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.

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.

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.

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.

Psychophysiological responses to various slow, deep breathing techniques.

Deep breathing exercises are commonly used for several health conditions including pain and hypertension. Various techniques are available to practice deep breathing, whereas possible differential psychophysiological effects have not been investigated. We compared four deep breathing techniques and examined outcomes in blood pressure variability, respiratory sinus arrhythmia, baroreflex function, and emotional state. Healthy adult volunteers performed pursed-lips breathing, left and right unilateral nostril breathing, and deep breathing with an inspiratory threshold load (loaded breathing), all at a frequency of 0.1 Hz (i.e., controlled breathing) and for three minutes each. Results showed that blood pressure variability was higher during loaded breathing versus other conditions and higher during pursed-lips breathing versus left and right unilateral nostril breathing. Respiratory sinus arrhythmia was higher during loaded breathing versus other conditions and higher during pursed-lips breathing versus left unilateral nostril breathing. The effect of breathing condition on respiratory sinus arrhythmia was mediated by alterations in blood pressure variability. There was no difference between the breathing conditions in baroreflex sensitivity or effectiveness. Participants rated pursed-lips breathing as more calming and pleasant and with more sense of control (vs. other conditions). Overall, among the four tested deep breathing techniques, loaded breathing was associated with enhanced cardiovascular effects and pursed-lips breathing with better emotional responses, while also enhancing cardiovascular effects (albeit less than loaded breathing). These findings can be informative in applying deep breathing techniques as self-management interventions for health conditions, in which baroreceptors stimulation and autonomic and emotional modulations can be beneficial, such as pain and hypertension.

Can Slow Deep Breathing Reduce Pain? An Experimental Study Exploring Mechanisms.

Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed 4 breathing patterns: 1) unpaced breathing, 2) paced breathing (PB) at the participant's spontaneous breathing frequency, 3) SDB at 6 breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at 6 breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of 3 different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to unpaced breathing, participants reported less intense pain during each of the 3 instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. PERSPECTIVES: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.

Influence of inspiratory threshold load on cardiovascular responses to controlled breathing at 0.1 Hz.

Slow, deep breathing is being used as a self-management intervention for various health conditions including pain and hypertension. Stimulation of the arterial baroreceptors and increased vagal modulation are among the proposed mechanisms for the therapeutic effects of slow, deep breathing. We investigated whether adding inspiratory threshold load can enhance the cardiovascular responses to controlled breathing at the frequency of 0.1 Hz, a common form of slow, deep breathing. Healthy volunteers (N = 29) performed controlled breathing at 0.1 Hz (6 breaths/minute) without load and with inspiratory threshold loads of 5 cmH2 O and 10 cmH2 O. Respiratory airflow, heart rate, and blood pressure were continuously recorded. The amplitude of the systolic blood pressure variation during respiratory cycles increased with increasing loads. Respiratory sinus arrhythmia was higher during controlled breathing at 0.1 Hz with the load of 10 cmH2 O compared to without load. Baroreflex sensitivity was not affected by loads. The effect of loads on respiratory sinus arrhythmia was mediated by increasing the amplitude of systolic blood pressure variation during respiratory cycles. These results suggest that applying small inspiratory threshold loads during controlled breathing at 0.1 Hz increases cardiac vagal modulation by this breathing exercise. This effect seems to be mediated by stronger stimulation of the arterial baroreceptors because of larger systolic blood pressure swings along the respiratory cycle. The potential benefit of long-term practice of controlled breathing at 0.1 Hz with inspiratory threshold loads on baroreflex function and cardiac vagal control needs to be investigated, particularly in pain and hypertension patients.

Effect of Vitamin D Therapy on Sexual Function in Women with Sexual Dysfunction and Vitamin D Deficiency: A Randomized, Double-Blind, Placebo Controlled Clinical Trial.

PURPOSE: We investigated the effect of vitamin D therapy on sexual function in women with low vitamin D levels and sexual dysfunction. MATERIALS AND METHODS: We performed this randomized, double-blind, placebo controlled trial in women 18 to 45 years old with sexual dysfunction, defined as a FSFI (Female Sexual Functioning Index) score less than 26.55, and serum 25[OH]D less than 30 ng/ml. Participants received an intramuscular injection of 300,000 IU cholecalciferol or a placebo at baseline and then after 4 weeks. Sexual function was evaluated with the FSFI at baseline, and 4 and 8 weeks. The serum level of 25[OH]D was measured and depression symptoms were evaluated by the BDI (Beck Depression Inventory) at baseline and 8 weeks. RESULTS: A total of 38 women in each group completed the study. Serum 25[OH]D levels increased only in the cholecalciferol group by a mean ± SD of 14.4 ± 3.2 ng/ml (p <0.001). The FSFI score was higher in the intervention group at study week 4 (19.6 vs 16.3, p = 0.002) and week 8 (25.0 vs 17.1, p <0.001). The BDI score was significantly decreased only in the cholecalciferol group by a mean of -21.0 ± 12.3 (p <0.001). The effect of treatment on sexual function was independent of its effect on depression symptoms. CONCLUSIONS: Vitamin D therapy in women with sexual dysfunction and vitamin D deficiency can improve sexual function. This effect does not seem to be mediated by an improvement in depression symptoms.

Hypnotherapy as an adjuvant for the management of inflammatory bowel disease: a case report.

Idiopathic inflammatory bowel diseases (IBDs) significantly affect the quality of life of sufferers. Improved quality of life and patient symptom management may be achieved through integrating psychological/behavioral interventions with pharmacologic treatments. Here is our experience with hypnotherapy as an adjuvant management for an 18-year-old female with Crohn's Disease (CD) in remission (patient I) and a 24-year-old female with CD in active phase (patient II). The patients participated in 12 weekly one-hour sessions of hypnotherapy. Gut-directed, ego-strengthening, and post-hypnotic suggestions and immune-directed imaginations were used. After the hypnotherapy course, symptoms, psychological state, and quality of life improved in patient I, but not patient II (according to questionnaires). After a 6 month follow-up, symptoms and quality of life were the same as at the end of hypnotherapy sessions in both patients. The patients reported the greatest benefit of hypnotherapy was in helping them to cope better with their disease and also in improving their psychological state. Hypnotherapy may improve quality of life of IBD patients in remission and help them to cope better with their disease. Well-designed controlled clinical trials are needed in this field.

How to put hypnosis into a placebo pill?

Many case studies and several controlled clinical trials have indicated the effectiveness of hypnotherapy for some medical conditions. However, because of methodological inadequacies hypnotherapy is still criticized for not having strong scientific evidence to support its claims. While randomized placebo-controlled clinical trial is generally accepted as the gold standard study design, creating a credible placebo control for hypnotherapy is a major challenge. This paper recommends "neutral hypnosis" as a credible placebo control for hypnotherapy trials.

Hypnotherapy in management of pain and reexperiencing of trauma in burn patients.

This study examined the effects of hypnosis on both pain and reexperiencing of trauma in burn patients. Forty-four patients hospitalized for burn care were randomly assigned to either hypnotherapy or a control group. Direct and indirect hypnotic suggestions were used to reduce pain and reexperiencing of trauma. All patients received routine burn care. Pain reports were quantified by using a self-report numeric rating scale ranging from 0 to 5. The number of recalled vivid, troubling events of the trauma in 24-hour intervals was used for rating the reexperiencing of trauma. The hypnotherapy group showed significantly lower pain ratings than the control group and reported a significant reduction in pain from baseline. There was a significant reduction in trauma reexperience scores in the hypnotherapy group but not the control group. The findings support the efficacy of hypnotherapy in the management of both pain and reexperiencing of trauma in burn patients.

Where does hypnotherapy stand in the management of irritable bowel syndrome? A systematic review.

BACKGROUND: Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. Despite its prevalence, there remains a significant lack of efficient medical treatment for IBS to date. However, according to some previous research studies, hypnosis has been shown to be effective in the treatment of IBS. AIM: To determine the definite efficacy of hypnosis in the treatment of irritable bowel syndrome. METHODS: A systematic review of the literature on hypnosis in the treatment of IBS from 1970 to 2005 was performed using MEDLINE. Full studies published in English were identified and selected for inclusion. We excluded case studies and those studies in which IBS symptoms were not in the list of outcome measures. All studies were reviewed on the basis of the Rome Working Team recommendations for design of IBS trials. RESULTS: From a total of 22 studies, seven were excluded. The results of the reviewed studies showed improved status of all major symptoms of IBS, extracolonic symptoms, quality of life, anxiety, and depression. Furthermore these improvements lasted 2-5 years. CONCLUSIONS: Although there are some methodologic inadequacies, all studies show that hypnotherapy is highly effective for patients with refractory IBS, but definite efficacy of hypnosis in the treatment of IBS remains unclear due to lack of controlled trials supporting this finding.