existing studies demonstrate that the pandemic worsened the landscape of symptoms of OCD, both in diagnosed patients as well as in previously healthy individuals. However literature is still limited thus, multinational and cross-cultural, longitudinal studies are warranted to gain further insights on this topic.Disclosure of InterestNone Declared

Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease.

Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

Eculizumab versus rituximab in generalised myasthenia gravis

ObjectiveMyasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction. However, evidence shaping treatment decisions, particularly for treatment-refractory cases, is sparse. Both rituximab and eculizumab may be...

SYmbicort given as needed in mild asthma (SYGMA study): a retrospective subanalysis of the Russian population

Introduction While mild asthma is generally better controlled than more severe disease, patients with mild asthma may experience severe exacerbations. Definite differences between countries in terms of asthma severity and control were described previously. Since SYGMA was a global study, this sub-analysis was conducted in geographic region to investigate potential regional specificities. Methods The SYGMA2 trial is double-blind multicenter study involving patients ≥12 years of age with mild asthma (n = 4176), eligible for regular treatment with inhaled corticosteroid (ICS). We conducted an open-label descriptive subanalysis of the baseline characteristics of the Russian population (n = 579) comparing to rest of participants of SYGMA2 trial from other 24 countries. The subanalysis is solely descriptive and will be used for hypothesis generation. Results The Russian population of patients with mild asthma hardly differs from the population in other countries in terms of baseline demographic and anthropometric characteristics, smoking status, and duration of asthma. At the study entry few patients from Russia received maintenance therapy with ICS and had symptom control, but the majority was uncontrolled on short-acting bronchodilators, thus the uncontrolled/controlled ratio was 52%/48% vs 45%/55% in other countries. More patients with mild asthma in the Russian group had faced at least one severe exacerbation in the previous year (30.1% vs 20.7%). Conclusions The subanalysis revealed a delayed prescription of controller (ICS) therapy and overuse of short-acting bronchodilators in the Russian population with mild asthma. These factors can lead to insufficient symptom control and higher risk of severe exacerbation in the Russian population with mild asthma.

Refractory suffering at the end of life and the assisted dying debate: An interview study with palliative care nurses and doctors

Background How often does refractory suffering, which is suffering due to symptoms that cannot be adequately controlled, occur at the end of life in modern palliative care? What are the causes of such refractory suffering? Should euthanasia be offered for refractory suffering at the end of life? We sought to shed light on these questions through interviews with palliative care specialists. Methods Semi-structured interviews with six nurses and six doctors working in palliative care in five Norwegian hospitals. Transcripts were analysed with systematic text condensation, a qualitative analysis framework. Results Informants find that refractory suffering is rare, and that with palliative sedation satisfactory symptom control can nearly always be achieved at the end of life. However, the process of reaching adequate symptom control can be protracted, and there can be significant suffering in the meantime. Both somatic, psychological, social and existential factors can contribute to refractory suffering and potentiate each other. However, informants also place significant weight on factors pertaining to the organization of palliative care services as contributing to insufficient symptom control. Conclusions If refractory suffering is indeed rare, then this arguably weakens a common prima facie argument for the legalization of assisted dying. However, the process of reaching adequate symptom control can be protracted and involve significant suffering. The experiences of palliative care clinicians constitute important empirical premises for the assisted dying debate. The study points to several areas in which palliative care can be improved.

The Role of Urodynamic Testing Prior to Third-Line OAB Therapy

This review outlines current guidelines and evidence for the use of urodynamic testing prior to the initiation of third-line overactive bladder (OAB) treatment options. OAB currently affects many patients with a significant impact on quality of life as well as health care resources. Treatment algorithms proceed from least to most invasive in an attempt to ameliorate symptoms, namely, urgency, frequency, and urgency incontinence. The current third-line OAB management strategies include percutaneous tibial nerve stimulation (PTNS), sacral nerve stimulation (SNS), and onabotulinumtoxinA injection. These modalities are reserved for patients that have gained insufficient symptom control or are intolerant of less invasive treatments. Urodynamic studies (UDS) are typically performed to help guide treatment planning and/or to evaluate for harmful urologic conditions. Currently available studies do not show a clear link between UDS results and treatment OAB success. The finding of detrusor overactivity (DO) has not been clearly established as a prerequisite to have clinical benefit with third-line OAB treatments in the uncomplicated idiopathic OAB patient population. There is some evidence that patients with DO on UDS may benefit more; however, additional blinded placebo-controlled studies are needed. Urodynamics should be used judiciously for patients with known or suspected voiding phase dysfunction, those with rapidly changing symptoms, those in whom the diagnosis is not clear, those who have medical or urological histories that can affect outcomes of treatment, and in those with known or suspected neurological disease. Although urodynamics may influence clinical decision-making, our review does not support the role of these investigations as predictors of outcomes in patients with uncomplicated, idiopathic overactive bladder.

Omalizumab Re-Treatment and Step-Up in Patients with Chronic Spontaneous Urticaria: OPTIMA Trial

Omalizumab shows greater clinical benefit with 300 mg dose than with the 150 mg dose. To determine outcomes postwithdrawal, relapse, and re-treatment in omalizumab responders, and from stepping up to 300 mg after insufficient symptom control with 150 mg. This was a prospective, randomized (3:4), open-label, noncomparator study (clinicaltrials.gov: NCT02161562). A total of 314 adult patients with chronic spontaneous urticaria and symptomatic on H1-antihistamines were enrolled between August 1, 2014, and November 6, 2015. Patients received 150 mg/300 mg omalizumab, every 4 weeks for 24 weeks. Omalizumab 150 mg dose could be stepped up to 300 mg between week 8 and week 24, if the 7-day sum of the daily Urticaria Activity Score (UAS7) was more than 6. If patients relapsed after treatment withdrawal at week 24, they could be re-treated with the same dose on which omalizumab was started. Patients on 300 mg could extend treatment by 12 weeks if they did not achieve symptom control on 300 mg in the initial dosing phase. The primary end point was the proportion of well-controlled patients who relapsed postwithdrawal, and achieved symptom control at the end of re-treatment. Symptom control was assessed using UAS7 (UAS7 ≤ 6= well controlled). Overall, 115 of 314 patients had adequate symptom control at week 24 (end of the initial dosing period) and 56 were re-treated after relapse postwithdrawal; 87.8% (95% CI, 78.6%-96.9%) regained symptomatic control (UAS7 ≤ 6). Most (141 of 178) patients initially treated with 150 mg required step-up to 300 mg, which resulted in a 9.5-point (95% CI, 7.6-11.3) improvement in UAS7 over the mean change observed initially on 150 mg. Step-up to 300 mg helps a greater proportion of patients achieve symptom control, and re-treatment with omalizumab is as effective as initial therapy.

Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study.

Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32±7.71 to 7.84±5.16 (p<0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06±118.7 to 60.86±18.68, p<0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76±8.04 to 8.82±6.63 (p =0.004). This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.

Influence of adherence to medical recommendations on symptom control in children with bronchial asthma

The search for factors affecting the efficacy of bronchial asthma (BA) therapy in children is an actual problem. subject of many modern scientific studies. Authors note that adherence to therapy in patients with asthma ranges from 30 to 70%. Often this index does not exceed 50%. Analysis of adherence to medical recommendations in children with asthma and the search for compliance reduction factors is one of the ways for optimizing therapy and improving the quality of life for children with asthma.Purpose. In order to optimize bronchial asthma therapy in pediatric practice, we analysed adherence to medical recommendations and its effect on the controllability of the disease in children with asthma.Materials and methods. The study included 94 children aged 6 to 17 years with an established diagnosis of bronchial asthma. All patients had previously been recommended basic therapy in the form of inhaled glucocorticosteroids (ICS) or their fixed combinations with long-acting beta2-adrenomimetikami (LABA). An assessment of BA control symptoms was carried out, and factors affecting adherence to medical recommendations were analyzed. The effect of decreased patient compliance on the control of asthma symptoms was evaluated.Results. 61.7% of children with asthma have insufficient disease control. In 42.55% of patients, a survey revealed insufficient adherence to medical recommendations. 88.3% of children and their parents reported the presence of factors capable of influencing the decrease in compliance. The most frequently occurring factor in reducing adherence to therapy turned out to be insufficient patient awareness of the disease itself, the mechanisms of therapy action, and the prospect of treatment. Statistical data processing showed a statistically significant decrease in adherence to medical recommendations in the group of patients with insufficient asthma symptom control (p = 0.038).Conclusion. Only 38.3% of children had complete asthma symptom control. The statistically significant reduction in adherence to medical recommendations in the group of children with insufficient symptom control suggests the need for educational activities for children with BA and their parents in order to increase adherence to medical recommendations, optimize the effectiveness of therapy and improve the quality of patients’ life.

UK prescribing practices as proxy markers of unmet need in allergic rhinitis: a retrospective observational study.

Little data on UK prescribing patterns and treatment effectiveness for allergic rhinitis (AR) are available. We quantified unmet pharmacologic needs in AR by assessing AR treatment effectiveness based on the prescribing behaviour of UK general practitioners (GP) during two consecutive pollen seasons (2009 and 2010). We conducted a retrospective observational study with the data from the Optimum Patient Care Research Database. We assessed diagnoses and prescription data for patients with a recorded diagnosis of rhinitis who took rhinitis medication during the study period. We assessed the data from 25,069 patients in 2009 and 22,381 patients in 2010. Monotherapy was the initial prescription of the season for 67% of patients with seasonal AR (SAR) and 77% of patients with nonseasonal upper airways disease (NSUAD), for both years. Initial oral antihistamine (OAH) or intranasal corticosteroid (INS) monotherapy proved insufficient for >20% of SAR and >37% of NSUAD patients. Multiple therapy was the initial prescription for 33% of SAR and 23% of NSUAD in both years, rising to 45% and >50% by season end, respectively. For NSUAD, dual-therapy prescriptions doubled and triple-therapy prescriptions almost tripled during both seasons. Many patients revisited their GP regardless of initial prescription. Initial OAH or INS monotherapy provides insufficient symptom control for many AR patients. GPs often prescribe multiple therapies at the start of the season, with co-prescription becoming more common as the season progresses. However, patients prescribed multiple therapies frequently revisit their GP, presumably to adjust treatment. These data suggest the need for more effective AR treatment and management strategies.

Sa1314 Inadequate Symptom Control on Long-Term PPI Therapy in GERD - Fact or Fiction?

Conclusions Inadequate control of symptoms is common in GERD patients prescribed PPI therapy for >1 year and is often overlooked in daily practice. 46% of patients taking PPI >1 year seen in general practice complain of heartburn or regurgitation symptoms at least 2 days per week. 10% of patients are considered “Lost Patients”. These patients with insufficient symptom control should be methodically identified and considered for further diagnostics and/or treatment modification, for example with a screening questionnaire. Interdisciplinary reflux centers have the potential to improve the care of GERD patients.

SCUAD and chronic rhinosinusitis. Reinforcing hypothesis driven research in difficult cases

Background: Our objective is to present recent research findings on recalcitrant chronic rhinosinusitis (CRS) in relation to "Severe Chronic Upper Airway Disease" (SCUAD). Methodology: Literature review using Medline and Em base databases (search terms 'chronic rhinosinusitis'; "chronic sinusitis" or"Severe Chronic Upper Airway Disease") limited to articles published in the English language. Results: Complex pathophysiological mechanisms characterize various forms of chronic rhinitis and rhinosinusitis (CRS), where inflammation persists in spite of adequate medical treatment. In these cases, a multifactorial etiology often underlies the development of sino-nasal inflammation. The interaction between chronic upper and lower airway inflammation via neurogenic and systemic pathways may complicate the therapy of these patients, and lead to insufficient symptom control. Conclusion: The recently introduced definition of "Severe Chronic Upper Airway Disease" (SCUAD) increases awareness of those patients with persistent inflammation and symptoms despite guideline-driven pharmacologic treatment. The concept of SCUAD may prove helpful in directing research towards clarifying the definition, diagnosis and pathophysiology of rhinitis and rhinosinusitis, their limits and overlap. In this review, a hypothesis on SCUAD immunopathology is also presented.

SCUAD and chronic rhinosinusitis. Reinforcing hypothesis driven research in difficult cases

Our objective is to present recent research findings on recalcitrant chronic rhinosinusitis (CRS) in relation to "Severe Chronic Upper Airway Disease" (SCUAD). Literature review using Medline and Em base databases (search terms 'chronic rhinosinusitis'; "chronic sinusitis" or"Severe Chronic Upper Airway Disease") limited to articles published in the English language. Complex pathophysiological mechanisms characterize various forms of chronic rhinitis and rhinosinusitis (CRS), where inflammation persists in spite of adequate medical treatment. In these cases, a multifactorial etiology often underlies the development of sino-nasal inflammation. The interaction between chronic upper and lower airway inflammation via neurogenic and systemic pathways may complicate the therapy of these patients, and lead to insufficient symptom control. The recently introduced definition of"Severe Chronic Upper Airway Disease" (SCUAD) increases awareness of those patients with persistent inflammation and symptoms despite guideline-driven pharmacologic treatment. The concept of SCUAD may prove helpful in directing research towards clarifying the definition, diagnosis and pathophysiology of rhinitis and rhinosinusitis,their limits and overlap. In this review, a hypothesis on SCUAD immunopathology is also presented.

Wann sollten wir mit der medikamentösen Therapie beim Morbus Parkinson beginnen?

There is still uncertainty when to start medical treatment in Parkinson disease (PD). Lack of availability of an unambiguous neuroprotective treatment and concern of potential short or long term adverse effects of medication often lead to an "wait and see" policy regarding initiation of medical treatment. This can result in insufficient symptom control and potentially reduced quality of life. There is increasing evidence of negative influence on disease progression by delayed onset of medical drug treatment in PD. It is under discussion whether symptomatic treatment in PD supports compensatory mechanisms of the cortico-basalganglionar system which might have been responsible for a physically intact motor function despite considerable and increasing nigro-striatal dopaminergic deficit during the preclinical phase of the disease. Therefore, symptomatic treatment might modify disease progression by supporting compensatory mechanisms within the basal ganglia. In this paper we discuss pro and contra of early medical treatment onset in PD under consideration of hitherto available scientific investigations.

Illness perception in pediatric somatization and asthma: complaints and health locus of control beliefs

BackgroundHealth- and illness-related cognitions of pediatric patients with asthma or somatization and of their caregivers are considered relevant for patient education and for cognitive-behavioral interventions. This study investigates the relationship between diagnosis and illness perception by child and parent in two different chronic conditions such as somatization disorder and asthma.Methods25 patients with somatoform disorders and 25 patients with asthma bronchiale completed the Giessen Complaint List and the Multidimensional Health Locus of Control Scale. Primary caregivers independently answered parallel proxy-report instruments. Analyses of variance were performed to determine the impact of diagnosis and perspective. Correlations were calculated to determine the concordance between patient and caregiver reports.ResultsNo statistically significant differences in illness locus of control beliefs were found between asthma and somatoform disorder children or parents. Parents reported more internal and fatalistic locus of control beliefs compared with their children. Correlations between patient and caregiver reports of symptoms and health locus of control beliefs were low to moderate.ConclusionClinicians should take into account a sense of insufficient symptom control in both diagnostic groups and different viewpoints of patients and their parents.

New information relevant to long‐term management of endoscopy‐negative reflux disease

SUMMARYDespite the fact that the endoscopic appearance of the mucosa is normal in the majority of patients who present with moderate to severe symptoms of acid reflux, valid clinical information on both the natural course of endoscopy‐negative reflux disease and the need for and design of long‐term therapy is still lacking. The aim of this study was to determine the natural course of endoscopy‐negative acid reflux disease over a period of 6 months; to determine whether 10 mg omeprazole once daily is sufficient to control symptoms in patients with symptomatic acid reflux disease, when given either as a strict daily dose or at the discretion of the patient (on‐demand therapy); and to compare the efficacy of 10 and 20 mg omeprazole with that of placebo, in resolving symptoms. A total of 495 patients with endoscopy‐negative acid reflux disease were recruited to compare 10 mg omeprazole daily with placebo, the clinical endpoint being unwillingness to continue in the study due to insufficient symptom control (i.e. heartburn). In a parallel study, 424 patients were randomized, after initial treatment with acid inhibition therapy to maintain symptom control during on‐demand therapy, to 10 or 20 mg omeprazole daily, or placebo. The Psychological General Well‐Being Index was used to compare the quality of life of patients in remission with those suffering a relapse. In the study in which continuous treatment with 10 mg omeprazole daily was compared with placebo, 48% of the patients allocated to placebo were in clinical remission after 6 months compared with 73% of those randomized to omeprazole (P &lt; 0.01). Furthermore, heartburn, the predominant acid reflux symptom, was completely controlled in 80% of omeprazole‐treated patients, compared with 51% of those receiving placebo. In the parallel on‐demand study, 56% of patients allocated to placebo (although consuming significantly more antacids) had adequate symptom control and thus remained in the study for 6 months. In patients receiving either 10 or 20 mg omeprazole daily, 69 and 83%, respectively, experienced adequate symptom control (P = 0.01 and P &lt; 0.01, respectively, compared with placebo). Mean scores on the Psychological General Well‐Being Index of 105.3 ± 2.0 (S.E.M.) were seen in patients in clinical remission, compared with 98.3 ± 2.6 in those experiencing relapse of reflux symptoms (P &lt; 0.05). When studied over a 6‐month period, about half of endoscopy‐negative reflux patients required drug intervention to achieve symptom control. In these patients continuous maintenance therapy with 10 mg omeprazole daily considerably increased the proportion of those experiencing symptom control. Another viable therapeutic strategy in such patients appears to be on‐demand therapy using 20 mg omeprazole.