Total Daily Dose Research Articles

The effect of neuromuscular electrical stimulation on serum glucose levels in children and adolescents with type-1 diabetes mellitus: a single group clinical trial

BackgroundThis study aimed to evaluate the effect of Neuromuscular Electrical Stimulation (NMES) on serum glucose level in children and adolescents with type-1 diabetes.MethodsThis before-after, single-group, clinical trial was conducted on 29 patients with type-1 diabetes mellitus with the age range of 7–18 years. The patients underwent NMES in two 20-minute phases on the quadriceps and hamstrings muscles, three sessions per week for a period of 8 weeks. Fasting Blood Sugar (FBS), measured in two ways, by glucometer and laboratory testing, was considered as the primary outcome and the glycated hemoglobin (HbA1c) and the total daily dose (TDD) of insulin were measured as the secondary outcomes. The laboratory FBS and HbA1c were measured 1 day before the intervention (as a baseline value) and then 2 and 6 weeks after the last session of intervention. FBS by glucometer and total daily dose of insulin were recorded daily from 2 weeks before the intervention to the last day of the intervention and consequently, the weekly average of these variables was calculated and used for statistical analysis.ResultsThe serum level of FBS (measured by glucometer) and the total daily dose of insulin reduced significantly 2 weeks after beginning of intervention. The laboratory serum level of FBS decreased significantly in the second week after the end of intervention compared to the baseline values. Although the HbA1c level decreased at follow-up period (2 and 6 weeks after the intervention), it was not significant.ConclusionIt seems that 8 weeks of NMES has beneficial effects on the reduction of FBS and TDD of insulin therefore, it could be suggested as the contributory treatment in management of children and adolescents with type-1 diabetes.Trial registrationThe study was registered at https://fa.irct.ir/user/trial/51739/view (IRCT20100523003998N1) in date of 25/10/2020.

MPN-141 Retrospective Comparison of Patient Outcomes on Pacritinib Versus Ruxolitinib in Patients With Myelofibrosis and Thrombocytopenia.

Pacritinib (PAC) is a JAK2/IRAK1 inhibitor for patients with myelofibrosis (MF) and thrombocytopenia. Unlike the JAK1/2 inhibitor ruxolitinib (RUX), which is used at lower doses in patients with thrombocytopenia, PAC has been studied at full dose regardless of platelet count. This analysis focused on PERSIST-2 patients with platelet counts ≤100 × 109/L who were randomized to PAC 200mg BID and patients who received RUX on best available therapy (BAT) prior to week 24. Endpoints included percent of patients with 35% spleen volume reduction (SVR), 50% modified total symptom score (mTSS) reduction (based on early satiety, abdominal discomfort, night sweats, itching, bone pain, and rib pain), and improvement in disease symptoms measured by Patient Global Impression of Change (PGIC). Safety analyses were based on all treated patients; efficacy analyses were based on the intention-to-treat population randomized at least 22 weeks prior to study end. The Fisher Exact test was used to describe differences in response. Logistic and Cox regression was used to adjust for differences in baseline characteristics. Safety analysis included 106 patients on PAC and 44 on RUX; efficacy analysis included 74 on PAC and 32 on RUX (median total daily dose 10 mg). Baseline characteristics were similar between groups, including median platelet count (55 vs 61 × 109/L) and percent receiving RBC transfusion (46% vs 43%). Patients treated with PAC vs RUX achieved higher rates of SVR (22% vs 3%, p=0.02) and numerically higher rates of mTSS response (35% vs 19%; p=0.11) and "much" or "very much" improved symptoms (35% vs 16%, p=0.06) at week 24. Among RUX patients with an available PGIC measure at week 24, 50% reported either no improvement or worsening symptoms, while 76% of PAC patients reported improvement. The adjusted hazard ratio on PAC vs RUX was 0.46 [95% CI: 0.15-1.43]. Bleeding occurred at similar rates (43% vs 41%) on PAC vs RUX. Fatal AEs occurred in 8% on PAC compared to 11% on RUX. PAC yielded higher response rates and a similar safety profile to lower-dose RUX in patients with MF who have moderate or severe thrombocytopenia. This study was supported by CTI BioPharma.

Comparison between two methods of intravenous titration of morphine: Optimizing BI mode of patient-controlled analgesia versus conventional method.

204 Background: The titration of opioids to the optimal dose without side effects is an important and essential gateway in cancer pain management. However, sufficient pain control may not be achievable until the titration is complete because the change in the dose of opioids is calculated based on the opioid demand over the previous 24 hours. A recent patient-controlled analgesia (PCA) device could perform in an optimizing B.I. mode in which the background infusion rate was adjustable in accordance with the patient’s use of a bolus button. Therefore, we aimed to compare the efficacy and safety of the conventional method and the optimizing B.I. method of PCA in the titration of intravenous morphine in patients with cancer pain. Methods: This was a prospective, randomized, open-label, active-controlled study. After randomization, the previously administered opioids were switched to intravenous morphine and dose titration was initiated. In the conventional group, the dosage of continuous infusion morphine over the next day was adjusted based on the total amount of morphine administered during the previous 24 hours. In the PCA group, morphine titration was performed by increasing or decreasing the background infusion rate immediately in accordance with the frequency and interval of pressing the bolus button. The patients received pain management in this manner for at least three days and we compared the two groups by collecting their pain-related outcomes via medical records and questionnaires. Results: A total of 39 patients were enrolled, of whom 20 were assigned to the conventional group and 19 to the PCA group. The number of breakthrough pain complaints (NRS ≥ 4) by patients to the medical staff decreased in the PCA group, showing a difference from the conventional group within 24 hours (p = 0.012). The total daily dose of morphine was increased significantly at 0–24 hours in the PCA group (p < 0.001) and then slightly increased until 72 hours. The patient-reported pain reduction rate increased at 24–48 hours (p = 0.022) and was maintained until 72 hours in the PCA group. There was no statistically significant change in the conventional group during the study period for the above items. The conversion rate to oral or transdermal opioids after 72 hours was higher in the PCA group (p = 0.010). There were no uncontrolled side effects due to morphine titration in either group. Conclusions: Patients using the PCA with optimizing B.I. mode showed faster intravenous morphine titration and higher morphine consumption than the conventional method and achieved tolerable and rapid pain relief. This study revealed that early active opioid titration is necessary for patients admitted for pain control. It also suggested that the patient's actual opioid demands for pain control may be greater than the amount of opioid used through conventional titration methods. Clinical trial information: KCT0004008.

Out-of-pocket costs for oral anticancer drugs.

14 Background: Oral anticancer drug annual out-of-pocket costs (OOPCs) for Medicare beneficiaries are frequently > $10,000. Many of these medications are available as multiple formulations (e.g., tablet/capsule) and multiple strengths (e.g., 25mg/50mg). Oral medications are typically priced per unit (pill), allowing for more cost-effective prescribing when patients use fewer pills to obtain a recommended dose. It is unclear whether cancer drugs follow this traditional paradigm. We sought to assess the relationship between drug formulation features and OOPCs. Methods: We included 20 oral anticancer drugs with the highest spending in Medicare Part D in 2020. For each drug, we identified formulations, strengths, and schedules using NCCN guidelines and UptoDate. For each product, we calculated a lowest expected annual drug OOPC for all relevant strengths/schedules using the 2022 Part D Plan Finder. For example, the drug osimertinib is available in 40 and 80 mg tablets, with total daily doses of 80 and 160mg, reflecting 4 pricing scenarios. We assessed costs for 1 year of monthly fills. We compared cost ratios across formulations for each drug. Results: Of the 20 drugs, 17 (85%) were available as brand-name only; 3 (15%) were also available as generic. Fifteen (75%) were available as a single formulation only (e.g., tablet only); 5 (25%) were available as multiple formulations (e.g., tablet and capsule). Eighteen (90%) were available in multiple strengths. Median annual drug OOPCs was $12,979. For brand vs generic comparisons (n = 4, keeping other variables constant, 1 drug could have > 1 comparison due to different strengths), brand coverage for imatinib and 250 mg abiraterone tablets was limited, leading to high cost ratios (brand/generic > 50). For 2 other comparisons, the brand was less costly (abiraterone 500 mg tablets, ratio 0.85) and more costly (everolimus 10 mg tablets, ratio 1.18) for 1 each. For tablet vs capsules/others (n = 4), tablets were cheaper for 2 (ratio, 0.63- 0.96), a little more costly for 1 (ratio 1.04), and a lot more costly for 1 (ratio 2.13, ibrutinib 140 mg). For comparisons across strengths of the same formulation to achieve the same total dose (n = 14), using lower strength/higher fill quantity was more costly for 10 drugs (median ratio 1.79), the same for 1, and less costly for 3 (ratios 0.35- 0.89). Conclusions: Even when considering the least costly Part D plan, 2022 oral anticancer drug OOPCs remain high. Counter to expectations, in some cases generics were more costly than brands, and more pills at a lower dose were less costly than fewer pills. There was no consistent pattern. Oncologists and pharmacists cannot be expected to know the unpredictable OOPC ramifications of biologically equivalent prescription decisions. As cancer primarily affects older adults, often living on fixed incomes, policy-level change to lower OOPCs are necessary to avoid financial ruin and enhance access for Medicare beneficiaries.

S775 Major Cardiovascular Adverse Events by Baseline Cardiovascular Risk Stratification in Patients With Ulcerative Colitis Treated With Tofacitinib: Data From the OCTAVE Clinical Program

S775 Major Cardiovascular Adverse Events by Baseline Cardiovascular Risk Stratification in Patients With Ulcerative Colitis Treated With Tofacitinib: Data From the OCTAVE Clinical Program

Insulin edema after initiation of hybrid closed-loop insulin pump therapy with continuous glucose monitoring: a case report

BackgroundInsulin edema is a rare complication which can present after initiation or intensification of insulin therapy in people with diabetes. Initiation of closed-loop hybrid insulin pump therapy can result in rapid improvement in glycemic control for people with diabetes. We present a case in which transition to a closed-loop hybrid insulin pump system, followed by significant improvement in glycemic control, led to development of insulin edema in a person with type 1 diabetes.Case presentationWe present a 51-year-old woman with type 1 diabetes of 16 years duration, on insulin pump therapy for more than 10 years, who presented for follow-up 7 weeks after transitioning to a hybrid closed-loop insulin pump system with continuous glucose monitoring (CGM). She complained of weight gain and bilateral lower extremity edema which had started two weeks after the change in pump modality. Laboratory studies and echocardiogram did not reveal any etiology of the acute edema. HbA1c was 3.3% lower than the previous measurement 15 weeks earlier, and there was a significant increase in the daily total insulin dose. With exclusion of other causes of acute edema, the patient was diagnosed with insulin edema and started on hydrochlorothiazide. On follow up, her lower extremity edema significantly improved although her weight did not return to baseline.ConclusionTo our knowledge, this is the first case of insulin edema reported in a person with type 1 diabetes using CGM and a hybrid closed-loop insulin pump system. The increase in total daily insulin dose, rapid improvement of glycemic control, and lack of hypoglycemic episodes were important factors to consider in evaluation of this case. Use of hybrid closed-loop systems can help achieve rapid improvement in glycemic control in people with diabetes. This case suggests that consideration should be given to adjusting initial blood glucose targets when starting these remarkable new technologies in people with baseline poor glycemic control.

Glycemic Outcomes of Hospitalized Patients on Ambulatory Humulin-R U-500 Insulin

ObjectiveManaging hospitalized patients on ambulatory U-500 insulin is challenging because of limited guidance on how to safely adjust insulin doses during admission. We sought to evaluate glycemic outcomes in relation to inpatient insulin doses in patients receiving U-500 prior to hospitalization. MethodsRetrospective study of hospitalized patients on ambulatory U-500 seen consecutively from January 2015 to December 2019. Primary outcomes were inpatient hypoglycemia, hyperglycemia, and normoglycemia at different insulin dosages expressed as weight-based (unit/kg/d) inpatient total daily dose (TDD) and ratio of inpatient to outpatient TDD. ResultsWe identified 66 admissions of 46 unique patients. The median (interquartile range) body mass index was 41.0 kg/m2 (35.1, 46.8), home TDD 212 units (120, 300), and home insulin dose 1.6 units/kg/d (1.1, 2.2). The median (interquartile range) inpatient insulin dose was 0.7 unit/kg/d (0.3, 1.0) and the ratio of inpatient to outpatient TDD was 0.4 (0.2, 0.8). Hyperglycemia persisted throughout the hospitalization. For the outcomes of hyperglycemia and normoglycemia, we found no association between increased levels of insulin dosages. For the outcome of hypoglycemia, significantly higher odds were observed when non-fasting patients received an inpatient TDD that was either > 40% of their home TDD or > 0.6 unit/kg/d of insulin. ConclusionPatients on ambulatory U-500 have significant hyperglycemia during admission. Inpatient insulin doses of 40% of home TDD or ≤ 0.6 unit/kg were not associated with increased hypoglycemia risk. Further prospective studies are needed to determine effective doses in these high-risk patients.

Medical cannabis for the treatment of comorbid symptoms in children with autism spectrum disorder: An interim analysis of biochemical safety.

Background: Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder and no effective treatment for the core symptoms is currently available. The present study is part of a larger clinical trial assessing the effects of cannabis oil on autism co-morbidities. Objectives: The aim of the present study was to assess the safety of a CBD-rich oil treatment in children and adolescents with ASD. Methods: Data from 59 children and young adults (ages 5–25 years) from a single-arm, ongoing, prospective, open-label, one center, phase III study was analyzed. Participants received the Nitzan Spectrum® Oil, with cannabis extracts infused in medium chain triglyceride (MCT) oil with a cannabidiol:THC ratio of 20:1, for 6 months. Blood analysis was performed before treatment initiation, and after 3 months. Complete blood count, glucose, urea, creatinine, electrolytes, liver enzymes (AST, ALT, gamma glutamyl transferase), bilirubin, lipid profile, TSH, FT4, thyroid antibodies, prolactin, and testosterone measurements were performed at baseline, prior to starting treatment and at study midpoint, after 3 months of treatment. Results: 59 children (85% male and 15% female) were followed for 18 ± 8 weeks (mean ±SD). The mean total daily dose was 7.88 ± 4.24 mg/kg body weight. No clinically significant differences were found in any of the analytes between baseline and 3 months follow up. Lactate dehydrogenase was significantly higher before treatment (505.36 ± 95.1 IU/l) as compared to its level after 3 months of treatment (470.55 ± 84.22 IU/L) (p = 0.003). FT4 was significantly higher after 3 months of treatment (15.54 ± 1.9) as compared to its level before treatment (15.07 ± 1.88) (p = 0.03), as was TSH [(2.34 ± 1.17) and (2.05 ± 1.02)] before and after 3 months of treatment, respectively (p = 0.01). However, all these values were within normal range. A comparison of the group with additional medications (n = 14) to those who received solely medical cannabis (n = 45) showed no difference in biochemical analysis, including liver enzymes, which remained stable, except for change in potassium level which was significantly higher in the group that did not receive additional medications (0.04 ± 0.37) compared to the group receiving concomitant drug therapy (-0.2 ± 0.33) (p = 0.04). A comparison of patients who received a high dose of the cannabis oil (upper quartile-16 patients), with those receiving a low dose (lower quartile—14 patients) showed no significant difference between the two groups, except for the mean change of total protein, which was significantly higher among patients receiving high dose of CBD (0.19 ± 2.74) compared to those receiving a low dose of CBD (1.71 ± 2.46 (p = 0.01), and mean change in number of platelets, that was significantly lower among patients who received high dose of CBD (13.46 ± 31.38) as compared to those who received low dose of CBD (29.64 ± 26.2) (p = 0.0007). However, both of these changes lack clinical significance. Conclusion: CBD-rich cannabis oil (CBD: THC 20:1), appears to have a good safety profile. Long-term monitoring with a larger number of participants is warranted.

Evaluation of Levetiracetam Dosing Strategies for Seizure Prophylaxis Following Traumatic Brain Injury.

Although levetiracetam has been increasingly used as an alternative to phenytoin for early posttraumatic seizure prophylaxis following traumatic brain injury (TBI), an optimal dosing strategy has not been elucidated. The objective of this study is to determine whether different dosing strategies of levetiracetam are associated with the incidence of early posttraumatic seizures when used as prophylaxis following TBI. This retrospective single-center cohort study included admitted patients ≥ 18years of age with a diagnosis of TBI and receiving levetiracetam for early posttraumatic seizure prophylaxis between July 1, 2013, and September 1, 2019. The primary outcome of this study was to evaluate three different dosing strategies of levetiracetam (≤ 1000mg/day, 1500mg/day, and ≥ 2000mg/day) and associated rates of early posttraumatic seizures. Secondary outcomes were to summarize absolute total daily maintenance doses of levetiracetam among patients who experienced early posttraumatic seizures compared with those who did not, to determine the impact of three different dosing strategies on hospital length of stay and in-hospital mortality, and to assess patient-specific variables on the occurrence of posttraumatic seizures. Overlap propensity score weighting was used to address the potential for confounding. Of the 1287 patients who received levetiracetam for early posttraumatic seizure prophylaxis during the study time frame, 866 patients met eligibility criteria and were included in the study cohort (289 patients in the ≤ 1000mg/day group, 137 patients in the 1500mg/day group, and 440 patients in the ≥ 2000mg/day group). After weighting, the cumulative incidence of early posttraumatic seizure was 2.9% in the ≤ 1000mg/day group, 8.8% in the 1500mg/day group, and 9% in the ≥ 2000mg/day group. The 1500mg/day and ≥ 2000mg/day levetiracetam groups had a 209% and 216% increase in the subdistribution hazard of early posttraumatic seizures compared with the ≤ 1000mg/day levetiracetam group, respectively, but these differences were not statistically significant. In conclusion, the results of this study demonstrate no statistically significant difference in the cumulative incidence of early posttraumatic seizures within 7days of TBI between three different levetiracetam dosing strategies. After weighting, the ≤ 1000mg/day levetiracetam group had the lowest rates of early posttraumatic seizures, death without seizure, and in-hospital mortality.

Evaluation of Vancomycin Accumulation in Patients With Obesity

BackgroundCurrent vancomycin guidelines recommend early and frequent area-under-the-curve monitoring in patients with obesity. Vancomycin's volume of distribution is likely altered in patients with obesity, which may result in lower serum concentrations initially but lead to accumulation with continued use. The objective of this study was to evaluate the incidence of vancomycin accumulation in patients with obesity and identify potential factors associated with accumulation.MethodsThis was a single-center, retrospective, observational study at a tertiary academic medical center. Adult patients with a body mass index (BMI) ≥ 30 kg/m2 and ≥ 2 vancomycin serum trough concentrations drawn in 2019 were screened for inclusion. The major endpoint was the incidence of vancomycin accumulation defined as ≥ 20% increase in trough concentration within the first 10 days of therapy. Key minor endpoints included incidence of acute kidney injury (AKI) and factors associated with accumulation.ResultsOf the 443 patients screened, 162 were included. The median age was 56.5 years (interquartile range [IQR], 43–65.3), and 62.3% were male. The median weight was 112.7 kg (IQR, 99.8–122.6) and the median BMI was 36.8 kg/m2 (IQR, 33.1–41). The total daily dose median at initiation was 28.7 mg/kg per day (IQR, 25.4–31.2). Accumulation occurred in 99 of 162 patients (61.1%) and AKI occurred in 20 of 140 patients (14.3%). No specific factors were found to be associated with accumulation.ConclusionsPatients with obesity are likely to experience vancomycin accumulation within the first 10 days of therapy. Clinicians should use frequent monitoring of vancomycin and use caution when interpreting early concentrations in patients with obesity.

Population pharmacokinetics of everolimus in adult liver transplant patients: Comparison to tacrolimus disposition and extrapolation to pediatrics.

Everolimus has recently been used to prevent graft rejection in liver transplantation and reduces the incidence of kidney dysfunction caused by calcineurin inhibitors. In this study, a population pharmacokinetic analysis was conducted to improve the individualization of everolimus therapy. Japanese post-liver transplant patients whose blood everolimus concentrations were measured between March 2018 and December 2020 were included in this study. A nonlinear mixed-effect modeling program was used to explore covariates that affect everolimus pharmacokinetics. Individual everolimus pharmacokinetic parameters estimated by the post-hoc Bayesian analysis using the final model were compared with the tacrolimus dose per trough concentration (D/C) ratio in each patient. The final model was extrapolated to pediatric liver transplant patients for external evaluation. A total of 937 concentrations from 87 adult patients were used in the model-building process. Everolimus clearance was significantly affected by the estimated glomerular filtration rate, concomitant use of fluconazole, sex, as well as total daily dose of everolimus (TDM effect). The estimated individual apparent clearance of everolimus by the post-hoc Bayesian analysis was moderately correlated with the D/C ratio of tacrolimus in each patient (R2 =0.330, p < 0.0001). The estimation accuracy in pediatric patients was considerably high, except for one infant out of 13 patients. In conclusion, population pharmacokinetic analysis clarified several significant covariates for everolimus pharmacokinetics in liver transplant patients. Everolimus pharmacokinetics moderately correlated with tacrolimus pharmacokinetics and could be extrapolated from adult to pediatric patients by body size correction, except for infants.

Pharmacokinetics of immediate and sustained-release formulations of paroxetine: Population pharmacokinetic approach to guide paroxetine personalized therapy in chinese psychotic patients.

Paroxetine is one of the most potent selective serotonin reuptake inhibitors (SSRIs) approved for treating depression, panic disorder, and obsessive-compulsive disorder. There is evidence linking genetic polymorphisms and nonlinear metabolism to the Paroxetine’s pharmacokinetic (PK) variability. The purpose of the present study was to develop a population PK (PPK) model of paroxetine in Chinese patients, which was used to define the paroxetine’s PK parameters and quantify the effect of clinical and baseline demographic factors on these PK characteristics. The study included 184 inpatients with psychosis (103 females and 81 males), with a total of 372 serum concentrations of paroxetine for PPK analyses. The total daily dosage ranged from 20 to 75 mg. One compartment model could fit the PKs characterize of paroxetine. Covariate analysis revealed that dose, formulation, and sex had a significant effect on the PK parameters of paroxetine; however, there was no evident genetic influence of CYP2D6 enzymes on paroxetine concentrations in Chinese patients. The study determined that the population’s apparent distribution volume (V/F) and apparent clearance (CL/F), respectively, were 8850 and 21.2 L/h. The CL/F decreased 1-2-fold for each 10 mg dose increase, whereas the different formulations caused a decrease in V/F of 66.6%. Sex was found to affect bioavailability (F), which decreased F by 47.5%. Females had higher F values than males. This PPK model described data from patients with psychosis who received paroxetine immediate-release tablets (IR-T) and/or sustained-release tablets (SR-T). Paroxetine trough concentrations and relative bioavailability were different between formulations and sex. The altered serum concentrations of paroxetine resulting from individual variants and additive effects need to be considered, to optimize the dosage regimen for individual patients.

Pre- and peri-operative characteristics, complications and outcomes of patients with biochemically silent pheochromocytomas; a case series.

Pheochromocytomas are rare tumors and biochemically silent ones with normal catecholamine levels are even rarer. Up to date, biochemically inactive pheochromocytomas are poorly investigated. We aimed to systematically assess the pre- and peri-operative characteristics and the outcomes of patients with these tumors who had been treated and followed-up in 2 tertiary centers. Clinical, laboratory and imaging data, treatment outcomes and follow-up of biochemically silent pheochromocytoma patients were recorded. Ten patients (5 men) [median age at diagnosis 52.5 years (24-72)] were included. Adrenal masses were incidentally discovered in all patients except from one who presented with pheochromocytoma-related manifestations. Twenty-four-hour urine metanephrine and normetanephrine levels were in the low-normal, normal and high-normal range in 4, 4 and 2 patients and in 1, 6 and 3 patients, respectively. Tumors were unilateral [median size 46 mm (17-125)] and high density on pre-contrast CT imaging or high signal intensity on T2-weighted MRI scans were found in all cases. Pre-operatively, 5 patients were treated with phenoxybenzamine [median total daily dose 70 mg (20-100)]. Intra-operatively, 4 patients developed hypertension requiring vasodilator administration and 8 developed hypotension; vasoconstrictors were required in 5 cases. One patient, not pre-operatively treated with phenoxybenzamine, developed Takotsubo cardiomyopathy. During a median 24-month (12-88) follow-up period, one patient had disease progression. The majority (90%) of patients with biochemically silent pheochromocytomas developed hemodynamic instability during adrenal surgery. In patients with biochemically silent adrenal lesions and a high suspicion index for pheochromocytoma based on tumor imaging characteristics, pre-operative alpha-blockade treatment may be advisable.

Treatment with Paracetamol Can Interfere with the Intradialytic Optical Estimation in Spent Dialysate of Uric Acid but Not of Indoxyl Sulfate.

Optical online methods are used to monitor the haemodialysis treatment efficiency of end stage kidney disease (ESKD) patients. The aim of this study was to analyse the effect of the administration of UV-absorbing drugs, such as paracetamol (Par), on the accuracy of optical monitoring the removal of uremic toxins uric acid (UA) and indoxyl sulfate (IS) during standard haemodialysis (HD) and haemodiafiltration (HDF) treatments. Nine patients received Par in daily dosages 1–4 g for 30 sessions. For 137 sessions, in 36 patients the total daily dosage of UV-absorbing drugs was less than 500 mg, and for 6 sessions 3 patients received additional UV-absorbing drugs. Par administration slightly affected the accuracy of optically assessed removal of UA expressed as bias between optically and laboratory-assessed reduction ratios (RR) during HD but not HDF employing UV absorbance of spent dialysate (p < 0.05) at 295 nm wavelength with the strongest correlation between the concentration of UA and absorbance. Corresponding removal of IS based on fluorescence at Ex280/Em400 nm during HD and HDF was not affected. Administration of UV-absorbing drugs may in some settings influence the accuracy of optical assessments in spent dialysate of the removal of uremic solutes during haemodialysis treatment of ESKD patients.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD). The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy. We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio. We collected demographic and clinical data at baseline and 6 and 12months after thalamotomy. We included 10 patients in the PD-FUS group and 20 patients in the PD-ODT group. We found a significant increase in total levodopa equivalent daily dose and levodopa plus monoamine oxidase B inhibitors dose in the PD-ODT group 6 months after thalamotomy. In early-stage tremor-dominant PD, MRgFUS thalamotomy may be useful to reduce tremor and avoid the need to increase dopaminergic medications. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Practical approaches to improve vancomycin-related patient outcomes in pediatrics- an alternative strategy when AUC/MIC is not feasible

BackgroundAnecdotal experience and studies have shown that most pediatric patients fail to reach target therapeutic vancomycin trough levels (VTLs) and required higher total daily doses (TDD). This retrospective study aims to evaluate the frequency of hospitalized children who achieved target VTLs with a vancomycin (VNCO) dosing regimen of 40-60 mg/kg/d q6h and to assess the VNCO-TDD required to attain the target and their effects on clinical outcomes in pediatric patients.MethodsAfter ethical approval, patients of 3 month-12 years were evaluated in this chart review study who received ≥ 3 intravenous-VNCO doses and appropriately drawn blood samples of VTLs between October 2019 to June 2020. Data were retrieved for demographic and clinical characteristics, culture reports, VNCO-regimen, subsequent steady-state VTLs, concomitant nephrotoxic medications, and serum creatinine. Clinical pharmacists made interventions in VNCO therapy and higher VNCO-TDD were used. Safety of higher vs standard daily doses and their clinical impact on duration of therapy, hospital stay, and survival were evaluated.ResultsA total of 89 (39.1%) patients achieved target VTLs (SD-group). The smallest proportion (18.2%) of 2–6 years patients achieved target VTLs and reported the lowest mean value of 10.1 ± 0.2 mg/L which was a significant difference (p < 0.05) from all subgroups. Subtherapeutic VTLs were observed in 139 (60.9%) cases (HD-group), who received higher VNCO-TDD of 72 ± 8.9 mg/kg/d q6h to achieve the targets. Duration of therapy in culture-proven septic patients was significantly (p = 0.025) longer in SD-group [18.4 ± 12.2 days] than HD-group [15.1 ± 8.9 days]. Nephrotoxicity and electrolyte imbalance were comparable in groups. Length of hospital stay was significantly (p = 0.011) longer [median 22 (range 8–55) days] in SD-group compared to HD-group [median 16 (range 8–37) days]. Number of patients survived in HD-group were significantly (p = 0.008) higher than SD-group [129 (92.8%) vs 75 (84.3%)].ConclusionInitial Vancomycin doses of 72 ± 8.9 mg/kg/day q6h are required to achieve therapeutic target in 3 months to 12 years patients. High doses are not associated with higher nephrotoxicity than reported with low doses. In addition, efficient pharmacist intervention for the use of higher VNCO-TDD may improve clinical outcomes in terms of duration of therapy, hospital stay, and survival.

Use of Andrographis paniculata (Burm.f.) Wall. ex Nees and risk of pneumonia in hospitalised patients with mild coronavirus disease 2019: A retrospective cohort study.

BackgroundAndrographis paniculata (Burm.f.) Wall. ex Nees (AP) has been widely used in Thailand to treat mild COVID-19 infections since early 2020; however, supporting evidence is scarce and ambiguous. Thus, this study aimed to examine whether the use of AP is associated with a decreased risk of pneumonia in hospitalised mild COVID-19 patients.Materials and methodsWe collected data between March 2020 and August 2021 from COVID-19 patients admitted to one hospital in Thailand. Patients whose infection was confirmed by real-time polymerase chain reaction, had normal chest radiography and did not receive favipiravir at admission were included and categorised as either AP (deriving from a dried and ground aerial part of the plant), given as capsules with a total daily dose of 180 mg andrographolide for 5 days or standard of care. They were followed for pneumonia confirmed by chest radiography. Multiple logistic regression was used for the analysis controlling for age, sex, diabetes, hypertension, statin use, and antihypertensive drug use.ResultsA total of 605 out of 1,054 patients (mostly unvaccinated) were included in the analysis. Of these, 59 patients (9.8%) developed pneumonia during the median follow-up of 7 days. The incidence rates of pneumonia were 13.93 (95% CI 10.09, 19.23) and 12.47 (95% CI 8.21, 18.94) per 1,000 person-days in the AP and standard of care groups, respectively. Compared to the standard of care group, the odds ratios of having pneumonia in the AP group were 1.24 (95% CI 0.71, 2.16; unadjusted model) and 1.42 (95% CI 0.79, 2.55; fully adjusted model). All sensitivity analyses were consistent with the main results.ConclusionThe use of AP was not significantly associated with a decreased risk of pneumonia in mild COVID-19 patients. While waiting for insights from ongoing trials, AP’s use in COVID-19 should be done with caution.

Botulinum Toxin as an Effective Treatment for Trigeminal Neuralgia in Surgical Practices

Background: Trigeminal neuralgia (TN) is a common cause of craniofacial pain with many medical and surgical therapies, all of which are imperfect. We examine the use of botulinum toxin type-A (BTX-A) as an intermediary approach in surgical practices. Methods: We retrospectively identified TN patients seen by both pain neurology and neurosurgery at our center. Demographics were collected. Pain intensity was assessed using the numerical rating scale (NRS) and compared from baseline to after BTX-A treatment via paired t test. Responder status was assessed, and success of BTX-A was determined for each cohort. Doses of common medications were compared between baseline visit and the most recent BTX-A administration visit. Results: Thirty-one patients underwent BTX-A therapy for TN, 24 (77%) female and 7 (23%) male. Mean age was 62.5 ± 3.1 years and 29 (94%) identified as white. When divided into cohorts according to indication, 11 (35%) failed prior TN surgery, 9 (29%) either declined surgery or were poor surgical candidates, 4 (13%) had multiple sclerosis, 4 (13%) had trigeminal neuropathic pain, and 3 (10%) had atypical TN with pain in additional dermatomes outside the trigeminal distribution. Significant reductions in NRS from baseline to following initial BTX-A treatment were seen in the declined/high risk for surgery (p = 0.004) and those who failed prior TN surgery (p = 0.035) groups. No significant variation in demographics was found between any two groups (p > 0.05 for all). Finally, there was no significant reduction in total daily dose of gabapentin, carbamazepine, oxcarbazepine, baclofen, or lamotrigine in BTX-A responders (p > 0.05 for all). Discussion: Indication is an important predictor for BTX-A, with classical TN patients exhibiting the highest response rates. This research highlights the viability of BTX-A as an important tool in the arsenal of providers seeking to treat TN in a minimally invasive manner.

A comparison of the rapid-acting insulin analogue glulisine with lispro and aspart for the pump treatment of patients with type 1 diabetes.

(1) To describe the population of patients with type 1 diabetes (T1DM) using the rapid-acting insulin analogue glulisine versus lispro and aspart during continuous subcutaneous insulin infusion (CSII); (2) to describe insulin relative effectiveness based on hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and dose; (3) to determine rates of hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA). The analysis used March 2021 data from the Diabetes-Patienten-Verlaufsdokumentation registry, which contains data of 618,903 patients with diabetes. Patients were propensity-matched by age, sex, and diabetes duration. Overall, 42,736 patients of any age were eligible for analysis based on insulin pump usage with either glulisine (N = 707) or lispro/aspart (N = 42,029) between 2004 and 2020. Patients receiving glulisine were older (median 20.0 vs. 16.2years), equally often male (47.2% vs. 47.8%) and had a longer diabetes duration (median 9.4 vs. 7.4years). After propensity score matching, 707 pairs remained (total N = 1414). Patient characteristics between groups were similar. Achieved HbA1c values were also comparable: 8.04%, 64mmol/mol versus 7.96%, 63mmol/mol for glulisine and lispro/aspart [LS mean difference 0.08 (95%CI -0.08, 0.25)]. FBG was 9.37mmol/L (168.9mg/dL) and 9.58mmol/L (172.6mg/dL) in the glulisine and lispro/aspart groups [LS mean diff. -0.21; (95%CI -1.13, 0.72)]. Total daily insulin doses and prandial to total insulin ratios were also similar. Glulisine group patients had higher rates of lipodystrophy (0.85% vs. 0.71%) (LS mean diff. 0.18 [95% CI -1.01, 1.38]) and non-severe DKA (3.11% vs. 0.57%; p = 0.002). Fewer patients in the glulisine group had severe hypoglycemic events (7.66 vs. 9.09; p = 0.333) and severe ketoacidosis events (0.57% vs. 1.56%; p = 0.082) but more had hypoglycemic coma events (p = 0.773), although the differences were not statistically significant. Insulin glulisine had comparable glucose control to lispro/aspart. The use of glulisine was less frequent in the present analysis compared to the previous trials.

Sensor-Augmented Insulin Pump with Predictive Low-Glucose Suspend (PLGS): Determining Optimal Settings of Pump and Sensor in a Multicenter Cohort of Patients with Type 1 Diabetes.

IntroductionThe use of predictive low-glucose suspend (PLGS) sensor-augmented pumps has been shown to lead to a significant reduction in hypoglycemic episodes in patients with type 1 diabetes (T1D), but their effects on hyperglycemia exposure are heterogeneous. The aim of this study was to determine the settings of the Medtronic 640G system to obtain the optimal balance between occurrence of both hypoglycemia and hyperglycemia.MethodsThe hypo- and hyperglycemia area under the curve (AUC), as well as system settings [hypoglycemic threshold, mean insulin total daily dose (TDD), mean basal insulin percentage, and mean daily duration of PLGS] were collected between 2 and 12 times during 1 year in patients from four university hospital centers. Univariate/multivariate analyses and receiver operating characteristics (ROC) curves were performed to determine factors associated with hyper- and hypoglycemia AUC.ResultsA total of 864 observations were analyzed from 110 patients with T1D. Two preselected settings predictive of low hyperglycemia AUC were a basal insulin percentage < 52.0% [sensitivity (Se) = 0.66 and specificity (Sp) = 0.53] and a PLGS duration > 157.5 min/day (Se = 0.47 and Sp = 0.73). The preselected setting predictive of a low hypoglycemia AUC was a PLGS duration ≤ 174.4 min (Se = 0.83 and Sp = 0.51). Between-visit variation of PLGS and TDD was positively correlated (r = 0.61; p < 0.0001).ConclusionThe most important Medtronic 640G setting was the mean daily PLGS duration, where a value between 157.5 and 174.4 min/day was associated with the best reduction in both hypo- and hyperglycemia AUC. In this study, we showed that PLGS duration could be indirectly modified through total daily insulin dose adaptation.Trial Registration: This study is registered in clinicaltrials.gov (NCT 03047486).