A safety evaluation of aripiprazole in the treatment of schizophrenia.

INTRODUCTION: Aripiprazole is a third generation antipsychotic approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. Aripiprazole is available as oral and long-acting injectable (LAI) depot formulations, with a unique mechanism of action comprising partial D2 and serotonin 5-HT1A agonism and antagonism at serotonin 5-HT2A receptors. AREAS COVERED: We review short-and-long-term clinical trials, meta-analyses of clinical trials and product information pertaining to the safety and efficacy of aripiprazole in adults with schizophrenia. Formulations of aripiprazole reviewed include oral aripiprazole, Aripiprazole monohydrate LAI (Abilify Maintena©) and Aripiprazole lauroxil LAI (Aristada©). Clinical studies and product information were collected from PubMed, Psychinfo, Embase, and other web sources. EXPERT OPINION: Aripiprazole is a generally well-tolerated third-generation antipsychotic with low rates of motor side effects and metabolic adverse effects that occur commonly with several alternative antipsychotics. Akathisia and tremor appear to occur at higher rates with aripiprazole compared to placebo but are still generally uncommon with incidences of 10-11% or less. Uniquely, aripiprazole treatment is associated with reduced serum prolactin levels and QTc interval. A variety of LAI options with dosing intervals as infrequent as every 8 weeks provide a compelling reason to select aripiprazole in patients with limited oral treatment adherence.

Cryptococcal meningitis in a daily cannabis smoker without evidence of immunodeficiency.

Cryptococcal meningitis is a life-threatening condition most commonly observed in immunocompromised individuals. We describe a daily cannabis smoker without evidence of immunodeficiency presenting with confirmed Cryptococcus neoformans meningitis. An investigation of cannabis samples from the patient's preferred dispensary demonstrated contamination with several varieties of Cryptococcus, including C. neoformans, and other opportunistic fungi. These findings raise concern regarding the safety of dispensary-grade cannabis, even in immunocompetent users.

Quality of life and functioning of Hispanic patients with Major Depressive Disorder before and after treatment.

BACKGROUND: Similar rates of remission from Major Depressive Disorder (MDD) have been documented between ethnic groups in response to antidepressant treatment. However, ethnic differences in functional outcomes, including patient-reported quality of life (QOL) and functioning, have not been well-characterized. We compared symptomatic and functional outcomes of antidepressant treatment in Hispanic and non-Hispanic patients with MDD. METHODS: We analyzed 2280 nonpsychotic treatment-seeking adults with MDD who received citalopram monotherapy in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression study. All subjects (239 Hispanic, 2041 non-Hispanic) completed QOL, functioning, and depressive symptom severity measures at entry and exit. RESULTS: Hispanic participants had significantly worse QOL scores at entry and exit (p < 0.01). However, after controlling for baseline QOL, there was no difference between Hispanic and non-Hispanic patients' QOL at exit (p = 0.21). There were no significant between-group differences at entry or at exit for depressive symptom severity or functioning. Both groups had significant improvements in depressive symptom severity, QOL, and functioning from entry to exit (all p values < 0.01). Patients with private insurance had lower depressive symptom severity, greater QOL, and better functioning at exit compared to patients without private insurance. LIMITATIONS: This study was a retrospective data analysis, and the Hispanic group was relatively small compared to the non-Hispanic group. CONCLUSIONS: Hispanic and non-Hispanic participants with MDD had similar responses to antidepressant treatment as measured by depressive symptom severity scores, quality of life, and functioning. Nevertheless, Hispanic patients reported significantly worse quality of life at entry.

Hemodialysis treatment engenders anxiety and emotional distress
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AIMS: Anxiety is common in maintenance hemodialysis (MHD) patients. The extent to which anxiety is engendered by the dialysis treatment itself is not known. We investigated whether anxiety occurs with individual hemodialysis treatments and examined factors associated with these symptoms. MATERIALS AND METHODS: This was a cross-sectional study examining 246 MHD patients. Anxiety and other emotional distresses associated with hemodialysis treatments were examined with a questionnaire. Patients were also assessed with the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). RESULTS: Patients were 57 ± 15 (SD) years; 58% male, 46% diabetic, and undergoing MHD for a median of 40 months (range: 6 - 210 months). 32 - 51% of patients reported anxiety when coming to dialysis, hearing an alarm sound, being connected to the dialysis machine by a new person or seeing paramedics in the dialysis unit. 12 - 18% of patients experienced severe anxiety with one or more of these events. Dialysis-related anxiety correlated with severity of anxiety and depression as determined by BAI and BDI (p < 0.0001 for each comparison) but generally not with dialysis vintage. Even among patients with no or minimal anxiety according to BAI, 9 - 23% reported a little bit to moderate anxiety and 9 - 15% described quite a bit to extreme anxiety with hemodialysis treatments. The frequency that patients described distressing thoughts and feelings correlated directly with their degree of anxiety or depression as determined by BAI and BDI. CONCLUSION: Patients commonly experience anxiety, which is often severe, with MHD treatments. Hemodialysis-induced anxiety is directed related to the presence and severity of underlying anxiety and depression. Hemodialysis-associated anxiety is prevalent and may be severe even in patients with minimal or no anxiety and/or depression, as determined by BAI and BDI. The frequency and severity of hemodialysis anxiety does not decrease with greater dialysis vintage except for a reduction in anxiety when hearing the dialysis machine alarm.
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Dietary energy requirements in relatively healthy maintenance hemodialysis patients estimated from long-term metabolic studies.

BACKGROUND: Studies that examined dietary energy requirements (DERs) of patients undergoing maintenance hemodialysis (MHD) have shown mixed results. Many studies reported normal DERs, but some described increased energy needs. DERs in MHD patients have been estimated primarily from indirect calorimetry and from nitrogen balance studies. The present study measured DERs in MHD patients on the basis of their dietary energy intake and changes in body composition. OBJECTIVE: This study assessed DERs in MHD patients who received a constant energy intake while changes in their body composition were measured. DESIGN: Seven male and 6 female sedentary, clinically stable MHD patients received a constant mean (±SD) energy intake for 92.2 ± 7.9 d while residing in a metabolic research ward. Changes in fat and fat-free mass, measured by dual-energy X-ray absorptiometry, were converted to calorie equivalents and added to energy intake to calculate energy requirements. RESULTS: The average DER was 31 ± 3 kcal · kg(-1) · d(-1) calculated from energy intake and change in fat and fat-free calories, which was 28 ± 197 kcal/d over the 92 d of the study. DERs of MHD patients correlated strongly with their body weight (r = 0.81, P = 0.002) and less closely with their measured resting energy expenditure expressed as kcal/d (r = 0.69, P = 0.01). Although the average observed DER in MHD patients was similar to published estimated values for normal sedentary individuals of similar age and sex, there was wide variability in DER among individual patients (range: 26-36 kcal · kg(-1) · d(-1)). CONCLUSIONS: Average DERs of sedentary, clinically stable patients receiving MHD are similar to those of sedentary normal individuals. Our data do not support the theory that MHD patients have increased DERs. Due to the high variability in DERs, careful monitoring of the nutritional status of individual MHD patients is essential. This trial was registered at clinicaltrials.gov as NCT02194114.

Association of Height with Mortality in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Body mass index (BMI), determined as kilograms in body weight divided by the square of the height in meters (m(2)), is inversely associated with mortality in patients undergoing maintenance hemodialysis (MHD). It is commonly inferred that differences in the weight component of the BMI equation are responsible for this negative correlation. However, there are almost no data on the relationship between height and mortality in these patients. This study was conducted to examine the association between height and mortality in MHD patients and to evaluate the contribution of height to the BMI-mortality relationship. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective study conducted from July 1, 2001, through June 30, 2006, enrolled a nationally representative cohort of 117,644 MHD patients receiving treatment in DaVita, Inc. outpatient dialysis facilities with (1) known height and weight, (2) age ≥18 years, (3) dialysis vintage ≥90 days, and (4) nonoutlying BMI values (≥12 to ≤60 kg/m(2)). The end date of follow-up was June 30, 2007, and median follow-up was 852 days (interquartile range, 504-1367 days). Mortality hazard ratios were computed within sex-standardized deciles of height and weight, and outcomes included all-cause mortality and cardiovascular, gastrointestinal, cancer, and infection mortality. Hazard models were unadjusted, adjusted for case-mix variables, or adjusted for case-mix variables plus laboratory variables. RESULTS: Mean age was 61±15 years; 45% of patients were women and 57% had diabetes. In adjusted models, height, also adjusted for weight, was directly associated with all-cause mortality and cardiovascular, infection, and cancer mortality. Compared with the median height decile, mortality risk in the highest height decile was 1.18 (95% confidence interval, 1.14 to 1.23) in fully adjusted analyses (P<0.001). Receiver-operating characteristic curves indicated that in adjusted analyses the contribution of height to the relationship between BMI and mortality was almost identical to that of weight. CONCLUSIONS: In MHD patients, height is positively associated with mortality risk and contributes similarly to weight with regard to the negative BMI-mortality relationship.

Factors affecting daily physical activity and physical performance in maintenance dialysis patients.

Maintenance hemodialysis (MHD) patients display reduced daily physical activity (DPA) and physical performance (PP). Previous studies did not differentiate the effects of kidney failure and MHD treatments from comorbidities as causes for reduced DPA and PP. In relatively healthy MHD patients and normal adults, we evaluated DPA and PP and examined relationships between DPA and PP and possible associations between anxiety or depression and DPA and PP. DPA, 6-minute walk distance (6-MWD), sit-to-stand (STS), and stair-climbing tests were measured in 72 MHD patients (40% diabetics) with limited comorbidities and 39 normal adults of similar age and gender mix. Anxiety and depression were measured by the Beck anxiety and depression inventories. DPA, time-averaged over 7 days, and all 3 PP tests were impaired in MHD patients, to about 60% to 70% of normal values (P < .0001 for each measurement). MHD patients spent more time sleeping or physically inactive (P < .0001) and less time in ≥ moderate activity (P < .0001). Adjusted DPA correlated with 6-MWD but not STS or stair-climbing. Anxiety and depression were identified in 43% and 33% of MHD patients and 2.5% and 5.1% of normals (P < .0001 for each comparison). Most of the impairment in DPA and PP tests were also observed in MHD patients without anxiety or depression. However, MHD patients with both anxiety and depression generally had the most impaired DPA and PP. In MHD patients, higher adjusted anxiety scores were correlated with impaired 6-MWD and STS, whereas adjusted average DPA was negatively correlated with depression (r = -0.33, P = .006) but not anxiety. DPA on the hemodialysis day (P = .01), day after dialysis (P = .03), and day 2 after dialysis (P = .03) each correlated negatively with degree of depression but not with anxiety. MHD patients displayed negative-adjusted correlations between anxiety and 6-MWD (P = .03) and STS (P = .04). In relatively healthy MHD patients, DPA and PP are substantially impaired and correlated with each other, even in patients without evidence for anxiety or depression. Anxiety and depression are common in MHD patients and are associated with further impairment in DPA and PP.

Self-Reported Interview-Assisted Diet Records Underreport Energy Intake in Maintenance Hemodialysis Patients.

OBJECTIVES: Studies suggest that maintenance hemodialysis (MHD) patients report dietary energy intakes (EIs) that are lower than what is actually ingested. Data supporting this conclusion have several important limitations. The present study introduces a novel approach of assessing underreporting of EI in MHD patients. DESIGN: Comparisons of EI of free-living MHD patients determined from food records to their measured energy needs. SETTING: Metabolic research ward. SUBJECTS: Thirteen clinically stable MHD patients with unchanging weights whose EI was assessed by dietitian interview-assisted 3-day food records. INTERVENTION: EI was compared with (1) patients' resting energy expenditure (REE), measured by indirect calorimetry, and estimated total energy expenditure (TEE) and (2) patients' dietary energy requirements (DER) measured while patients underwent nitrogen balance studies and consumed a constant energy diet in a research ward for a mean duration of 89.5 days. DER was calculated as the actual EI during the research study corrected for changes in body fat and lean body mass measured by Dual X-Ray Absorptiometry. MAIN OUTCOME MEASURE: Underreporting of EI was determined by an EI:REE ratio <1.27 and an EI:TEE ratio or EI:DEE ratio <1.0. RESULTS: Seven of the 13 MHD patients studied were male. Patient's ages were 47.7 ± standard deviation 9.7 years; body mass index averaged 25.4 ± 2.8 kg/m2, and dialysis vintage was 53.3 ± 37.1 months. The EI:REE ratio (1.03 ± 0.23) was significantly less than the cutoff value for underreporting of 1.27 (P = .001); 12 of 13 patients had EI:REE ratios <1.27. The mean EI:TEE ratio was significantly less than the cutoff value of 1.0 (0.73 ± 0.17, P < .0001), and 12 MHD patients had EI:TEE ratios <1.0. The EI:DER ratio was also <1.0 (0.83 ± 0.25, P = .012), and 10 MHD had EI:DER ratios <1.0. CONCLUSIONS: Dietitian interview-assisted diet records by MHD patients substantially underestimate the patient's dietary EI.

The relationship between ultraviolet light exposure and mortality in dialysis patients.

BACKGROUND: Emerging data suggest that reduced exposure to ultraviolet (UV) radiation is associated with increased mortality in the general population. To date, the association between UV exposure and mortality in dialysis patients has not been examined. METHODS: We examined the association between UV index, a proxy of UV exposure, and all-cause mortality among 47,286 US dialysis patients (entry period 2001-2006, with follow-up through 2009) from a large national dialysis organization using multivariable Cox regression. The UV index was ascertained by linking individual patients' residential zip codes to National Oceanic and Atmospheric Administration data, and was categorized as low (0-<3), moderate (3-<5), moderate-high (5-<6), high (6-<7), and very-high (≥7). In secondary analyses, we examined the UV index-mortality association within subgroups of age (<65 vs. ≥65 years old), sex, and race (white vs. non-white). RESULTS: The study population's mean ± SD age was 60 ± 16 and included 46% women and 56% diabetics. Compared to patients residing in moderate-high UV index regions, those residing in high and very-high UV index regions had a lower mortality risk: adjusted HRs 0.84 (95% CI) 0.81-0.88 and 0.83 (95% CI) 0.75-0.91, respectively. A similar inverse association between UV index and mortality was observed across all subgroups, although there was more pronounced reduction in mortality among whites vs. non-whites. CONCLUSION: These data suggest that dialysis patients residing in higher UV index regions have lower all-cause mortality compared to those living in moderate-high UV regions. Further studies are needed to determine the mechanisms underlying the UV index-mortality association.

Relation between anxiety, depression, and physical activity and performance in maintenance hemodialysis patients.

OBJECTIVE: Maintenance hemodialysis (MHD) patients have a high prevalence of anxiety and depression and decreased daily physical activity (DPA) and exercise capacity. Because affective disorders may affect DPA and physical performance, we investigated possible relationships between anxiety or depression and DPA and physical performance in relatively healthy MHD patients. DESIGN AND METHODS: This cross-sectional study included 72 relatively healthy MHD patients and 39 normal adults. DPA was measured for 7 days with an Actigraph Activity Monitor®. Physical performance was assessed using the 6-minute walk (6-MWT), sit-to-stand (STS), and stair-climbing tests. Subjects completed the Beck Anxiety Inventory (BAI), the Beck Depression Inventory-II (BDI), and the Hospital Anxiety and Depression Scale (HADS). Main outcome measures were physical activity counts (expressed as vector magnitude), in the 6-MWT, STS, stair-climbing test, BAI, BDI, and HADS scores. RESULTS: Anxiety and depression by BAI and BDI were identified in 43% and 33% of MHD patients and 2.5% and 5% of normals, respectively (P < .0001 for each comparison). MHD patients without anxiety or depression had decreased DPA and physical performance compared with normals, indicating that these disorders were also independent of anxiety or depression. MHD patients with anxiety and depression generally had the most impaired DPA and physical performance. Higher BAI and BDI scores were each associated with impaired physical performance. In fully adjusted analyses, DPA in MHD patients was negatively correlated with the BDI (r = -0.33, P = .01) but not with the BAI. DPA on the day of hemodialysis (P = .01), and day 1 (P = .03) and day 2 (P = .03) after dialysis each correlated negatively with degree of depression by BDI. In MHD patients, BAI was negatively correlated with 6-MWT (P = .03) and STS (P = .04). CONCLUSIONS: In relatively healthy adult MHD patients, anxiety and depression are common and are associated with impaired physical performance. There was a trend toward stronger negative associations between BDI scores and DPA than between BAI scores and DPA.

Revisiting the association between altitude and mortality in dialysis patients.

It was recently reported that residential altitude is inversely associated with all-cause mortality among incident dialysis patients; however, no adjustment was made for key case-mix and laboratory variables. We re-examined this question in a contemporary patient database with comprehensive clinical and laboratory data. In a contemporary 8-year cohort of 144,892 maintenance dialysis patients from a large dialysis organization, we examined the relationship between residential altitude and all-cause mortality. Using data from the US Geological Survey, the average residential altitudes per approximately 43,000 US zip codes were compiled and linked to the residential zip codes of each patient. Mortality risks for these patients were estimated by Cox proportional hazard ratios. The study population's mean ± standard deviation age was 61 ± 15 years. Forty-five percent of patients were women, and 57% of patients had diabetes. In fully adjusted analysis, those residing in the highest altitude strata (≥ 6000 ft) had a lower all-cause mortality risk in fully adjusted analyses: death hazard ratio: 0.92 (95% confidence interval, 0.86-0.99), as compared with patients in the reference group (<250 ft). Residential altitude is inversely associated in all-cause mortality risk in maintenance dialysis patients notwithstanding the unknown and unmeasured confounders.