Parsaik, Ajay K.

Abstract Aims Lithium is Food and Drug Administration‐approved for bipolar disorder (BD) and is also used in depressive disorders but is underutilized due to concerns about chronic kidney disease (CKD). We explored clinical and demographic profiles of patients on long‐term lithium therapy (LTLT) and assessed kidney function. Our aims were to identify the predictors for CKD stage ≥3 and the impact of lithium discontinuation post‐CKD diagnosis. Methods We conducted a population‐based historical cohort study of adult patients with mood disorders on LTLT at the Marshfield Clinical Health System from 1990 to 2019. Data on lithium therapy and kidney‐related information (estimated glomerular filtration rate and CKD) were extracted from electronic medical records. Results Among 1603 patients with mood disorders (mean age 42.1 years, 60% females), 15.3% ( n = 246) developed CKD stage ≥3. Patients without CKD were on lithium for 4.5 years, compared to 6.6 years for those with CKD. Hypertension, age, and BD were significant CKD risk factors. Kidney function declined linearly with lithium duration, returning to pre‐treatment trajectory in patients without CKD but showed no improvement in those with CKD after lithium discontinuation. Conclusion The findings suggest that CKD occurs in 15% of patients with mood disorder receiving LTLT, with its progression potentially influenced by existing comorbidities rather than lithium alone. These results underscore the importance of monitoring kidney function in patients on LTLT and considering individual risk factors for CKD development. In patients who developed CKD, Li discontinuation did not impact change in kidney function.

Abstract Background Ketamine, a glutamate N-methyl-d-aspartate receptor antagonist, has shown rapid antidepressant effects in treatment-resistant depression. We conducted a systematic review of studies evaluating the efficacy of intravenous ketamine augmentation in treatment-resistant depression patients with bipolar disorder. Methods Major databases were searched for open-label and randomized controlled trials (RCT). Two independent reviewers screened and selected the studies that met the inclusion criteria. Studies were selected following the standard Cochrane methodology, and the findings are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Methodological quality of the included studies was assessed using standardized measures. Results A total of 1442 articles were screened. Five studies were included in the systematic review (3 RCTs and 2 open-label studies) enrolling 110 subjects (mean age, 45.54 ± 12.65 years; 68.18% female). All the RCTs and open-label studies showed improvement in depressions symptoms after receiving a single infusion of ketamine. Included studies also suggested improvement in suicidal ideation and anhedonia after ketamine infusion. Dissociation and transient increase in blood pressure were the most common reported adverse effects with ketamine. Ketamine infusions did not increase mania symptoms. Conclusions Limited data show efficacy and feasibility of intravenous racemic ketamine in treatment-resistant bipolar depression. Further studies with larger sample size are required to strengthen the evidence.

AbstractNeurological and autonomic presentation in multiple system atrophy (MSA) may predict early mortality. Quantification of early autonomic failure as a mortality predictor is lacking. Early neurological and autonomic clinical features were retrospectively reviewed in 49 MSA cases (median age at onset, 56.1 years; 16 women) confirmed by autopsy at Mayo Clinic. When available, the 10‐point composite autonomic severity score derived from the autonomic reflex screen provided quantification of the degree of autonomic failure and thermoregulatory sweat test quantitated body surface anhidrosis. Symptoms at onset were autonomic in 50%, parkinsonian in 30%, and cerebellar in 20% of cases. Survival (median [95% confidence interval]) was 8.6 [6.7‐10.2] years. Survival was shorter in patients with early laboratory evidence of generalized (composite autonomic severity score ≥ 6) autonomic failure (7.0 [3.9‐9.8] vs. 9.8 [4.6‐13.8] years; P = 0.036), and early requirement of bladder catheterization (7.3 [3.1‐10.2] vs. 13.7 [8.5‐14.9] years; P = 0.003) compared with those without these clinical features. On Cox proportional analysis, prognostic indicators of shorter survival were older age at onset (hazard ratio [95% confidence interval], 1.04 [1.01‐1.08]; P = 0.03), early requirement of bladder catheterization (7.9 [1.88‐38.63]; P = 0.004), and early generalized (composite autonomic severity score ≥ 6) autonomic failure (2.8 [1.01‐9.26]; P = 0.047). Gender, phenotype, and early development of gait instability, aid‐requiring ambulation, orthostatic symptoms, neurogenic bladder, or significant anhidrosis (thermoregulatory sweat test ≥ 40%) were not indicators of shorter survival. Our data suggest that early development of severe generalized autonomic failure more than triples the risk of shorter survival in patients with MSA. © 2014 International Parkinson and Movement Disorder Society

Objective: We evaluate the prevalence, etiology, and outcomes of hypoglycemia requiring emergency medical services (EMS) in patients without diabetes mellitus (non-DM). Methods: We reviewed medical records of all ambulance calls for non-DM with blood glucose <70 mg/dl in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2009. Results: A total of 131 patients (age 51 ± 19 years; 54 % females) made 142 EMS calls, while 10 patients made repeated calls. Causes of hypoglycemia were critical illness (42; 32%), alcohol and polysubstance use (36; 27.5 %), insulinoma/ bariatric surgery (10; 8%), restricted oral intake (7; 5%), and multiple factors (3; 27.5 %). Patients with alcohol and polysubstance abuse were younger ( p = .002). A total of 54 patients had additional hypoglycemia predisposing comorbidities/factors [adrenal insufficiency (2), end-stage renal disease (11) and chronic liver disease (7), beta blockers use (34), and pentamidine use (1)]. Repeated calls and emergency room transportation were similar, but hospitalization varied across the etiologies, with the lowest proportion in the multiple-factor-related hypoglycemia group ( p = .01). Duration of follow-up was 1.28 (interquartile range 0.13–2.70) years. A total of 38 patients died, and age-adjusted mortality varied across different etiologies ( p < .001), with highest among critically ill. Cancer caused the highest number of deaths (7/38; 18%), while 1 death was due to hypoglycemia. Conclusions: There were multiple etiologies for hypoglycemic episodes in community-dwelling non-DM that required EMS. Critical illness, multifactorial causes, and alcohol/polysubstance abuse were common causes. Hospitalization and mortality were higher with critical illnesses.

Objective: The objective is to report a contemporary population-based estimate of hypoglycemia requiring emergency medical services (EMS), its burden on medical resources, and its associated mortality in patients with or without diabetes mellitus (DM, non-DM), which will enable development of prospective strategies that will capture hypoglycemia promptly and provide an integrated approach for prevention of such episodes. Methods: We retrieved all ambulance calls activated for hypoglycemia in Olmsted County, Minnesota, between January 1, 2003 and December 31, 2009. Results: A total of 1473 calls were made by 914 people (DM 8%, non-DM 16%, unknown DM status 3%). Mean age was 60 ± 16 years with 49% being female. A higher percentage of calls were made by DM patients (87%) with proportionally fewer calls coming from non-DM patients (11%) (chi-square test, p < .001), and the remaining 2% calls by people with unknown DM status. Emergency room transportation and hospitalization were significantly higher in non-DM patients compared to DM patients ( p < .001) and type 2 diabetes mellitus compared to type 1 diabetes mellitus ( p < .001). Sulphonylureas alone or in combination with insulin varied during the study period ( p = .01). The change in incidence of EMS for hypoglycemia was tracked during this period. However, causality has not been established. Death occurred in 240 people, 1.2 (interquartile range 0.2–2.7) years after their first event. After adjusting for age, mortality was higher in non-DM patients compared with DM patients ( p < .001) but was not different between the two types of DM. Conclusions: The population burden of EMS requiring hypoglycemia is high in both DM and non-DM patients, and imposes significant burden on medical resources. It is associated with long-term mortality.

Background: Safe and effective glucose control in the intensive care unit (ICU) continues to be actively pursued. Large clinical trials have examined the safety and efficacy of insulin infusion protocols in medical and surgical ICUs. We report experiences of a single-center standardized nurse-driven insulin infusion protocol in three ICUs in an observational quality-improvement study. Method: We analyzed the hourly point-of-care arterial blood glucose obtained during ICU insulin infusion protocol (protocol A) with a glucose target of 80–130 mg/dl in medical and surgical ICUs in February 2009. Following Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study results, the protocol was amended (protocol B) to achieve target glucose of 110–150 mg/dl. The performance of protocol B was assessed in the ICUs in May 2010 and compared with protocol A with respect to glucose concentrations and rates of severe (<40 mg/dl) and moderate (40–60 mg/dl) hypoglycemia. Results: With protocol A, in medical ( n = 44) and surgical ( n = 164) ICUs taken together, median glucose was 119 mg/dl, with severe and moderate hypoglycemia rates 1.4% (3/208) and 7.7% (16/208), respectively, which were significantly lower than those reported by the NICE-SUGAR and the Leuven studies. With protocol B, in medical ( n = 44) and surgical ( n = 167) ICUs taken together, median glucose was 132 mg/dl, with severe and moderate hypoglycemia of 0 % (0/211) and 0.5% (1/211), respectively. Conclusion: The current ICU insulin infusion protocol (protocol B) reduces severe and moderate hypoglycemia without compromising glucose control when compared with protocol A. This could potentially impact patient-important outcomes.