This JAMA Pediatrics Patient Page discusses the most common causes of poisoning in children and safety tips to prevent poisoning.
Importance: Adrenal insufficiency is a syndrome of cortisol deficiency and is categorized as primary, secondary, or glucocorticoid induced. Although primary and secondary adrenal insufficiency are rare, affecting less than 279 per 1 million individuals, glucocorticoid-induced adrenal insufficiency is common.
Observations: Primary adrenal insufficiency, which involves deficiency of all adrenocortical hormones, is caused by autoimmune destruction, congenital adrenal hyperplasia, pharmacological inhibition (eg, high doses of azole antifungal therapy), infection (eg, tuberculosis, fungal infections), or surgical removal of adrenal cortical tissue. Secondary adrenal insufficiency is caused by disorders affecting the pituitary gland, such as tumors, hemorrhage, inflammatory or infiltrative conditions (eg, hypophysitis, sarcoidosis, hemochromatosis), surgery, radiation therapy, or medications that suppress corticotropin production, such as opioids. Glucocorticoid-induced adrenal insufficiency is caused by administration of supraphysiological doses of glucocorticoids. Patients with adrenal insufficiency typically present with nonspecific symptoms, including fatigue (50%-95%), nausea and vomiting (20%-62%), and anorexia and weight loss (43%-73%). Glucocorticoid-induced adrenal insufficiency should be suspected in patients who have recently tapered or discontinued a supraphysiological dose of glucocorticoids. Early-morning (approximately 8 am) measurements of serum cortisol, corticotropin, and dehydroepiandrosterone sulfate (DHEAS) are used to diagnose adrenal insufficiency. Primary adrenal insufficiency is typically characterized by low morning cortisol levels (<5 µg/dL), high corticotropin levels, and low DHEAS levels. Patients with secondary and glucocorticoid-induced adrenal insufficiency typically have low or intermediate morning cortisol levels (5-10 µg/dL) and low or low-normal corticotropin and DHEAS levels. Patients with intermediate early-morning cortisol levels should undergo repeat early-morning cortisol testing or corticotropin stimulation testing (measurement of cortisol before and 60 minutes after administration of cosyntropin, 250 µg). Treatment of adrenal insufficiency involves supplemental glucocorticoids (eg, hydrocortisone, 15-25 mg daily, or prednisone, 3-5 mg daily). Mineralocorticoids (eg, fludrocortisone, 0.05-0.3 mg daily) should be added for patients with primary adrenal insufficiency. Adrenal crisis, a syndrome that can cause hypotension and shock, hyponatremia, altered mental status, and death if untreated, can occur in patients with adrenal insufficiency who have inadequate glucocorticoid therapy, acute illness, and physical stress. Therefore, all patients with adrenal insufficiency should be instructed how to increase glucocorticoids during acute illness and prescribed injectable glucocorticoids (eg, hydrocortisone, 100 mg intramuscular injection) to prevent or treat adrenal crisis.
Conclusions and relevance: Although primary and secondary adrenal insufficiency are rare, glucocorticoid-induced adrenal insufficiency is a common condition. Diagnosis of adrenal insufficiency involves early-morning measurement of cortisol, corticotropin, and DHEAS. All patients with adrenal insufficiency should be treated with glucocorticoids and instructed how to prevent and treat adrenal crisis.
The American Society of Addiction Medicine (ASAM) developed this National Practice Guideline for the Treatment of Opioid Use Disorder to provide information on evidence-based treatment of opioid use disorder. This guideline is an update and replacement of the 2015 ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use.
Background: Less than 20% of individuals with opioid use disorder (OUD) are receiving a medication treatment for OUD in the United States. Though nurses can assume critical roles in outpatient models of OUD care, there are no published reports of buprenorphine standing orders for nurses that guide a nuanced response for patients returning as expected versus those re-engaging after a treatment lapse, without requiring real-time prescriber consultation.
Methods: Standing orders for buprenorphine were created with multiple stakeholders within an urban community health center that includes traditional clinics as well as non-traditional homeless care sites. After more than two years of use, an anonymous survey assessed staff perception of usability and safety of the standing orders using the validated system usability scale (SUS) and a 5-item Likert scale. Patient retention rates at 12 and 18 months were compared for sites that were early- and late-adopters of the standing orders.
Results: Of 24 clinicians and 7 nurses who responded to the survey, 46% had used the standing orders. More than 85% reported a perception that the standing orders improved team-based care and increased access to buprenorphine refills. None reported any safety concerns. The median SUS score was 75.0 (SD 15.4), rated as “excellent”. There was no statistically significant difference in 12- or 18-month retention rates between early- and late-adopter sites of the standing orders.
Conclusions: Nurse standing orders for buprenorphine follow-up and re-engagement care are feasible, usable and perceived as safe in varied community health center settings.
In an effort to address the opioid epidemic, a prominent goal of current research is to identify alternative treatments with equal or better benefits for pain while avoiding potential unintended consequences that could result in harms.
This 'living' systematic review assesses the effectiveness and harms of cannabis and other plant-based treatments for chronic pain conditions. For the purposes of this review, plant-based compounds (PBCs) included are those that are similar to opioids in effect and that have the potential for addiction, misuse, and serious adverse effects; other PBCs such as herbal treatments are not included. The intended audience includes policy and decision makers, funders and researchers of treatments for chronic pain, and clinicians who treat chronic pain.
The report will be updated on a quarterly basis.
Importance: Although prescription opioids are the most common way adolescents and young adults initiate opioid use, many studies examine population-level risks following the first opioid prescription. There is currently a lack of understanding regarding how patterns of opioid prescribing following the first opioid exposure may be associated with long-term risks.
Objective: To identify distinct patterns of opioid prescribing following the first prescription using group-based trajectory modeling and examine the patient-, clinician-, and prescription-level factors that may be associated with trajectory membership during the first year.
Design, setting, and participants: This cohort study examined Pennsylvania Medicaid enrollees' claims data from 2010 through 2016. Participants were aged 10 to 21 years at time of first opioid prescription. Data analysis was performed in March 2020.
Main outcomes and measures: This study used group-based trajectory modeling and defined trajectory status by opioid fill.
Results: Among the 189 477 youths who received an initial opioid prescription, 107 562 were female (56.8%), 81 915 were non-Latinx White (59.6%), and the median age was 16.9 (interquartile range [IQR], 14.6-18.8) years. During the subsequent year, 47 477 (25.1%) received at least one additional prescription. Among the models considered, the 2-group trajectory model had the best fit. Of those in the high-risk trajectory, 65.3% (n = 901) filled opioid prescriptions at month 12, in contrast to 13.1% (n = 6031) in the low-risk trajectory. Median age among the high-risk trajectory was 19.0 years (IQR, 17.1-20.0 years) compared with the low-risk trajectory (17.8 years [IQR, 15.8-19.4 years]). The high-risk trajectory received more potent prescriptions compared with the low-risk trajectory (median dosage of the index month for high-risk trajectory group: 10.0 MME/d [IQR, 5.0-21.2 MME/d] vs the low-risk trajectory group: 4.7 MME/d [IQR, 2.5-7.8 MME/d]; P < .001). The trajectories showed persistent differences with more youths in the high-risk trajectory going on to receive a diagnosis of opioid use disorder (30.0%; n = 412) compared with the low-risk group (10.1%; n = 4638) (P < .001).
Conclusions and relevance: This study's results identified 2 trajectories associated with elevated risk for persistent opioid receipt within 12 months following first opioid prescription. The high-risk trajectory was characterized by older age at time of first prescription, and longer and more potent first prescriptions. These findings suggest even short and low-dose opioid prescriptions can be associated with risks of persistent use for youths.
Physicians have a legal and ethical duty to protect their patients and support them during times of clinical need; the decision to end a doctor-patient relationship should not be made lightly. However, in a recent survey of 794 primary care practices, 90% reported discharging patients in the previous two years, often for opioid-related issues.1 Disruptive or inappropriate behavior was the most common reason for discharge (81%), but 78% reported dismissing patients for violations of a chronic pain or controlled substance agreement. We find this practice worrisome, particularly since many controlled substance agreements use coercive and stigmatizing language that patients may reluctantly sign or have trouble understanding.2 Although violent, threatening, or disruptive behavior may be a valid reason to discharge patients in certain circumstances, opioid misuse should rarely rise to this threshold
Importance: Mind-body therapies (MBTs) are emerging as potential tools for addressing the opioid crisis. Knowing whether mind-body therapies may benefit patients treated with opioids for acute, procedural, and chronic pain conditions may be useful for prescribers, payers, policy makers, and patients.
Objective: To evaluate the association of MBTs with pain and opioid dose reduction in a diverse adult population with clinical pain.
Data sources: For this systematic review and meta-analysis, the MEDLINE, Embase, Emcare, CINAHL, PsycINFO, and Cochrane Library databases were searched for English-language randomized clinical trials and systematic reviews from date of inception to March 2018. Search logic included (pain OR analgesia OR opioids) AND mind-body therapies. The gray literature, ClinicalTrials.gov, and relevant bibliographies were also searched.
Study selection: Randomized clinical trials that evaluated the use of MBTs for symptom management in adults also prescribed opioids for clinical pain.
Data extraction and synthesis: Independent reviewers screened citations, extracted data, and assessed risk of bias. Meta-analyses were conducted using standardized mean differences in pain and opioid dose to obtain aggregate estimates of effect size with 95% CIs.
Main outcomes and measures: The primary outcome was pain intensity. The secondary outcomes were opioid dose, opioid misuse, opioid craving, disability, or function.
Results: Of 4212 citations reviewed, 60 reports with 6404 participants were included in the meta-analysis. Overall, MBTs were associated with pain reduction (Cohen d = -0.51; 95% CI, -0.76 to -0.26) and reduced opioid dose (Cohen d = -0.26; 95% CI, -0.44 to -0.08). Studies tested meditation (n = 5), hypnosis (n = 25), relaxation (n = 14), guided imagery (n = 7), therapeutic suggestion (n = 6), and cognitive behavioral therapy (n = 7) interventions. Moderate to large effect size improvements in pain outcomes were found for meditation (Cohen d = -0.70), hypnosis (Cohen d = -0.54), suggestion (Cohen d = -0.68), and cognitive behavioral therapy (Cohen d = -0.43) but not for other MBTs. Although most meditation (n = 4 [80%]), cognitive-behavioral therapy (n = 4 [57%]), and hypnosis (n = 12 [63%]) studies found improved opioid-related outcomes, fewer studies of suggestion, guided imagery, and relaxation reported such improvements. Most MBT studies used active or placebo controls and were judged to be at low risk of bias.
Conclusions and relevance: The findings suggest that MBTs are associated with moderate improvements in pain and small reductions in opioid dose and may be associated with therapeutic benefits for opioid-related problems, such as opioid craving and misuse. Future studies should carefully quantify opioid dosing variables to determine the association of mind-body therapies with opioid-related outcomes.
Medications to treat disease and extend life in our patients often amass in quantities, resulting in what has been termed "polypharmacy." This imprecise label usually describes the accumulation of 5, and often more, medications. Polypharmacy in advancing age frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and nonadherence. Polypharmacy is associated with resulting increased hospitalizations and higher costs of care for individuals and health care systems. To reduce polypharmacy, we delineate a systematic, consultative approach to identify highest-risk medications and drug-therapy problems. We address strategic reductions (deprescribing) of medications in palliative care, long-term care, and ambulatory older adults. Best practices for reducing opioids, benzodiazepines, and other high-risk medications include education about risk and agreement by patients and their families, advocates, and care teams. Addressing deprescribing should be within the framework of patients' health status as their care and goals transition from longevity to a plan of maintaining alertness, comfort, and satisfaction of quality of life. A team approach to address polypharmacy and avoidance of high-risk therapy is optimal within long-term care. Patients with terminal illnesses or those moving toward a comfort-care emphasis benefit from medication adjustments that are recognized beneficially within each patient's care goals. In caring for older adults, the acknowledgement that complicated regimens and high-risk medications requires a care plan to reduce or prevent medication-related problems and costs that are associated with polypharmacy.
Importance: Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations.
Objective: To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder.
Design, setting, and participants: This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder.
Interventions: Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group).
Main outcomes and measures: Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority.
Results: A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group.
Conclusions and relevance: Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages.
