Adequate Symptom Control Research Articles

Sleep abnormality in neuromyelitis optica spectrum disorder.

Objectives:We investigated the sleep structure of patients with neuromyelitis optica spectrum disorder (NMOSD) and the association of abnormalities with brain lesions.Methods:This was a prospective cross-sectional study. Thirty-three patients with NMOSD and 20 matched healthy individuals were enrolled. Demographic and clinical characteristics of patients were collected. Questionnaires were used to assess quality of sleep, daytime sleepiness, fatigue, and depression. Nocturnal polysomnography was performed.Results:Compared with healthy controls, patients with NMOSD had decreases in sleep efficiency (7%; p = 0.0341), non-REM sleep N3 (12%; p < 0.0001), and arousal index (6; p = 0.0138). REM sleep increased by 4% (p = 0.0423). There were correlations between arousal index and REM% or Epworth Sleepiness Scale (r = −0.0145; p = 0.0386, respectively). Six patients with NMOSD (18%, 5 without infratentorial lesions and 1 with infratentorial lesions) had a hypopnea index >5, and all of those with sleep apnea had predominantly the peripheral type. The periodic leg movement (PLM) index was higher in patients with NMOSD than in healthy controls (20 vs 2, p = 0.0457). Surprisingly, 77% of the patients with PLM manifested infratentorial lesions.Conclusions:Sleep architecture was markedly disrupted in patients with NMOSD. Surveillance of nocturnal symptoms and adequate symptomatic control are expected to improve the quality of life of patients with NMOSD.

Why Personalized Treatment Decisions Are Important

Why Personalized Treatment Decisions Are Important

Novel Buccal Film Formulation of Buprenorphine-Naloxone for the Maintenance Treatment of Opioid Dependence: A 12-Week Conversion Study

PurposeThe purpose of this study was to provide a preliminary assessment of the safety, tolerability, symptom control, and acceptability of buprenorphine-naloxone buccal film (BBN) for the maintenance treatment of opioid dependence in patients converted from buprenorphine-naloxone sublingual tablet or film (SLBN), as well as to determine the conversion ratio for switching patients from SLBN to BBN. MethodsThis open-label study included adult opioid-dependent subjects stabilized on 8/2 to 32/8 mg/d of SLBN for a minimum of 30 days. Study subjects were converted to a bioequivalent dose of BBN and maintained for 12 weeks. FindingsA total of 249 subjects (mean age 38.7 years, 65.9% male) were converted from SLBN to a single daily dose of BBN, and 79.1% completed the 12-week study. Adverse events and withdrawal symptoms led to discontinuation in 2.4% and 2.0% of BBN-treated subjects, respectively. Rates of constipation reported at baseline declined from 41% just before the initial BBN dose and within 24 hours of the last SLBN dose to 13% after 12 weeks of BBN treatment; treatment-emergent constipation was reported by 2.8% of BBN-treated subjects. Oral mucosal abnormalities were identified in 5% and 0.6% of systematic oral examinations in SLBN- and BBN-treated subjects, respectively. A total of 34 subjects had Clinical Opiate Withdrawal Scale total scores ranging from 10 to 25 (overall mean, 13.8) within 24 hours of taking their last SLBN dose, and scores for these subjects were reduced to a range of 0 to 3 (overall mean, 0.7) at 3 hours after the initial dose of BBN. Treatment compliance was high (108%); <1% of urine samples were buprenorphine-free, and 92.4% of BBN-treated subjects did not have a urine sample that tested positive for a non-prescribed opioid. A total of 91.3% subjects rated the taste of BBN as pleasant or neutral, and 82.5% rated BBN ease of use as easy or neutral. The overall mean final dose of BBN was 8.0/1.4 mg/d, yielding a 2:1 buprenorphine conversion ratio. ImplicationsAlthough these results should be considered preliminary due to the open-label design, BBN was overall safe and well tolerated, and seemed to provide adequate symptom control, in the treatment of opioid-dependent subjects previously controlled on SLBN for a minimum of 30 days. There was good adherence to study medication and favorable patient acceptance of the buccal formulation. The SLBN/BBN buprenorphine conversion ratio was 2:1. ClinicalTrials.gov identifier: NCT01666119.

A wearable epidural catheter infusion system for patients with intractable spontaneous intracranial hypotension.

Spontaneous intracranial hypotension is an important cause of secondary headaches, and most patients respond well to epidural blood patching or direct repair of the underlying spinal cerebrospinal fluid leak. However, options are limited for those patients who have exhausted these traditional treatments, especially when spinal imaging is normal. We describe a wearable epidural catheter infusion system for patients with intractable spontaneous intracranial hypotension. Six patients with intractable spontaneous intracranial hypotension (4 women and 2 men; mean age, 53 years; mean duration of symptoms, 50 months) underwent placement of a permanent indwelling spinal epidural catheter attached to an external infusion pump. The Migraine Disability Assessment questionnaire was used to assess the severity of the symptoms, before and during treatment. The infusion resulted in complete or near-complete symptom relief in 5 of 6 patients (Migraine Disability Assessment score decreased from grade IV to grade I or II). However, the epidural catheter infusion system was removed in 2 patients because of infection, in 1 patient because of delayed failure to provide adequate symptom control, and in 1 patient because of minimal symptom relief. Two patients reported excellent and sustained symptom relief over 27 and 36 months of follow-up. This wearable epidural catheter infusion system showed promising efficacy results but the high rate of complications limits its use to a very select group of patients.

Off-label Use of Drugs in Childhood Asthma

Asthma is among the most common illnesses in childhood and may require off-label drug use for adequate symptom control. Several studies have assessed that this use is common mainly due to a lack of clinical research. The leading concerns are the increased risk of adverse drug reactions and prescription errors. However, off-label prescriptions are not necessarily incorrect. The European Medicines Agency released the Paediatric Regulation to promote research in the medicines for children; yet, recent data suggest only a minor impact.

P54 Which Secondary Care Asthma Patients Are Most Likely To Overestimate Their Control? A Cross-sectional Study

Introduction Asthma is a global health issue affecting 300 million people worldwide; with increasing prevalence and morbidity and preventable mortality. Despite advances in management the number of asthma related deaths has not improved. Asthma is a heterogeneous condition, with a variety of clusters of clinical presentations and courses, objective measures and treatment responses. A common feature of asthma is the under-reporting of poor symptom control by patients and under-recognition by clinicians. Poor asthma control in the preceding 12-months prior to admission has been linked to asthma related deaths. The significance of measuring asthma control independently from asthma severity has been demonstrated. However, considerable differences in perceived and actual control are apparent. There is a need to identify patient groups at risk of under-reporting symptoms and not recognising poor control. Aim To establish which patient features are associated with overestimation of disease control. Setting Secondary care consultant led asthma clinic. Population 108 patients recruited over 10 weeks. Measures Objective measures of disease severity were mapped against perceived symptom control using the Asthma Control Test; age, gender, co-morbidities, medications, induced sputum, lung function, IgE, blood eosinophil, histamine challenge test, exhaled nitric oxide, ECG CXR, smoking status and BMI. Analysis Significant associations between patient groups and perceptions of symptom control are described. Results 61 (56.6%) of patients had difficult asthma according to BTS guidance. 95 (88.0%) had poorly controlled asthma, with 70 (64.8%) of these perceiving adequate control of symptoms. All patients with good perceived and actual control of symptoms; 13 (12.0%), had never smoked. 85.5% of patients who did not recognise their symptoms prevalence were overweight, obese or morbidly obese. All patients with raised IgE or blood eosinophillia had poorly controlled asthma; though 58.6% of this group perceived good control. Conclusion This single centre cross-sectional study suggests smokers, overweight patients and those with inflammation predominant asthma are most likely to under-report severity. These findings are in keeping with the cluster analyses of Haldar and Moore. Further work is required to follow-up these patients to establish if poor perception of symptoms changes over time, or is associated with future asthma attack frequency.

Modern dying: from securing rights to meeting needs.

Modern medicine has transformed the dying experience. In the developed world, most of us no longer die from infectious diseases and sudden accidents, but from chronic illnesses that progressively worsen. Yet the U.S. healthcare system is not designed to meet the needs of people with chronic illness or of frail elders. In addition, our system incentivizes the use of technologies that are often helpful when an underlying condition is reversible but, when used very near the end of life, may only postpone the dying process and increase burdens on the patient. This state of affairs renders many people near the end of life without adequate symptom control, little or no social and psychological support, and inadequate involvement in decisions about when and how best to use modern technologies. This paper traces efforts over the last three decades to address problems related to modern dying. The author sees three phases: early work focused on securing patients' rights to refuse unwanted treatments, the next phase focused on building the specialty of palliative medicine, and the third and future phase must redesign our healthcare system to better align with how we die in the 21st century.

Revisit rates and diagnoses following pediatric tonsillectomy in a large multistate population.

Investigate the incidence and characteristics of revisits following ambulatory pediatric tonsillectomy/adenotonsillectomy. Cross-sectional study using national databases. Ambulatory pediatric (age <18.0 years) tonsillectomy or adenotonsillectomy cases were extracted from the 2010 State Ambulatory Surgery, Emergency Department, and Inpatient databases for New York, Florida, Iowa, and California. First and second revisits within the 14-day postoperative period were tabulated. Diagnoses, procedure codes, and mortality were examined. There were 36,221 pediatric tonsillectomies/adenotonsillectomies (mean age 7.4 years, 51.4% male). Overall, 2,740 patients (7.6%) had a revisit after pediatric tonsillectomy; 402 patients (1.1%) had a second revisit. Among revisits, 6.3% revisited the ambulatory surgery center, 77.5% revisited the emergency department, and 16.2% were readmitted as an inpatient. Among all tonsillectomies, bleeding occurred in 2.0% and 0.5% within the first and second revisits, respectively. A second revisit had a statistically higher association with a primary bleeding diagnosis than the first revisit (P < .001). Among all cases, 0.75% underwent a surgical procedure for bleeding at a first revisit compared to 0.25% during a second revisit. Acute pain was the primary diagnosis in 18.4% and 11.2% of first and second revisits; fever/vomiting/dehydration were primary diagnoses in 28.2% and 17.9%, respectively. There were two mortalities (0.0055%) within the 14-day postoperative interval. This large-scale analysis describes the current rates and diagnoses of revisits, hospital readmission, and surgical intervention following ambulatory pediatric tonsillectomy. Many revisits centered on pain control and dehydration, suggesting that more adequate symptom control may prevent a large proportion of revisits. 2b.

AB0730 Evaluation of Neuropathic Pain in A Spondyloarthritis Cohort

BackgroundPain is the most common symptom in rheumatic diseases. Its physiopathology generally involves a disturbance in nociceptive perception by tissue damage that often evolves to central pain with features of...

Cannabinoids and Schizophrenia: Therapeutic Prospects

Approximately one third of patients diagnosed with schizophrenia do not achieve adequate symptom control with standard antipsychotic drugs (APs). Some of these may prove responsive to clozapine, but non-response to APs remains an important clinical problem and cause of increased health care costs. In a significant proportion of patients, schizophrenia is associated with natural and iatrogenic metabolic abnormalities (obesity, dyslipidaemia, impaired glucose tolerance or type 2 diabetes mellitus), hyperadrenalism and an exaggerated HPA response to stress, and chronic systemic inflammation. The endocannabinoid system (ECS) in the brain plays an important role in maintaining normal mental health. ECS modulates emotion, reward processing, sleep regulation, aversive memory extinction and HPA axis regulation. ECS overactivity contributes to visceral fat accumulation, insulin resistance and impaired energy expenditure. The cannabis plant synthesises a large number of pharmacologically active compounds unique to it known as phytocannabinoids. In contrast to the euphoric and pro-psychotic effects of delta-9-tetrahydrocannabinol (THC), certain non-intoxicating phytocannabinoids have emerged in pre-clinical and clinical models as potential APs. Since the likely mechanism of action does not rely upon dopamine D2 receptor antagonism, synergistic combinations with existing APs are plausible. The anti-inflammatory and immunomodulatory effects of the non-intoxicating phytocannabinoid cannabidiol (CBD) are well established and are summarised below. Preliminary data reviewed in this paper suggest that CBD in combination with a CB1 receptor neutral antagonist could not only augment the effects of standard APs but also target the metabolic, inflammatory and stress-related components of the schizophrenia phenotype.

Update on the Treatment of Chronic Urticaria

Chronic spontaneous urticaria, also known as chronic idiopathic urticaria or simply chronic urticaria, is a common disorder that has a prevalence in the general population that ranges between 0.5% and 1%. This condition negatively affects the patient's quality of life and has considerable impact on direct and indirect health-related costs. Chronic urticaria is difficult to manage. Nonsedating H1 antihistamines are the first line of therapy, but fewer than 50% of patients experience relief at recommended dosages. Although guidelines call for increasing the dosage when response is inadequate, some patients still do not achieve adequate control of symptoms. New treatment alternatives, with proven efficacy under the standards of evidence-based medical practice, must therefore be developed.

Dopamine Transporter Genotype and Stimulant Dose-Response in Youth with Attention-Deficit/Hyperactivity Disorder

This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD). Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS. Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype. ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control.

Anti-Complement Treatment in Paroxysmal Nocturnal Hemoglobinuria: Where we Stand and Where we are Going.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, non-malignant, hematological disorder characterized by the expansion of hematopoietic stem cells and progeny mature blood cells which are deficient in some surface proteins, including the two complement regulators CD55 and CD59. PNH is the paradigm of diseases implying complement dysregulation as main pathogenic mechanism; in fact, PNH erythrocytes are uncapable to modulate on their surface physiologic complement activation, which eventually leads to the typical clinical hallmark of PNH - the chronic complement-mediated intravascular anemia. Indeed, due to the lack of CD55 complement is continuously activated on erythrocyte surface, which subsequently enables the terminal lytic complement because of the lack of CD59, finally resulting in erythrocyte lysis. The availability of eculizumab as the first complement inhibitor for clinical use renewed the interest for this rare hematological disease. Indeed, in the last decad the anti-C5 monoclonal antibody has proven effective for the treatment of PNH, resulting in a sustained control of complement-mediated intravascular hemolysis, with a remarkable clinical benefit. Anti-complement treatment allowed transfusion independence in at least half of PNH patients receiving eculizumab, with adequate control of all hemolysis-associated symptoms even in almost all remaining patients. In addition, the risk of thromboembolic events - an other clinical hallmark of PNH, which significantly affects prognosis and survival - seems substantially reduced on eculizumab treatment, apparently resulting in improved survival. Even with all these remarkable effects, eculizumab treatment does not result in hemoglobin normalization, and most patients remain anemic. It has been demonstrated that this is due to persistent activation of the early phases of complement activation (upstream the C5), leading to complement-mediated extravascular hemolysis. Ongoing researches are focusing on possible strategies to improve current anti-complement therapies, aiming to develop second-generation complement therapeutics. Here we review PNH and its complement-mediated pathophysiology, summarizing available data on anti-complement treatment; we'll also discuss recent pathogenic insights which drive the development of novel strategies of complement inhibition.

Effectiveness of a Clinical Pathway With Methadone Treatment Protocol for Treatment of Neonatal Abstinence Syndrome Following In Utero Drug Exposure to Substances of Abuse*

To evaluate the effectiveness of methadone for the treatment of neonatal abstinence syndrome when used according to a preexisting clinical pathway. This is a 3-year retrospective study conducted at a single institution. In this study, neonates who received methadone for the treatment of neonatal abstinence syndrome according to a predefined clinical treatment pathway were evaluated for treatment success: defined as adherence to the methadone regimen with no residual signs of withdrawal. Data were collected for methadone dosages, Lipsitz scores, length of methadone treatment, total length of hospital stay, and relevant clinical data. Level III neonatal ICU. Newborn infants with in utero exposure to substances of abuse. None. Sixty patients were included. The mean gestational age and birth weight were 37.07 ± 3.05 weeks and 2.77 ± 0.6 kg. All 60 patients exhibited neonatal abstinence syndrome within first 72 hours of life. Fifty-seven of 60 patients (95%) initiated methadone treatment according to protocol. There was deviation from the protocol at 48 and 72 hours of treatment with approximately 59% and 13% of the patients still on methadone at more than the prescribed amount to control neonatal abstinence syndrome. The mean ± SD total methadone exposure was 1.99 ± 1.63 mg/kg, length of treatment 11.66 ± 9.02 days, and total hospital length of stay 22.43 ± 29.3 days, suggesting significant variability in response. No significant correlation was found between birth weight or gestational age and length of treatment. Clinical pathway for treating neonatal abstinence syndrome was closely followed at the initial diagnosis. The doses of methadone used in the first 24-48 hours of this study were insufficient for adequate symptom control. Despite a formal treatment protocol, there was substantial variability in total methadone exposure, length of treatment, and length of stay, suggesting other contributory factors for the observed variability.

Treatment of mild asthma: Is it necessary to keep regular inhaled corticosteroids?

The main goal of asthma treatment is an adequate control of symptoms and a reduction in future exacerbations. To achieve the goal, international guidelines recommend daily use of controllers, such as inhaled corticosteroids (ICSs), even in patients with mild asthma. However, poor adherence is an unavoidable issue in the management of mild asthma. In addition, there is concern about possible adverse reactions and economic burden by unnecessary treatment. Recently, several studies have shown that as-needed use of ICSs has similar effects as regular use of ICSs on the prevention of acute asthmatic exacerbations. However, daily regular use of ICSs seems to be superior in terms of symptom-free days or airway inflammation suppression. Further studies are needed to determine whether symptom-driven use of ICSs can be an effective strategy for the management of mild asthma. Also, it is necessary to develop proper methods that can predict mild asthmatics who experience frequent exacerbations if they stop regular ICSs.

Intestinal constipation in patients with advanced oncological disease in use of opioides

Constipation is a very common disorder in oncologic patients with advanced disease, and it may cause pain, abdominal distension,nausea and vomit. This study had as its aim to identify available evidences on the literature about actions of palliativecare for oncologic patients, considering these actions to be the result from the necessities of care that may contribute to thecontrol of this symptom. This investigation is a literature integrative review; and to select scientific publications, we accessedthe databases from Virtual Health Library (VHL), specifically LILACS and SciELO. Inclusion criteria were adapted: the articlesportraying palliative care to patients with constipation due to the use of opioids, with were indexed in the databases mentionedabove, which were published in Portuguese in the period from 2002 to 2012 and whose abstracts and texts were availableonline in its entirety. We excluded studies with restricted access. At the end of the research, we found 20 references but onlyseven met the criteria for inclusion. The articles included in this study pointed out that constipation is a very common symptomin cancer patients with advanced disease using opioids. This review showed that a proper evaluation, nutritional management,rational use of medicines and laxatives opioids antagonists, as well as new features such as the use of diet-therapeutic drugsbased on Agaricus sylvaticus can promote adequate control of symptoms, preventing complications and invasive procedures.

Effectiveness and safety of rapid clozapine titration in schizophrenia

Clinical guidelines recommend slow clozapine dose titration in order to decrease the risk of seizures and hypotension. The recommendation may delay adequate control of severe psychotic symptoms. We evaluated the safety and effectiveness of rapid clozapine titration in patients who had been previously exposed to the drug and in patients who received clozapine for the first time after failing to respond to other antipsychotics. Analysis of hospital course of a consecutive cohort of schizophrenia patients (N = 111) who received 25-100 mg of clozapine as needed every 6 h the first treatment day, followed by upward adjustments of 25-100 mg/day. Symptom control was obtained with an average dose of 353 ± 174 mg/day after 4.1 ± 3.1 days in the 73 patients previously treated with clozapine. For the 38 patients initially started on other antipsychotics, the average clozapine dose required for symptom control (409 ± 188 mg/day) was reached after 7.1 ± 4.8 days. None of the patients had seizures, severe hypotension or other major adverse reactions. In this naturalistic cohort study rapid clozapine titration appeared safe and effective for the treatment of schizophrenia. The results justify controlled clinical trials of this treatment method.

Management of severe asthma in childhood – State of the art and novel perspectives

The majority of children with asthma have mild or moderate disease and can obtain adequate control of symptoms through avoidance of triggering factors and/or with the help of medications. There is still a group of children with severe asthma in whom symptom control is poor depending either on identifiable aggravating factors or on true therapy resistance. These children have a poor quality of life and are limited by the severity of their disease. There is a need for a staged approach to the assessment and treatment of this small but vulnerable and resource-consuming group. The current review will provide an overview of a possible standardized approach to characterize this heterogeneous group of severely sick children including some newly developed ways of assessing asthma severity and potentialities of new asthma therapies. Furthermore, the umbrella term 'problematic severe asthma' is described. The term encompasses children whose severe asthma is due to identifiable exacerbating factors, as well as children who are resistant to any conventional therapeutic approach. Characteristics of these two groups of children are described, as are possible biomarkers and current and emerging diagnostic tools for allergy evaluation. Some recent advances and future possibilities for treatment of severe asthma are also presented in this review.

Treat-to-target in spondyloarthritis—do we have a plan?

Clinicians now have the therapies and outcome tools to implement treat-to-target strategies aimed at achieving and maintaining adequate function and control of symptoms in spondyloarthritis and psoriatic arthritis. However, validation of surrogate markers of structural progression is a prerequisite for treat-to-target strategies aimed at improving long-term outcomes such as joint damage.

Actualización en el tratamiento de la urticaria crónica

Chronic spontaneous urticaria, also known as chronic idiopathic urticaria or simply chronic urticaria, is a common disorder that has a prevalence in the general population that ranges between 0.5% and 1%. This condition negatively affects the patient's quality of life and has considerable impact on direct and indirect health-related costs. Chronic urticaria is difficult to manage. Nonsedating H1 antihistamines are the first line of therapy, but fewer than 50% of patients experience relief at recommended dosages. Although guidelines call for increasing the dosage when response is inadequate, some patients still do not achieve adequate control of symptoms. New treatment alternatives, with proven efficacy under the standards of evidence-based medical practice, must therefore be developed.