Initiating second-line antidiabetic medication among older adults with type 2 diabetes on Metformin.

BACKGROUND: Antidiabetic medications (ADM), especially sulfonylureas (SFU) and basal insulin (BI), are associated with increased risk of hypoglycemia, which is especially concerning among older adults in poor health. The objective of this study was to investigate prescribing patterns of ADM in older adults according to their health status. METHODS: This case control study analyzed administrative claims between 2013 and 2017 from a large national payer. The study population was derived from a nationwide database of 84,720 U.S. adults aged ≥65, who were enrolled in Medicare Advantage health insurance plans. Participants had type 2 diabetes on metformin monotherapy, and started a second-line ADM during the study period. The exposure was a binary variable for health status, with poor health defined by end-stage medical conditions, dementia, or residence in a long-term nursing facility. The outcome was a variable identifying which second-line ADM class was started, categorized as SFU, BI, or other (i.e. all other ADM classes combined). RESULTS: Over half of participants (54%) received SFU as initial second-line ADM, 14% received BI, and 32% received another ADM. In multivariable models, the odds of filling SFU or BI was higher for participants in poor health than those in good or intermediate health [OR 1.13 (95% CI 1.05-1.21) and OR 2.34 (95% CI 2.14-2.55), respectively]. SFU and BI were also more commonly filled by older adults with poor glycemic control. CONCLUSIONS: Despite clinical consensus to use caution prescribing SFU and BI among older adults in poor health, these medications remain frequently used in this particularly vulnerable population.

Inpatient Management of T2DM and Hyperglycemia in Older Adults.

PURPOSE OF REVIEW: This review aims to provide a summary of the evaluation and treatment of older adults (≥ 65 years) with type 2 diabetes and/or hyperglycemia in the hospital. RECENT FINDINGS: Caring for these older adults requires special considerations. Diabetes is a risk factor for hospitalization and hyperglycemia in the hospital is associated with increased complications and mortality. Treatment plans for hospitalized older adults with diabetes should include a comprehensive geriatric assessment. This team-based approach aims to develop an individualized care plan, with consideration of the patients' personal goals, comorbidities, functional status, life expectancy, and hypoglycemia risk. Studies from hospitalized middle age and older adults with hyperglycemia can help guide diabetes treatment goals and management in older adults. Further studies, examining both glucose targets and care management assessments and treatment plan specifically targeting older adults in the hospital setting, are needed.

Lack of correlation between immunohistochemical expression of CKIT and KIT mutations in atypical acral nevi.

BACKGROUND: Given the correlation between KIT mutations and immunohistochemical expression of CKIT in acral melanoma, our aim was to confirm the utility of CKIT detection as a screening tool for KIT genotyping in atypical acral nevi and to ascertain the frequency of KIT mutations in the same. DESIGN: Immunohistochemical staining for CKIT was performed and staining criteria were the following: negative = <10%, 1 = 11%-49%, and 2 = >50% of cells. Intensity grading was as follows: negative = 0, weak = 1, moderate = 2, and strong = 3. Genomic amplification was performed on KIT exons commonly mutated in acral melanomas (11, 13, and 17) from atypical acral nevi (23) ranging in severity from mild (9), moderate (10), and severe (4). The control group included acral nevi without atypia (19). For purposes of statistical analyses, cases with 11% or more staining of cells were compared with negative cases and cases with a staining intensity of 1 or higher were compared with the negatives. RESULTS: Immunohistochemical analyses revealed the following: positive staining with an intensity 1 or more in 18 of 22 (82%) of cases with atypia (5 mild; 9 moderate and 4 severe) and in 13 of 17 (76%) nevi without atypia with no statistically significant differences between both groups. Genomic analyses of exon regions revealed no abnormalities in "hotspots" frequently associated with point mutations in acral melanomas. CONCLUSIONS: Our findings indicate a lack of correlation between immunohistochemical expression of CKIT and KIT mutations in atypical acral nevi. Atypical acral nevi do not exhibit genetic alterations in KIT associated with acral melanomas.

Management of Inpatient Hyperglycemia and Diabetes in Older Adults.

Diabetes is one of the world's fastest growing health challenges. Insulin therapy remains a useful regimen for many elderly patients, such as those with moderate to severe hyperglycemia, type 1 diabetes, hyperglycemic emergencies, and those who fail to maintain glucose control on non-insulin agents alone. Recent clinical trials have shown that several non-insulin agents as monotherapy, or in combination with low doses of basal insulin, have comparable efficacy and potential safety advantages to complex insulin therapy regimens. Determining the most appropriate diabetes management plan for older hospitalized patients requires consideration of many factors to prevent poor outcomes related to dysglycemia.

Double hit! A unique case of resistant hypertension.

A middle-aged woman with obesity, hyperlipidaemia and diet-controlled diabetes was referred for resistant hypertension. Her blood pressure (BP) was uncontrolled on five medications, including a diuretic. Physical exam revealed a systolic ejection murmur, and ECHO demonstrated moderate hypertrophy. Laboratory examination revealed elevated aldosterone level (20.7 ng/dL) and elevated aldosterone:renin ratio (41.4 (ng/dL)/(ng/mL/h)), meeting criteria for primary aldosteronism (PA), and confirmed by saline infusion testing. CT scan of the adrenals was non-localising. Adrenal venous sampling confirmed bilateral idiopathic adrenal hyperplasia. Concurrent primary hyperparathyroidism was demonstrated by elevated calcium and parathyroid hormone levels and localised by sestamibi scan. Idiopathic adrenal hyperplasia was treated medically with spironolactone. Her BP remained elevated until postparathyroidectomy. Evidence shows that a hyperfunctioning parathyroid gland may contribute to maintaining hyperaldosteronism in PA making this bidirectional link unique. The significance of this case is in the potential for further understanding of the pathophysiology of common causes of secondary hypertension.

Homeless Individuals Approaching the End of Life: Symptoms and Attitudes.

CONTEXT: Over a million individuals in the United States experience homelessness annually and homeless individuals die at a higher rate than domiciled peers. Homeless individuals often have unique experiences at the end of life (EOL). OBJECTIVES: This study examined the symptoms experienced by homeless individuals nearing the EOL and explored social background, attitudes, and experiences. METHODS: Investigators conducted surveys of homeless individuals approaching the EOL at a medical respite home. Eligibility required a serious medical condition and for the patient's medical provider to answer "no" to the question "Would you be surprised if this patient were not alive in one year?" Interviews explored symptoms using the Memorial Symptom Assessment Survey. Symptoms were compared with those of relevant comparator groups in other studies. RESULTS: Participants (n = 20) were young to face the EOL (median age = 58) and suffered high rates of substance use disorders (n = 18; 90%) and psychiatric diagnoses (n = 16; 80%). Symptom frequency was high, especially as regarded pain and psychological symptoms. Previous experience with death among family and peers was universal (n = 20; 100%). Mistrust of others' decisions about the EOL was common, as was concern about receiving too little (n = 11; 55%) or too much (n = 8; 40%) care at the EOL. The frequency of symptoms was higher than in three comparator studies and those studies' subgroups (P < 0.01 for each comparison). CONCLUSION: Homeless individuals may experience a high frequency of pain and other symptoms as they approach the EOL. Care for such individuals may require a tailored approach.

Laser capture microdissection: methods and applications.

Laser microdissection is a nonmolecular, minimally disruptive method to obtain cytologically and/or phenotypically defined cells or groups of cells from heterogeneous tissues. It is a versatile technology and allows the preparation of homogenous isolates of specific subpopulations of cells from which RNA/DNA or protein can be extracted for RT-polymerase chain reaction (PCR), quantitative PCR, Western blot analyses, and mass spectrophotometry.

Oncogenic BRAF-positive dysplastic nevi and the tumor suppressor IGFBP7--challenging the concept of dysplastic nevi as precursor lesions?

Oncogenic BRAF as an early and fundamental feature of melanocytic neoplasia has been confirmed with its identification in both melanoma and nevi. Oncogenic BRAF has been shown to induce senescence/apoptosis by up-regulating the tumor suppressor IGFBP7, which acts through autocrine/paracrine pathways to inhibit BRAF-MEK-ERK signaling. Given the putative neoplastic potential of dysplastic nevi, our aim was to ascertain in dysplastic nevi from intermittently sun-exposed skin and of varying severity the frequency of oncogenic BRAF and NRAS and to assess expression of IGFBP7 in the same. BRAF and NRAS genotyping was performed on genomic DNA (isolated using laser capture microdissection) from dysplastic nevi ranging in severity from mild (12), to moderate (11), and to severe (11). Immunohistochemical staining for IGFBP7 was performed on all. Overall, 9 (26%) of 34 cases (2 severely atypical dysplastic nevi, 2 moderately atypical dysplastic nevi, and 5 mildly atypical dysplastic nevi) exhibited the BRAFV600E mutation (P = .22), with lack of IGFBP7 expression in 4 (44.4%) of 9 cases (1 severely atypical, 1 moderately atypical, and 2 mildly atypical); and 25 (73.5%) of 34 cases (9 severely atypical, 9 moderately atypical, and 7 mildly atypical) were BRAFWT, with enhanced IGFBP7 expression in 12 (48%) of 25 cases (6 severely atypical, 3 moderately atypical, and 3 mildly atypical). All cases were NRASWT. The disparate expression of IGFBP7 in BRAFV600E-positive dysplastic nevi (enhanced in 56% and diminished/absent in 44%) indicates that the behavior of oncogenic BRAF in dysplastic nevi, unlike that in malignant melanoma, does not appear to consistently induce senescence/apoptosis through pathways mediated by IGFBP7.