Average Daily Dose Research Articles

Study on Risk Factors and Receiver Operator Characteristic Curve of Iatrogenic Withdrawal Syndrome in Pediatric Intensive Care Units: A Retrospective Study

Introduction: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. Methods: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. Results: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610–0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. Conclusion: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.

Spatial distribution of drinking, irrigation water quality, and health risk indices of high-altitude lakes

High-altitude lakes (HAL) play a key role in several ecological services of the environment by managing the water supply and flood control. The slow rate of inflowing contaminant circulation results in a buildup of higher levels of contamination level and makes these lakes more vulnerable. The present study focused on determining HAL's water quality parameters (WQP) in the Swat District, northern Pakistan. Water samples (n = 32) were collected and analyzed for basic parameters, anions, and potentially harmful elements (PHE). Results of examined parameters were noted under WHO threshold values, except for a few samples of iron (Fe) and arsenic (As). The concentrations of WQP in HAL were used to calculate drinking and irrigation water quality indices (WQI). Results revealed that the water of HAL was excellent and suitable for drinking and irrigation purposes. Gibbs plot and Piper model were used to identify water as a mixed type and source characterization of rock dominance. Water quality data were used for average daily dose (ADD) and hazard quotient (HQ) to find HAL water's potential health risks. The highest ADD value of 188 μg/kg-day was observed for nitrate (NO3), and the lowest of 0.31 μg/kg-day was noted for arsenic (As). However, maximum HQ values of 0.18 were reported for As and were observed to be less than the threshold of 1. Therefore, based on water quality, the HAL was recommended for use in drinking, domestic, and irrigation purposes.

Higher First 30-Day Dose of Buprenorphine for Opioid Use Disorder Treatment Is Associated With Decreased Mortality.

Buprenorphine is a medication for opioid use disorder that reduces mortality. This study aims to investigate the less well-understood relationship between the dose in the early stages of treatment and the subsequent risk of death. We used Kentucky prescription monitoring data to identify adult Kentucky residents initiating transmucosal buprenorphine medication for opioid use disorder (January 2017 to November 2019). Average daily buprenorphine dose for days covered in the first 30 days of treatment was categorized as ≤8 mg, >8 to ≤16 mg, and >16 mg. Patients were followed for 365 days after the first 30 days of buprenorphine treatment. Endpoints were opioid-involved overdose death and death from other causes. Causes and dates of death were obtained using Kentucky death certificate records. Associations were evaluated using multivariable Fine and Gray models adjusting for patient baseline characteristics. In the cohort of 49,857 patients, there were 227 opioid-involved overdose deaths and 459 deaths from other causes. Compared with ≤8 mg, the adjusted subdistribution hazard ratio (aSHR) of opioid-involved overdose death decreased by 55% (aSHR, 0.45; 95% confidence interval [CI], 0.34-0.60) and 64% (aSHR, 0.36; 95% CI, 0.25-0.52) for patients receiving doses of >8 to ≤16 mg and >16 mg, respectively. The incidence of death from other causes was lower in patients receiving >8 to ≤16 mg (aSHR, 0.78; 95% CI, 0.62-0.98) and >16 mg (aSHR, 0.62; 95% CI, 0.47-0.80) versus ≤8 mg dose. Higher first 30-day buprenorphine doses were associated with reduced opioid-involved overdose death and death from other causes, supporting benefit of higher dosing in reducing mortality.

Building Capacity for Injectable Diacetylmorphine and Hydromorphone for the Treatment of Opioid Use Disorder: Identifying Typical Doses

ABSTRACT Identifying typical doses of existing opioid use disorder medications, such as injectable opioid agonist treatment (iOAT), can support client and program needs, and potentially increase iOAT expansion. Longitudinal data from participants in a cohort study (n = 131), along with clinic dispensation records from August 2014 to April 2020, were used to examine physician prescribed as well as used doses of injectable diacetylmorphine and hydromorphone. Dosage groups, by medication and prescribed dose per session, were created for both hydromorphone and diacetylmorphine. A total of 534, 522 injections were registered during the study period among 129 participants. Mean received diacetylmorphine doses ranged from 106 to 989 mg per day, with most clients using 125–262 mg per session (mean 192.99 mg) and attending 2.40 sessions per day. Mean received hydromorphone doses ranged from 51.09 to 696.06 mg per day, with the majority using 88–154 mg per session (mean 121.32 mg; 2.43 sessions). Average daily doses remained stable overtime and, while mid-range doses were most typical, participants used the whole spectrum of allowable dose prescriptions. Evidence supporting typical doses of iOAT can be integrated into program planning to better allow providers and prescribers to anticipate program needs and engage in individualized care.

Structuring medication signeturs as a language regression task: comparison of zero- and few-shot GPT with fine-tuned models.

Electronic health record textual sources such as medication signeturs (sigs) contain valuable information that is not always available in structured form. Commonly processed through manual annotation, this repetitive and time-consuming task could be fully automated using large language models (LLMs). While most sigs include simple instructions, some include complex patterns. We aimed to compare the performance of GPT-3.5 and GPT-4 with smaller fine-tuned models (ClinicalBERT, BlueBERT) in extracting the average daily dose of 2 immunomodulating medications with frequent complex sigs: hydroxychloroquine, and prednisone. Using manually annotated sigs as the gold standard, we compared the performance of these models in 702 hydroxychloroquine and 22104 prednisone prescriptions. GPT-4 vastly outperformed all other models for this task at any level of in-context learning. With 100 in-context examples, the model correctly annotates 94% of hydroxychloroquine and 95% of prednisone sigs to within 1 significant digit. Error analysis conducted by 2 additional manual annotators on annotator-model disagreements suggests that the vast majority of disagreements are model errors. Many model errors relate to ambiguous sigs on which there was also frequent annotator disagreement. Paired with minimal manual annotation, GPT-4 achieved excellent performance for language regression of complex medication sigs and vastly outperforms GPT-3.5, ClinicalBERT, and BlueBERT. However, the number of in-context examples needed to reach maximum performance was similar to GPT-3.5. LLMs show great potential to rapidly extract structured data from sigs in no-code fashion for clinical and research applications.

Psychometric assessment of patients with treatment-resistant schizophrenia

IntroductionTreatment-resistant schizophrenia (TRS) is one of the most pressing issues in the field of treatment and research of psychotic disorders. The pronounced decline in social and professional functioning in this group of patients as well as high costs of therapy determine high interest in TRS. This is a part of an ongoing study on the clinical and biological features of TRS.ObjectivesThe aim of this study is to identify the leading symptoms in patients with TRS.MethodsUsing the Personal and Social Performance Scale (PSP), Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for schizophrenia (CDSS), 30 male patients (age 28.99 ± 8.08 years) diagnosed with paranoid schizophrenia (F20.0) were examined. All patients had persistent productive symptoms and met the criteria for TRS. The average daily doses of antipsychotics in chlorpromazine equivalent were 1382.07 ± 897.15 mg/day. The average age of onset of the disease was 19.52 ± 5.97 years, the average disease was 9.47 ± 7.61 years.ResultsThe average scores were: on the PSP scale: 46.05 ± 9.17, on the CDSS scale 8.10 ± 4.53, on the PANSS positive symptoms subscale - 21.52 ± 4.24, on the PANSS negative symptoms subscale - 24.67 ± 4.42, on the general psychopathology subscale PANSS – 45.62 ± 6.11 . Positive symptoms were represented mainly by delusions (P1, 4.14 ± 0.85 points) and hallucinations (P3, 4.10 ± 1.76 points). Blunted affect (N1, 4.29 ± 0.56 points) and emotional withdrawal (N2, 3.67 ± 0.73 points) predominated among negative symptoms, while the least prominent negative symptom was poor rapport (N3, 3.24 ± 0.94). The most pronounced general psychopathology symptoms were depression (G6, 4.00 ± 1.10 ) and lack of judgment and insight (G12, 4.05 ± 0.92). The total score on the PANSS was 91.81 ± 12.40.ConclusionsThe CDSS score indicates a high incidence of depressive symptoms in patients with TRS. A low PSP score reflects poor social functioning. The most common symptoms according to the PANSS are delusions, hallucinations, blunted affect, emotional withdrawal, depression and lack of judgment and insight.Disclosure of InterestNone Declared

Pharmacological enhancement of cholinergic neurotransmission alleviates neuroinflammation and improves functional outcomes in a triple transgenic mouse model of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting the elderly population worldwide. Due to the multifactorial nature of the disease, involving impairment of cholinergic neurotransmission and immune system, previous attempts to find effective treatments have faced challenges. Methods: In such scenario, we attempted to investigate the effects of alpha-glyceryl-phosphoryl-choline (α-GPC), a cholinomimetic molecule, on neuroinflammation and memory outcome in the triple transgenic mouse model of AD (3xTg-AD). Mice were enrolled at 4 months of age, treated orally with α-GPC dissolved in drinking water at a concentration resulting in an average daily dose of 100mg/kg for 8 months and sacrificed at 12 months of age. Thereafter, inflammatory markers, as well as cognitive parameters, were measured. Results: Chronic α-GPC treatment reduced accumulation of amyloid deposits and led to a substantial re-balance of the inflammatory response of resident innate immune cells, astrocytes and microglia. Specifically, fluorescent immunohistochemistry and Western blot analysis showed that α-GPC contributed to reduction of cortical and hippocampal reactive astrocytes and pro-inflammatory microglia, concurrently increasing the expression of anti-inflammatory molecules. Whereas α-GPC beneficially affect the synaptic marker synaptophysin in the hippocampus. Furthermore, we observed that α-GPC was effective in restoring cognitive dysfunction, as measured by the Novel Object Recognition test, wherein 3xTg-AD mice treated with α-GPC significantly spent more time exploring the novel object compared to 3xTg-AD untreated mice. Discussion: In conclusion, chronic treatment with α-GPC exhibited a significant anti-inflammatory activity and sustained the key function of hippocampal synapses, crucial for the maintenance of a regular cognitive status. In light of our results, we suggest that α-GPC could be exploited as a promising therapeutic approach in early phases of AD.

Impact of early-morning administration of rapid-acting insulin on the increase in blood glucose levels related to the dawn phenomenon in individuals with type 1 diabetes.

An early-morning elevation of blood glucose levels known as the dawn phenomenon and consequent postbreakfast hyperglycemia occur in some individuals with type 1 diabetes (T1D). Whereas insulin pump therapy can mitigate this phenomenon, some individuals prefer or are limited to alternative treatments. We have now assessed the effectiveness of early-morning administration of rapid-acting insulin for amelioration of the dawn phenomenon in individuals with T1D. Thirteen individuals with T1D who experienced the dawn phenomenon as determined by continuous glucose monitoring (CGM) and who received a small dose of rapid-acting insulin on waking were included in this retrospective study. We evaluated the change in sensor glucose levels during a 2-h period from before to after breakfast consumed at 0700h. The change in blood glucose levels during additional time intervals, average daily sensor glucose values, CGM indices, and insulin dose were also evaluated. The early-morning administration of 0.5-1 unit of rapid-acting insulin was associated with a significant reduction in 2-h glucose variability between before (0700h) and after breakfast from a median of 90.7-51.0mg/dL. The glucose variability from 0300 to 0700 or 0900h was also significantly decreased, from 67.7 to 29.0mg/dL and from 172.5 to 78.3mg/dL, respectively. Average sensor glucose levels throughout the day were significantly reduced (from 192.7 to 156.7mg/dL), as was the daily total insulin dose. Early-morning administration of rapid-acting insulin effectively managed the dawn phenomenon and subsequent postbreakfast hyperglycemia in individuals with T1D. The online version contains supplementary material available at 10.1007/s13340-024-00709-6.

Nationwide Analysis of Risk Factors Related to Opioid Weaning Following Lumbar Decompression Surgery – A Retrospective Database Study

BackgroundOpioids are often prescribed for patients who eventually undergo lumbar decompression. Given the potential for opioid-related morbidity and mortality, postoperative weaning is often a goal of surgery. The purpose of this study was to examine the relationship between preoperative opioid use and postoperative complete opioid weaning among lumbar decompression patients. MethodsWe surveyed the IBM Marketscan Databases for patients who underwent lumbar decompression in 2008-2017, had >30 days of opioid use in the year preceding surgery, and consumed a daily average of >0 morphine milligram equivalents (MME) in the 3 months preceding surgery. We used multivariable logistic regression and marginal standardization to examine the association between preoperative opioid use duration, average daily dose, and their interactions with complete opioid weaning in the 10-12 months after surgery. ResultsOf the 11,114 patients who met inclusion criteria, most (54.7%, n=6083) had a preoperative average daily dose of 1-20 MME. Postoperatively, 6144 patients (55.3%) remained on opioids. For patients with >180 days of preoperative use, the adjusted probability of weaning increased as the preoperative dose decreased. Obesity increased the likelihood of weaning, whereas older age, several comorbidities, female sex, and Medicaid decreased the odds of weaning. ConclusionsPatients who used opioids for longer preoperatively were less likely to completely wean following surgery. Among patients with >180 days of preoperative use, those with lower preoperative doses were more likely to wean. Weaning was also associated with several clinical and demographic factors. These findings may help shape expectations regarding opioid use following lumbar decompression.

Effect of a Dietary Intervention on Insulin Requirements and Glycemic Control in Type 1 Diabetes: A 12-Week Randomized Clinical Trial.

This study compared the effects of a low-fat vegan diet to those of a portion-controlled diet in people with type 1 diabetes. Over 12 weeks, the average total daily dose of insulin decreased significantly and insulin sensitivity increased significantly in the vegan group, while no significant changes were observed in the group receiving the portion-controlled diet. Total and LDL cholesterol decreased in the vegan group, as did the ratio of blood urea nitrogen to creatinine. A1C decreased in both groups. These findings suggest that a low-fat vegan diet may yield improvements in insulin sensitivity, insulin requirements, glycemic control, and markers of cardiovascular and renal health compared with a portion-controlled diet in people with type 1 diabetes.

Enoxaparin thromboprophylaxis in hospitalized obese pediatric patients.

Enoxaparin is an anticoagulant used for pharmacologic thromboprophylaxis in pediatrics. Enoxaparin pharmacokinetics can be altered in the setting of obesity. Optimal enoxaparin dosing for thromboprophylaxis in children with obesity remains unclear. A retrospective review was conducted of pediatric patients who weighed ≥60kg with BMI≥95th percentile, received enoxaparin for thromboprophylaxis, and had at least one appropriately drawn anti-factor Xa(anti-Xa) from 2013 to 2022. Anti-Xa levels were reviewed for patients initially treated with enoxaparin 30mg every 12h. The average daily enoxaparin dose required to achieve an anti-Xa of 0.2-0.4 unit/mL, which was stratified by BMI percentile and weight, was calculated. Of 116 patients (median age 15.8 years) included for analysis, 106 patients were initially treated with enoxaparin 30mg every 12h. Anti-Xa levels were<0.2 unit/mL in 53% of patients with BMI>99th percentile and 54% of patients>100kg. Ninety-one patients had at least one anti-Xa 0.2-0.4unit/mL with an average daily enoxaparin dosing of 66mg. When stratified by severity of obesity, higher doses were required to attain an anti-Xa 0.2-0.4 unit/mL in patients with BMI>99th percentile compared with those with 95th-99th percentile (67.8±15.7 vs. 62±5.6mg/day, p=.01). Patients>100kg required significantly higher dose than those ≤100kg (69.1±15.5 vs 61.2±7.3mg/day, p=.002). Increased initial dosing and/or anti-Xa level monitoring should be considered in adolescents with severe obesity receiving enoxaparin thromboprophylaxis.

Longitudinal evaluation of adverse events due to steroid use in primary immune thrombocytopenia: A population-based study.

This study aimed to investigate the association between the steroid use patterns and the risk of AEs in patients with primary immune thrombocytopenia (ITP). A total of 2691 newly diagnosed adults with ITP between 2011 and 2018 were identified from the National Health Insurance Research Database in Taiwan, and the date of first steroid use was defined as the index date. Post-index steroid use was calculated on a 90-day basis as a time-dependent variable and categorized by the average prednisolone-equivalent daily dose (<10 mg vs. ≥10 mg) and intensity (medication possession ratio <80% vs. ≥80%). Patients were followed up for 1 year from the index date for acute AE events, while chronic AEs were assessed until death, or end of 2019. Compared to patients with low-dose+low-intensity steroid use, those with high-dose+high-intensity steroid use were associated with a higher risk of acute AE (adjusted incident rate ratio [aIRR]: 1.57, 95% confidence interval [CI]: 1.38-1.78, p < 0.01) and chronic AE (aIRR: 1.26, 95% CI: 1.08-1.47, p < 0.01). Metabolic/endocrine and ophthalmologic disorders demonstrated the strongest correlation with a high dose and intensity. The joint effect of steroid dose and intensity was observed in patients with ITP, and the findings suggest that steroids should be used carefully.

Food waste compost and digestate as novel fertilizers: Impacts on antibiotic resistome and potential risks in a soil-vegetable system

As a novel agricultural practice, the reuse of food waste compost and digestate as fertilizers leads to a circular economy, but inevitably introduces bio-contaminants such as antibiotic resistance genes (ARGs) into the agroecosystem. Moreover, heavy metal and antibiotic contamination in farmland soil may exert selective pressures on the evolution of ARGs, posing threats to human health. This study investigated the fate, influencing mechanisms and potential risks of ARGs in a soil-vegetable system under different food waste fertilization and remediation treatments and soil contamination conditions. Application of food waste fertilizers significantly promoted the pakchoi growth, but resulted in the spread of ARGs from fertilizers to pakchoi. A total of 56, 80, 84, 41, and 73 ARGs, mobile genetic elements (MGEs) and metal resistance genes (MRGs) were detected in the rhizosphere soil (RS), bulk soil (BS), control soil (CS), root endophytes (RE), and leaf endophytes (LE), respectively. Notably, 7 genes were shared in the above five subgroups, indicating a specific soil-root-endophytes transmission pathway. 36 genes were uniquely detected in the LE, which may originate from airborne ARGs. The combined application of biochar and fertilizers reduced the occurrence of ARGs and MGEs to some extent, showing the remediation effect of biochar. The average abundance of ARGs in the RS, BS and CS was 3.15 × 10−2, 1.31 × 10−2 and 2.35 × 10−1, respectively. Rhizosphere effects may reduce the abundance of ARGs in soil. The distribution pattern of ARGs was influenced by the types of soil, endophyte and contaminant. MGEs is the key driver shaping ARGs dynamics. Soil properties and pakchoi growth status may affect the bacterial composition, and consequently regulate ARGs fate, while endophytic ARGs were more impacted by biotic factors. Moreover, the average daily doses of ARGs from pakchoi consumption is 107–109 copies/d/kg, and its potential health risks should be emphasized.

Cannabinoids in the Treatment of Selected Mental Illnesses: Practical Approach and Overview of the Literature.

Although an increasing number of patients suffering from mental illnesses self-medicate with cannabis, current knowledge about the efficacy and safety of cannabis-based medicine in psychiatry is still extremely limited. So far, no cannabis-based finished product has been approved for the treatment of a mental illness. There is increasing evidence that cannabinoids may improve symptoms in autism spectrum disorder (ASD), Tourette syndrome (TS), anxiety disorders, and post-traumatic stress disorder (PTSD). According to surveys, patients often use cannabinoids to improve mood, sleep, and symptoms of attention deficit/hyperactivity disorder (ADHD). There is evidence suggesting that tetrahydrocannabinol (THC) and THC-containing cannabis extracts, such as nabiximols, can be used as substitutes in patients with cannabis use disorder.Preliminary evidence also suggests an involvement of the endocannabinoid system (ECS) in the pathophysiology of TS, ADHD, and PTSD. Since the ECS is the most important neuromodulatory system in the brain, it possibly induces beneficial effects of cannabinoids by alterations in other neurotransmitter systems. Finally, the ECS is an important stress management system. Thus, cannabinoids may improve symptoms in patients with mental illnesses by reducing stress.Practically, cannabis-based treatment in patients with psychiatric disorders does not differ from other indications. The starting dose of THC-containing products should be low (1-2.5 mg THC/day), and the dose should be up-titrated slowly (by 1-2.5 mg every 3-5 days). The average daily dose is 10-20 mg THC. In contrast, cannabidiol (CBD) is mainly used in high doses>400 mg/day.

Potential pathogenic microorganisms in rural wastewater treatment process: Succession characteristics, concentration variation, source exploration, and risk assessment

Pathogenic microorganisms can cause infection, sepsis, and other diseases in humans. Although municipal wastewater plants are important sources and sinks for potential pathogenic microorganisms, data on rural wastewater treatment processes are limited. The proximity of rural wastewater facilities to human settlements and the trend toward wastewater resourcing could pose risks to humans. Here, a typical village in southern China was selected to analyze potential pathogenic microorganisms in wastewater, sewage sludge, and aerosols during the collection, treatment, and discharge of domestic wastewater. The succession characteristics and concentration variations of potential pathogenic microorganisms throughout the wastewater treatment process were identified using high-throughput sequencing and culture methods. Bacteria-associated health risks in facility aerosols were estimated based on average daily dose rates from inhalation and dermal exposure. Lower amounts of pathogenic bacteria and pathogenic fungi were detected in the effluent of the 1-ton treatment scale and the 10-ton treatment scale facilities, compared to those in the influent. Pathogen effluent concentrations were significantly lower than influent concentrations after treatment in rural wastewater facilities. 16 and 29 potential pathogenic bacteria and fungi were detected in aerosols from wastewater treatment facilities, respectively. Furthermore, the potential pathogen concentrations were higher than those in the background air. Aerobic units are the main source of pathogen emissions from aerosols. There were 42 potential pathogenic bacteria and 34 potential pathogenic fungi in the sewage sludge. Biochemical units were the main source of potential pathogens in sewage sludge, and more potential airborne pathogens originated from wastewater. In rural wastewater resourcing processes with greater pollutant exposure, the effluent of rural wastewater treatment facilities (WWTFs), downstream rivers, and facility aerosols, could be important potential sources of microbial risk. Inhalation is the main pathway of human exposure to airborne bacteria. Therefore, more attention should be focused on microbiological risk in rural wastewater treatment processes.

Characteristics and outcomes of peripheral neuropathic pain patients with repeated applications of high-concentration capsaicin cutaneous patch: Results of a retrospective chart review in Germany.

The aim of this study was to evaluate patient characteristics, concomitant analgesic medication, and pain intensity in a real-world setting in Germany, focusing on the repeated application of high-concentration capsaicin patch (HCCP) for neuropathic pain. Data were collected from electronic medical records of patients who received at least two HCCP treatments between January 2011 and July 2022. Subgroup analyses were performed based on the number of HCCP treatments, age groups, and specific neuropathic pain conditions. The study was conducted at an outpatient pain center in Wiesbaden, Germany. The study included 97 patients, primarily diagnosed with neuropathic back pain, postoperative or post-traumatic neuropathic pain, and postherpetic neuralgia. The daily dose of concomitant medications (eg, opioids and anticonvulsants) at the start of capsaicin therapy was compared with the average within 2 years of capsaicin therapy. The last observation carried forward method was used if HCCP treatment was discontinued before the end of the 2-year period. The majority of patients received concomitant medications, with opioids, anticonvulsants, and antidepressants being the most common. The average daily morphine equivalent dose decreased significantly during HCCP treatment. Pain intensity at baseline was generally high, but substantial improvements were observed in patients who received at least three HCCP applications. This study provides evidence for the effectiveness of HCCP treatment in reducing pain intensity and concomitant opioid use in patients with neuropathic pain. Further research is needed to explore the long-term outcomes and optimal treatment regimens for different patient populations.

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Pregnant/Puerperal Women with COVID-19 Admitted to ICU in Turkey: A Multicenter, Retrospective Study from a Middle-Income Country.

Coronaviruses have been the cause of 3 major outbreaks during the last 2 decades. Information on coronavirus diseases in pregnant women is limited, and even less is known about seriously ill pregnant women. Data are also lacking regarding the real burden of coronavirus disease 2019 (COVID-19) infection in pregnant women from low/middle-income countries. The aim of this study was to determine the characteristics and clinical course of COVID-19 in pregnant/puerperal women admitted to ICUs in Turkey. This was a national, multicenter, retrospective study. The study population comprised all SARS-CoV-2-infected pregnant/puerperal women admitted to participating ICUs between 1 March 2020 and 1 January 2022. Data regarding demographics, comorbidities, illness severity, therapies, extrapulmonary organ injuries, non-COVID-19 infections, and maternal and fetal/neonatal outcomes were recorded. LASSO logistic regression and multiple logistic regression analyses were used to identify predictive variables in terms of ICU mortality. A total of 597 patients (341 pregnant women, 255 puerperal women) from 59 ICUs in 44 hospitals were included and of these patients, 87.1% were unvaccinated. The primary reason for ICU admission was acute hypoxemic respiratory failure in 522 (87.4%), acute hypoxemic respiratory failure plus shock in 14 (2.3%), ischemic cerebrovascular accident (CVA) in 5 (0.8%), preeclampsia/eclampsia/HELLP syndrome in 6 (1.0%), and post-caesarean follow-up in 36 (6.0%). Nonsurvivors were sicker than survivors upon ICU admission, with higher APACHE II (p < 0.001) and SOFA scores (p < 0.001). A total of 181 (30.3%) women died and 280 (46.6%) had received invasive mechanical ventilation (IMV). Myocardial injury, the highest SOFA score during ICU stay, LDH levels on admission, the highest levels of AST during ICU stay, average daily dose of corticosteroids, IMV, prophylactic dose anticoagulation (compared with therapeutic dose anticoagulation), PaO2/FiO2 ratio <100, pulmonary embolism, and shock were identified as predictors of mortality. Rates of premature birth (46.4%), cesarean section (53.7%), fetal distress (15.3%), stillbirth (6.5%), and low birth weight (19.4%) were high. Rates of neonatal death (8%) and respiratory distress syndrome (21%) were also high among live-born infants. Severe/critical COVID-19 infection during the pregnancy/puerperal period was associated with high maternal mortality and fetal/neonatal complication rates in Turkey.

Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide health insurance claims database in Japan.

Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). Patients aged 50years who were prescribed GC (≥ 70mg prednisolone or equivalent; PSL) in the initial 90days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC 5mg PSL/day had a significantly increased fracture risk in the stratum of 30-59days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5mg PSL/day) for 90days in the initial 90days of GC therapy had a significantly increased fracture risk. GC exposure in the initial 90days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.

Patterns of corticosteroid use among remdesivir and matched patients and associated clinical outcomes in hospitalized COVID-19 patients

ABSTRACT Introduction We aimed to investigate patterns of corticosteroid use and their relationship with remdesivir use and clinical outcomes in a large real-life cohort of COVID-19 patients treated in a tertiary-level institution. Methods We retrospectively analyzed a total of 1558 severe and critical COVID-19 patients, including 779 patients treated with remdesivir and 779 matched control patients. Results A total of 167 (10.7%) patients received none, 710 (45.6%) low, 539 (34.6%) high, and 142 (9.1%) very high corticosteroid doses. Patients treated with remdesivir had significantly longer exposure to corticosteroids, received higher average and maximal daily doses, and cumulative corticosteroid doses. In the multivariate analysis remdesivir use, lower cumulative comorbidity burden, higher severity of COVID-19 symptoms, and mechanical ventilation were recognized as mutually independent predictors of the use of higher corticosteroid doses. Higher corticosteroid doses were associated with significantly increased mortality. Among non-remdesivir treated patients, there was a U-shaped relationship between maximal daily corticosteroid dose and mortality. Among remdesivir treated patients gradual increase in mortality with increasing corticosteroid doses was observed. Conclusion Patterns of corticosteroid use differ regarding the use of remdesivir and may moderate its association with survival among severe and critical COVID-19 patients.

Recovery of adrenal function after stopping mitotane in patients with adrenocortical carcinoma.

Mitotane is the standard therapy of adrenocortical carcinoma (ACC) due to its relative selectivity of its cytotoxic effects toward adrenocortical cells. Therefore, it virtually always leads to adrenal insufficiency. Frequency and characteristics of hypothalamic-pituitary-adrenal axis recovery after discontinuation are ill-defined. This was a retrospective study of patients with ACC adjuvantly treated with mitotane for ≥12 months who were disease-free at mitotane stop and had a minimum follow-up ≥1 year. Primary endpoint was adrenal recovery. Cox regression analyses were used to identify predictive factors. Moreover, mitotane plasma elimination rate and hormonal changes after mitotane stop were investigated. Fifty-six patients (36 women) treated with mitotane for a median time of 25 months and an average daily dose of 2.8 g were included. Median time after discontinuation until mitotane levels dropped below 5 and 2 mg/L, and the detection limit was 152 days (interquartile range: 114-202), 280 days (192-370), and 395 days (227-546), respectively. Full adrenal recovery was documented in 32 (57%) patients after a median time of 26 months (95% confidence interval [CI] = 19.6-32.4). In 4 patients (7.1%), adrenal insufficiency persisted >5 years after discontinuation. Mitotane peak ≥ 27 mg/L significantly correlated with longer time to adrenal recovery (hazard ratio [HR] = 0.2, 95% CI = 0.1-0.8, P = .03). Twenty-seven of 38 patients (71%) followed in reference centers achieved adrenal recovery compared with only 5/18 (28%) followed up in non-reference centers (HR = 4.51, 95% CI = 1.71-11.89, P = .002). Other investigated factors were not associated with adrenal function after discontinuation. Our study demonstrates that adrenal recovery occurs in most patients after stopping mitotane, particularly when followed up in specialized centers, but not in all. Elimination time of mitotane after treatment discontinuation is very long but individually quite variable.