A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

A rating scale for drug-induced akathisia

The aim of this study was to develop levosulpiride-loaded solid lipid nanoparticles (SLNs) with enhanced solubilisation and bioavailability. The levosulpiride loaded-SLNs were composed of levosulpi...

Development of levosulpiride-loaded solid lipid nanoparticles and their in vitro and in vivo comparison with commercial product

Herein, we investigate the potential of levosulpiride-loaded nanostructured lipid carriers (LEVO-NLCs) for effective brain delivery with anti-psychotic and antidepressant effects.Micro-emulsion method was used to prepare LEVO-NLCs, followed by its optimization using Design Expert®, investigation of the particles properties and entrapment efficiency (%EE). Moreover, in-vitro release, in-vivo plasma and brain kinetic studies of LEVO-NLCs were executed. Anti-psychotic activity of LEVO-NLCs was accomplished in LPS-induced psychosis mice model. Additionally, expressions of neuro inflammatory mediators, neurodegeneration and neuro-inflammation in brain tissues was investigated.The optimized LEVO-NLCs were rounded shaped nanoparticles (157.2 nm) with suitable zeta potential (-29.6 mV), low PDI (0.395) and high EE (83.67 %). No chemical interactions were found, however, the crystalline drug was changed to amorphous. LEVO-NLCs displayed sustained drug release behavior when compared with drug suspension. Moreover, a meaningfully higher AUC (106,642.27 ± 876.44 ng.h/mL) and Cmax (38,534.72 ± 2344.10 ng/mL) of the LEVO-NLCs in brain was observed as compared to the AUC (15,684.33 ± 1005.49 ng.h/mL) and Cmax (7717.56 ± 871.23 ng/mL) of LEVO-Suspension. Similar profiles of both the formulations were perceived in plasma pharmacokinetic studies. Furthermore, LEVO-NLCs exhibited a meaningfully improved anti-psychotic activity in LPS-induced psychosis mice model with reduced immobility time and enhanced struggling time. Likewise, treatment with LEVO-NLCs showed reduced levels of neuro inflammatory markers (p-NF-κB and COX-2) in LPS-induced mice. Additionally, no neuro-degeneration and neuro-inflammation in brain tissues treated with LEVO-NLCs mice group was detected.These results concluded that NLCs may effectively be used for the brain delivery of various active pharmaceutical agents with enhanced biopharmaceutical performance. 

Levosulpiride-loaded nanostructured lipid carriers for brain delivery with antipsychotic and antidepressant effects.

Background The coronavirus disease 2019 (COVID-19) is a systemic illness that implies neurological features and complications. Persistent (>48 hours) hiccups (ie, singultus or hiccoughs) have been recently described as a rare presentation of COVID-19. Even when considered benign, the frequency and duration of hiccup spells can be burdensome and sometimes difficult to treat. Case presentation We report the case of a 62-year-old man known by the treating physicians for vascular cognitive impairment, who consulted for progressive persistent hiccups that commenced 5 days earlier, about 24 hours after testing positive for the severe acute respiratory syndrome coronavirus 2 by real-time reverse transcription polymerase chain reaction. The patient could barely sleep because the hiccups reached the highest rate of 47 per minute in a spell lasting almost 72 hours. The patient initially received levomepromazine 25 mg by mouth, but sedation and delirium impeded the continuation of treatment, which only reduced the frequency of the hiccup spells by about 25%. Afterward, the patient was offered levosulpiride 25 mg thrice a day by mouth, resulting in a steady reduction in the hiccups rate, as well as the duration and daily frequency of spells, which disappeared after 3 days of levosulpiride treatment. COVID-19 pneumonia was moderate by chest computed tomography scan imaging and biomarkers, meriting continuous oxygen therapy, dexamethasone 6 mg once a day by mouth for 10 days, and enoxaparin 40 mg once a day, subcutaneously, for 7 days (due to elevated D-dimer serum concentration). Oxygen therapy was gradually withdrawn after 12 days. Conclusions Oral levosulpiride is a suitable option in persistent hiccups that occur in patients with COVID-19 pneumonia. To our knowledge, this is the fourth published case of persistent hiccups as a clinical feature of COVID-19.

Levosulpiride Relieved Persistent Hiccups in a Patient With COVID-19 and Vascular Cognitive Impairment.

Background and aims Liver diseases are frequent causes of morbidity and mortality worldwide. Liver diseases can lead to cirrhosis, with the risk of acute-on-chronic liver failure (ACLF). For the detection of changes in hepatic hemodynamics, Doppler ultrasonography is a well-established method. We investigated hepatic hemodynamics via serial Doppler ultrasonography to determine the predictive value of changes in hepatic perfusion for the outcome in patients with severe liver diseases compared to established prognostic models such as the MELD (Model for End-Stage Liver Disease) or CLIF-C (Chronic Liver Failure-Consortium) ACLF score. Methods In this prospective cohort study, hepatic perfusion was quantified at baseline before the initiation of treatment and every third day by means of serial measurements of the hepatic artery resistance index (HARI) and the maximum portal vein velocity (PVv) using Doppler ultrasonography in 50 consecutive patients with severe liver diseases admitted to a medical intensive care unit (MICU). The recorded hemodynamic parameters were compared to the MELD score, and the CLIF-C ACLF score to analyze their utility for the prediction of the outcome of patients with severe liver diseases, liver cirrhosis, and ACLF. Results The changes (delta) obtained by serial measurements of the MELD score, HARI, and PVv were analyzed through scatter plots. Bivariate correlation analysis yielded a new positive linear correlation between the delta-HARI and the delta-MELD score (r = 0.469; p < 0.001). In addition, our data revealed a new negative linear correlation between delta-PVv and the delta-MELD score (r = −0.279, p = 0.001). The leading cause of MICU mortality was acute-on-chronic liver failure (ACLF). A subgroup analysis of patients with liver cirrhosis revealed a positive linear correlation between the delta-HARI and the delta-CLIF-C-ACLF score (r = 0.252, p = 0.005). Of clinical relevance, non-survivors of ACLF exhibited a significantly higher mean value for the delta-HARI (0.010 vs. −0.005; p = 0.015) and a lower mean value for the delta-PVv (−0.7 vs. 1.9 cm/s; p = 0.037) in comparison to survivors of ACLF. Conclusion This study shows the prognostic value of the assessment of hepatic perfusion in critical care patients with severe liver diseases by bedside Doppler ultrasound examination and its utility as an accurate predictor of the outcome in patients with ACLF. Increasing HARI and a decreasing PVv are predictors of an adverse outcome. Delta-HARI and delta-PVv are new biomarkers of prognosis and ACLF-related mortality in patients with liver diseases. Delta-HARI and delta-PVv may be helpful in guiding clinical decision-making, especially in catecholamine and fluid management.

/pdf/hepatic-perfusion-as-a-new-predictor-of-prognosis-and-182d981g.pdf

Hepatic perfusion as a new predictor of prognosis and mortality in critical care patients with acute-on-chronic liver failure

A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial].

Background: Injectable antipsychotics are frequently required for controlling agitation and aggression in acute psychosis. No study has examined the use of injectable levosulpiride for this indication.
Objective: To compare the efficacy and safety of injectable levosulpiride and haloperidol in patients with acute psychosis.
Methods: This was a randomized, double-blind, parallel-group study in which 60 drug-naive patients having acute psychosis were randomly assigned to receive either intramuscular haloperidol (10–20 mg/d) or levosulpiride (25–50 mg/d) for 5 days. All patientswere rated on Brief Psychiatric Rating Scale (BPRS), Overt Agitation Severity Scale (OASS), Overt Aggression Scale–Modified (OAS-M) scores, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS).
Results: Repeated-measures ANOVA for BPRS scores showed significant effect of time (P < 0.001) and a trend toward greater reduction in scores in haloperidol group as shown by group � time interaction (P = 0.076). Repeated-measures ANOVA for OASS showed significant effect of time (P < 0.001) but no group � time interaction. Repeatedmeasures ANOVA for OAS-M scores showed significant effect of time (P < 0.001) and greater reduction in scores in haloperidol group as shown by group � time interaction (P = 0.032). Lorazepam requirement was much lower in haloperidol group as compared with those receiving levosulpiride (P = 0.022). Higher rates of akathisia and extrapyramidal symptoms were noted in the haloperidol group.
Conclusions: Haloperidol was more effective than levosulpiride injection for psychotic symptoms, aggression, and severity of agitation in acute psychosis, but extrapyramidal adverse effects were less frequent with levosulpiride as compared with those receiving haloperidol.

Efficacy and safety of levosulpiride versus haloperidol injection in patients with acute psychosis: A randomized double-blind study

Background and aim The major barrier to oral health care for geriatrics is access to dental care. Teledentistry is the field of dentistry that uses telecommunication with digital imaging for the exchange of valid information for diagnosis, treatment, and continuing dental education, enabling some means of approach to oral health care. This study aimed to assess the accuracy of diagnosing dental caries in the older age group by examining intraoral photographs taken by smartphone camera compared with standard clinical dental examination. Methods and material A calibrated dentist examined 18 patients aged 60-75 for six variables: sound tooth, decayed tooth, filled tooth with and without caries, missing tooth, and the presence of prosthesis. Intraoral photographs of each patient were taken using a smartphone. The photographs were then sent to six different examiners through WhatsApp. The accuracy of the diagnosis was measured by applying Cohen's kappa, sensitivity, and specificity. Fleiss' kappa was used to measure the agreement index using the software R (R Foundation for Statistical Computing, Vienna, Austria) version 4.2.1. Results The overall agreement between the tele-examiners and the control was measured, with the kappa scores ranging from 0.897 to 0.921, and the mean kappa score was 0.909. There was high specificity and sensitivity in the value observed. The agreement index, measured through Fleiss' kappa for six teeth conditions, reported the perfect agreement (0.867) among six examiners. Conclusions Under the limitations of the study, teledentistry using a mobile phone has acceptable accuracy for diagnosing caries in the older age group compared to a standard clinical dental examination.

/pdf/the-efficacy-of-dental-caries-telediagnosis-using-smartphone-11cb37er.pdf

Abhinav Kumar

Papers

A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial].

Efficacy and safety of levosulpiride versus haloperidol injection in patients with acute psychosis: A randomized double-blind study

The Efficacy of Dental Caries Telediagnosis Using Smartphone: A Diagnostic Study in Geriatric Patients