Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?

PURPOSE OF REVIEW: Antagonists of mu-opioid receptor role in cancer progression remains to be elucidated. The objective of this review was to summarize the available evidence on antagonists of mu-opioid receptor effect on tumor progression and prognosis in different types of cancers and an evaluation of the available findings on their mechanism of action. RECENT FINDINGS: We have found studies related to methylnaltrexone (MNTX) and naltrexone (NTX) usage in cancer outcomes-related setting. We found consistent preclinical evidence of a potential action of MNTX and NTX on cancer growth and spread mediated mainly by effect on the opioid growth factor receptor (OGFr) axis, which results in depressed cell replication. However, clinical results are scarce and limited to poor-quality evidence. Further high-quality studies are warranted to study antagonists of mu-opioid receptor role as a therapeutic option in different types of cancer, especially in patients where the classical treatment causes unacceptable side effects.

Intraabdominal Pressure Targeted Positive End-expiratory Pressure during Laparoscopic Surgery: An Open-label, Nonrandomized, Crossover, Clinical Trial.

BACKGROUND: Pneumoperitoneum for laparoscopic surgery is associated with a rise of driving pressure. The authors aimed to assess the effects of positive end-expiratory pressure (PEEP) on driving pressure at varying intraabdominal pressure levels. It was hypothesized that PEEP attenuates pneumoperitoneum-related rises in driving pressure. METHODS: Open-label, nonrandomized, crossover, clinical trial in patients undergoing laparoscopic cholecystectomy. "Targeted PEEP" (2 cm H2O above intraabdominal pressure) was compared with "standard PEEP" (5 cm H2O), with respect to the transpulmonary and respiratory system driving pressure at three predefined intraabdominal pressure levels, and each patient was ventilated with two levels of PEEP at the three intraabdominal pressure levels in the same sequence. The primary outcome was the difference in transpulmonary driving pressure between targeted PEEP and standard PEEP at the three levels of intraabdominal pressure. RESULTS: Thirty patients were included and analyzed. Targeted PEEP was 10, 14, and 17 cm H2O at intraabdominal pressure of 8, 12, and 15 mmHg, respectively. Compared to standard PEEP, targeted PEEP resulted in lower median transpulmonary driving pressure at intraabdominal pressure of 8 mmHg (7 [5 to 8] vs. 9 [7 to 11] cm H2O; P = 0.010; difference 2 [95% CI 0.5 to 4 cm H2O]); 12 mmHg (7 [4 to 9] vs.10 [7 to 12] cm H2O; P = 0.002; difference 3 [1 to 5] cm H2O); and 15 mmHg (7 [6 to 9] vs.12 [8 to 15] cm H2O; P < 0.001; difference 4 [2 to 6] cm H2O). The effects of targeted PEEP compared to standard PEEP on respiratory system driving pressure were comparable to the effects on transpulmonary driving pressure, though respiratory system driving pressure was higher than transpulmonary driving pressure at all intraabdominal pressure levels. CONCLUSIONS: Transpulmonary driving pressure rises with an increase in intraabdominal pressure, an effect that can be counterbalanced by targeted PEEP. Future studies have to elucidate which combination of PEEP and intraabdominal pressure is best in term of clinical outcomes.

A multifaceted individualized pneumoperitoneum strategy for laparoscopic colorectal surgery: a multicenter observational feasibility study.

BACKGROUND: While guidelines for laparoscopic abdominal surgery advise using the lowest possible intra-abdominal pressure, commonly a standard pressure is used. We evaluated the feasibility of a predefined multifaceted individualized pneumoperitoneum strategy aiming at the lowest possible intra-abdominal pressure during laparoscopic colorectal surgery. METHODS: Multicenter prospective study in patients scheduled for laparoscopic colorectal surgery. The strategy consisted of ventilation with low tidal volume, a modified lithotomy position, deep neuromuscular blockade, pre-stretching of the abdominal wall, and individualized intra-abdominal pressure titration; the effect was blindly evaluated by the surgeon. The primary endpoint was the proportion of surgical procedures completed at each individualized intra-abdominal pressure level. Secondary endpoints were the respiratory system driving pressure, and the estimated volume of insufflated CO2 gas needed to perform the surgical procedure. RESULTS: Ninety-two patients were enrolled in the study. Fourteen cases were converted to open surgery for reasons not related to the strategy. The intervention was feasible in all patients and well-accepted by all surgeons. In 61 out of 78 patients (78%), surgery was performed and completed at the lowest possible IAP, 8 mmHg. In 17 patients, IAP was raised up to 12 mmHg. The relationship between IAP and driving pressure was almost linear. The mean estimated intra-abdominal CO2 volume at which surgery was performed was 3.2 L. CONCLUSION: A multifaceted individualized pneumoperitoneum strategy during laparoscopic colorectal surgery was feasible and resulted in an adequate working space in most patients at lower intra-abdominal pressure and lower respiratory driving pressure. ClinicalTrials.gov (Trial Identifier: NCT03000465).

Do bread-crust-derived Maillard reaction products affect the retention and tissue distribution of trace elements?

PURPOSE: To investigate the effects of the consumption of Maillard reaction products (MRPs) from bread crust (BC) on iron, copper and zinc body retention and tissue distribution, determining whether these effects are related to the molecular weight of browning products. METHODS: During an 88-day study period, rats were fed a Control diet or diets containing BC as source of MRPs, its soluble high or low molecular weight fractions (BC, LMW or HMW diets). A mineral balance was conducted throughout the experiment to determine iron, copper and zinc retention. At day 88, animals were killed, blood was drawn for haemoglobin determination and some organs removed to analyse minerals. RESULTS: Copper and zinc balances were unchanged, and scant modification detected in their body delivery. However, the Fe retention rate from the diet increased (13, 22 and 32 % for BC, LMW and HMW diets), and a parallel higher Fe body concentration was observed (13-18 % higher than the Control group). Incoming iron accumulated particularly in the liver, femur and small intestine, but functional iron tended to decrease, as reflected by haemoglobin levels. CONCLUSIONS: The long-term intake of BC or derivatives did not produce a notable effect on copper or zinc balances, although slightly increased iron retention rate and the body concentration of this mineral were observed. Iron accumulated in some organs, but the production of haemoglobin was not improved. In view of the differences observed between the effects of BC and its derivatives, our results underline the importance of working with real food matrices, where the joint presence of different components modulates the in vivo final effects.

Effects of dietary bread crust Maillard reaction products on calcium and bone metabolism in rats.

Maillard reaction products (MRP) consumption has been related with the development of bone degenerative disorders, probably linked to changes in calcium metabolism. We aimed to investigate the effects of MRP intake from bread crust on calcium balance and its distribution, and bone metabolism. During 88 days, rats were fed control diet or diets containing bread crust as source of MRP, or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a calcium balance was performed, then animals were sacrified and some organs removed to analyse calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention. Biochemical parameters and bone metabolism markers were measured in serum or urine. Global calcium bioavailability was unmodified by consumption of bread crust or its isolate fractions, corroborating the previously described low affinity of MRP to bind calcium. Despite this, a higher calcium concentration was found in femur due to smaller bones having a lower relative density. The isolate consumption of the fractions altered some bone markers, reflecting a situation of increased bone resorption or higher turnover; this did not take place in the animals fed the bread crust diet. Thus, the bread crust intake does not affect negatively calcium bioavailability and bone metabolism.

Influence of Maillard products from bread crust on magnesium bioavailability in rats.

BACKGROUND: Consumption of Maillard reaction products (MRPs) present in food has been related to deterioration of protein digestibility and changes in mineral bioavailability. We aimed to investigate the effects of MRP intake from bread crust on magnesium balance and tissue distribution, seeking causative factors among its different components. RESULTS: During the final stage of the trial, magnesium digestibility improved by around 15% in rats fed diets containing bread crust or its derivatives compared with the control diet. Despite certain enhancements in magnesium bioavailability in this stage, for the experimental period as a whole, this parameter remained unchanged. However, specific changes in the content and/or concentration in some organs were observed, particularly in the femur, where magnesium levels were higher due to the smaller size of the bones. CONCLUSIONS: Consumption of MRPs from bread crust or its different components did not modify the magnesium balance. Nevertheless, the bread crust fractions led to some changes in magnesium tissue distribution which did not match the effects induced by complete bread crust intake, suggesting the importance of designing studies with real-food systems, in order to reinforce the validity of the findings obtained.

An Individualized Low-Pneumoperitoneum-Pressure Strategy May Prevent a Reduction in Liver Perfusion during Colorectal Laparoscopic Surgery.

High intra-abdominal pressure (IAP) during laparoscopic surgery is associated with reduced splanchnic blood flow. It is uncertain whether a low IAP prevents this reduction. We assessed the effect of an individualized low-pneumoperitoneum-pressure strategy on liver perfusion. This was a single-center substudy of the multicenter 'Individualized Pneumoperitoneum Pressure in Colorectal Laparoscopic Surgery versus Standard Therapy II study' (IPPCollapse-II), a randomized clinical trial in which patients received an individualized low-pneumoperitoneum strategy (IPP) or a standard pneumoperitoneum strategy (SPP). Liver perfusion was indirectly assessed by the indocyanine green plasma disappearance rate (ICG-PDR) and the secondary endpoint was ICG retention rate after 15 min (R15) using pulse spectrophotometry. Multivariable beta regression was used to assess the association between group assignment and ICG-PDR and ICG-R15. All 29 patients from the participating center were included. Median IAP was 8 (25th-75th percentile: 8-10) versus 12 (12,12) mmHg, in IPP and SPP patients, respectively (p < 0.001). ICG-PDR was higher (OR 1.42, 95%-CI 1.10-1.82; p = 0.006) and PDR-R15 was lower in IPP patients compared with SPP patients (OR 0.46, 95%-CI 0.29-0.73; p = 0.001). During laparoscopic colorectal surgery, an individualized low pneumoperitoneum may prevent a reduction in liver perfusion.

Quantum Molecular Resonance Radiofrequency Disc Decompression and Percutaneous Microdiscectomy for Lumbar Radiculopathy.

Within the practice of pain management, one of the most commonly encountered events is low back pain. Lumbar radiculopathy (LR) is a pain syndrome caused by the compression or irritation of the nerve roots in the lower back due to lumbar disc herniation, vertebra degeneration, or foramen narrowing. Symptoms of LR include low back pain that propagates toward the legs, numbness, weakness, and loss of reflexes. The aim of this study is to assess the long-term effectiveness of quantum molecular resonance disc decompression and its combination with a percutaneous microdiscectomy using Grasper© forceps (QMRG) in patients with persistent lumbar radiculopathy (LR) in relation to patient physical stress status. The main outcome measures of this prospective observational study were DN4, NRS, ODI, SF12, PGI, CGI, and MOS Sleep Scale. An improvement 12 months post-intervention was observed in patients without physical stress, presenting better overall results. The mean change was over the minimal clinically important difference in 64.3% of outcome measures studied for the whole sample. QMRG appears to be an effective treatment option for LR, but a reduction in physical stress is needed to ensure long-term effectiveness.

Preliminary data from a 4-year mirror-image and multicentre study of patients initiating paliperidone palmitate 6-monthly long-acting injectable antipsychotic: the Paliperidone 2 per Year study.

Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.

Influence of bread crust-derived Maillard reaction products on phosphorus balance in rats.

BACKGROUND: Maillard reaction products (MRP) improve food palatability and are linked to some positive biological actions. However, diverse negative consequences, some related to protein damage and mineral availability, have been established. AIM OF STUDY: We investigated the effects of MRP, from a bread crust diet, on phosphorus bioavailability and tissue distribution in rats to determine whether these effects are related to the molecular weight of browning products. METHODS: During a study period of 88 days, rats were fed either a control diet or one of the following: with bread crust as a source of MRP, or one with its soluble high molecular weight, soluble low molecular weight or insoluble fraction (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a phosphorus balance was performed, after which the animals were sacrificed and some organs removed to analyse phosphorus content. A second balance was carried out throughout the experimental period to calculate phosphorus retention. RESULTS: Phosphorus balance in the last week was unchanged. However, considering the whole experimental period, a trend towards improved bioavailability, significant in the HMW group, was observed. Higher phosphorus concentrations were measured in the small intestine and bone. CONCLUSIONS: The consumption of MRP derived from bread did not alter phosphorus retention, due to increased bioavailability, especially concerning HMW compounds. The overall phosphorus body content remained unchanged and there were no changes in the bone, its principal metabolic destination. However, MRP consumption markedly raised phosphorus levels at the digestive level, especially when consumed as isolate fractions. The slower rate of stomach emptying is assumed to be related to this effect.

Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project.

Background: Opioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long-term oncologic outcomes. Methods: We investigated the normalized gene expression of µ, κ, δ opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors' gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease-free interval (DFI) and overall survival (OS). Results: We retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63-0.87], KOR: 1.27 [1.17-1.37], DOR: 1.66 [1.48-1.87], TLR4: 0.29 [0.26-0.32], OGFR: 2.39 [2.05-2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long-term oncologic outcomes. Conclusion: Opioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive.

Prevalence of inappropriate prescribing in complex chronic patients: Time trends in a health department of Valencia, Spain (2015-2019).

BACKGROUND AND OBJECTIVE: Inappropriate prescribing (IP) is an important cause of health problems among elderly and complex chronic patients (CCPs). OBJECTIVE: Surveillance of IP prevalence among elderly and CCPs in a health department. IP time trends across the period 2015-2019. METHOD: Descriptive population-based study. SETTING: 'València-Clínic-Malvarrosa' Health Department, Valencia, Spain. PERIOD: 2015-2019. SUBJECTS: Complete set of CCPs in the department, defined by clinical risk groups. Number of CCPs (annual average in the period): 9102 (75% ≥65 years of age). IP was measured using an indicator consisting of 13 specific types of prescriptions defined as inappropriate. ANALYSES: frequencies and time trends, both overall and by specific type. RESULTS: Overall prevalence of IP ranged from 0.276 (2015) to 0.289 (2018) per patient, without time trend. The most frequent inappropriate prescription was type 1: "≥75 years of age with inappropriate medication", which showed a stable rate across the period. Some types of inappropriate prescriptions displayed favourable decreasing time trends, while others showed no change or an unfavourable trend (i.e., joint prescription of absorbents and urinary antispasmodics). CONCLUSIONS: IP prevalence is a serious and persistent problem among the elderly and CCPs, especially in the oldest. It is therefore necessary its continuous surveillance (overall and by specific types of prescription). As well as interventions to optimise prescribing, thus improving the quality and efficiency of care for the elderly and CCPs.

Opioid Receptor Expression in Colorectal Cancer: A Nested Matched Case-Control Study.

Background: There is growing interest in the possible effect of perioperative anesthetic management on the growth and spread of cancer. The impact of perioperative use of opioids on cancer recurrence remains controversial and an assessment cannot yet be established based on current publications. This study aimed to assess the differential expression of opioid receptors between healthy and tumor tissues in patients with stage II and III colorectal cancer undergoing elective surgery by immunohistochemistry (IHC). Methods: Propensity-score matched case-control study nested in a retrospective cohort of patients with stage II or III colorectal. The primary endpoint was the difference in µ-opioid receptor (MOR) expression measured by IHC between tumor and healthy tissue in subject with or without recurrence. Secondary endpoints were to evaluate the differences in Opioid Growth Factor Receptor (OGFR), cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) in the matched sample and from a from samples of colorectal cancer stored in the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Project (GTEx). Results: There was a significant difference in MOR receptor (median 3 [intequartile range IQR: 1-3] and 0 [IQR: 0-2], P<0.001) and OGFR receptor (median 6 [IQR: 5-6] and 2 [IQR: 1-2], P<0.001) in tumor and control tissue respectively. However, there were no significant differences in cAMP nor PKA expression between both types of tissues and in expression in any of the analyzed variables by recurrence status. The MOR and OGFR expression data from TCGA database were similar to our sample size data with lower expression of MOR and higher expression of OGFR in tumoural samples with a skewed distribution for MOR expression in tumor tissue both in patients with and without recurrence. Conclusion: In patients with stage II and III colorectal cancer, overall expression of MOR and OGFR was significantly increased but was not different between previously matched patients with or without recurrence. No differences were found in the analyzed metabolic pathway of cAMP-PKA: These results were confirmed by an in silico analysis of samples from the TCGA-GTEx database.

Modeling intra-abdominal volume and respiratory driving pressure during pneumoperitoneum insufflation-a patient-level data meta-analysis.

During pneumoperitoneum, intra-abdominal pressure (IAP) is usually kept at 12-14 mmHg. There is no clinical benefit in IAP increments if they do not increase intra-abdominal volume IAV. We aimed to estimate IAV (ΔIAV) and respiratory driving pressure changes (ΔPRS) in relation to changes in IAP (ΔIAP). We carried out a patient-level meta-analysis of 204 adult patients with available data on IAV and ΔPRS during pneumoperitoneum from three trials assessing the effect of IAP on postoperative recovery and airway pressure during laparoscopic surgery under general anesthesia. The primary endpoint was ΔIAV, and the secondary endpoint was ΔPRS. The endpoints' response to ΔIAP was modeled using mixed multivariable Bayesian regression to estimate which mathematical function best fitted it. IAP values on the pressure-volume (PV) curve where the endpoint rate of change according to IAP decreased were identified. Abdomino-thoracic transmission (ATT) rate, that is, the rate ΔPRS change to ΔIAP was also estimated. The best-fitting function was sigmoid logistic and linear for IAV and ΔPRS response, respectively. Increments in IAV reached a plateau at 6.0 [95%CI 5.9-6.2] L. ΔIAV for each ΔIAP decreased at IAP ranging from 9.8 [95%CI 9.7-9.9] to 12.2 [12.0-12.3] mmHg. ATT rate was 0.65 [95%CI 0.62-0.68]. One mmHg of IAP raised ΔPRS 0.88 cmH2O. During pneumoperitoneum, IAP has a nonlinear relationship with IAV and a linear one with ΔPRS. IAP should be set below the point where IAV gains diminish.NEW & NOTEWORTHY We found that intra-abdominal volume changes related to intra-abdominal pressure increase reached a plateau with diminishing gains in commonly used pneumoperitoneum pressure ranges. We also found a linear relationship between intra-abdominal pressure and respiratory driving pressure, a known marker of postoperative pulmonary complications.

Off-label use of second-generation antipsychotics in borderline personality disorder: a comparative real-world study among oral and long-acting injectables in Spain.

The aim of the present study was to evaluate the use of oral vs. long-acting injectables (LAIs) antipsychotics, as well as, to compare the effectiveness of different LAI antipsychotics [aripiprazole-1-month, paliperidone-1-month (PP1M), paliperidone-3-month (PP3M) and risperidone long-acting injectable (RLAI)] in patients diagnosed with borderline personality disorder (BPD), by evaluating the following clinical outcomes: (1) the number of hospital admissions; (2) the number of documented suicidal behaviour/attempts; and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics and biperiden. We included a total of 116 patients diagnosed with BPD and treated with antipsychotic medication: 50 using a LAI antipsychotic formulation and 66 using the equivalent main oral antipsychotic. Patients treated with LAIs showed a decreased ratio of visits to emergency compared with the oral treatment group, and between LAIs, PP3M vs. aripiprazole-1-month group. Furthermore, patients treated with LAIs used lower number and dose of concomitant antipsychotics compared with patients treated with oral antipsychotics. Moreover, PP1M and PP3M used lower daily dose of diazepam equivalents compared with the aripiprazole-1-month and RLAI treatment groups. In conclusion, the use of LAIs may play a role in the management of BPD.

Evaluation of Risk Factors Associated to Prescription of Benzodiazepines and its Patterns in a Cohort of Patients from Mental Health: A Real World Study in Spain.

Purpose: we aimed 1) to evaluate the risk factors associated to the benzodiazepines intake; 2) to assess the impact about the use of long acting injectables antipsychotics (LAIs); 3) to assess the risk in severe and affective disorders and 4) to identify the prescription patterns of use in mental health in a cohort of patients from Spain. Methods: 735 outpatients from Mental Health were included. Demographic and clinical data were collected. In order to compare the use of benzodiazepines we calculated the daily dose equivalents (mg/day) to diazepam as standard. Results: The most commonly prescribed benzodiazepine was clonazepam (33%) and the mean daily dose of diazepam equivalents was 24.9 mg. It was higher in affective disorders (40.35 ± 3.36) and lower in patients using LAIs antipsychotics (17.50 ± 1.39; p = 0.001). Multivariate analysis showed that to be women (OR = 1.559, 95% CI = 1.059-2.295, p = 0.024), the use of drugs (OR = 1.671, 95% CI = 1.127-2.477, p = 0.011) and suffering any affective disorder (OR = 1.542, 95% CI = 1.355-1.826, p = 0.040) increased the risk of benzodiazepine intake. In contrast, the use of LAIs antipsychotics significantly reduced it versus oral antipsychotics (OR = 5.226, 95% CI = 3.185-8.575, p = 0.001). Conclusions: benzodiazepines are widely prescribed, mainly clonazepam followed by lorazepam and diazepam. Most of patients used at least one benzodiazepine and the mean daily intake was 25 mg diazepam equivalents. Therefore, benzodiazepines are extensively prescribed and used at higher doses than desirable. These, findings could be useful for clinicians and their practice.

Evaluation of long-acting injectable antipsychotics with the corresponding oral formulation in a cohort of patients with schizophrenia: a real-world study in Spain.

To date, only a few studies compared some long-acting injectables (LAIs) antipsychotics showing similar symptom improvement, relapse rates and adherence to treatment. We evaluated the use of LAIs antipsychotics [aripiprazole-1-month (A1M); paliperidone-1-month and 3-month (PP1M and PP3M) and biweekly (2w)-LAIs] and their corresponding oral formulations through (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviour/attempts and (3) the use of concomitant benzodiazepines, oral antipsychotics and biperiden. A total of 277 patients, ≥18 years old, were included if were treated with the corresponding oral or LAI antipsychotic during at least 12 months and were previously diagnosed with schizophrenia. Our results showed that LAIs associated significantly lower suicidal behaviour, reduced the number of hospital admissions, lower diazepam and haloperidol equivalents and mean daily dose of biperiden intake versus oral antipsychotics. Furthermore, significant differences were found between LAIs. Specifically, PP3M was associated to lower hospital admissions versus A1M; PP1M and PP3M lower doses of diazepam equivalents versus 2w-LAIs and finally, PP1M lower antipsychotic intake versus 2w-LAIs. In conclusion, LAIs improved clinical outcomes by reducing the need for concomitant treatments and hospital admissions over oral antipsychotics. PP1M and PP3M showed better outcomes versus A1M and biweekly LAIs.

Pharmacokinetics of micafungin in patients treated with extracorporeal membrane oxygenation: an observational prospective study. / Farmacocinética da micafungina em pacientes tratados com oxigenação por membrana extracorpórea: um estudo observacional prospectivo.

OBJECTIVE: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. METHODS: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. RESULTS: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. CONCLUSION: The pharmacokinetic parameters of micafungin were not significantly altered.

Long-Acting Injectable Antipsychotics: Analysis of Prescription Patterns and Patient Characteristics in Mental Health from a Spanish Real-World Study.

BACKGROUND AND OBJECTIVE: Long-acting injectable antipsychotics (LAIs) have been widely studied in schizophrenia and evidence suggests that they could be also used for the treatment of bipolar and schizoaffective disorders. Nonetheless, there are no studies evaluating their role in other psychiatric disorders. We aimed to evaluate the use of the newest monthly and 3-monthly LAIs-aripiprazole once monthly, paliperidone 1- and 3-monthly (PP1M, PP3M)-against the 2-weekly LAIs, using the following clinical outcomes: (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviors/attempts, and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics, and biperiden. METHODS: A total of 431 patients were included who were treated with the corresponding LAI over at least 12 months and were previously diagnosed with a psychiatric disorder. Statistical analyses were performed using an ANCOVA model, Student's t test, and the Pearson's r test. RESULTS: Our results showed significantly decreased re-admissions using PP3M versus the bi-weekly LAIs and aripiprazole once monthly, while no significant differences were found in suicidal behavior. Furthermore, we found a significantly lower intake of benzodiazepines in PP1M and PP3M groups versus the bi-weekly and aripiprazole once-monthly groups. In addition, patients treated with PP1M and PP3M used a significantly lower dose of haloperidol equivalents versus the bi-weekly LAIs group. Finally, significantly higher doses of biperiden were used by the bi-weekly LAIs group. CONCLUSION: In conclusion, paliperidone LAIs reduced hospital re-admissions and, as aripiprazole once monthly, lowered concomitant psychiatric medication versus the bi-weekly LAIs. Further research and analysis of subgroups are needed; however, these findings might be useful for clinicians.

Mu Opioid Receptor 1 (MOR-1) Expression in Colorectal Cancer and Oncological Long-Term Outcomes: A Five-Year Retrospective Longitudinal Cohort Study.

Preclinical evidence has shown increased expression of mu opioid receptor 1 (MOR-1) in colorectal cancer although its association with disease-free and overall survival (DFS and OS) has not been investigated. We hypothesized that MOR-1 was overexpressed in tumor samples compared to normal tissue and this was associated with decreased DFS and OS. We carried out a retrospective study assessing the association of MOR-1 tumor expression with long-term outcomes by immunohistochemistry in normal and tumor samples from 174 colorectal cancer patients. The primary endpoint was five years of DFS. Secondary endpoints were five years of OS, the difference in MOR-1 expression between normal and tumor tissue and the occurrence of postoperative complications. Multivariable Cox regression showed no significant association between MOR-1 expression and DFS (HR 0.791, 95% CI 0.603-1.039, p = 0.092). MOR-1 expression was higher in tumor tissue compared to non-tumor tissue. No associations were found between MOR-1 expression and OS or postoperative complications. These findings suggest that although MOR-1 is over-expressed in colorectal cancer samples there is no association to increased risk of recurrence or mortality. Future studies are warranted to elucidate the role of cancer stage, genetic polymorphism, and quantitative assessment of MOR-1 over-expression on long-term outcomes in colorectal cancer.