Routine Clinical Care Of Patients Research Articles

The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis

BackgroundAlpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. SPARKLE is an alpha-mannosidosis registry intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis. It is a post-approval commitment to European marketing authorization for Velmanase alfa (Lamzede®), the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild to moderate alpha-mannosidosis. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively.ResultsThe SPARKLE registry is designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting patient enrollment in 2020. Patients will be followed for up to 15 years. Safety and effectiveness as post-authorization outcomes under routine clinical care in patients with treatment will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality-of-life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned.ConclusionThis study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.

Clinical Efficacy of Tumor Treating Fields for Newly Diagnosed Glioblastoma.

Whether adding tumor treating fields (TTF) to the Stupp protocol increases survival for glioblastoma (GBM) patients in routine clinical care remains unknown. We retrospectively identified adult patients with newly diagnosed GBM (n=104) treated with the Stupp protocol or TTF at our Institution. Thirty-six percent (37/104) of patients received TTF in conjunction with the Stupp protocol and these patients had increased 6-month (p=0.006) and 1-year (p=0.170), but not 2-year survival rates compared to the 67-patients who received Stupp alone. The improvement of survival rate at 6-month was further confirmed by a modified Poisson model (p=0.010). However, we did not observe any improvement in overall survival (OS) with a Cox model. While adding TTF to the Stupp protocol appeared to benefit patients with newly diagnosed GBM, this effect was mild and may be largely due to selection bias.

Implementing a Patient-Reported Outcome Measure for Hemodialysis Patients in Routine Clinical Care: Perspectives of Patients and Providers on ESAS-r:Renal.

The Edmonton Symptom Assessment System Revised: Renal is a patient-reported outcome measure used to assess physical and psychosocial symptom burden in patients treated with maintenance dialysis. Studies of patient-reported outcome measures suggest the need for deeper understanding of how to optimize their implementation and use. This study examines patient and provider perspectives of the implementation process and the influence of the Edmonton Symptom Assessment System Revised: Renal on symptom management, patient-provider communication, and interdisciplinary communication. Eight in-facility hemodialysis programs in Ontario, Canada, assessed patients using the Edmonton Symptom Assessment System Revised: Renal every 4-6 weeks for 1 year. Screening and completion rates were tracked, and pre- and postimplementation surveys and midimplementation interviews were conducted with patients and providers. A chart audit was conducted 12 months postimplementation. In total, 1459 patients completed the Edmonton Symptom Assessment System Revised: Renal; 58% of eligible patients completed the preimplementation survey (n=718), and 56% of patients who completed the Edmonton Symptom Assessment System Revised: Renal at least once completed the postimplementation survey (n=569). Provider survey response rates were 71% (n=514) and 54% (n=319), respectively. Nine patients/caregivers from three sites and 48 providers from all sites participated in interviews. A total of 1207 charts were audited. Seven of eight sites had mean screening rates over 80%, suggesting that routine use of the Edmonton Symptom Assessment System Revised: Renal in clinical practice is feasible. However, the multiple data sources painted an inconsistent picture of the value and effect of the Edmonton Symptom Assessment System Revised: Renal. The Edmonton Symptom Assessment System Revised: Renal standardized symptom screening processes across providers and sites; improved patient and provider symptom awareness, particularly for psychosocial symptoms; and empowered patients to raise issues with providers. Yet, there was little, if any, statistically significant improvement in the metrics used to assess symptom management, patient-provider communication, and interdisciplinary communication. The Edmonton Symptom Assessment System Revised: Renal patient-reported outcome measure may be useful to standardize symptom screening, enhance awareness of psychosocial symptoms among patients and providers, and empower patients rather than to reduce symptom burden.

Comparison of commonly used screening tools for determining obstructive sleep apnea amongst aviation employees

IntroductionEpidemiological evidence suggests the prevalence of Obstructive Sleep Apnea (OSA) ranges 9–38%. Multiple screening tools are used to aid diagnosis. In professions that require high levels of attentiveness, safety, and responsibility for other's lives, inaccuracies and biases are probable for self-reported data. We sought to assess the best screening tool for OSA amongst aircraft pilots and air traffic controllers (ATCs). MethodsData were collected as part of routine clinical care for patients presenting to Sleep Disorders Specialized Clinic. A total 1384 patients attended the clinic (2012–2018), of which 254 were either pilots or ATCs. Patients responded to three questionnaires, regularly used for OSA screening: 1) Epworth Sleepiness Scale (ESS); 2) Berlin Questionnaire (BQ); 3) STOP-BANG Questionnaire (SBQ). We used non-parametric ROC analysis, sensitivity, and specificity measures, along with positive and negative predictive values (PPV/NPV) to determine the most accurate diagnostic instrument. ResultsThe ROC (95% CI) for the ESS, BQ, and SBQ was 0.49 (0.39–0.59), 0.58 (0.49–0.67), and 0.56 (0.47–0.65), respectively. When the SBQ was used in combination with the ESS, the sensitivity was high at 100% (78.2–100.0), as were the PPV and NPV, 83.3% (58.6–96.4) and 100.0 (2.5–100.0), respectively. ConclusionThe SBQ, in combination with the ESS, was the most reliable diagnostic tool for OSA in pilots and ATCs. Physicians should prioritize use of these screening tools for predicting OSA when assessing those working in the aviation industry and similar occupational groups, such as drivers. Given the scarcity of literature in this population, we recommend future studies replicate ours to either confirm or refute the findings.

Association of Skin Psoriasis and Somatic Comorbidity With the Development of Psychiatric Illness in a Nationwide Swedish Study

Psoriasis is a complex systemic disease with skin involvement, somatic comorbidity, and psychiatric illness (PI). Although this view of psoriasis is widely accepted, potential synergies within this triad of symptoms have not been adequately investigated. To investigate the independent association of skin psoriasis and somatic comorbidity with the development of PI and to assess whether skin psoriasis and somatic comorbidity act synergistically to produce a risk of PI that is greater than the additive associations. Participants were enrolled between January 2005 and December 2010, in this retrospective matched case-control study using secondary (ie, administrative), population-based registry data from Swedish patients in routine clinical care. The dates of analysis were March 2017 to December 2019. Participants were patients with skin psoriasis and control participants without psoriasis matched on age, sex, and municipality, who were all free of preexisting PI. Presence of skin psoriasis and somatic comorbidity (captured through the Charlson Comorbidity Index and the Elixhauser Comorbidity Index). Risk of PI onset (composite of depression, anxiety, and suicidality) is shown using Kaplan-Meier curves stratified by the presence of skin psoriasis and somatic comorbidity. Adjusted associations of skin psoriasis and somatic comorbidity with the development of PI were analyzed using Cox proportional hazards regression models, including interactions to assess synergistic associations. The 3 components of PI were also assessed individually. A total of 93 239 patients with skin psoriasis (mean [SD] age, 54 [17] years; 47 475 men [51%]) and 1 387 495 control participants (mean [SD] age, 54 [16] years; 702 332 men [51%]) were included in the study. As expected, patients with skin psoriasis were more likely to have somatic comorbidity and PI than control participants. Compared with those without skin psoriasis or somatic comorbidity, patients with psoriasis without somatic comorbidity had a 1.32 times higher risk of PI onset (hazard ratio [HR], 1.32; 95% CI, 1.27-1.36; P < .001), whereas patients with psoriasis with somatic comorbidity had a 2.56 times higher risk of PI onset (HR, 2.56; 95% CI, 2.46-2.66; P < .001). No synergistic associations of skin psoriasis and somatic comorbidity with the development of PI were found (HR, 0.93; 95% CI, 0.81-1.04; P = .21). This study found that somatic comorbidity appeared to alter PI onset even more than skin psoriasis. The observed association of skin psoriasis and somatic comorbidity with the development of PI reinforces the need for proactive, holistic treatment of patients with psoriasis.

Assessment of actionable findings in radiology reports

PurposeThe American College of Radiology (ACR) Actionable Reporting Work Group defined three categories of imaging findings that require additional, nonroutine communication with the referring physician because of their urgency or unexpectedness. The objective of this study was to determine the prevalence of actionable findings in radiology reports, and to assess how well radiologists agree on the categorisation of actionable findings. MethodFrom 124,909 consecutive radiology reports stored in the electronic health record system of a large university hospital, 1000 reports were randomly selected. Two radiologists independently annotated all actionable findings according to the three categories of urgency defined by the ACR Work Group. Annotation differences were resolved in a consensus meeting and a final category was established for each report. Interannotator agreement was measured by accuracy and the kappa coefficient. ResultsThe prevalence of the three categories of actionable findings together was 32.5 %. Of all reports, 10.9 % were from patients seen in the emergency department. Prevalence of actionable findings for these patients (45.9 %) was considerably higher than for patients in routine clinical care (30.9 %). Interannotator agreement scores on the categorisation of actionable findings were 0.812 for accuracy and 0.616 for kappa coefficient. ConclusionsThe prevalence of actionable findings in radiology reports is high. The interannotator agreement scores are moderate, indicating that categorisation of actionable findings is a difficult task. To avoid unneeded increase in the workload of radiologists, in particular in routine practice, clinical context may need to be considered in deciding whether a finding is actionable.

The significance of angiotensin II type 1 receptor (AT1 receptor) in renal transplant injury.

Humoral response beyond human leukocyte antigen (HLA) is of great interest in the transplant community. We decided to summarize the data on a new antigenic target called angiotensin II type 1 receptor (AT1 receptor). Non-HLA antibodies can now be detected in routine clinical care of patients after transplantation, but their role is not fully understood. Numerous analyses showed that non-HLA response may exert a higher risk of allograft rejection and allograft loss independently of the HLA system. Non-HLA response may even have a higher rate of antibody-mediated rejection. Information regarding antigen target, as well as the pathophysiology of its antibodies and diagnostic tools, is essential for a better understanding of non-HLA humoral response. Angiotensin II type 1 receptors are the most recognized target for non-HLA antibodies. Anti-AT1R Abs (anti-angiotensin II type 1-receptor-activating antibodies) may identify renal transplant patients at higher risk of graft rejection and loss. The presence of AT1 receptor expression analyzed together with anti-AT1R Abs should be considered for better transplant immunological risk assessment. Further assessment is required for a better understanding and to create appropriate therapeutic strategies.

Impact of the size of the normal database on the performance of the specific binding ratio in dopamine transporter SPECT

BackgroundThis study investigated the impact of the size of the normal database on the classification performance of the specific binding ratio (SBR) in dopamine transporter (DAT) SPECT with [123I]FP-CIT in different settings.MethodsThe first subject sample comprised 645 subjects from the Parkinson’s Progression Marker Initiative (PPMI), 207 healthy controls (HC), and 438 Parkinson’s disease (PD) patients. The second sample comprised 372 patients from clinical routine patient care, 186 with non-neurodegenerative parkinsonian syndrome (PS) and 186 with neurodegenerative PS. Single-photon emission computed tomography (SPECT) images of the clinical sample were reconstructed with two different reconstruction algorithms (filtered backprojection, iterative ordered subsets expectation maximization (OSEM) reconstruction with resolution recovery). The putaminal specific binding ratio (SBR) was computed using an anatomical region of interest (ROI) predefined in standard (MNI) space in the Automated Anatomic Labeling (AAL) atlas or using hottest voxels (HV) analysis in large predefined ROIs. SBR values were transformed to z-scores using mean and standard deviation of the SBR in a normal database of varying sizes (n = 5, 10, 15,…, 50) randomly selected from the HC subjects (PPMI sample) or the patients with non-neurodegenerative PS (clinical sample). Accuracy, sensitivity, and specificity for identifying patients with PD or neurodegenerative PS were determined as performance measures using a predefined fixed cutoff on the z-score. This was repeated for 10,000 randomly selected normal databases, separately for each size of the normal database. Mean and 5th percentile of the performance measures over the 10,000 realizations were computed. Accuracy, sensitivity, and specificity when using the whole set of HC or non-neurodegenerative PS subjects as normal database were used as benchmark.ResultsMean loss of accuracy of the putamen SBR z-score was below 1% when the normal database included at least 15 subjects, independent of subject sample (PPMI or clinical), reconstruction method (filtered backprojection or OSEM), and ROI method (AAL or HV). However, the variability of the accuracy of the putamen SBR z-score decreased monotonically with increasing size of normal database and was still considerable at size 15. In order to achieve less than 5% “maximum” loss of accuracy (defined by the 5th percentile) in all settings required at least 25 to 30 subjects in the normal database. Reduction of mean and “maximum” loss of accuracy of the putamen SBR z-score by further increasing the size of the normal database was very small beyond size 40.ConclusionsThe results of this study suggest that 25 to 30 is the minimum size of the normal database to reliably achieve good performance of semi-quantitative analysis in dopamine transporter (DAT) SPECT, independent of the algorithm used for image reconstruction and the ROI method used to estimate the putaminal SBR.

Fatigue: The Misunderstood Symptom of Heart and Lung Disease

Fatigue is a common symptom experienced by patients with chronic heart and lung failure that can lead to adverse health outcomes, such as frailty. To better understand the nature of fatigue in heart and lung failure, a meta-synthesis of qualitative studies was conducted to explore patients' experiences of fatigue while living with heart failure (HF) or chronic obstructive pulmonary disease (COPD). Understanding the nature and impact of fatigue in these chronic conditions can guide the evaluation and management of fatigue and inform future development of therapeutic interventions to decrease fatigue and improve quality of life. Three databases (Embase, PubMed, CINAHL) were searched for qualitative studies published in the last ten years that describe fatigue in patients with HF or COPD. Studies with descriptions of fatigue, either as the primary focus or as a component to a symptom profile, were synthesized, integrated, and interpreted. 13 studies describing the experience of fatigue in HF and COPD across 444 participants were identified and included in the analysis. Across studies, fatigue was described as an all-consuming experience of lethargy, lack of energy, and physical weakness that was refractory to rest and worsened over time. Fatigue was deeply disruptive to daily life, impacting both physical and social activities, and leading to a loss of independence and isolation. This disruption had significant physical and psychological consequences, which further emerged in two sub-themes; co-occurrence of symptoms (e.g. sleep disturbances, anxiety and depression, reduced appetite, and impaired cognition), and feeling that the extent of their suffering and capabilities were either under recognized or misunderstood by both loved ones and clinicians. Findings highlight the pervasive experiences of fatigue in chronic heart failure and COPD. Fatigue deeply impacts physical, psychological, and social domains and decreases quality of life. Fatigue is commonly under recognized or misunderstood by family, friends, and clinicians. Assessment and management of fatigue needs to be incorporated in routine clinical care of patients with heart and lung failure. Themes of commonly occurring co-symptoms highlight key physical and psychological elements that mediate or exacerbate fatigue, and may serve as targets in future interventional studies.

CAREGIVER-RELATED FACTORS ASSOCIATED WITH THE DESIRE TO INSTITUTIONALIZE CARE RECIPIENTS WITH DEMENTIA

Introduction Institutionalization of individuals with dementia within the first five years of diagnosis occurs at a rate of 10% per year. However, surveys show that most older adults prefer to age in place in the community. Research in the past two decades indicates numerous variables are associated with increased risk of institutionalization, including both sociodemographic factors (e.g., caregiver employment, financial resources, and older care recipient age), as well as psychosocial and care recipient factors (e.g., care recipient disability level and problem behaviors). Care recipient (CR) characteristics associated with greater risk for institutionalization include increased dependence in activities of daily living, severity of cognitive impairment, and frequency and severity of behavioral symptoms of dementia. Previously investigated caregiver (CG) characteristics, such as physical well-being and self-care behaviors, CG burden and social support, may also contribute to the risk of institutionalization. However, these identified CG factors have not yet been routinely assessed in clinical practice. Additionally, CGs are at a greater risk for poor health, depression, and use of psychotropic drugs and health services. Our aim was to examine the relationship between CG-related factors (e.g., depressive symptomatology, CG burden, perceived health, and social support) and the desire to institutionalize the CR among a real-world community sample of CGs of older adults with dementia. We hypothesized that specific CG domains, including greater perceived health and social support, would decrease the desire to institutionalize the CR. Methods The sample included 334 caregivers (CGs) of older (aged 65+), community-dwelling, low-income care recipients (CRs) prescribed a cholinesterase inhibitor or memantine who met criteria for dementia. CRs were identified from a sample of older adults receiving pharmaceutical assistance from the Pennsylvania Department of Aging's Pharmaceutical Assistance Contract for the Elderly (PACE) program. All eligible CGs who gave verbal consent to participate were enrolled in the Caregiver Resources, Education, and SupporT (CREST) program, a state-sponsored, University-delivered service, with assessment and support provided by behavioral health clinicians (nurses, social worker and psychologist) via telephone. Upon commencing the program, CGs completed a comprehensive assessment that captured sociodemographics and CR's clinical characteristics (including the Revised Memory and Behavior Problems Checklist (RMBPC) for dementia-related symptoms, frequency and severity), the REACH Risk Appraisal Measure (with sub-scales for CG depressive symptoms, social support, and perceived caregiving strain), the Zarit Burden Interview (for caregiving-related burden, perceived general health), and the Desire to Institutionalize Scale (e.g., ever considered placing CR in a nursing home, taken steps to place CR, etc.). Results CGs were on average 65.6?years old (SD=12.1) and primarily female (73.1%) and non-Hispanic White (79.6%). Over half (58.4%) of CGs were adult children of the CRs and providing full-time care (60.5%). Bivariate analyses revealed that greater desire to institutionalize was positively correlated with the following variables: CR's total ADL/IADL difficulty and frequency of dementia-related behavioral symptoms, younger CG age, caregiving burden, caregiving strain, less social support, and being a non-spousal CG. An adjusted regression model revealed that only greater ADL/IADL difficulty (p=0.02), caregiving strain (p=0.003), and social support (p=0.01) were uniquely and significantly associated with CGs’ desire to institutionalize, after controlling for all other variables. Conclusions Findings from this real-world, clinical, community-based sample identified three variables that independently predict increased CG desire to institutionalize the CR. The findings point to the potential value of systematically addressing CG-level factors and incorporating CG assessments into routine clinical care for patients with dementia. Routine CG assessment may increase opportunities for families, health care providers, health systems and community agencies to identify cases in which providing increased ADL/IADL support, reducing caregiver strain, or increasing social supports might lead to reductions in CGs' desire to institutionalize, and increase the chances for care recipients to age in place. This research was funded by: Commonwealth of Pennsylvania, Department of Aging, PACE Program, PACE/PACENET.

Development and Validation of the Continuous Subcutaneous Insulin Infusion-Related Quality-of-Life (CSII-QOL) Scale.

Background: Continuous subcutaneous insulin infusion (CSII) is associated with improved glycemic control, a reduced incidence of hypoglycemia, and improved quality of life (QOL). To date, however, there has been no QOL scale specific to CSII. The objective of this study was to develop and validate a scale to measure CSII-QOL for people with type 1 diabetes (T1D). Methods: A total of 50 people with T1D aged ≥15 years who used CSII (28% males; age, 47.6 ± 17.0 years; duration of diabetes, 14.7 ± 9.7 years; duration of CSII use, 6.1 ± 3.3 years; HbA1c, 7.4% ± 0.8%) took part in the CSII-QOL study. Twenty-eight potential CSII-QOL items were developed in a combined approach consisting of semistructured patient interviews, expert input, and a literature search. The resulting CSII-QOL was tested for factor analysis, validity, reliability, and influencing factors. Results: The final 25-item questionnaire had a 3-domain structure ("convenience," "social restriction," and "psychological problems"), high internal consistency (Cronbach's alpha = 0.870), and substantial test-retest reliability (intraclass correlation coefficient = 0.65). The CSII-QOL score was correlated negatively with the Problem Areas in Diabetes score. Conclusion: The CSII-QOL is the first CSII-related QOL scale for people with T1D. This short, validated, and reliable instrument might potentially be useful in future clinical studies and routine clinical patient care. Further validation is required to confirm these issues because of the small and potentially biased sample (UMIN-CTR: UMIN000031595).

Measuring atopic eczema symptoms in clinical practice: The first consensus statement from the Harmonising Outcome Measures for Eczema in clinical practice initiative

Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema patients in routine clinical care. Prioritize outcome domains to measure atopic eczema in clinical practice and select valid and practical outcome measurement instruments for the highest-priority domain. An online survey of HOME members identified and ranked 21 possible health domains. Suitable instruments were then selected for the top-prioritized domain at the HOME VI meeting, using established consensus processes informed by systematic reviews of instrument quality. Patient-reported symptoms was the top-prioritized domain. In accordance with psychometric properties and feasibility, there was consensus that the recommended instruments to measure atopic eczema symptoms in clinical practice are the POEM, the PO-SCORAD index, or both. The numeric rating scale for itch received support pending definition and validation in atopic eczema. Following the first step of the HOME Clinical Practice initiative, we endorse using the POEM, the PO-SCORAD index, or both for measuring atopic eczema symptoms in clinical practice. Additional high-priority domains for clinical practice will be assessed at subsequent HOME meetings.

The complete costs of genome sequencing: a microcosting study in cancer and rare diseases from a single center in the United Kingdom

PurposeThe translation of genome sequencing into routine health care has been slow, partly because of concerns about affordability. The aspirational cost of sequencing a genome is $1000, but there is little evidence to support this estimate. We estimate the cost of using genome sequencing in routine clinical care in patients with cancer or rare diseases. MethodsWe performed a microcosting study of Illumina-based genome sequencing in a UK National Health Service laboratory processing 399 samples/year. Cost data were collected for all steps in the sequencing pathway, including bioinformatics analysis and reporting of results. Sensitivity analysis identified key cost drivers. ResultsGenome sequencing costs £6841 per cancer case (comprising matched tumor and germline samples) and £7050 per rare disease case (three samples). The consumables used during sequencing are the most expensive component of testing (68–72% of the total cost). Equipment costs are higher for rare disease cases, whereas consumable and staff costs are slightly higher for cancer cases. ConclusionThe cost of genome sequencing is underestimated if only sequencing costs are considered, and likely surpasses $1000/genome in a single laboratory. This aspirational sequencing cost will likely only be achieved if consumable costs are considerably reduced and sequencing is performed at scale.

Dexamethasone premedication suppresses vaccine-induced immune responses against cancer

ABSTRACT Glucocorticosteroids (GCS) have an established role in oncology and are administered to cancer patients in routine clinical care and in drug development trials as co-medication. Given their strong immune-suppressive activity, GCS may interfere with immune-oncology drugs. We are developing a therapeutic cancer vaccine, which is based on a liposomal formulation of tumor-antigen encoding RNA (RNA-LPX) and induces a strong T-cell response both in mice as well as in humans. In this study, we investigated in vivo in mice and in human PBMCs the effect of the commonly used long-acting GCS Dexamethasone (Dexa) on the efficacy of this vaccine format, with a particular focus on antigen-specific T-cell immune responses. We show that Dexa, when used as premedication, substantially blunts RNA-LPX vaccine-mediated immune effects. Premedication with Dexa inhibits vaccine-dependent induction of serum cytokines and chemokines and reduces both the number and activation of splenic conventional dendritic cells (cDC) expressing vaccine-encoded antigens. Consequently, priming of functional effector T cells and therapeutic activity is significantly impaired. Interestingly, responses are less impacted when Dexa is administered post-vaccination. Consistent with this observation, although many inflammatory cytokines are reduced, IFNα, a key cytokine in T-cell priming, is less impacted and antigen expression by cDCs is intact. These findings warrant special caution when combining GCS with immune therapies relying on priming and activation of antigen-specific T cells and suggest that careful sequencing of these treatments may preserve T-cell induction.

Shared decision making in routine clinical care of patients with rheumatoid arthritis: an assessment of audio-recorded consultations

ObjectivesAlthough shared decision making (SDM) is advocated in rheumatoid arthritis (RA) treatment, it is largely unclear when, how and to what extent SDM is applied in routine clinical care of...

Sahaj Samadhi meditation vs a Health Enhancement Program in improving late-life depression severity and executive function: study protocol for a two-site, randomized controlled trial

BackgroundRecent estimates suggest an 11% prevalence of current late-life depression (LLD) and a lifetime prevalence of 16–20%. LLD leads to cognitive disturbance as well as a nearly two to three times increased risk of dementia. We conducted a recent randomized controlled trial (RCT) which demonstrated that Sahaj Samadhi meditation (SSM), an easy-to-implement, meditation-based augmentation strategy, led to higher rates of symptom remission when compared to treatment as usual (40.0 vs 16.3%; odds ratio, 3.36; 95% CI 1.06–10.64; p = 0.040). Here we present a protocol describing a two-site, blinded, RCT, comparing an SSM arm to an active-control arm – a Health Enhancement Program (HEP) intervention – in their ability to reduce depressive symptoms and improve executive functioning, among several other exploratory outcomes.Methods/designOne hundred and ninety-two (n = 192) participants with LLD will be recruited at two sites (London, ON, Canada, and Montreal, QC, Canada). Participants will undergo stratified randomization with regards to site and the presence of treatment-resistant-LLD (TR-LLD) or not, to either SSM or HEP. We will assess change in (1) depression severity using the Hamilton Depression Rating Scale (HAM-D), (2) executive functioning, and (3) other exploratory physiological and mood-based measures, at baseline (0 weeks), post intervention (12 weeks), and 26 weeks after baseline. Raters, clinicians, and care providers will be blinded to group allocation while participants will be blinded to the study hypotheses.DiscussionThis study should more definitively assess whether SSM can be used as an augmentation strategy in routine clinical care for patients suffering from LLD and TR-LLD. If the effects of SSM are significantly better than HEP, it will offer support for the routine use of this intervention to manage LLD/TR-LLD and comorbid declines in executive dysfunction. The results of this study could also inform whether SSM can improve/prevent cognitive decline in LLD.Trial registrationClinicalTrials.gov, ID: NCT03564041. Registered on 20 June 2018.

Desmopressin and the risk of hyponatremia: A population-based cohort study.

BackgroundDesmopressin was approved by the Food and Drug Administration (FDA) in 1978 for use in diabetes insipidus and bleeding disorders, but it is also prescribed off-label for patients with nocturia. Quantifying the potential risks facing adult patients taking desmopressin has taken on added importance because a new intranasal formulation of desmopressin was approved by the FDA in 2017. Like the old formulation, the main active ingredient is desmopressin acetate, but the new formulation also contains an excipient designed to enhance absorption. Our objective was to quantify the rate of hyponatremia in routine clinical care for patients prescribed the older formulation of desmopressin.Methods and findingsWe conducted a population-based new-user cohort study from 1 February 2006 to 1 February 2017 using a nationwide commercial health plan database. Patients newly prescribed the older formulation of desmopressin were propensity-score (PS)–matched to patients newly prescribed oxybutynin. As a sensitivity analysis, tamsulosin was used as the comparator rather than oxybutynin. The primary outcome was a primary position diagnosis of hyponatremia. Proportional hazard models after 1:1 PS matching were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). We identified 3,137 adults who were newly prescribed desmopressin and matched them to 3,137 adults who were newly prescribed oxybutynin. Mean age was 70, 55% were male, 13% filled a prescription for a diuretic during the baseline time period, and the mean baseline sodium prior to receiving either study drug was 140 mmol/L (normal: 135–145). The rate of hyponatremia was 146 per 1,000 person-years for adults prescribed desmopressin compared to 11 per 1,000 person-years for adults prescribed oxybutynin, corresponding to a 13-fold higher rate (HR 13.19; 95% CI 6.69, 26.01; p < 0.01). When follow-up was truncated at 30 days, a similar increased rate was observed (HR 19.41; 95% CI 7.11, 52.99; p < 0.01). A higher rate of hyponatremia was also observed with desmopressin when tamsulosin was the comparator (HR 12.10; 95% CI 6.54, 22.37; p < 0.01). Important limitations of our study include unmeasured confounding (for example, over-the-counter medication use, dietary intake), missing data (i.e., only 20% of patients had a baseline serum sodium), and a lack of data on the newer formulation of desmopressin.ConclusionsUse of an older formulation of desmopressin was associated with a marked increased rate of subsequent hyponatremia compared to use of other medications indicated for lower urinary tract symptoms. Such risks should be clearly communicated to patients prescribed this formulation of desmopressin.

PKG Movement Recording System Use Shows Promise in Routine Clinical Care of Patients With Parkinson's Disease.

Parkinson's disease (PD) is a debilitating, neurodegenerative disorder that affects nearly one million people. It's hallmark signs and symptoms include slow movements, rigidity, tremor, and unstable posture. Additionally, non-motor symptoms such as sleeplessness, depression, cognitive impairment, impulse control behaviors (ICB) have been reported. Today, treatment regimens to modify disease progression do not exist and as such, treatment is focused on symptom relief. Additionally, physicians are challenged to base their diagnoses and treatment plans on unreliable self-reported symptoms, even when used in conjunction to validated assessments such as the Unified Parkinson's Disease Rating Scale (UPDRS) and clinical exams. Wearable technology may provide clinicians objective measures of motor problems to supplement current subjective methods. Global Kinetics Corporation (GKC) has developed a watch-device called the Personal KinetiGraph (PKG) that records movements and provides patients medication dosing reminders. A separate clinician-use report supplies longitudinal motor and event data. The PKG was FDA-cleared in September 2016. We studied 63 PD patients during 85 routine care visits in 2 US academic institutions, evaluating the clinical utility of the PKG. Patients wore a PKG for 6 continuous days before their visit. Next, PKG data was uploaded to produce a report. In clinic, physicians discussed PD symptoms with patients and conducted a motor examination prior to reviewing the PKG report and comparing it to their initial assessments. Lastly, patient, caregiver and physician satisfaction surveys were conducted by each user. Across all visits when patients did not report bradykinesia or dyskinesia, the PKG reported these symptoms (50 and 33% of the time, respectively). The PKG provided insights for treatment plans in 50 (79%) patients across 71 (84%) visits. Physicians found improved patient dialogue in 50 (59%) visits, improved ability to assess treatment impact in 32 (38%) visits, and improved motor assessment in 28 (33%) visits. Patients stated in 82% of responses that they agreed or strongly agreed in PKG training, usability, performance, and satisfaction. In 39% of responses, they also reported a very valuable impact on their care. PKG use in 63 PD patients within our clinical practice showed clinically relevant utility in many areas.

114 Opportunistic Screening of Bone Mineral Density With CT Scans in Chronic Pancreatitis

INTRODUCTION: Osteoporosis and fragility fractures have been repeatedly shown to increase morbidity, mortality and socioeconomic costs. Chronic pancreatitis (CP) has multiple shared risk factors and complications that promote an imbalance in bone mineralization and remodeling which ultimately contributes to a high prevalence of metabolic bone disease. However, in the absence of societal guidelines regarding screening, dual-energy x-ray absorptiometry (DEXA) scans are not routinely performed and are not universally covered by insurance. While DEXA scan is the gold standard to assess bone mineral density, a Computed Tomography (CT) L1 vertebral density less than 135 Hounsfield Units (HU) has been validated to diagnose osteoporosis in the general population. The aim of this proof of concept study was to determine if the CT L1 vertebral threshold of 135 HU is also valid as an opportunistic screening cut-point for osteoporosis in chronic pancreatitis patients. METHODS: We selected patients with a definitive diagnosis of CP (according to the American Pancreatic Association guidelines) who were enrolled into The Ohio State Wexner Medical Center Pancreas Disease Biobank. Basic demographic information was abstracted including age, sex, race, BMI, smoking and alcohol history. Pertinent laboratory values and imaging studies, including DEXA scans, were also obtained from these patients. Baseline L1 vertebral HU values on CT scans were determined for BMD assessment (Pickhardt et al, Annals of Internal Medicine 2013). RESULTS: Sixty-four patients with definite CP were identified, including 27 (42%) with a CT and DEXA scan. Of these, 15/27 (56%) had evidence of metabolic bone disease (z-score &lt; −1.5), including 15% with osteoporosis. Mean L1 HU value in those with osteoporosis was 106. There was a statistically significant association between osteoporosis (z score &lt; −2.5) and the CT L1 HU threshold of 135 (P = 0.025, positive likelihood ratio of 8.62, PPV 60%). The L1 HU threshold of 135 had sensitivity of 75% and specificity of 91.3% for osteoporosis and a NPV of 95.45%. CONCLUSION: CT scans performed during routine clinical care of patients with CP may be useful for opportunistic screening for osteoporosis using L1 HU attenuation, especially at a threshold of 135. Larger sample sizes of patients are needed to further develop risk stratification models in CP considering other clinical risk factors.

Automatic classification of dopamine transporter SPECT: deep convolutional neural networks can be trained to be robust with respect to variable image characteristics.

This study investigated the potential of deep convolutional neural networks (CNN) for automatic classification of FP-CIT SPECT in multi-site or multi-camera settings with variable image characteristics. The study included FP-CIT SPECT of 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls, and 438 Parkinson's disease patients. SPECT images were smoothed with an isotropic 18-mm Gaussian kernel resulting in 3 different PPMI settings: (i) original (unsmoothed), (ii) smoothed, and (iii) mixed setting comprising all original and all smoothed images. A deep CNN with 2,872,642 parameters was trained, validated, and tested separately for each setting using 10 random splits with 60/20/20% allocation to training/validation/test sample. The putaminal specific binding ratio (SBR) was computed using a standard anatomical ROI predefined in MNI space (AAL atlas) or using the hottest voxels (HV) analysis. Both SBR measures were trained (ROC analysis, Youden criterion) using the same random splits as for the CNN. CNN and SBR trained in the mixed PPMI setting were also tested in an independent sample from clinical routine patient care (149 with non-neurodegenerative and 149 with neurodegenerative parkinsonian syndrome). Both SBR measures performed worse in the mixed PPMI setting compared to the pure PPMI settings (e.g., AAL-SBR accuracy = 0.900 ± 0.029 in the mixed setting versus 0.957 ± 0.017 and 0.952 ± 0.015 in original and smoothed setting, both p < 0.01). In contrast, the CNN showed similar accuracy in all PPMI settings (0.967 ± 0.018, 0.972 ± 0.014, and 0.955 ± 0.009 in mixed, original, and smoothed setting). Similar results were obtained in the clinical sample. After training in the mixed PPMI setting, only the CNN provided acceptable performance in the clinical sample. These findings provide proof of concept that a deep CNN can be trained to be robust with respect to variable site-, camera-, or scan-specific image characteristics without a large loss of diagnostic accuracy compared with mono-site/mono-camera settings. We hypothesize that a single CNN can be used to support the interpretation of FP-CIT SPECT at many different sites using different acquisition hardware and/or reconstruction software with only minor harmonization of acquisition and reconstruction protocols.