There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Measuring Health: A Guide to Rating Scales and Questionnaires

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Applied Longitudinal Data Analysis Modeling Change And Event Occurrence

Ghrelin is a peptide predominantly produced by the stomach. Ghrelin displays strong GH-releasing activity. This activity is mediated by the activation of the so-called GH secretagogue receptor type 1a. This receptor had been shown to be specific for a family of synthetic, peptidyl and nonpeptidyl GH secretagogues. Apart from a potent GH-releasing action, ghrelin has other activities including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, and influence on pancreatic exocrine and endocrine function as well as on glucose metabolism. Cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system, are other actions of ghrelin. Therefore, we consider ghrelin a gastrointestinal peptide contributing to the regulation of diverse functions of the gut-brain axis. So, there is indeed a possibility that ghrelin analogs, acting as either agonists or antagonists, might have clinical impact.

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Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin.

The acute effect of a new GH-releasing peptide, hexarelin (1 mg, iv), on GH secretion and the mechanisms involved in its changes were investigated in conscious sheep. Peripheral GH levels and GH-releasing hormone (GHRH) and somatostatin concentrations in hypophysial portal blood were measured in six rams. An increase in jugular GH levels was observed 15 min after hexarelin injection (9.1 +/- 1.8 vs. 3.9 +/- 0.8 ng/ml; P < 0.05). This was associated with a stimulation of GHRH release into hypophysial portal blood (145.4 +/- 19.9 vs. 59.2 +/- 10.8 pg/ml; P < 0.01) without a change in somatostatin secretion. Our data indicate that GH-releasing peptide-induced GH stimulation in the sheep involves an activation of GHRH neurons in addition to the previously demonstrated direct effect on the pituitary cells.

Growth Hormone (GH)-Releasing Hormone Secretion Is Stimulated by a New GH-Releasing Hexapeptide in Sheep

Importance Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about risks related to tapering, including overdose and mental health crisis. Objective To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids. Design, Setting, and Participants Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion. Exposures Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period. Main Outcomes and Measures Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity. Results The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6]; aIRR, 1.68 [95% CI, 1.53-1.85]). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3]; aIRR, 2.28 [95% CI, 1.96-2.65]). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21). Conclusions and Relevance Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.

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Association of Dose Tapering With Overdose or Mental Health Crisis Among Patients Prescribed Long-term Opioids

Importance Prior studies suggesting clinician fulfillment or denial of requests affects patient satisfaction included limited adjustment for patient confounders. The studies also did not examine distinct request types, yet patient expectations and clinician fulfillment or denial might vary among request types. Objective To examine how patient satisfaction with the clinician is associated with clinician denial of distinct types of patient requests, adjusting for patient characteristics. Design, Setting, and Participants Cross-sectional observational study of 1319 outpatient visits to family physicians (n = 56) by 1141 adults at one Northern California academic health center. Main Outcomes and Measures We used 6 Consumer Assessment of Healthcare Providers and Systems Clinician and Group Adult Visit Survey items to measure patient satisfaction with the visit physician. Standardized items were averaged to form the satisfaction score (Cronbach α = 0.80), which was then percentile-transformed. Seven separate linear mixed-effects models examined the adjusted mean differences in patient satisfaction percentile associated with denial of each of the following requests (if present)—referral, pain medication, antibiotic, other new medication, laboratory test, radiology test, or other test—compared with fulfillment of the respective requests. The models adjusted for patient sociodemographics, weight, health status, personality, worry over health, prior visit with clinician, and the other 6 request categories and their dispositions. Results The mean (SD) age of the 1141 patients was 45.6 (16.1) years, and 902 (68.4%) were female. Among 1319 visits, 897 (68.0%) included at least 1 request; 1441 (85.2%) were fulfilled. Requests by category were referral, 294 (21.1%); pain medication, 271 (20.5%); antibiotic, 107 (8.1%); other new medication, 271 (20.5%); laboratory test, 448 (34.0%); radiology test, 153 (11.6%); and other tests, 147 (11.1%). Compared with fulfillment of the respective request type, clinician denials of requests for referral, pain medication, other new medication, and laboratory test were associated with worse satisfaction (adjusted mean percentile differences, −19.75 [95% CI, −30.75 to −8.74], −10.72 [95% CI, −19.66 to −1.78], −20.36 [95% CI, −29.54 to −11.18], and −9.19 [95% CI, −17.50 to −0.87]), respectively. Conclusions and Relevance Clinician denial of some types of requests was associated with worse patient satisfaction with the clinician, but not for others, when compared with fulfillment of the requests. In an era of patient satisfaction-driven compensation, the findings suggest the need to train clinicians to deal effectively with requests, potentially enhancing patient and clinician experiences.

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Association of Clinician Denial of Patient Requests With Patient Satisfaction.

Importance A 2016 Centers for Disease Control and Prevention prescribing guideline cautioned against higher-dose long-term opioid therapy and recommended tapering daily opioid doses by approximately 10% per week if the risks outweigh the benefits. Warnings have since appeared regarding potential hazards of rapid opioid tapering. Objectives To characterize US trends in opioid dose tapering among patients prescribed long-term opioids from 2008 to 2017 and identify patient-level variables associated with tapering and a more rapid rate of tapering. Design, Setting, and Participants This retrospective cohort study used deidentified medical and pharmacy claims and enrollment records for 99 874 commercial insurance and Medicare Advantage enrollees, representing a diverse mixture of ages, races/ethnicities, and geographical regions across the United States. Adults with stable, higher-dosage (mean, ≥50 morphine milligram equivalents [MMEs]/d) opioid prescriptions for a 12-month baseline period and 2 or more months of follow-up from January 1, 2008, to December 31, 2017, were included in the study. Main Outcomes and Measures Tapering was defined as 15% or more relative reduction in mean daily MME during any of 6 overlapping 60-day windows within a 7-month follow-up period. The rate of tapering was computed as the maximum monthly percentage dose reduction. Results Among the 99 874 participants (53 358 [53.4%] women; mean [SD] age, 57.4 [11.8] years), from 2008 to 2015, the age- and sex-standardized percentage of patients tapering daily opioid doses increased from 12.7% to 16.2% (adjusted incidence rate ratio [aIRR] per year, 1.05 [95% CI, 1.05-1.06]) before increasing to 18.6% in 2016 and 23.1% in 2017 (aIRR in 2016-2017 vs 2008-2015, 1.16 [95% CI, 1.12-1.20]). Patient-level covariates associated with tapering included female sex (aIRR, 1.09 [95% CI, 1.07-1.11]) and higher baseline dose (aIRR for ≥300 MMEs/d vs 50-89 MMEs/d, 2.19 [95% CI, 2.12-2.27]). Among patients tapering daily opioid doses, the mean (SD) maximum dose reduction was 34.0% (27.4%) per month, and 26.5% of patients had a maximum tapering rate exceeding 40% per month (ie, faster than 10% per week). Higher maximum dose reduction rate was associated with age 18 to 34 years (vs older age groups), male sex, a high school education or less (vs more education), small town or rural residence (vs metropolitan, micropolitan, or unknown), a Charlson Comorbidity Index score of 3 or higher (vs 0) (adjusted difference, 1.9% [95% CI, 0.9%-2.9%]), lower baseline doses (50-89 MMEs vs 150-299 or ≥300 MMEs), and a recent drug overdose (adjusted difference, 10.2% [95% CI, 6.8%-13.6%]). Conclusions and Relevance Patients using long-term opioid therapy are increasingly undergoing dose tapering, particularly women and those prescribed higher doses; in addition, dose tapering has become more common since 2016. Many patients undergoing tapering reduce daily doses at a rapid maximum rate.

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Trends and Rapidity of Dose Tapering Among Patients Prescribed Long-term Opioid Therapy, 2008-2017.

Aims
Most patients with diabetes have comorbid chronic conditions that could support (concordant) or compete with (discordant) diabetes care. We sought to determine the impact of the number of concordant and discordant chronic conditions on diabetes care quality.

E. Magnan

Papers

Growth Hormone (GH)-Releasing Hormone Secretion Is Stimulated by a New GH-Releasing Hexapeptide in Sheep

Association of Dose Tapering With Overdose or Mental Health Crisis Among Patients Prescribed Long-term Opioids

Association of Clinician Denial of Patient Requests With Patient Satisfaction.

Trends and Rapidity of Dose Tapering Among Patients Prescribed Long-term Opioid Therapy, 2008-2017.

The Impact of a Patient’s Concordant and Discordant Chronic Conditions on Diabetes Care Quality Measures