Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria.

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response

Therapeutic alliance in telephone-administered cognitive–behavioral therapy for hematopoietic stem cell transplant survivors.

A strong therapeutic alliance has been found to predict psychotherapeutic treatment success across a variety of therapeutic modalities and patient populations. However, only a few studies have examined therapeutic alliance as a predictor of psychotherapy outcome among cancer survivors, and none have examined this relation in telephone administered cognitive behavioral therapy (T-CBT). This study evaluated the extent to which therapeutic alliance affected psychotherapy outcomes in survivors of hematopoietic stem cell transplantation (HSCT), a treatment for some cancers

Self-Efficacy Beliefs Mediate the Relationship between Subjective Cognitive Functioning and Physical and Mental Well-Being after Hematopoietic Stem Cell Transplant

Cognitive problems are commonly reported by hematopoietic stem cell transplant (HSCT) survivors, and are associated with poorer physical and mental well-being. It was hypothesized that adverse effects of subjective cognitive impairment occur because cognitive difficulties reduce survivors’ confidence that they can manage HSCT-related symptoms—that is, self-efficacy for symptom management

Randomized Controlled Trial of a Computer-Based, Tailored Intervention to Increase Smoking Cessation Counseling by Primary Care Physicians

OBJECTIVE: The primary care visit represents an important venue for intervening with a large population of smokers. However, physician adherence to the Smoking Cessation Clinical Guideline (5As) remains low. We evaluated the effectiveness of a computer-tailored intervention designed to increase smoking cessation counseling by primary care physicians. METHODS: Physicians and their patients were randomized to either intervention or control conditions. In addition to brief smoking cessation training, intervention physicians and patients received a one-page report that characterized the patients’ smoking habit and history and offered tailored recommendations. Physician performance of the 5As was assessed via patient exit interviews. Quit rates and smoking behaviors were assessed 6 months postintervention via patient phone interviews. Intervention effects were tested in a sample of 70 physicians and 518 of their patients. Results were analyzed via generalized and mixed linear modeling controlling for clustering. MEASUREMENTS AND MAIN RESULTS: Intervention physicians exceeded controls on “Assess” (OR 5.06; 95% CI 3.22, 7.95), “Advise” (OR 2.79; 95% CI 1.70, 4.59), “Assist–set goals” (OR 4.31; 95% CI 2.59, 7.16), “Assist–provide written materials” (OR 5.14; 95% CI 2.60, 10.14), “Assist–provide referral” (OR 6.48; 95% CI 3.11, 13.49), “Assist–discuss medication” (OR 4.72;95% CI 2.90, 7.68), and “Arrange” (OR 8.14; 95% CI 3.98, 16.68), all p values being < 0.0001. Intervention patients were 1.77 (CI 0.94, 3.34,p = 0.078) times more likely than controls to be abstinent (12 versus 8%), a difference that approached, but did not reach statistical significance, and surpassed controls on number of days quit (18.4 versus 12.2, p < .05) but not on number of quit attempts. CONCLUSIONS: The use of a brief computer-tailored report improved physicians’ implementation of the 5As and had a modest effect on patients’ smoking behaviors 6 months postintervention

Automated Internet-based pain coping skills training to manage osteoarthritis pain: a randomized controlled trial

Osteoarthritis (OA) places a significant burden on worldwide public health because of the large and growing number of people affected by OA and its associated pain and disability. Pain coping skills training (PCST) is an evidence-based intervention targeting OA pain and disability. To reduce barriers that currently limit access to PCST, we developed an 8-week, automated, Internet-based PCST program called PainCOACH and evaluated its potential efficacy and acceptability in a small-scale, 2-arm randomized controlled feasibility trial. Participants were 113 men and women with clinically confirmed hip or knee OA and associated pain. They were randomized to a group completing PainCOACH or an assessment-only control group. Osteoarthritis pain, pain-related interference with functioning, pain-related anxiety, self-efficacy for pain management, and positive and negative affect were measured before intervention, midway through the intervention, and after intervention. Findings indicated high acceptability and adherence: 91% of participants randomized to complete PainCOACH finished all 8 modules over 8 to 10 weeks. Linear mixed models showed that, after treatment, women who received the PainCOACH intervention reported significantly lower pain than that in women in the control group (Cohen d = 0.33). Intervention effects could not be tested in men because of their low pain and small sample size. Additionally, both men and women demonstrated increases in self-efficacy from baseline to after intervention compared with the control group (d = 0.43). Smaller effects were observed for pain-related anxiety (d = 0.20), pain-related interference with functioning (d = 0.13), negative affect (d = 0.10), and positive affect (d = 0.24). Findings underscore the value of continuing to develop an automated Internet-based approach to disseminate this empirically supported intervention

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Targeted Sequencing of 10,198 Samples Confirms Abnormalities in Neuronal Activity and Implicates Voltage-Gated Sodium Channels in Schizophrenia Pathogenesis

Background Sequencing studies have pointed to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes; however, larger samples are required to reveal novel genes and specific biological mechanisms. Methods We sequenced 187 genes, selected for prior evidence of association with schizophrenia, in a new dataset of 5207 cases and 4991 controls. Included among these genes were members of ARC and NMDAR postsynaptic protein complexes, as well as voltag

Mental health mediators of subjective cognitive concerns among World Trade Center responders

Decline in cognitive functioning among rescue and recovery workers who responded in the aftermath of the September 11, 2001, World Trade Center (WTC) attacks is of emerging interest. Responders are vulnerable to cognitive decline from exposure to airborne toxins present at the WTC site, as well as from WTC-related mental and physical health conditions. To better understand the relationship between occupational WTC exposure, mental health, physical health and subjective cognitive functioning, we examined the mediating role of health status in the association between exposure and subjective cognitive concerns in a multi-site, longitudinal investigation of the WTC General Responder cohort (n = 16,380 responders; n = 58,575 visits) for the period 2002-2015. Through latent class analyses, we identified a four-level marker of cognitive concerns based on information from a Self-Administered Mental Health Questionnaire. Using generalized linear mixed models with random intercepts, we observed that a higher intensity WTC exposure composite was associated with greater cognitive concerns, and that this association was operating almost entirely through mental health comorbidities, not physical health comorbidities. In fully adjusted models, the inclusion of probable depression, anxiety, PTSD and use of psychotropic medications attenuated the association between highest WTC exposure and greatest cognitive concerns. Physical health did not appear to be on the pathway between WTC exposure and cognitive concerns. Understanding the underlying sources of cognitive concerns may help identify vulnerable members of the General Responder cohort and potentially aid clinical decision-making, such as treatment choice and enhanced screening options. Earlier diagnosis and symptom treatment may help preserve functional independence