Challenges in Diagnosing and Managing the Spectrum of Primary Aldosteronism.

Primary aldosteronism, characterized by the dysregulated production of aldosterone from 1 or both adrenal glands, is the most common endocrine cause of hypertension. It confers a high risk of cardiovascular, renal, and metabolic complications that can be ameliorated with targeted medical therapy or surgery. Diagnosis can be achieved with a positive screening test (elevated aldosterone to renin ratio) followed by confirmatory testing (saline, captopril, fludrocortisone, or oral salt challenges) and subtyping (adrenal imaging and adrenal vein sampling). However, the diagnostic pathway may be complicated by interfering medications, intraindividual variations, and concurrent autonomous cortisol secretion. Furthermore, once diagnosed, careful follow-up is needed to ensure that treatment targets are reached and adverse effects, or even recurrence, are promptly addressed. These challenges will be illustrated in a series of case studies drawn from our endocrine hypertension clinic. We will offer guidance on strategies to facilitate an accurate and timely diagnosis of primary aldosteronism together with a discussion of treatment targets which should be achieved for optimal patient outcomes.

Efficacy and safety of mineralocorticoid receptor antagonists for the treatment of low-renin hypertension: a systematic review and meta-analysis.

Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by -6.8 mmHg (95% confidence interval -9.6 to -4.1) and -4.8 mmHg (95% confidence interval -11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.

The impact of ageing on adults with cerebral palsy: the results of a national online survey.

BACKGROUND: Cerebral palsy (CP) is one of the most common neurological disorders in children and results in lifelong physical impairments. Adults with CP have approximately the same life expectancy as their non-disabled peers, so helping them to stay healthy throughout the life course will have long-term cost benefits via reductions in hospital admissions, long-term care, and unemployment rates. AIM: To explore how adults with CP experience ageing. DESIGN & SETTING: National online survey given to adults with CP in the UK. METHOD: The participants were adults with CP. Items for the online survey were taken from existing self-report measures, with additional items developed for the survey. Several domains of functioning were assessed including mobility, dexterity, fatigue, pain, speech, mental health, swallowing and health maintenance/self-care as well as healthcare usage. Data were analysed using χ2 to examine the relationships between the demographic variables and the survey responses. RESULTS: The survey was completed by 395 participants, of whom 74.2% were female and approximately 59.3% aged <45 years. Responders reported having problems with mobility, pain, and fatigue with older participants reporting higher levels of pain and more mobility problems, although the correlations were fairly small. Healthcare usage was surprisingly low. CONCLUSION: The study found that age was associated with a decline in mobility and a higher level of pain, although the relationships were weak. It is possible that the low healthcare usage among the responders is owing to services not being available to respond to their needs.

Predictors of Matching into Anesthesiology and Surgery: Analysis of One Program's Results.

PURPOSE: The objectives of this study were to use a multivariable regression model to determine what application factors made anesthesiology and surgery applicants more or less likely to match into an anesthesiology or surgery residency program. METHODS: Surgery and Anesthesiology applicants listed on the final National Resident Matching Program (NRMP) Rank Order Lists from WMC in the 2020-2021 application cycle were included in analysis. All applicant data were collected through the Electronic Residency Application Service (ERAS). All ERAS and letters of recommendation (LOR) data were deidentified and LOR were subsequently inputted into a linguistics software to analyze the language use in LOR. Descriptive analyses were conducted to compare variables between applicants that matched to a specific residency program and those who matched elsewhere. A multivariable regression model was then used to determine characteristics of anesthesiology and surgery applicants that were indicative of matching to a specific rank of residency program. RESULTS: A total of 116 anesthesiology and 78 surgery applicants were included in final analysis. Analysis of anesthesiology applicants yielded four significant application characteristics that influenced matching to a higher or lower ranked residency program: USMLE Step 2 CK scores, medical school attended, insight category words in LOR, and anger category words in LOR. Similarly, analysis of surgery applicants yielded four significant characteristics: Race, USMLE Step 1 scores, insight category words, and see category words. CONCLUSION: Our results demonstrated that specialties of anesthesiology and surgery considered different metrics regarding the residency application process. Among the many factors that were analyzed, USMLE scores and language in LOR were considered significant in both specialties. As the application process continues to evolve, we may see a shift in what application factors are considered more important than others.

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity.

Purpose: To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. Methods: This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow-up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. Results: We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31-56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42-55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%-29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%-63%) compared to eyes without APROP (13.4%, 95%CI, 8%-22%) (P < 0.001). Conclusion: Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

An insight into the iPSCs-derived two-dimensional culture and three-dimensional organoid models for neurodegenerative disorders.

The use of induced pluripotent stem cells (iPSCs) is a promising approach when used as models to study neurodegenerative disorders (NDDs) in vitro. iPSCs have been used in in vitro two-dimensional cultures; however, these two-dimensional cultures do not mimic the physiological three-dimensional cellular environment. The use of iPSCs-derived three-dimensional organoids has risen as a powerful alternative to using animal models to study NDDs. These iPSCs-derived three-dimensional organoids can resemble the complexity of the tissue of interest, making it an approachable, cost-effective technique, to study NDDs in an ethical manner. Furthermore, the use of iPSCs-derived organoids will be an important tool to develop new therapeutics and pharmaceutics to treat NDDs. Herein, we will highlight how iPSCs-derived two-dimensional cultures and three-dimensional organoids have been used to study NDDs, as well as the advantages and disadvantages of both techniques.

Assessment of diversity in skin colour in dermatology medical education resources.

One hundred and fifty-three patient images from the general resources and 3583 images from Dermatology were evaluated. The majority of images were Fitzpatrick Type II (54%), followed by Type III (27%). Our findings demonstrate the lack of skin diversity continues across many medical school resources, with fair skin (Fitzpatrick Type II) accounting for the majority of images.

Barriers and enablers to participating in regular screening programmes for women with cerebral palsy: A qualitative life course study.

AIMS: To determine the barriers and enablers to regular, women-oriented screening programmes for women with cerebral palsy (CP); and to discuss the participants' suggestions for change. DESIGN: Qualitative life course approach. METHODS: Twenty-five life course interviews were conducted with women in 2020 who identified as having a diagnosis of CP. Interviews were conducted in person or using electronic platforms. Framework analysis was used to interpret the data. FINDINGS: Access and utilization of regular screening programmes for women with CP across the life course are determined by multiple socioecological factors. Three themes are discussed focusing particularly on cervical and breast screening: 1. barriers, 2. enablers and 3. women's suggestions for change. Some women chose to opt out of sexual health checks for fear they would be too uncomfortable or the procedure would be too difficult. Practitioner attitudes towards disability in general, as well as the extent to which they understood the effects of CP for women, was highlighted as a barrier. Accessibility and adaptability of the environment also influenced women's uptake of screening. CONCLUSION: Women with CP face many challenges to their sexual and reproductive healthcare. These can deter them from participating in regular women-oriented screening programmes, which puts them at higher risk of preventable diseases. Understanding the lifelong effects of CP for women, and the interaction with their reproductive health could help to reduce unmet needs and increase participation in relevant screening across the life course. IMPACT: Knowledge of the challenges to regular screening programmes experienced by women with CP across the life course is crucial to provide appropriate preventative healthcare for women with CP across different stages of life. Elements of this knowledge could have benefits for the care of all disabled women.

Should Q-CT Be the Gold Standard for Detecting Spinal Osteoporosis?

STUDY DESIGN: Prospective comparative study. OBJECTIVE: Refinement of the guidelines for screening of osteoporosis and considering quantitative computed tomography (Q-CT) for detecting spinal osteoporosis. SUMMARY OF BACKGROUND DATA: Spinal osteoporosis is often underestimated and under-evaluated due to either lack of availability of the diagnostic modality or lack of awareness about the possibility of overestimation by dual X-ray absorptiometry (DXA) scan. There is a need for reconsidering osteoporosis evaluation with a site specific and patient specific inclination. METHODS: Post-menopausal women that underwent bone mineral density (BMD) evaluation from January-2018 to December-2020 with either Q-CT or DXA were evaluated. Comparison studies of the distribution of age and T-scores of the bone densities obtained from the two study groups: age-matched, sex-matched, and common skeletal site of interest (L1-4 vertebrae) were performed. Mann-Whitney U test, correlation and regression analyses were performed and bell curves were plotted. RESULTS: Of the 718 women evaluated, 447 underwent Q-CT and 271 underwent DXA. There was no significant difference among the age distribution of the two study groups (P-value > 0.05). The mean and mode T-scores obtained by Q-CT and DXA were found to be -2.71, -3.8 and -1.63, -1.7 respectively. A highly significant difference in the T-scores was observed in the Q-CT and DXA groups (P-value < 0.0001). Among those who were screened by Q-CT, 58.16% were osteoporotic, 37.58% were osteopenic, and 4.25% were normal. The respective percentages in the DXA group were 30.63%, 49.82%, and 19.55%. CONCLUSION: Q-CT provides more precise estimation of cancellous bone mineral density than DXA. With the reliance on DXA for spinal BMD estimation being questionable, new standards have to be established for spinal osteoporosis evaluation. Q-CT can be a better alternative to replace DXA as the gold standard for the evaluation of spinal osteoporosis.Level of Evidence: 2.

Real-world outcomes in locally advanced or metastatic urothelial carcinoma following platinum and PD-1/L1 inhibitor therapy.

Aim: To investigate real-world overall survival (rwOS) and real-world progression-free survival (rwPFS) in locally advanced/metastatic urothelial carcinoma postplatinum and postprogrammed death receptor-1/death ligand 1 inhibitors. Patients & methods: Adult patients diagnosed with locally advanced/metastatic urothelial carcinoma from 1 January 2011 to 31 December 2018 and treated with taxane monotherapy or any therapy postplatinum and post-PD-1/L1 inhibitors were included from a nationwide electronic health record-derived oncology database. Results: Median rwOS among 72 patients treated with taxane monotherapy was 7.6 months (95% CI: 5.2-14.4) and rwPFS was 2.9 months (95% CI: 2.4-4.0). Among 208 patients treated with any therapy, median rwOS was 8.9 months (95% CI: 7.3-10.6) and rwPFS was 3.6 months (95% CI: 2.7-4.7). Conclusion: Short duration of rwOS and rwPFS were observed, highlighting the need for effective and safe treatments in this patient population.

Lay abstract Few studies have evaluated survival outcomes in patients with advanced urothelial cancer who have disease relapse after chemotherapy and PD-1/L1 inhibitor therapy in clinical practice. In this study, we used electronic health records from a nationwide cancer database to assess survival in adult patients who received further treatment in this setting from 2011 to 2018. Among 72 patients who were treated with taxane monotherapy after chemotherapy and a PD-1/L1 inhibitor, average overall survival was 7.6 months and progression-free survival was 2.9 months. Among 208 patients who were treated with any therapy, average overall survival was 8.9 months and progression-free survival was 3.6 months. These results highlight the need for safer and more effective therapies in patients with advanced urothelial cancer who have disease relapse after chemotherapy and PD-1/L1 inhibitor therapy.

Real-world burden of illness and unmet need in locally advanced or metastatic urothelial carcinoma following discontinuation of PD-1/L1 inhibitor therapy: A Medicare claims database analysis.

BACKGROUND: Several programmed death-1 or death-ligand 1 (PD-1/L1) inhibitors are approved first- or second-line therapies for locally advanced or metastatic urothelial carcinoma (la/mUC); however, clinical trials show that only ∼20% of patients respond and all ultimately progress. This study elucidated real-world treatment patterns, healthcare resource utilization (HRU), and economic burden among Medicare beneficiaries with la/mUC who discontinue PD-1/L1 inhibitor therapies. METHODS: We conducted a retrospective claims analysis of patients aged ≥65 years diagnosed with la/mUC (2015-2017) who initiated and subsequently discontinued PD-1/L1 inhibitor therapy (index=date of last administration) using Medicare Fee-for-Service Research Identifiable Files. Included patients had ≥12 months pre- and ≥3 months post-index continuous Medicare enrollment, and were followed until disenrollment, death, or data cutoff. RESULTS: Among 28,063 patients, 17% (n=4652) received ≥1 PD-1/L1 inhibitor following la/mUC diagnosis. Of these, 791 discontinued PD-1/L1 inhibitor therapy and met inclusion criteria (study cohort); 73% male, median age 76 years. Post-discontinuation, 3% received a different PD-1/L1 inhibitor, 46% chemotherapy, and 51% no further systemic treatment. HRU was high during follow-up: 97% had ≥1 outpatient visit and 52% ≥1 hospitalization. Healthcare costs per-patient-per-month were $7153 pre- and $7745 (adjusted) post-index; systemic therapy costs were higher pre- vs. post-index ($2978 vs. $1195) but other costs were higher post-index: hospitalization ($1120 vs. $2200), outpatient ($1437 vs. $2064), hospice ($3 vs. $536), skilled nursing facility ($106 vs. $384). CONCLUSIONS: Over half of Medicare beneficiaries with la/mUC received no disease-directed therapy post-PD-1/L1 inhibitor treatment. Patients who discontinued PD-1/L1 inhibitor therapy had intensive HRU unrelated to therapy costs, highlighting the significant burden of la/mUC and need for treatments that extend survival.

COVID-19 prevalence and predictors in United States adults during peak stay-at-home orders.

BACKGROUND: Early recognition of COVID-19 cases is essential for effective public health measures aimed at isolation of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). The objective of this study was to describe characteristics, self-reported symptoms, and predictors of testing positive for SARS-CoV-2 infection in a community-based sample. METHODS AND FINDINGS: This was a cross-sectional nationwide survey of adults in the US conducted between April 24 through May 13, 2020. The survey targeted a representative sample of approximately 5,000 respondents. The rate of COVID-19 cases and testing, most frequently reported symptoms, symptom severity, treatment received, impact of COVID-19 on mental and physical health, and factors predictive of testing positive were assessed. Most of the 5,203 participants (85.6%) reported no COVID-19-like symptoms. Of the 747 (14.5%) participants reporting COVID-19-like symptoms, 367 (49.1%) obtained a diagnostic test. Eighty-nine participants (24.3%) reported a positive COVID-19 test result, representing 1.7% of the total sample. For those testing positive, the most common symptoms were dry cough, fever, and shortness of breath/difficulty breathing. Those who tested positive were more likely to report greater symptom severity versus those who tested negative. Severe dry cough, new loss of taste or smell, trouble waking up, living with someone experiencing symptoms, recent international travel, respiratory issues, and reporting ethnicity of Black or African American were predictive of testing positive. CONCLUSIONS: This study assessed the impact of COVID-19 using community-level self-reported data across the US during the peak of most stay at home' orders. Self-reported symptoms and risk factors identified in this study are consistent with the clinical profile emerging for COVID-19. In the absence of widespread testing, this study demonstrates the utility of a representative US community-based sample to provide direct-reported symptoms and outcomes to quickly identify high-risk individuals who are likely to test positive and should consider taking greater precautions.

Epidemiology and treatment patterns for locally advanced or metastatic urothelial carcinoma: a systematic literature review and gap analysis.

BACKGROUND: Several immuno-oncology (IO) agents targeting programmed death-1 or programmed death-ligand 1 (PD-1/L1) are approved second-line therapy options for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with platinum-based chemotherapy or first-line options in patients ineligible for cisplatin whose tumors express PD-L1 or for any platinum-based chemotherapy regardless of PD-L1 expression levels. However, literature on the epidemiology of la/mUC is limited, and real-world treatment patterns are not well established, especially with respect to therapies used following IO. OBJECTIVES: To (a) report the epidemiology of urothelial carcinoma (UC) and la/mUC; (b) identify and summarize the published literature on la/mUC treatment patterns, including IO and post-IO treatment; and (c) identify evidence gaps. METHODS: A systematic literature review was conducted using Cochrane dual-reviewer methodology and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Literature databases and selected congress abstracts (2017-2018) were searched for retrospective studies published January 2013-August 2018 in English reporting epidemiological and treatment data (all lines of therapy) for adult patients with la/mUC. RESULTS: Among 6,584 database references and 1,832 congress abstracts screened, 45 publications (29 manuscripts, 1 poster, 15 abstracts; reporting 37 unique studies) were retained. All studies related to treatment patterns, and the majority were from the United States (n = 17), Japan (n = 8), and the United Kingdom (n = 5). Epidemiological data were not identified among the searches thus online registries were leveraged. Among the identified publications, 21 (20 unique) reported on cisplatin versus non-cisplatin regimens, 14 (8 unique) on IO, and 9 (7 unique) on vinflunine. Cisplatin use varied both within and among countries (ranging from 18.4% in 1 U.S. study to 87.9% in 1 Japanese study). The use of IO was higher in later lines of therapy, ranging from 1.4% to 7.9% as first-line therapy to 57.8% as second-line and 64.4% as third-line therapy. Among studies reporting IO discontinuation rates, 41.4%-71% of patients were reported to discontinue IO across the studies, and the median time to discontinuation ranged from 2.7 to 5.8 months. Only 25%-35.5% of patients received subsequent therapy following IO discontinuation; post-IO treatments varied widely. CONCLUSIONS: Additional published data on the country-specific epidemiology of UC and la/mUC are needed, including rates of progression from early-stage disease to la/mUC. There was large variation in treatment rates, particularly cisplatin use, within and across countries. The few published real-world IO studies reported high levels of discontinuation with only a small percentage of patients receiving subsequent therapy. As IO therapies continue to be granted regulatory approval in countries outside the United States and novel therapies gain approval in the post-IO setting, the treatment paradigm for patients with la/mUC is shifting, and future studies with more recent data will be required. DISCLOSURES: This study was funded by Astellas/Seagen. Hepp is an employee of and owns stock in Seagen. Shah was a contractor for Astellas Pharma at the time of the study and owns stock in Pfizer. Smoyer is an employee and shareholder of Envision Pharma Group, paid consultants to Seagen. Vadagam was an employee of Envision Pharma Group, paid consultants to Seagen, at the time of the study. Parts of these data have been presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2019 Annual Meeting; May 18-22, 2019; New Orleans, LA.

Using Facebook to tell stories of premature ageing and sexual and reproductive healthcare across the life course for women with cerebral palsy in the UK and USA.

OBJECTIVE: To enhance understanding of the bodily and lifestyle effects of ageing with cerebral palsy (CP) for women, with a particular focus on experiences with sexual and reproductive healthcare (SRH) services in the UK and North America. DESIGN: A qualitative study underpinned by feminist disability theory and drawing on digital ethnographies to capture health and healthcare experiences for women with CP. SETTING: A global community of 140 women with CP, who are members of the closed international Facebook group, Women Ageing with Cerebral Palsy (WACP). PARTICIPANTS: Forty-five members of WACP who were based in the UK and North America. The women were aged between 21 and 75. METHODS: Messages posted on WACP between January 2018 and October 2018 were collated and underwent thematic analysis to identify themes relating to effects of ageing and experiences of SRH for women with CP at different points over the female life course. RESULTS: The breadth of experiences in relation to the effects of ageing and access to reproductive and sexual healthcare for women with CP can be divided into three themes: (1) bodily effects of ageing; (2) lifestyle effects of ageing; (3) experiences of reproductive and sexual healthcare. CONCLUSIONS: Giving women with CP a platform to 'speak for themselves' in relation to effects of ageing and SRH provides health professionals with an informed knowledge base on which to draw. This might improve treatment for this growing adult patient community whose experiences have not received attention in health discourse or services. Including these experiences in public medical and social discourse can also bring a new knowledge to girls with CP about what ageing could mean for them so plans can be put in place for their future.

Optimizing Investigations for Evaluation of Enlargements of the Roots, Plexuses and Nerves: A Study of 133 Patients.

BACKGROUND AND AIMS: A wide variety of neurological diseases result in clinical and/or radiological enlargement of nerves, roots and plexuses. With the advancement in techniques and use of magnetic resonance neurography (MRN), aided by electrophysiology, proximal segments of the lower motor neuron (LMN) can be well studied. The relative merits of investigative modalities have not been well defined and comprehensive information on this subject is sparse. METHODS: This retrospective study included data from January 2010 to June 2018. Patients having clinical and/or radiological enlargements of lower motor neuron were included. Clinical and laboratory work up, electrophysiology, MRN and biopsy studies were documented and analyzed. RESULTS: 133 patients fulfilled the inclusion criteria. The diagnostic categories were of leprosy (32%), immune neuropathies (27.8%), nerve infiltrations (8.2%), inherited neuropathies (9%), diabetic radiculopathies (9%) and others (12.7%). MRN was essential to diagnosis in 24.8% and supportive in 31.5% patients. Electrophysiology was essential in diagnosis in 70.6%, biopsy in 45.8% and genetic studies in 6.4% patients. CONCLUSION: The manuscript presents a large cohort of diseases causing enlargement of LMN with clinical and investigative aspects of 7 patients of the most unusual condition of chronic immune sensorimotor polyradiculopathy (CISMP) and details of 7 other patients with chronic mononeuropathies at non-entrapment sites. A table of comparative utility and an algorithm depicting the optimization of investigations has been presented.

Economic Impact of Adherence to Pain Treatment Guidelines in Chronic Pain Patients.

OBJECTIVES: This research compared health care resource use (HCRU) and costs for pharmacotherapy prescribing that was adherent vs nonadherent to published pain management guidelines. Conditions included osteoarthritis (OA) and gout (GT) for nociceptive/inflammatory pain, painful diabetic peripheral neuropathy (pDPN) and post-herpetic neuralgia (PHN) for neuropathic pain, and fibromyalgia (FM) for sensory hypersensitivity pain. METHODS: This retrospective cohort study used claims from MarketScan Commercial and Medicare Databases identifying adults newly diagnosed with OA, GT, pDPN, PHN, or FM during July 1, 2006, to June 30, 2013, with 12-month continuous coverage before and after initial (index) diagnosis. Patients were grouped according to their pharmacotherapy pattern as adherent, nonadherent, or "unsure" according to published pain management guidelines using a claims-based algorithm. Adherent and nonadherent populations were compared descriptively and using multivariate statistical analyses for controlling bias. RESULTS: Final cohort sizes were 441,465 OA, 76,361 GT, 10,645 pDPN, 4,010 PHN, and 150,321 FM, with adherence to guidelines found in 51.1% of OA, 25% of GT, 59.5% of pDPN, 54.9% of PHN, and 33.5% of FM. Adherent cohorts had significantly (P < 0.05) fewer emergency department (ED) visits and lower proportions with hospitalizations or ED visits. Mean health care costs increased following diagnosis across all conditions; however, adherent cohorts had significantly lower increases in adjusted costs pre-index to postindex (OA $5,286 vs $9,532; GT $3,631 vs $7,873; pDPN $9,578 vs $16,337; PHN $2,975 vs $5,146; FM $2,911 vs $3,708; all P < 0.001; adherent vs nonadherent, respectively). CONCLUSIONS: Adherence to pain management guidelines was associated with significantly lower HCRU and costs compared with nonadherence to guidelines.