Development of an In Vitro Drug Release Method to Enable In Vitro-In Vivo Correlation of Potassium Chloride Extended-Release Tablets.

An in vitro drug release test was developed to establish a level A in vitro-in vivo correlation (IVIVC) for predicting the in vivo performance of potassium chloride extended-release (ER) matrix tablets. Three ER formulations of potassium chloride with different in vitro release rates were designed using the USP dissolution test, and their urinary pharmacokinetic profiles were evaluated in healthy subjects. Due to the lack of IVIVC with the USP method, experiments were designed to investigate the effects of in vitro test conditions on drug release in order to match in vitro drug release with in vivo behaviors of different formulations. The evaluated in vitro variables included the type of USP apparatus, surfactant, and ionic strength of the dissolution medium. Based on the study findings and data analysis, a discriminatory drug release method was successfully developed that enabled the establishment and validation of a level A IVIVC model of the potassium chloride ER tablet using urinary pharmacokinetic data. This method uses USP apparatus I at 50 rpm in 900 mL of 150 mM NaCl solution containing 40 mM sodium dodecyl sulfate at 37 °C. The current study highlights the value of investigating test conditions in developing a predictive in vitro test method for establishing IVIVC.

A comparative study of surgical outcomes using a Colorado microdissection needle versus standard-size needle electrocautery in one-stage hypospadias repair using a transverse preputial island flap.

BACKGROUND: The purpose of this study was to compare the surgical outcomes of a Colorado microdissection needle (CMN) with that of a standard-size electrocautery needle in one-stage hypospadias repair using a transverse preputial island flap (TPIF). METHODS: The records of patients who received hypospadias repair from September 2012 to October 2013 were retrospectively reviewed. Patients were divided into a group that received repair using a CMN and those in which a standard-size electrocautery needle was used. Data collected and compared included age, types of hypospadias, duration of surgery, intraoperative blood loss, and postoperative edema and complications. RESULTS: There were 51 patients in the CMN group and 44 in the standard needle group, and the groups were similar with respect to age and type of hypospadias. The median surgery time for the CMN group was significantly shorter than that of the standard group (15.7 minutes vs. 20.6 minutes, respectively, P<0.001). At postoperative day 7 and day 30, the CMN group had significantly less patients with edema than the standard needle group (31.4% vs. 65.9%, P<0.01; and 37.3% vs. 79.5%, P<0.001, respectively). The overall complication rate has no significant difference between two groups. CONCLUSIONS: The use of CMN for tissue dissection and separation in hypospadias repair can facilitate foreskin degloving, shape the flap in a more efficient way, and help maintain adequate blood supply for the new urethra and its skin coverage.

Joint parameter estimation in the QTL mapping of ordinal traits.

With the rapid development of statistical genetics, the deep researches of ordinal traits have been gradually emphasized. The data of these traits bear relatively less information than those of continuous phenotypes, therefore it is more complex to map the quantitative trait loci (QTL) of ordinal traits. In this paper, the multiple-interval mapping method is considered in the genetic mapping of ordinal traits. By combining threshold model and statistical model, we build a cumulative logistic regression model to express the relationship between the ordinal data and the QTL genotypes. In order to make the interval mapping more straightforward, we treat the recombination rates as unknown parameters, and then simultaneously obtain the estimates of QTL positions, QTL effects and threshold parameters via the EM algorithm. We perform simulation experiments to investigate and compare the proposed method. We also present a real example to test the reasonableness of the considered model and estimate both model parameters and QTL parameters. Both results of simulations and example show that the method we proposed is reasonable and effective.

Development of In Vitro-In Vivo Correlation for Potassium Chloride Extended Release Tablet Formulation Using Urinary Pharmacokinetic Data.

PURPOSE: To develop and validate a Level A in vitro-in vivo correlation (IVIVC) for potassium chloride extended-release (ER) formulations. METHODS: Three prototype ER formulations of potassium chloride with different in vitro release rates were developed and their urinary pharmacokinetic profiles were evaluated in healthy subjects. A mathematical model between in vitro dissolution and in vivo urinary excretion, a surrogate for measuring in vivo absorption, was developed using time-scale and time-shift parameters. The IVIVC model was then validated based on internal and external predictability. RESULTS: With the established IVIVC model, there was a good correlation between the observed fraction of dose excreted in urine and the time-scaled and time-shifted fraction of the drug dissolved, and between the in vitro dissolution time and the in vivo urinary excretion time for the ER formulations. The percent prediction error (%PE) on cumulative urinary excretion over the 24 h interval (Ae0-24h) and maximum urinary excretion rate (Rmax) was less than 15% for the individual formulations and less than 10% for the average of the two formulations used to develop the model. Further, the %PE values using external predictability were below 10%. CONCLUSIONS: A novel Level A IVIVC was successfully developed and validated for the new potassium chloride ER formulations using urinary pharmacokinetic data. This successful IVIVC may facilitate future development or manufacturing changes to the potassium chloride ER formulation.

Enhancing tube feeding method for neurosurgery: the application of improved PICC technique.

BACKGROUND AND PURPOSE: Peripherally inserted central catheter (PICC) used in neurosurgical patients requires changes in patients' head positions. However, such changes can worsen pressure on the brain tissue, lead to sudden acute brain herniation and respiratory arrest, resulting in a higher chance of patient death. This paper addresses the aforementioned problems by introducing a new PICC catheterization method. METHOD: In a retrospective study, the records of patients with PICC from April 2020 to April 2023 were reviewed, and they were divided into three groups based on the methods employed. The first group as the conventional group, involved changing patients' body positions during catheterization. The second group, as the intracavitary electrocardiographic (IECG) group, utilized intracavitary electrocardiographic monitoring and involved changing patients' body positions during catheterization. The third group as the intracavitary electrocardiographic with improved body positioning (IECG-IBP) group, catheterization was performed with guidance from intracavitary electrocardiographs and without changing the patients' body positions. The ECG changes among patients undergoing different catheter delivery methods were then compared, as well as the rate of catheter tip misplacement. RESULT: The study encompassed a total of 354 cases. Our findings reveal distinct P wave amplitude percentages among the groups: 0% in the conventional group, 88.46% in the IECG group, and 91.78% in the IECG-IBP group. Furthermore, the following catheter tip misplacement rates were recorded: 11.54% for the conventional group, 5.39% for the IECG group, and 5.47% for the IECG-IBP group. Significantly notable differences were observed in these two key indicators between the conventional group and the IECG-IBP group. Notably, the IECG-IBP group demonstrated a more favorable outcome compared to the IECG group. CONCLUSION: In patients with neurosurgical diseases, especially those with tracheostomy and nuchal stiffness, the IECG-IBP PICC catheter insertion method can effectively reduce the patient's neck resistance, does not increase the patient's headache and dizziness symptoms, and does not reduce the success of one-time catheterization. Rate and does not increase the incidence of jugular venous ectopia.

Phosphene object perception employs holistic processing during early visual processing stage.

Psychophysical studies have verified the possibility of recovering the visual ability by the form of low-resolution format of images, that is, phosphene-based representations. Our previous study has found that early visual processing for phosphene patterns is configuration based. This study further investigated the configural processing mechanisms of prosthetic vision by analyzing the event-related potential components (P1 and N170) in response to phosphene face and non-face stimuli. The results reveal that the coarse processing of phosphenes involves phosphene-specific holistic processing that recovers separated phosphenes into a gestalt; low-level feature processing of phosphenes is also enhanced compared with that of normal stimuli due to increased contrast borders introduced by phosphenes; while fine processing of phosphene stimuli is impaired reflected by reduced N170 amplitude because of the degraded detailed features in the low-resolution format representations. Therefore, we suggest that strategies that can facilitate the specific holistic processing stages of prosthetic vision should be considered in order to improve the performance when designing the visual prosthesis system.

Prevention of hospital-acquired transnasal tube-related pressure injuries: a quality improvement project.

BACKGROUND: Nurses certified in wound, ostomy, and continence (WOC) monitored an increasing incidence of hospital-acquired transnasal tube-related pressure injuries (TTPIs) in a tertiary hospital. Hospital-acquired pressure injuries are one of the most common preventable complications of hospitalization; however, the significance of TTPI prevention must be considered alongside the safety of tube fixation to prevent unplanned extubations (UEs), which are serious adverse events. Thus, exploring a quality improvement (QI) project to effectively reduce the risk of TTPIs while safeguarding tube safety is urgently needed. PURPOSE: To decrease the incidence of TTPIs. METHODS: Inpatients from 2017 to 2018 were set as the control group, using routine precautions. Inpatients from 2019 to 2020 were set as the experimental group, and a bundle of training and clinical practice interventions was implemented to compare the incidence of TTPIs and UEs between the 2 groups. RESULTS: After improvement, the incidence of TTPIs reduced from 1.20% to 0.69%, the incidence of UEs reduced from 2.40% to 1.63%, and the differences were both statistically significant (P < .05). CONCLUSION: The QI project reduced the incidence of TTPIs and UEs, thereby protecting the nasal skin/mucosal surfaces, safeguarding tube fixation, and ultimately improving the quality of clinical care.

Prognostic Factors Influencing the Tinnitus Improvement After Idiopathic Sudden Sensorineural Hearing Loss Treatment.

PURPOSE: Logistic regression analysis was used to explore the factors that influence tinnitus improvement after idiopathic sudden sensorineural hearing loss (ISSNHL) treatment. MATERIALS AND METHODS: In this retrospective study, 137 ISSNHL patients with tinnitus were recruited at the Sun Yatsen Memorial Hospital of Sun Yat-sen University, China. They underwent audiological examinations, vestibular assessments, tinnitus examinations, a Tinnitus Handicap Inventory (THI) assessment and ISSNHL treatments. Logistic regression analysis was performed to investigate factors that affected tinnitus improvement. RESULTS: Participants were divided into an effective group (73 patients) and noneffective group (64 patients) according to THI scores before and after treatment. The effective group had better averaged hearing threshold than the noneffective group (effective group vs. noneffective group: 74.47 vs. 87.66 dB HL; t = 3.03, p < 0.05). Additionally, before intervention there were significant difference in profound audiogram configuration (effective group vs. noneffective group: 17.81% vs. 46.88%, x2 = 23.63; p < 0.001), mid tinnitus pitch (effective group vs. noneffective group: 19.18% vs. 35.94%, x2 = 6.58; p = 0.037) and mean THI scores (effective group vs. noneffective group: 57.07 ± 22.27 vs. 36.78 ± 24.41, t = -5.09, p < 0.001) between the effective and noneffective tinnitus groups. Logistic regression analysis showed that audiogram configurations (profound audiogram: OR = 0.10, 95% CI 0.01-0.72, p = 0.022), tinnitus pitch (mid tinnitus pitch: OR = 0.16, 95% CI 0.05-0.57, p = 0.004) and THI scores (OR = 1.05, 95% CI 1.03-1.07, p < 0.001) were independent factors associated with tinnitus improvement. CONCLUSION: Audiogram configuration, tinnitus pitch, and THI scores before intervention appear to be predictive of the effectiveness of acute tinnitus improvement following ISSNHL treatment.

Early event-related potential components in face perception reflect the sequential neural activities.

Event-related potential (ERP) studies report that early components P120, N170 and VPP are associated with face processing. Several lines of evidence suggest that VPP is the positive counterpart of N170, and they are generated by the same brain sources. However, whether P120 has a negative counterpart and the relations among these early components (i.e. P120, N170, VPP) remain unclear. In this study, the scalp electroencephalogram was recorded when the subjects passively viewed different stimuli, and ERP was calculated. The synchronization of electroencephalography signals between fronto-central and bilateral occipitotemporal sites was evaluated, and independent component analysis was employed to seek the face-sensitive independent components and their corresponding sources. We found that P120 had the negative counterpart, i.e., VN120; moreover, VN120-VPP and P120-N170 complexes were generated by the same sources located in fusiform gyrus, which reflected the same sequential neural activities of face processing.

Configuration-based processing of phosphene pattern recognition for simulated prosthetic vision.

Visual prosthesis can elicit phosphenes by stimulating the retina, optic nerve, or visual cortex along the visual pathway. Psychophysical studies have demonstrated that visual function can be partly recovered with phosphene-based prosthetic vision. This study investigated the cognitive process of prosthetic vision through a face recognition task. Both behavioral response and the face-specific N170 component of event-related potential were analyzed in the presence of face and non-face stimuli with natural and simulated prosthetic vision. Our results showed that: (i) the accuracy of phosphene face recognition was comparable with that of the normal one when phosphene grid increased to 25 x 21 or more; (ii) shorter response time was needed for phosphene face recognition; and (iii) the N170 component was delayed and enhanced under phosphene stimuli. It was suggested that recognition of phosphene patterns employ a configuration-based holistic processing mechanism with a distinct substage unspecific to faces.

Object recognition under distorted prosthetic vision.

Psychophysical studies have reported the efficacy of phosphene-based prosthetic vision in partly recovering the visual function of blind individuals. However, results by far have been based on evenly aligned phosphene arrays, which neglected the complicated visuotopy in the visual prosthesis system. In this study, we investigated how the objects were recognized under the stimuli with distorted phosphene arrays simulated by transformations of barrel distortion, rotation, or translation. The results revealed that distortions significantly decreased the accuracy of categorization (CA) and showed distinct interactive effects with the factors of object category and phosphene array density. Moreover, the CA changed differently with the increase of distortion levels. Regression analysis suggested a phosphene array of at least 10 × 10 be the essential for achieving a CA over the threshold value (CA(t)=62.5%) under distorted prosthetic vision. It is recommended that discriminative features be extracted to improve the performance of prosthetic vision.

Application of a surgical nursing cooperation program in laparoscopic pancreaticoduodenectomy.

BACKGROUND: To evaluate the value of programmed surgical nursing in laparoscopic pancreaticoduodenectomy (LPD) and summarize the experience. METHODS: The clinical data of 80 patients who received LPD in Sun Yat-sen Memorial Hospital from January 2017 to December 2018 were analyzed retrospectively. A total of 40 patients were treated with traditional surgical nursing as the control group in the earlier stage. Afterwards, another 40 cases in the experimental group were treated using the surgical nursing program. Operation time, blood loss, and satisfaction of surgeons were analyzed. RESULTS: In all, 80 cases were successfully completed, and no significant difference was observed in the preoperative data statistics between these two groups (P>0.05). Compared with the control group, the average operation time and the average blood loss of the experimental group were significantly reduced (288.9±11.14 vs. 364.5±10.84 min, P<0.05; 135.3±20.12 vs. 364.8±77.39 mL, P<0.05), and the satisfaction of surgeons was significantly higher (95% vs. 80%, P<0.05). CONCLUSIONS: Skilled execution of nursing cooperation is crucial in LPD. Through appropriate preoperative preparation, gaining mastery operation steps, remaining in sync with surgeons, and perfecting the management details, the surgical nursing cooperation program can improve the satisfaction of the surgeons and make operations more efficient.

Abnormal EEG complexity in patients with schizophrenia and depression.

OBJECTIVE: Schizophrenics are usually unable to perform well on cognitive tasks due to disturbances in cortical information processing that are observable as abnormalities in electroencephalogram (EEG) signals. However, whether such cortical disturbances can be assessed by quantitative EEG analysis remains unclear. The purpose of this study was to characterize EEG disturbances, using the Lempel-Ziv complexity (LZC), in the subjects with schizophrenia at rest or while performing mental arithmetic tasks. The results were compared to those from the subjects with depression and with healthy controls. METHODS: The subjects included 62 schizophrenia patients, 48 depression patients and 26 age-matched healthy controls. EEG was recorded under two conditions: (i) resting with eyes closed, and (ii) a mentally active condition wherein the subjects were asked to subtract 7 from 100 iteratively with their eyes closed. EEG signals were analyzed by LZC and conventional spectral methods. RESULTS: In all the groups, LZC of EEG decreased during the mental arithmetic compared with those under the resting conditions. Both the schizophrenia and the depression groups had a higher LZC (p<0.05) than the controls. Also, the schizophrenia group had a lower LZC (p<0.05) than the depression group during the mental arithmetic task as well as during the resting state. Significant differences in LZC, at some symmetrically located loci (FP1/FP2, F7/F8), between the two hemispheres were found in all the patient groups only during the arithmetic task. CONCLUSIONS: Compared with conventional spectral analysis, LZC was more sensitive to both the power spectrum and the temporal amplitude distribution. LZC was associated with the ability to attend to the task and adapt the information processing system to the cognitive challenge. Thus, it would be useful in studying the disturbances in the cortical information processing patients with depression or schizophrenia. SIGNIFICANCE: LZC of EEG is associated with mental activity. Thus, LZC analysis can be an important tool in understanding the pathophysiology of schizophrenia and depression in future studies.

Attention rivalry under irrelevant audiovisual stimulation.

Audiovisual integration has been known to enhance perception; nevertheless, another fundamental audiovisual interaction, i.e. attention rivalry, has not been well investigated. This paper studied the attention rivalry under irrelevant audiovisual stimulation using event-related potential (ERP) and behavioral analysis, and tested the existence of a vision dominated rivalry model. Participants need respond to the target in a bi- or unimodal audiovisual stimulation paradigm. The enhanced amplitude of central P300 under visual target bimodal stimulus indicated that vision demanded more cognitive resources, and the significant amplitude of frontal P200 under bimodal stimulus with non-target auditory stimulus implied that the brain mostly restrained the process of the non-target auditory information. ERP results, together with the analysis of the behavioral data and the subtraction waves, indicated a vision dominated attention rivalry model involved in audiovisual interaction. Furthermore, the latencies of P200 and P300 components implied that audiovisual attention rivalry occurred within the first 300ms after stimulus onset, i.e. significant differences were found in P200 latencies among three target bimodal stimuli, while no difference existed in P300 latencies. Attention shifting and re-directing might be the cause of such early audiovisual rivalry.

[Recurrence plot analysis of HRV for brain ischemia and asphyxia].

Heart rate variability (HRV) is the tiny variability existing in the cycles of the heart beats, which reflects the corresponding balance between sympathetic and vagus nerves. Since the nonlinear characteristic of HRV is confirmed, the Recurrence Plot method, a nonlinear dynamic analysis method based on the complexity, could be used to analyze HRV. The results showed the recurrence plot structures and some quantitative indices (L-Mean, L-Entr) during asphyxia insult vary significantly as compared to those in normal conditions, which offer a new method to monitor brain asphyxia injury.

[Review of visual prosthesis (I)--retinal prosthesis].

Research on how to totally or partially restore the vision has attracted more attention in the fields of neural engineering and tissue engineering. Neural interface and visual prosthesis offer alternative ways for partially repairing the visual impairment. The most widely used visual prosthetics are based on retinal stimulation. This article is a state-of-art review of the principles, technical details and the limitations of retinal prosthesis.

[Review of visual prosthesis (II)--cortical visual prosthesis, optic nerve prosthesis and vision substitution devices].

Cortical visual prosthesis, optic nerve visual prosthesis and vision substitution devices are alternative ways for repairing the visual impairment in case of optic nerve injury, retina lose or blindness without fully developed central visual system. This article is a state-of-art review of the principles, technical details and the limitations of different types of prostheses beyond the retinal prosthesis.

[Review of researches on retinal model].

Retinal model is an essential part in the retinal prosthesis. Based on the retinal physiology and the experimental data, the model is able to simulate the information processing in the retina, and can be used to investigate the relation between the input image and the neuron firing. We can categorize the models into circuit realization and algorithm realization. This article is a state-of-art review of different types of retinal models.

Complex character analysis of heart rate variability following brain asphyxia.

In the present study Renyi entropy and L-Z complexity were used to characterize heart rate variability (HRV) of rats that were suffered from brain asphyxia and ischemia. Two groups of rats were studied: (a) rats (n=5) injected with NAALADase inhibitor, 2-PMPA, which has been proven neuroprotective in asphyxia injury and (b) control subjects (n=5) without medication. Renyi entropy and L-Z complexity of the R-R intervals (RRI) at different experiment stages were investigated in the two groups. The results show that both measures indicate less injury and better recovery in the drug injection group. The dynamic change of 90 min RRI signal after the asphyxia was investigated. The sudden reduction of the two parameters shows their sensitivity to the asphyxia insult.

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory guidance should be reevaluated to assure consistent safety and efficacy among different strengths.