Barth Wilsey | University of California, Davis (original) (raw)

Papers by Barth Wilsey

Journal of General Internal Medicine

JAMA internal medicine, Jan 4, 2018

Individually designed single-patient multi-crossover (n-of-1) trials can facilitate tailoring of ... more Individually designed single-patient multi-crossover (n-of-1) trials can facilitate tailoring of treatments directed at various conditions, including chronic musculoskeletal pain (CMSP) but are potentially burdensome, which may limit uptake in research and practice. To determine whether patients randomized to participate in an n-of-1 trial supported by a mobile health (mHealth) app would experience less pain and improved global health, adherence, satisfaction, and shared decision making compared with patients assigned to usual care. This randomized clinical trial compared participation in an individualized, mHealth-supported n-of-1 trial vs usual care. The participating 215 patients had CMSP for at least 6 weeks, had a smartphone or tablet with a data plan, were enrolled in northern California from July 2014 through July 2016, and were followed for up to 1 year by 48 clinicians in academic, community, Veterans Affairs, and military settings. Intervention patients met with their clin...

Objective: Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administrat... more Objective: Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administration (FDA) approved for obesity, has utility for binge eating. With no randomized controlled trials (RCTs) yet performed, this trial aimed to evaluate PHEN/TPM-ERs efficacy and safety in a crossover RCT for patients with bingeeating disorder (BED) or bulimia nervosa (BN). Method: Participants were randomized to 12-weeks PHEN/TPM-ER (3.75 mg/23 mg-15 mg/92 mg) or placebo followed by 2-weeks drug washout, then 12-week crossover. Demographics, vitals, eating disorder behaviors, mood, and side effects were measured. Primary outcome was objective binge-eating (OBE) days/4-weeks; secondary outcomes included binge abstinence. Mixed-effect models estimated treatment effects, with fixed effects adjusting for treatment, study period, and diagnosis. Results: The 22 adults (BED = 18, BN = 4) were female (96%), Caucasian (55%), aged 42.9 (SD = 10.1) years with body mass index = 31.1 (SD = 6.2) kg/m 2. Baseline OBE days/4-weeks decreased from 16.2 (SD = 7.8) to 4.2 (SD = 8.4) after PHEN/TPM-ER versus 13.2 (SD = 9.1) after placebo (p < .0001), with abstinence rates = 63.6% on PHEN/ TPM-ER versus 9.1% on placebo (p < .0001). Weight changes = −5.8 kg on PHEN/ TPM-ER versus +0.4 kg on placebo. Drop-out = 2 (9%) on PHEN/TPM-ER and 2 (9%) on placebo, with few side effects. Vital sign changes with PHEN/TPM-ER were minimal and similar to placebo. Responses were not significantly different for BED versus BN. Discussion: This first RCT to evaluate the efficacy and safety of PHEN/TPM-ER for BED/BN found this drug combination significantly more effective at reducing binge eating than placebo and well tolerated. However, with only four participants with BN, findings regarding the safety of PHEN/TPM-ER in patients with BN must be taken with caution.

The journal of pain : official journal of the American Pain Society, 2016

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized canna... more Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effe...

Journal of pain research, 2016

A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo ... more A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease. Subjects received two administrations of the study medication in a 4-hour interval. Blood samples for pharmacokinetic evaluation were collected, and pain assessment tests were performed immediately after the second administration and 3 hours later. Pharmacokinetic data, although limited, were consistent with literature reports, namely dose-dependent increase in systemic exposure followed by rapid disappearance of THC. Dose-dependent improvement in pain score was evident across all pain scale elements. Using mixed model regression, an evaluation of the relationship between plasma concentrations of selected cannabinoids and percent change in items from the Neuropathic Pain Scale was conducted. Changes in the concentration of THC and its ...

Anesthesiology, 1998

... Cryoablation: A Novel Approach to Neurolysis of the Ganglion Impar. Loev, Marc A. MD; Varklet... more ... Cryoablation: A Novel Approach to Neurolysis of the Ganglion Impar. Loev, Marc A. MD; Varklet,Vickie L. MD; Wilsey, Barth L. MD; Ferrante, Michael F. MD. ... Cited Here... 2. Plancarte RB,Velazquez R, Patt RB: Neurolytic blocks of the sympathetic axis, Cancer Pain. ...

Journal of Pain and Symptom Management, Sep 1, 2002

We have extended the traditional use of opioid contracts to involve the primary care physician (P... more We have extended the traditional use of opioid contracts to involve the primary care physician (PCP). The PCP was asked to collaborate with the pain specialist's decision to use opioids by cosigning an opioid contract. Explicit in the agreement was the understanding that the primary care physician would assume prescribing the refills for these medications once the opioid regimen had become stabilized. The present study was a retrospective chart review of the first 81 patients with non-malignant chronic pain who received an opioid agreement requiring the participation of the primary care physician. Sixty-nine of the 81 patients (85%) agreed to the terms of the contract initially, but only 50 of these 69 individuals (72%) successfully obtained their PCP's written agreement for the prescribing of opioids for chronic pain management. Despite expecting reluctance on the part of the PCP to enter into this agreement, the low compliance rate was due to lack of commitment on the part of the patient, who either refused to sign the contract outright or, after initially agreeing to sign the contract, did not have it signed by the PCP. If the PCP did not agree to sign the opioid contract, the patient was tapered off the medication. If the contract was approved and signed by the PCP, there were no subsequent reversals by this physician in terms of agreeing to continue to prescribe opioids. In all cases in which a contract was completed, the patient was successfully stabilized on an appropriate opioid regimen and then discharged back to the care of the PCP for long-term opioid treatment. The opioid contract may be an effective tool for networking specialty and primary care services in the delivery of chronic opioid therapy.

The Journal of Pain, 2015

Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, re... more Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains under-diagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on inhaled cannabis for chronic neuropathic pain. We performed a systematic review and an individual patient data meta-analysis. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis to placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population averaged subject specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in five randomized controlled trials following patients for days to weeks and provides evidence that inhaled cannabis results in short term reductions in chronic neuropathic pain for one in every five to six patients treated (NNT 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors and parameter choices. We caution that small number of included studies and participants, the short follow-up, shortcomings in allocation concealment and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332 corresponding to a posterior probability of effect of 99.7%. This novel Bayesian individual patient data meta-analysis of five randomized trials suggests that inhaled cannabis may provide short term relief for one in five to six patients with neuropathic pain. Pragmatic trials are need to evaluate the long-term benefits and risks of this treatment.

Der Anaesthesist, 1978

In 25 patients undergoing coronary artery bypass grafting hemodynamic measurements (including val... more In 25 patients undergoing coronary artery bypass grafting hemodynamic measurements (including values obtained with Swan-Ganz catheterization in 21 of the patients) were made before and after administering a bolus injection of 64 or 96 mcg of nitroglycerin to relieve intraoperative hypertension. This pharmacological agent reduced afterload and preload without raising heart rate. The effect was apparent within 1-3 min and lasted 5-10 min. Untoward hypotension was not encountered in any instance. This intervention appears to be a safe approach to the treatment of intraoperative hypertension in patients with coronary artery disease.

Trials, 2015

Background: Chronic pain is prevalent, costly, and clinically vexatious. Clinicians typically use... more Background: Chronic pain is prevalent, costly, and clinically vexatious. Clinicians typically use a trial-and-error approach to treatment selection. Repeated crossover trials in a single patient (n-of-1 trials) may provide greater therapeutic precision. N-of-1 trials are the most direct way to estimate individual treatment effects and are useful in comparing the effectiveness and toxicity of different analgesic regimens. The goal of the PREEMPT study is to test the 'Trialist' mobile health smartphone app, which has been developed to make n-of-1 trials easier to accomplish, and to provide patients and clinicians with tools for individualizing treatments for chronic pain. Methods/design: A randomized controlled trial is being conducted to test the feasibility and effectiveness of the Trialist app. A total of 244 participants will be randomized to either the Trialist app intervention group (122 patients) or a usual care control group (122 patients). Patients assigned to the Trialist app will work with their clinicians to set up an n-of-1 trial comparing two pain regimens, selected from a menu of flexible options. The Trialist app provides treatment reminders and collects data entered daily by the patient on pain levels and treatment side effects. Upon completion of the n-of-1 trial, patients review results with their clinicians and develop a long-term treatment plan. The primary study outcome (comparing Trialist to usual care patients) is pain-related interference with daily functioning at 26 weeks. Discussion: Trialist will allow patients and clinicians to conduct personalized n-of-1 trials. In prior studies, n-of-1 trials have been shown to encourage greater patient involvement with care, which has in turn been associated with better health outcomes. mHealth technology implemented using smartphones may offer an efficient means of facilitating n-of-1 trials so that more patients can benefit from this approach. Trial registration: ClinicalTrials.gov: NCT02116621, first registered 15 April 2014.

The Clinical Journal of Pain, 2014

Over 20 states now approve medical marijuana for a long list of &amp;amp;amp;amp;amp;amp;... more Over 20 states now approve medical marijuana for a long list of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;indications,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and more states may well offer access in the near future. Surveys have demonstrated that pain is the most common indication for medical use of cannabis. As more individuals gain access to this botanical product through state ballot initiatives and legislative mandate, the pain specialist is likely to be confronted by patients either seeking such treatment where permitted, or otherwise inquiring about its potential benefits and harms, and alternative pharmaceuticals containing cannabinoids. Whether or not they are in the position to prescribe medical cannabis, pain physicians would seem to have an obligation to understand and inform their patients on key issues of the evidence base on cannabinoid therapeutics. One way to fulfill this obligation might be to borrow from concepts developed in the prescription of opioids: the use of a written agreement to describe and minimize risks. Regrettably, the widespread adoption of opioids was undertaken while harmful effects were minimized; obviously, no one wants to repeat this misstep. This article describes a method of educating patients in a manner analogous to other treatment agreements. Undoubtedly, the knowledge base concerning risks will be an iterative process as we learn more about the long-term use of medicinal cannabis. But we should start the process now so that patients may be instructed about our current conception of what the use of medicinal cannabis entails.

Pharmacoepidemiology and Drug Safety, 2011

Codeine schedule II, long-acting hydromorphone were excluded from consideration because their num... more Codeine schedule II, long-acting hydromorphone were excluded from consideration because their numbers were insignificant. Buprenorphine was not included as it was not utilized for the treatment of chronic pain during the period of study (1999-2007).

Pharmacoepidemiology and Drug Safety, 2014

To examine the age and gender-specific trends of Schedule II opioid use among California resident... more To examine the age and gender-specific trends of Schedule II opioid use among California residents, with special reference to multiple provider users (doctor shoppers). Utilizing data from the California Prescription Drug Monitoring Program, we examined age and gender-specific trends of Schedule II opioid use during calendar years 1999-2007. Specifically, we analyzed the following: (1) the prevalence of Schedule II opioid users among California&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s population and (2) the proportion of these opioid users who were doctor shoppers (defined as an individual who used more than five different prescribers for all Schedule II opioids he or she obtained in a calendar year). Among all age and gender groups, the prevalence of Schedule II opioid users in California increased by 150%-280% and the prevalence of doctor shoppers among users increased by 111%-213% over 9 years. The prevalence of opioid users was lowest among 18-44 year old men (1.25%) and highest among 65-year and older women (5.31%) by 2007. The prevalence of doctor shoppers was approximately 1.4% among those up to age 64 years and 0.5% among those 65 years and older. The gender difference in doctor shoppers among all age groups was negligible. On average, the cumulative morphine-equivalent amount of Schedule II opioid per individual obtained per year was threefold to sixfold higher for doctor shoppers than for the general population across different age and gender groups. Age and gender differences in opioid use were relatively small, whereas the trends for use of opioids and multiple providers grew at a disquieting rate.

Pain Medicine, 2008

We attempted to identify psychological comorbidities that are associated with the propensity for ... more We attempted to identify psychological comorbidities that are associated with the propensity for prescription opioid abuse. Interventions. Patients presenting to an emergency department seeking opioid refills for chronic pain were evaluated with five validated self-report instruments and structured clinical interviews. The potential for prescription opioid abuse was modeled with multiple regression analysis using depression, anxiety disorders, personality disorder, and addiction as independent variables. Results. Of the 113 patients studied, 91 (81%) showed a propensity for prescription opioid abuse as determined by scores on the Screener and Opioid Assessment for Patients with Pain instrument. Depression, anxiety, and a history of substance were common and panic attacks, posttraumatic stress disorder, and personality disorders were also found, albeit less frequently. Panic attacks, trait anxiety, and the presence of a personality disorder accounted for 38% of the variance in the potential for prescription opioid abuse. Conclusions. Patients in chronic pain should be assessed for psychological and addiction disorders because they are at increased risk for abusing opioids. They should also be referred for psychosocial treatment as part of their care, where appropriate.

Journal of Pain and Symptom Management, 2003

Drug and Alcohol Dependence, 2010

Background: The main objective of this study was to determine the prevalence of multiple provider... more Background: The main objective of this study was to determine the prevalence of multiple providers for different controlled substances using the largest electronic prescription monitoring program (PMP) in the United States. A secondary objective was to explore patient and medication variables associated with prescriptions involving multiple providers. PMPs monitor the final allocation of controlled substances from pharmacist to patient. The primary purpose of this scrutiny is to diminish the utilization of multiple providers for controlled substances. Methods: This is a secondary data analysis of the California PMP, the Controlled Substance Utilization Review and Evaluation System (CURES). The prevalence of multiple provider episodes was determined using data collected during 2007. A series of binomial logistic regressions was used to predict the odds ratio (OR) of multiple prescriber episodes for each generic type of controlled substance (i.e., opioid, benzodiazepine, stimulant, or diet pill (anorectic) using demographic and prescription variables. Results: Opioid prescriptions (12.8%) were most frequently involved in multiple provider episodes followed by benzodiazepines (4.2%), stimulants (1.4%), and anorectics (0.9%), respectively. The greatest associations with multiple provider episodes were simultaneously receiving prescriptions for different controlled substances. Conclusions: Opioids were involved in multiple provider prescribing more frequently than other controlled substances. The likelihood of using multiple providers to obtain one class of medications was substantially elevated as patients received additional categories of controlled substances from the same provider or from multiple practitioners. Polypharmacy represents a signal that requires additional vigilance to detect the potential presence of doctor shopping.

The Clinical Journal of Pain, 1998

Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA) and saline (S) block of sym... more Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA) and saline (S) block of sympathetic ganglia (stellate block, 4 patients; lumbar sympathetic block, 3 patients) were compared in 7 complex regional pain syndrome (CRPS) patients on a double-blind crossover basis to evaluate the diagnostic and therapeutic value of local anesthetic sympathetic blocks. Patients rated their pain on a visual analog scale before and after blocks and were tested for mechanical allodynia one-half hour after blocks. Thereafter, they rated their pain intensity in diaries four times a day for 7 days. Each patient received two blocks, S and LA, and served as his own control. Both S and LA injections of sympathetic ganglia produced large reductions in pain intensity in 6 of 7 patients 30 minutes after block. These large reductions were accompanied by the reversal of mechanical allodynia in both S and LA. The mean difference between initial peak reduction in pain intensity produced by saline (68.7%) and active local anesthetic (74.4%) did not approach statistical significance. In striking contrast, the mean duration of pain relief was reliably longer in the case of LA (3 days, 18 hours) as compared with S ( 19.9 hours), a difference that occurred in all 7 patients. In a larger sample of 41 CRPS patients, signs of sympathetic efferent blockade, including Homer' s syndrome or skin surface temperature change, were not predictive of initial peak magnitude of pain relief from sympathetic blockade but were predictive of duration of pain reduction. The combination of these results provides evidence that duration of pain relief is affected by injection of local anesthetics into sympathetic ganglia. These results indicate that both magnitude and duration of pain reduction should be closely monitored to provide optimal efficacy in procedures that use local anesthetics to treat CRPS.

Cannabis and Cannabinoid Research, 2016

The design of analgesic clinical trials invariably involves a comparison between placebo and acti... more The design of analgesic clinical trials invariably involves a comparison between placebo and active study medication. An assumption is made that treatment effects can be approximated by subtracting the response to placebo from that attained with the use of active study medication. However, the psychoactivity of cannabinoids may unmask their presence and lead to an expectation and/or conditioning of pain relief. For example, study participants biased toward the belief that cannabis is beneficial for their condition might be more inclined to report positive effects if they were to accurately identify the active treatment because of its psychoactivity. This may lead to incorrect assumptions regarding the efficacy of a cannabinoid. Methodologies designed to counteract unmasking need to be implemented in the design phase of a study. During the clinical trial, it is also important to query participants as to which treatment they believe they have received. Blinding can be considered to be preserved when the accuracy of treatment guesses is not considerably different than random guessing, which is estimated to be correct 50% of the time. After a study has been completed, the use of statistical methodologies such as regression and mediation analysis are worthy of consideration to see whether psychoactive effects biased the results.

Pain Medicine, 2016

To examine encounter-level factors associated with opioid dose increases during patients&amp... more To examine encounter-level factors associated with opioid dose increases during patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; first year on opioid therapy for chronic pain. Case-control study analyzing all opioid prescriptions for patients with chronic pain during their first year after opioid initiation. Cases were patients who experienced an overall dose escalation of ≥ 30 mg morphine equivalents over the 1-year period; controls did not experience overall dose escalation. Main measures were encounter type, opioid dose change, documented prescribing rationale, documentation of guideline-concordant opioid-prescribing practices. Two coders reviewed all encounters associated with opioid prescriptions. Analysis of factors associated with dose increases and provider documentation of prescribing rationale was conducted using multiple logistic regression. There were 674 encounters coded for 66 patients (22 cases, 44 controls). Fifty-three percent of opioid prescriptions were associated with telephone encounters; 13% were associated with e-mail encounters. No prescribing rationale was documented for 43% of all opioid prescriptions and 25% of dose increases. Likelihood of dose increase and documentation of prescribing rationale did not significantly differ for cases versus controls. Compared with face-to-face encounters, dose increases were significantly less likely for telephone (OR 0.18, 95% CI 0.11-0.28) and e-mail (OR 0.23, 95% CI 0.12-0.47) encounters; documentation of prescribing rationale was significantly more likely for e-mail (OR 5.06, 95% CI 1.87-13.72) and less likely for telephone (OR 0.30, 95% CI 0.18-0.51) encounters. CONCLUSION : Most opioid prescriptions were written without face-to-face encounters. One quarter of dose increases contained no documented prescribing rationale. Documented encounter-level factors were not significantly associated with overall opioid dose escalation.

Pain Medicine, 2014

To identify patient factors and health care utilization patterns associated with dose escalation ... more To identify patient factors and health care utilization patterns associated with dose escalation during the first year of long-term opioid therapy for chronic pain. Retrospective cohort study using electronic health record data. University health system. Opioid naïve adults with musculoskeletal pain who received a new outpatient opioid prescription between July 1, 2011 and June 30, 2012 and stayed on opioids for 1 year. Mixed-effects regression was used to estimate patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; rate of opioid dose escalation. Demographics, clinical characteristics, and health care utilization for patients with and without dose escalation were compared. Twenty-three (9%) of 246 patients in the final cohort experienced dose escalation (defined as an increase in mean daily opioid dose of ≥30-mg morphine equivalents over 1 year). Compared with patients without dose escalation, patients with escalation had higher rates of substance use diagnoses (17% vs 1%, P = 0.01) and more total outpatient encounters (51 vs 35, P = 0.002) over 1 year. Differences in outpatient encounters were largely due to more non face-to-face encounters (e.g., telephone calls, emails) among patients with dose escalation. Differences in age, race, concurrent benzodiazepine use, and mental health diagnoses between patients with and without dose escalation were not statistically significant. Primary care clinicians prescribed 89% of opioid prescriptions. Dose escalation during the first year of long-term opioid therapy is associated with higher rates of substance use disorders and more frequent outpatient encounters, especially non face-to-face encounters.