A digital health intervention to support patients with chronic pain during prescription opioid tapering: a pilot randomised controlled trial.

Introduction: Recent changes in opioid prescribing guidelines have led to an increasing number of patients with chronic pain being recommended to taper. However, opioid tapering can be challenging, and many patients require support. Objectives: We evaluated the feasibility, acceptability, and potential efficacy of a codesigned digital health intervention to support patients with chronic pain during voluntary prescription opioid tapering. Methods: In a pilot randomised controlled trial, participants received a psychoeducational video and 28 days of text messages (2 SMS/day) in addition to their usual care (intervention) or usual care alone (control). The feasibility, acceptability, and potential efficacy of the intervention were evaluated. The primary outcome was opioid tapering self-efficacy. Secondary outcomes were pain intensity and interference, anxiety and depression symptom severity, pain catastrophising, and pain self-efficacy. Results: Of 28 randomised participants, 26 completed the study (13 per group). Text message delivery was high (99.2%), but fidelity of video delivery was low (57.1%). Most participants rated the messages as useful, supportive, encouraging, and engaging; 78.5% would recommend the intervention to others; and 64.2% desired a longer intervention period. Tapering self-efficacy (Cohen d = 0.74) and pain self-efficacy (d = 0.41) were higher, and pain intensity (d = 0.65) and affective interference (d = 0.45) were lower in the intervention group at week 4. Conclusion: First evidence supports the feasibility, acceptability, and potentially efficacy of a psychoeducational video and SMS text messaging intervention to support patients with chronic pain during voluntary prescription opioid tapering. Definitive trials with longer intervention duration are warranted.

Text messaging intervention to support patients with chronic pain during prescription opioid tapering: protocol for a double-blind randomised controlled trial.

INTRODUCTION: Increases in pain and interference with quality of life is a common concern among people with chronic non-cancer pain (CNCP) who are tapering opioid medications. Research indicates that access to social and psychological support for pain self-management may help people to reduce their opioid dose without increasing pain and interference. This study evaluates the efficacy of a text messaging intervention designed to provide people with CNCP with social and psychological support for pain self-management while tapering long-term opioid therapy (LTOT) under the guidance of their prescriber. METHODS AND ANALYSIS: A double-blind randomised controlled trial will be conducted. Patients with CNCP (n=74) who are tapering LTOT will be enrolled from across Australia. Participants will continue with their usual care while tapering LTOT under the supervision of their prescribing physician. They will randomly receive either a psychoeducational video and supportive text messaging (two Short Message Service (SMS) per day) for 12 weeks or the video only. The primary outcome is the pain intensity and interference assessed by the Pain, Enjoyment of Life and General Activity scale. Secondary outcomes include mood, self-efficacy, pain cognitions, opioid dose reduction, withdrawal symptoms, and acceptability, feasibility, and safety of the intervention. Participants will complete questionnaires at baseline and then every 4 weeks for 12 weeks and will be interviewed at week 12. This trial will provide evidence for the efficacy of a text messaging intervention to support patients with CNCP who are tapering LTOT. If proven to be efficacious and safe, this low-cost intervention can be implemented at scale. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Northern Sydney Local Health District (Australia). Study results will be published in peer-reviewed journals and presented at scientific and professional meetings. TRIAL REGISTRATION NUMBER: ACTRN12622001423707.

A digital health intervention to support patients with chronic pain during prescription opioid tapering: a pilot randomised controlled trial.

Introduction: Recent changes in opioid prescribing guidelines have led to an increasing number of patients with chronic pain being recommended to taper. However, opioid tapering can be challenging, and many patients require support. Objectives: We evaluated the feasibility, acceptability, and potential efficacy of a co-designed psycho-educational video and SMS text messaging intervention to support patients with chronic pain during prescription opioid tapering. Methods: A pilot randomised controlled trial was conducted. In addition to their usual care, participants in the intervention group received a psycho-educational video and 28 days of text messages (two SMS/day). The control group received usual care. The feasibility, acceptability, and potential efficacy of the intervention were evaluated. The primary outcome was opioid tapering self-efficacy. Secondary outcomes were pain intensity and interference, anxiety and depression symptom severity, pain catastrophising, and pain self-efficacy. Results: Of 28 randomised participants, 26 completed the study (13 in each group). Text message delivery was 99.2% successful. Most participants rated the messages as useful, supportive, encouraging, and engaging, 78.5% would recommend the intervention to others, and 64% desired a longer intervention period. Tapering self-efficacy (Cohen's d = 0.74) and pain self-efficacy (d = 0.41) were higher and pain intensity (d = 0.65) and affective interference (d = 0.45) lower in the intervention group at week 4. Conclusions: It is feasible, acceptable, and potentially efficacious to support patients with chronic pain during prescription opioid tapering with a psycho-educational video and SMS text messaging intervention. A definitive trial has been initiated to test a 12-week intervention.

A Digital Video and Text Messaging Intervention to Support People With Chronic Pain During Opioid Tapering: Content Development Using Co-design.

BACKGROUND: People living with chronic pain report that tapering prescribed opioids is challenging and more support is needed. In our formative research, consumers indicated that mobile health (mHealth) technology could be an acceptable form of support for opioid tapering and may improve tapering self-efficacy. OBJECTIVE: We aimed to evaluate and improve the content of an mHealth intervention before pilot-testing, based on consumer and clinician feedback. METHODS: Participants were 12 consumers and 12 clinicians who evaluated an initial draft of a video script and 90 SMS text messages. Consumers and clinicians rated the appropriateness and likely usefulness (consumers) or likely effectiveness (clinicians) of a video script and a random selection of 15 SMS text messages using a 5-point Likert-type scale (1=totally disagree; 5=totally agree). Each draft SMS text message was reviewed by 2 consumers and 2 clinicians. Texts were deemed acceptable for inclusion in the pilot intervention only if the summed participant ratings of text appropriateness and usefulness or effectiveness were ≥8. Participants were also invited to provide open-text feedback on the draft script and SMS text messages. RESULTS: Consumers generally agreed that the draft video script and text content were likely to be appropriate (video: mean 4.4, SD 0.52; text: mean 4.3, SD 0.79) and useful (video: mean 4.3, SD 0.65; text: mean 4.2, SD 0.84). Similarly, clinicians generally agreed that the draft video script and text content were likely to be appropriate (video: mean 4.5, SD 0.67; text: mean 4.4, SD 0.81) and effective (video: mean 4.0, SD 0.43; text: mean 4.3, SD 0.76). Overall, 77% (69/90) of the draft texts met the threshold rating for acceptability for inclusion in the pilot test of mHealth intervention by consumers, and 82% (74/90) met the threshold for acceptability by clinicians. Consumers' and clinicians' ratings were used to rank order the texts. The top 56 draft texts (all meeting the threshold levels of acceptability) were selected for inclusion in the pilot intervention. When consumer or clinician feedback was provided, the texts meeting the criteria for inclusion in the pilot were further revised and improved. Feedback on the video script was also used to further improve the acceptability of the video script before pilot-testing the intervention. CONCLUSIONS: This study describes the process by which a 28-day mHealth intervention to support patients with chronic pain to taper opioid medications was evaluated and improved before pilot-testing. The mHealth intervention consisted of a 10-minute psychoeducational video about pain and opioid tapering and 56 unique SMS text messages providing information and reassurance (texts delivered twice per day for 28 days). Having established that the content of the mHealth intervention is acceptable to both consumer and clinician groups, the mHealth intervention will be piloted in future research.

Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn's disease.

BACKGROUND: Tumor necrosis factor-alpha inhibitors, including infliximab and adalimumab, are effective medical treatments for perianal fistulising Crohn's disease (CD), but not all patients achieve fistula healing. AIM: To determine the correlation between perianal fistula healing and closure with infliximab and adalimumab trough levels. METHODS: In this multicentre retrospective study conducted across four tertiary inflammatory bowel disease centres in Australia, we identified CD patients with perianal fistulae on maintenance infliximab or adalimumab who had a trough level within twelve weeks of clinical assessment. Data collected included demographics, serum infliximab and adalimumab trough levels (mg/L) within 12 wk before or after their most recent clinical assessment and concomitant medical or surgical therapy. The primary outcome was fistula healing, defined as cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing and closure of all external fistula openings. Differences between patients who did or did not achieve fistula healing were compared using the chi-square test, t test or Mann-Whitney U test. RESULTS: One hundred and fourteen patients (66 infliximab, 48 adalimumab) were included. Forty-eight (72.7%) patients on maintenance infliximab achieved fistula healing and 18 (27.3%) achieved fistula closure. Thirty-seven (77%) patients on maintenance adalimumab achieved fistula healing and 17 (35.4%) achieved fistula closure. Patients who achieved fistula healing had significantly higher infliximab and adalimumab trough levels than patients who did not [infliximab: 6.4 (3.8-9.5) vs 3.0 (0.3-6.2) mg/L, P = 0.003; adalimumab: 9.2 (6.5-12.0) vs 5.4 (2.5-8.3) mg/L, P = 0.004]. For patients on infliximab, fistula healing was associated with lower rates of detectable anti-infliximab antibodies and younger age. For patients on adalimumab, fistula healing was associated with higher rates of combination therapy with an immunomodulator. Serum trough levels for patients with and without fistula closure were not significantly different for infliximab [6.9 (4.3-10.2) vs 5.5 (2.5-8.3) mg/L, P = 0.105] or adalimumab [10.0 (6.6-12.0) vs 7.8 (4.2-10.0) mg/L, P = 0.083]. CONCLUSION: Higher maintenance infliximab and adalimumab trough levels are associated with perianal fistula healing in CD.

Exhausted Heart Rate Responses to Repeated Psychological Stress in Women With Major Depressive Disorder.

Past research links depression and blunted cardiac vagal reactivity to chronic stress. Yet, to our knowledge no experiment investigates heart rate (variability) responses to a repeated laboratory stressor in patients with depression. Repeated exposure may provide valuable information on stress reactivity in depression. Fifty-nine women (30 inpatients diagnosed with depression and 29 matched controls) underwent two consecutive runs of a mental arithmetic stress paradigm consisting of one baseline and two exposures to control, stress, and recovery phases of 5 min each, in a case-control design. Subjective stress and electrocardiography were recorded. Variance of heart rate (HR) and root mean square of successive RR interval differences (RMSSD) were analyzed using linear mixed models. Overall, physiological parameters (HR and RMSSD) and subjective stress showed a strong group effect (all p < 0.001). In both groups, subjective stress and HR increased in response to stress, but the subjective stress levels of patients with depression did not return to baseline levels after the first stressor and for the remainder of the experiment (all p < 0.004 compared to baseline). Patients' HR reactivity responded oppositely: while HR recovered after the first stress exposure, no reactivity was observed in response to the second exposure. These findings may suggest that the often-reported blunted HR/HRV response to stressors results from exhaustion rather than an incapacity to react to stress. The altered HR reactivity could indicate allostatic (over-) load in depression.

Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis.

OBJECTIVE: To review interventions to reduce long term opioid treatment in people with chronic non-cancer pain, considering efficacy on dose reduction and discontinuation, pain, function, quality of life, withdrawal symptoms, substance use, and adverse events. DESIGN: Systematic review and meta-analysis of randomised controlled trials and non-randomised studies of interventions. DATA SOURCES: Medline, Embase, PsycINFO, CINAHL, and the Cochrane Library searched from inception to July 2021. Reference lists and previous reviews were also searched and experts were contacted. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Original research in English. Case reports and cross sectional studies were excluded. DATA EXTRACTION AND SYNTHESIS: Two authors independently selected studies, extracted data, and used the Cochrane risk-of-bias tools for randomised and non-randomised studies (RoB 2 and ROBINS-I). Authors grouped interventions into five categories (pain self-management, complementary and alternative medicine, pharmacological and biomedical devices and interventions, opioid replacement treatment, and deprescription methods), estimated pooled effects using random effects meta-analytical models, and appraised the certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). RESULTS: Of 166 studies meeting inclusion criteria, 130 (78%) were considered at critical risk of bias and were excluded from the evidence synthesis. Of the 36 included studies, few had comparable treatment arms and sample sizes were generally small. Consequently, the certainty of the evidence was low or very low for more than 90% (41/44) of GRADE outcomes, including for all non-opioid patient outcomes. Despite these limitations, evidence of moderate certainty indicated that interventions to support prescribers' adherence to guidelines increased the likelihood of patients discontinuing opioid treatment (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1), and that these prescriber interventions as well as pain self-management programmes reduced opioid dose more than controls (intervention v control, mean difference -6.8 mg (standard error 1.6) daily oral morphine equivalent, P<0.001; pain programme v control, -14.31 mg daily oral morphine equivalent, 95% confidence interval -21.57 to -7.05). CONCLUSIONS: Evidence on the reduction of long term opioid treatment for chronic pain continues to be constrained by poor study methodology. Of particular concern is the lack of evidence relating to possible harms. Agreed standards for designing and reporting studies on the reduction of opioid treatment are urgently needed. REVIEW REGISTRATION: PROSPERO CRD42020140943.

Evaluating acceptability and feasibility of a mobile health intervention to improve self-efficacy in prescription opioid tapering in patients with chronic pain: protocol for a pilot randomised, single-blind, controlled trial.

INTRODUCTION: Opioid medications are no longer recommended as long-term therapy for chronic non-cancer pain, and many patients are advised to reduce or discontinue opioid medications. Many patients report difficulties in tapering opioid medications, necessitating supporting interventions. This protocol describes a pilot randomised controlled trial (RCT) to investigate the acceptability, feasibility and potential efficacy of a mobile health intervention to improve the opioid tapering self-efficacy of patients with chronic non-cancer pain. METHODS AND ANALYSIS: The trial will be a single-blind (clinician, data collector and statistician-blinded) pilot RCT with two parallel arms. Forty adult patients with chronic non-cancer pain who are voluntarily reducing their prescribed opioid medications under medical guidance will be recruited from two tertiary pain clinics (Start date 25 August 2021). Participants will be randomly assigned to an intervention or control group. Both groups will receive usual care, including multidisciplinary pain management. In addition to usual care, the intervention group will receive a short informational and testimonial video about opioid tapering and will receive two specifically text messages per day for 28 days. The intervention is codesigned with patients and clinicians to provide evidence-based informational, motivational and emotional support to patients with chronic pain to taper opioid medications. Feasibility of the intervention and a future definitive RCT will be evaluated by measuring patient acceptability, delivery of the intervention, rates and reasons of exclusions and drop-outs, completion rates and missing data in the study questionnaires, and obtaining estimates for sample size determination. Potential efficacy will be evaluated by comparing changes in opioid tapering self-efficacy between the two groups. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Northern Sydney Local Health District (Australia). Study results will be published in peer-reviewed journals and presented at scientific and professional meetings. TRIAL REGISTRATION NUMBER: ACTRN12621000795897.

Effect of slow, deep breathing on visceral pain perception and its underlying psychophysiological mechanisms.

BACKGROUND: Studies using somatic pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on visceral pain and explored putative mediating mechanisms including autonomic and emotional responses. METHODS: Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition. KEY RESULTS: Compared to uncontrolled breathing, pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on pain was not mediated by alterations in heart rate variability or arousal but was moderated by pain catastrophizing. CONCLUSIONS AND INFERENCES: Slow, deep breathing can reduce visceral pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) visceral pain warrants to be investigated.

Perioperative Cardiac Troponin T and Risk of Postoperative Atrial Fibrillation in Coronary Artery Bypass Graft Surgery.

BACKGROUND: Postoperative atrial fibrillation (AF) is a common complication after cardiac surgery. We investigated whether perioperative cardiac troponin T (cTnT) is associated with the risk of AF after coronary artery bypass grafting (CABG). METHODS: Two thousand four hundred twenty-one patients with isolated CABG were studied. High sensitivity cTnT (hs-cTnT) was assessed before and then at 80 hour and 24 hour after the operation. Logistic regression models were applied to investigate the association of perioperative hs-cTnT with postoperative AF. The ROC curve analysis was applied to determine the optimal cutoff values. RESULTS: Postoperative AF was occurred in 356 (14.7%) patients. Age (adjusted odds ratio [ORs] 1.087-1.090), male gender (OR 1.390), left atrium size (ORs 1.055-1.111), on-pump coronary bypass (OR 1.561), and application of intra-aortic balloon pump (ORs 2.890-2.966) were independently associated with AF. Preoperative hs-cTnT was associated with AF in patients with off-pump coronary bypass (ORs 1.997-2.375). However, the area under the curve for preoperative hs-cTnT was 0.625 in this group. On-pump coronary bypass had major influence on postoperative hs-cTnT levels regardless of the occurrence of AF. CONCLUSIONS: Preoperative hs-cTnT level is associated with the risk of AF after isolated CABG in patients undergoing off-pump coronary bypass, but the accuracy of this biomarker is yet inadequate. Postoperative levels of hs-cTnT have no predictive value considering large influence by the surgical technique and the cardiac surgery itself. Therefore, perioperative hs-cTnT is not a clinically useful biomarker for predicting AF following CABG.

Evidence for engagement of the nucleus of the solitary tract in processing intestinal chemonociceptive input irrespective of conscious pain response in healthy humans.

ABSTRACT: Neuroimaging studies have revealed important pathomechanisms related to disorders of brain-gut interactions, such as irritable bowel syndrome and functional dyspepsia. More detailed investigations aimed at neural processing in the brainstem, including the key relay station of the nucleus of the solitary tract (NTS), have hitherto been hampered by technical shortcomings. To ascertain these processes in more detail, we used multiecho multiband 7T functional magnetic resonance imaging and a novel translational experimental model based on a nutrient-derived intestinal chemonociceptive stimulus. In a randomized cross-over fashion, subjects received duodenal infusion of capsaicin (the pungent principle in red peppers) and placebo (saline). During infusion, functional magnetic resonance imaging data and concomitant symptom ratings were acquired. Of 26 healthy female volunteers included, 18 were included in the final analysis. Significantly increased brain activation over time during capsaicin infusion, as compared with placebo, was observed in brain regions implicated in pain processing, in particular the NTS. Brain activation in the thalamus, cingulate cortex, and insula was more pronounced in subjects who reported abdominal pain (visual analogue scale > 10 mm), as compared with subjects who experienced no pain. On the contrary, activations at the level of the NTS were independent of subjective pain ratings. The current experimental paradigm therefore allowed us to demonstrate activation of the principal relay station for visceral afferents in the brainstem, the NTS, which was engaged irrespective of the conscious pain response. These findings contribute to understanding the fundamental mechanism necessary for developing novel therapies aimed at correcting disturbances in visceral afferent pain processing.

Effects of Early Repolarization on Electrocardiography and Long-Term Cardiovascular Outcomes: A 15-Year Population-Based Cohort Study.

Background: We aimed to investigate the association between persistent early repolarization (ER) in healthy individuals and long-term cardiovascular events and mortality rates in a large cohort study. Methods: Demographic characteristics, medical records, 12-lead electrocardiograms (ECGs), and laboratory data were retrieved and analyzed from the Isfahan Cohort Study. The participants were followed up biannually via telephone interviews and 1 live structured interview in between until 2017. Individuals who had ER in all their ECGs were considered persistent ER cases. Study outcomes were cardiovascular events (unstable angina, myocardial infarction, stroke, and sudden cardiac death), cardiovascular-related mortality, and all-cause mortality. The independent t test, the χ2 test, the Mann-Whitney U test, and the Cox regression models were used for statistical analyses. Results: The study population consisted of 2696 subjects (50.5% female). Persistent ER was found in 203 subjects (7.5%), with a higher frequency in men (6.7% vs 0.8%; P<0.001). Cardiovascular events, cardiovascular-related mortality, and all-cause mortality occurred in 478 (17.7%), 101 (3.7%), and 241 (8.9%) individuals, respectively. After controlling for known cardiovascular risk factors, we found an association between ER and cardiovascular events (adjusted hazard ratio [95% confidence interval] =2.36 [1.19-4.68], P=0.014), cardiovascular-related mortality (4.97 [1.95-12.60], P=0.001), and all-cause mortality (2.50 [1.11-5.58], P=0.022) in women. No significant association was found between ER and any study outcomes in men. Conclusion: ER is common in young men with no apparent long-term cardiovascular risks. In women, ER is relatively rare, but it could be associated with long-term cardiovascular risks.

Slow deep breathing modulates cardiac vagal activity but does not affect peripheral glucose metabolism in healthy men.

Parasympathetic nervous system innervates peripheral organs including pancreas, hepatic portal system, and gastrointestinal tract. It thereby contributes to the regulation of whole-body glucose metabolism especially in the postprandial state when it promotes secretion of insulin and enhances its action in major target organs. We now aimed to evaluate the effect of parasympathetic modulation on human glucose metabolism. We used slow deep breathing maneuvers to activate the parasympathetic nervous system and tested for effects on metabolism during an oral glucose tolerance test in a randomized, controlled, cross-over trial in 15 healthy young men. We used projections towards the heart as a readout for parasympathetic activity. When analyzing heart rate variability, there was a significant increase of RMSSD (root mean square of successive differences) when participants performed slow deep breathing compared to the control condition, indicating a modulation of parasympathetic activity. However, no statistically significant effects on peripheral glucose metabolism or energy expenditure after the glucose tolerance test were detected. Of note, we detected a significant association between mean heart rate and serum insulin and C-peptide concentrations. While we did not find major effects of slow deep breathing on glucose metabolism, our correlational results suggest a link between the autonomic nervous system and insulin secretion after oral glucose intake. Future studies need to unravel involved mechanisms and develop potential novel treatment approaches for impaired insulin secretion in diabetes.

Assessment of pain between sedated and unsedated colonoscopy: Double-blind randomized clinical trail.

BACKGROUND: Colonoscopy plays a vital role for the diagnosis and treatment of colonic diseases but can be associated with anxiety and discomfort or pain. We tested whether unsedated colonoscopy impacts quality indicators and investigated predictors of pain during colonoscopy. MATERIALS AND METHODS: This randomized controlled trial was performed on candidates for elective colonoscopy at AL Zahra Hospital, Isfahan at 2018-2019. Balanced block randomization was used to allocate 275 cases into two groups. At finally, 124 patients in case and 122 patients in control group enrolled in analysis. Patients in the sedation group received midazolam with/out pethidine before colonoscopy. Pain intensity in rectal examination (PIREX), preprocedural anxiety, pain intensity during colonoscopy, hemodynamics, duration of colonoscopy, polyp detection rate, cecal intubation rate, bloating within 24 h after colonoscopy, and willingness to repeat colonoscopy were assessed and compared between two groups. RESULTS: Compared to the group with sedation, cecal intubation time was shorter and bloating was less frequent (7% vs. 16%, P = 0.02) in the unsedated group. There was no difference between the two groups regarding polyp detection rate, cecal detection rate, and willingness to repeat colonoscopy. Pain during rectal examination was significantly associated with pain during colonoscopy (P < 0.001, 95% confidence interval; 0.5-1.3). CONCLUSION: The assessment of pain intensity during rectal examination may help to identify patients who can benefit from sedation during colonoscopy. Colonoscopy with sedation does not seem to have a negative impact on colonoscopy quality indicators, and may even reduce cecal intubation time and bloating following procedure.

The Illness Belief Network Questionnaire: Development and Evaluation of a Psychosomatic Assessment Tool.

Objective: Patients' beliefs and emotions toward an illness can influence their coping responses, illness behaviors, adherence to treatment, quality of life, and even the psychoneuroimmune responses. The aim of present study was to develop and validate a novel questionnaire assessing both rational and irrational beliefs of patients regarding their illness. Method : In a cross sectional methodological study, the items of the Illness Belief Network (IBN) were developed regarding patients and clients' opinions about and attribution of their disease extracted from 400 clinical interviews and were coded based on Leventhal's self-regulation model. An expert panel coded the items. A total of 400 patients with different medical conditions completed the questionnaire. Participants additionally rated the Illness Perceptions Questionnaire in its revised form (IPQ-R) to assess convergent validity. Construct validity was examined by conducting exploratory and confirmatory factor analysis. The Cronbach alpha and Intracluster Correlation Coefficient (ICC) were used for examining Internal consistency and test-retest reliability of the IBN. Results: The IBN questionnaire was finalized with 84 items, and the results of factor analysis revealed 5 factors: psychosocial causes, environmental causes, control, meaning, and consequence/timeline; extracted factors were confirmed by confirmatory factor analysis. Cronbach's α coefficient for scale was 0.92 and it ranged from 0.79 to 0.89 for the subscales. IBN indicated excellent test-retest reliability results based on ICC 0.842(95%CI: 0.798-0.846). The correlation coefficients of all items exceeded the prespecified acceptable value of 0.40, indicating satisfactory item discriminant validity, and correlation between IBN and IPQ-R subscales were statistically significant (all p values < 0.01), indicating acceptable convergent validity. Conclusion: The IBN questionnaire is a valid and reliable phenomenological, non-judging, and clinical tool to assess patient's rational and irrational or faith-based beliefs about the illness. This tool can be used to improve doctor-patient communication by exploring the complex nature of human thinking.

Prospective randomised controlled trial of adults with perianal fistulising Crohn's disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol.

INTRODUCTION: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy. METHODS AND ANALYSIS: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate. ETHICS AND DISSEMINATION: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.

Controlled breathing and pain: Respiratory rate and inspiratory loading modulate cardiovascular autonomic responses, but not pain.

Slow, deep breathing (SDB) is a common pain self-management technique. Stimulation of the arterial baroreceptors and vagal modulation are suggested, among others, as potential mechanisms underlying the hypoalgesic effects of SDB. We tested whether adding an inspiratory load to SDB, which results in a stronger baroreceptor stimulation and vagal modulation, enhances its hypoalgesic effects. Healthy volunteers performed SDB (controlled at 0.1 Hz) with and without an inspiratory threshold load. Controlled breathing (CB) at a normal frequency (0.23 Hz) was used as an active control. Each condition lasted 90 s, included an electrical pain stimulation on the hand, and was repeated four times in a randomized order. Pain intensity, self-reported emotional responses (arousal, valence, dominance), and cardiovascular parameters (including vagally-mediated heart rate variability) were measured per trial. A cover story was used to limit the potential effect of outcome expectancy. Pain intensity was slightly lower during SDB with load compared with normal-frequency CB, but the effect was negligible (Cohens d < 0.2), and there was no other difference in pain intensity between the conditions. Heart rate variability was higher during SDB with/without load compared with normal-frequency CB. Using load during SDB was associated with higher heart rate variability, but less favorable emotional responses. These findings do not support the role of baroreceptor stimulation or vagal modulation in the hypoalgesic effects of SDB. Other mechanisms, such as attentional modulation, warrant further investigation.

Vitamin D supplementation for primary dysmenorrhea: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Recent studies have shown a possible association between vitamin D deficiency and the severity of primary dysmenorrhea. The present study aimed to investigate the effect of vitamin D supplementation on pain and systemic symptoms in patients with primary dysmenorrhea. METHODS: This double-blind, randomized, placebo-controlled trial was conducted on female students aged 18 to 32 years with primary dysmenorrhea and vitamin D deficiency (25 [OH]D <30 ng/mL). The participants (n=116) received either 50,000 IU of vitamin D3 (cholecalciferol) or placebo capsules on a weekly basis for eight consecutive weeks. The outcomes were pain intensity (scored 0 to 10), number of days with pain, number of consumed pain-relief medications (per day), and severity of systemic symptoms (fatigue, headache, nausea/vomiting, and diarrhea; total score of 0 to 12). RESULTS: Compared with baseline, our participants who received vitamin D experienced significant reductions in pain intensity (-1.0 and -1.5 score at weeks 4 and 8, P<0.001), the number of days with pain (-1.0 day at weeks 4 and 8, P<0.001), the number of consumed pain-relief medications (-1.0 at weeks 4 and 8, P<0.001), and systemic symptoms severity (-1.0 score at weeks 4 and 8, P<0.001). No significant improvements were observed in the placebo group in terms of these outcomes. CONCLUSION: Vitamin D supplementation in women with primary dysmenorrhea and vitamin D deficiency could improve systemic symptoms and reduce pain intensity, the number of days with pain, and the need for consuming pain-relief medications.