QbD driven targeted pulmonary delivery of dexamethasone-loaded chitosan microspheres: Biodistribution and pharmacokinetic study.

Inhaling drugs, on the other hand, is limited mainly by the natural mechanisms of the respiratory system, which push drug particles out of the lungs or make them inefficient once they are there. Because of this, many ways have been found to work around the problems with drug transport through the lungs. Researchers have made polymeric microparticles (MP) and nanoparticles as a possible way to get drugs into the lungs. They showed that the drug could be trapped in large amounts and retained in the lungs for a long time, with as little contact as possible with the bloodstream. MP were formulated in this study to get dexamethasone (DMC) into the pulmonary area. The Box-Behnken design optimized microspheres preparation to meet the pulmonary delivery prerequisites. Optimized formulation was figured out based on the desirability approach. The mass median aerodynamic diameter (MMAD) of the optimized formula (O-DMC-MP) was 8.46 ± 1.45 µm, and the fine particle fraction (FPF) was 77.69 ± 1.26%. This showed that it made suitable drug delivery system, which could make it possible for MP to settle deeply in the lung space after being breathed in. With the first burst of drug release, it was seen that drug release could last up to 16 h. Also, there was no clear sign that the optimized formulation was toxic to the alveoli basal epithelial cells in the lungs, as supported by cytotoxic studies in HUVEC, A549, and H1299 cell lines. Most importantly, loading DMC inside MP cuts the amount of drug into the bloodstream compared to plain DMC, as evident from biodistribution studies. Stability tests have shown that the product can stay the same over time at both the storage conditions. Using chitosan DMC-MP can be a better therapeutic formulation to treat acute respiratory distress syndrome (ARDS).

Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition.

Polyvinylpyrrolidone (PVP) is a water-soluble polymer obtained by polymerization of monomer N-vinylpyrrolidone. PVP is an inert, non-toxic, temperature-resistant, pH-stable, biocompatible, biodegradable polymer that helps to encapsulate and cater both hydrophilic and lipophilic drugs. These advantages enable PVP a versatile excipient in the formulation development of broad conventional to novel controlled delivery systems. PVP has tunable properties and can be used as a brace component for gene delivery, orthopedic implants, and tissue engineering applications. Based on different molecular weights and modified forms, PVP can lead to exceptional beneficial features with varying chemical properties. Graft copolymerization and other techniques assist PVP to conjugate with poorly soluble drugs that can inflate bioavailability and even introduces the desired swelling tract for their control or sustained release. The present review provides chemistry, mechanical, physicochemical properties, evaluation parameters, dewy preparation methods of PVP derivatives intended for designing conventional to controlled systems for drug, gene, and cosmetic delivery. The past and growing interest in PVP establishes it as a promising polymer to enhance the trait and performance of current generation pharmaceutical dosage forms. Furthermore, the scrutiny explores existing patents, marketed products, new and futuristic approaches of PVP that have been identified and scope for future development, characterization, and its use. The exploration spotlights the importance and role of PVP in the design of Povidone-iodine (PVP-I) and clinical trials to assess therapeutic efficacy against the COVID-19 in the current pandemic scenario.

Comprehensive cytokine profiling provides evidence for a multi-lineage Th responses in Guillain Barré Syndrome.

Guillain Barré Syndrome (GBS) is one of the commonest acquired immune-mediated neuropathies, often preceded by infections. Although cellular immune responses are shown to substantially account for the pathophysiology of GBS, the precise mechanistic basis of risk and disease course remains enigmatic till date. Cytokines are best known for their abilities to drive cellular immunity and inflammation through their co-ordinated actions. Data obtained from clinical and animal model studies suggest important implications of some of the cytokines in the progression and recovery of GBS. However, these studies were performed on few cytokines and small set of GBS patients, thereby lacking a complete understanding of the patterns of association of cytokines representing Th1, Th2, and Th17 responses with GBS. We studied 65 well-characterized GBS patients and 73 age- and sex-matched healthy controls. A panel of 15 cytokines representing Th1, Th2 and Th17 pathways was assayed using Multiplex Suspension Array platform. Plasma levels of five cytokines were found to be altered in GBS patients compared to healthy control subjects: (i) IL-1ß exhibited reduced levels, and (ii) IFN-γ, IL-4, IL-21 and IL-33 were elevated in GBS patients. The most important finding of this study was up-regulated expression of IL-21 and IL-33 in patients with GBS. Given the role of IL-33 as an alarmin, the elevated level of this cytokine provides important indication about a much broader role of cytokines in GBS. This study also provides evidence towards a multi-lineage Th cells (Th1, Th2 and Th17) associated cytokine responses in the pathophysiology of GBS.

A Comparative Study of Midazolam and Target-Controlled Propofol Infusion in the Treatment of Refractory Status Epilepticus.

BACKGROUND: The recommended treatment for refractory status epilepticus (RSE) is the use of anesthetic agents, but evidence regarding the agent of choice is lacking. This study was designed to compare target-controlled infusion of propofol versus midazolam for the treatment of RSE regarding seizure control and complications. METHODS: This prospective, randomized study recruited 23 adult patients with RSE due to any etiology and treated with either propofol or midazolam titrated to clinical seizure cessation and gradual tapering thereafter. The primary outcome measure was seizure control and the secondary outcomes were duration of the Intensive Care Unit stay and duration of mechanical ventilation, occurrence of super RSE (SRSE), and complications. RESULTS: We recruited 23 patients (male:female = 18:5) into this study (propofol Group-11; midazolam Group-12). Overall, seizure control was noted in 34.8%, with successful seizure control in 45% of patients in the propofol group and 25% in midazolam group (P = 0.4). Mortality was similar in both the groups (propofol group [8/11; 72.7%] compared to the midazolam group [7/12; 58.3%] [P = 0.667]). The duration of hospital stay was significantly shorter in the propofol group compared to midazolam (P = 0.02). The overall incidence of SRSE was 69.5% in this study. The complication rate was not significantly different between the groups. CONCLUSIONS: The choice of anesthetic agent does not seem to affect the overall outcome in RSE and SRSE. Target-controlled propofol infusion was found to be equal in its efficacy to midazolam for the treatment of RSE. High mortality might be due to SRSE secondary to the underlying brain pathology.

Effect of propofol anesthesia on resting state brain functional connectivity in Indian population with chronic back pain.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies in healthy volunteers have shown alterations in brain connectivity following anesthesia as compared to the awake state. It is not known if the anesthesia-induced changes in brain connectivity are different in a pathological state. This study aims to evaluate changes in the resting state functional connectivity in the brain, after propofol anesthesia, in patients with chronic back pain (CBP). MATERIALS AND METHODS: Fourteen adults with CBP were included in this prospective study over 6 months. After excluding structural brain pathology, a resting state fMRI was performed in the awake state, and the sequences were repeated after propofol anesthesia. The primary outcome measure was change in resting state connectivity after propofol. Student's t-test was performed between the pre and post-propofol sedation data of all patients with total brain volume as covariates of interest. A repeated measures analysis of variance was used to compare pre- and post-propofol changes in cardiorespiratory parameters. RESULTS: There were 8 male and 6 female patients in the study, and the mean age of the study population was 46.9 ± 11.3 years. Propofol sedation resulted in an increased strength of functional connectivity between the posterior cingulate cortex (PCC) and thalamus in patients with CBP, whereas there was a generalized decrease in functional integration within the large scale brain networks. The changes in cardiorespiratory parameters before and after propofol administration were not statistically significant. CONCLUSION: Strengthening of functional connectivity was seen between PCC and thalamus with decrease in large scale brain networks following propofol anesthesia in patients with CBP. These changes are similar to those previously described in normal volunteers.

Adsorption mechanism of graphene-like ZnO monolayer towards CO2 molecules: enhanced CO2 capture.

This work aims to efficiently capture CO2 on two-dimensional (2D) nanostructures for effective cleaning of our atmosphere and purification of exhausts coming from fuel engines. Here, we have performed extensive first principles calculations based on density functional theory (DFT) to investigate the interaction of CO2 on a recently synthesized ZnO monolayer (ZnO-ML) in its pure, defected and functionalized form. A series of rigorous calculations yielded the most preferential binding configurations of the CO2 gas molecule on a ZnO-ML. It is observed that the substitution of one oxygen atom with boron, carbon and nitrogen on the ZnO monolayer resulted into enhanced CO2 adsorption. Our calculations show an enriched adsorption of CO2 on the ZnO-ML when substituting with foreign atoms like B, C and N. The improved adsorption energy of CO2 on ZnO suggests the ZnO-ML could be a promising candidate for future CO2 capture.

The effect of blood transfusion on central venous oxygen saturation in critically ill patients admitted to a neurointensive care unit.

BACKGROUND: Literature suggests poorer outcomes during anaemia as well as following red blood cell transfusion (BT) in brain injured patients. Recently, central venous oxygen saturation (ScvO2 ) has been proposed as a physiological trigger to guide red BT. In this study, we looked at ScvO2 changes following BT in patients admitted to a neurointensive care unit (NICU). STUDY DESIGN: In this prospective, observational study, adult, acutely ill neurological patients of >18 years were recruited. The following parameters were measured before and immediately after transfusion and then at 6, 12, 18 and 24 h after transfusion: haemoglobin (Hb), ScvO2 and central venous oxygen partial pressure (PcvO2 ) (blood sampled from central venous catheter). Simultaneously, hemodynamic parameters [central venous pressure (CVP), heart rate (HR), mean arterial pressure (MAP) and systolic blood pressure (SBP)] were also noted. RESULTS: Data from 70 adult patients were analysed. Following BT, significant improvement was noted in Hb, ScvO2 and all hemodynamic parameters. The ScvO2 changes correlated significantly with the number of units of BT (P = 0·039), pre-transfusion Hb (P = 0·010), ScvO2 (P = 0·001) and PcvO2 (P = 0·001). When receiver operating characteristic (ROC) curves were drawn, optimum cut-off values of baseline ScvO2 and Hb to predict the need for transfusion in terms of oxygen delivery were 70% and 8·6 gm dL-1 respectively. DISCUSSION: Baseline ScvO2 <70% appears to be a useful physiological trigger for deciding the need for BT in brain injured patients. Whether improvement in ScvO2 leads to improvement in regional brain oxygenation needs to be studied.

Electrophysiological observations in critically ill Guillain-Barre syndrome.

BACKGROUND: Respiratory muscle paralysis is a serious complication of Guillain-Barre syndrome (GBS). Factors that govern duration and recovery from respiratory paralysis are unclear. AIM: To correlate electrophysiological parameters in critically ill GBS with duration of mechanical ventilation and outcome at discharge. MATERIALS AND METHODS: Data of a large cohort (n=93; M:F 59:34; mean age: 33.51+21.4 years) of critically-ill patients with GBS seen over one decade was retrospectively analyzed. RESULTS: The duration of mechanical ventilation was <15 days (n = 38), 16-30 days (n = 24), and >30 days (n = 31). Majority of the patients had a demyelinating electrophysiology. Reduced amplitude or absent motor potentials correlated with requirement for longer duration of ventilation. Inexcitable sensory nerves were more common in patients who could be weaned off from the ventilator within 15 days. There was no relation between the conduction blocks in motor nerves and the duration of ventilation. Low amplitude of median nerve correlated with a poor outcome at hospital discharge as assessed by Hughes disability scale. CONCLUSION: Distinct patterns of electrophysiological abnormalities are noted in patients and they correlate with the duration of mechanical ventilation. Future studies to unravel the underlying pathophysiological processes that govern the patterns of progression and recovery in the critically ill patients with GBS will pave way for the development of better and more potent therapies that will hasten recovery, when combined with the prevalent treatment modalities including plasmapheresis and intravenous immunoglobulin.

Hydrogen storage properties of light metal adatoms (Li, Na) decorated fluorographene monolayer.

Owing to its high energy density, the potential of hydrogen (H2) as an energy carrier has been immense, however its storage remains a big obstacle and calls for an efficient storage medium. By means of density functional theory (DFT) in spin polarized generalized gradient approximation (GGA), we have investigated the structural, electronic and hydrogen storage properties of a light alkali metal (Li, Na) functionalized fluorographene monolayer (FG). Metal adatoms bind to the FG with significantly high binding energy, much higher than their cohesive energies, which helps to achieve a uniform distribution of metal adatoms on the monolayer and consequently ensure reversibility. Due to a difference of electronegativities, each metal adatom transfers a substantial amount of its charge to the FG monolayer and attains a partial positive state, which facilitates the adsorption of multiple H2 molecules around the adatoms by electrostatic as well as van der Waals interactions. To get a better description of H2 adsorption energies with metal-doped systems, we have also performed calculations using van der Waals corrections. For both the functionalized systems, the results indicate a reasonably high H2 storage capacity with H2 adsorption energies falling into the range for the practical applications.

Embolisation of pulmonary vasculature during endovascular therapy­a case report.

Systemic complications following liquid glue embolisation of intracranial pial arteriovenous fistulae (AVF) are uncommonly reported. We report a patient who had a pulmonary embolism of a liquid glue during endovascular treatment of a pial AVF. The patient had haemodynamic instability, pulmonary hypertension, increased alveolar dead space and increased brain natriuretic peptide levels. In addition to other supportive measures, her pulmonary hypertension was controlled with sildenafil. Ten months after the event, the patient had a considerable improvement of the clinical and laboratory variables and a significant radiographic resolution of the glue from the pulmonary circulation.

A comparative study of dexmedetomidine and propofol as sole sedative agents for patients with aneurysmal subarachnoid hemorrhage undergoing diagnostic cerebral angiography.

PURPOSE: Subarachnoid hemorrhage is an acute neurological emergency requiring urgent confirmation of the diagnosis for planning definitive management. Due to altered consciousness, most patients require sedation for conducting this procedure smoothly. Currently, it is unclear if any one particular sedative drug has a favorable profile in patients undergoing cerebral angiography. The aim of this study was to compare the traditionally used sedative drug propofol with a newer alternative, dexmedetomidine, in patients with subarachnoid hemorrhage undergoing cerebral angiography. METHODS: Sixty adult patients with good grade subarachnoid hemorrhage undergoing diagnostic cerebral angiography were prospectively randomized to receive either propofol (n = 30) or dexmedetomidine (n = 30) following ethics committee approval and informed consent. RESULTS: Compared to dexmadetomidine, propofol was associated with an earlier time for onset of sedation (2.3 ± 1.9 min vs. 15.4 ± 5.7 min; P < 0.001), but with an increased number of adverse respiratory events (11/30 vs 1/30; P = 0.003) and movement during the procedure (5/30 vs. 0/30; P = 0.05), necessitating additional supplementation of sedation (13/30 vs. 7/30; P = 0.17) and repetition of the imaging sequences. The total procedure time and time for recovery were similar for the propofol and dexmedetomidine groups, while the heart rate was lower in patients in the dexmedetomidine group. CONCLUSION: Dexmedetomidine appears to be superior to propofol as a sole sedative agent for sedation during cerebral angiography in patients with subarachnoid hemorrhage.

Anesthetic factors and outcome in children undergoing indirect revascularization procedure for moyamoya disease: An Indian perspective.

BACKGROUND: Moya Moya disease (MMD) is one of the most common cerebro-vascular diseases in children resulting in stroke. Surgical revascularization aims at improving the perfusion to the 'at-risk' ischemic brain. Several factors including peri-operative anesthetic related ones, affect the outcome in these children. This study was performed with the aim to explore the role of anesthetic techniques, pharmacological agents and perioperative management strategies on the neurological outcome following an indirect revascularization procedure for the treatment of MMD. MATERIALS AND METHODS: This was a retrospective chart review of pediatric indirect revascularization procedures for MMD during a three year period at a tertiary neurosciences hospital in southern India. Demographic details, disease characteristics and variables related to anesthetic management were obtained from the patient's charts and analyzed. The main outcome measure was occurrence of postoperative new neurological complications; and, the secondary outcome was length of hospital stay after surgery. RESULTS: Twenty-two children underwent thirty indirect revascularization procedures, of which four patients had new postoperative neurological complications. One child died due to bilateral cerebral infarcts following bilateral surgery as a single stage under the same anesthesia. Female gender and a higher opioid dose were associated with occurrence of postoperative neurological deficits. Younger age, prolonged anesthetic duration and occurrence of postoperative neurological deficits were associated with prolonged postoperative hospital stay. However, none of these factors were predictive of either an adverse neurological outcome or a prolonged hospital stay. CONCLUSION: In this study, anesthetic techniques or medications did not influence the occurrence of postoperative neurological deficits or prolonged hospital stay after an indirect revascularization procedure in children with MMD.

Turpentine oil induced inflammation decreases absorption and increases distribution of phenacetin without altering its elimination process in rats.

Plasma concentrations and pharmacokinetics of phenacetin, a CYP1A2 substrate were determined in normal and experimentally induced inflamed rats by turpentine oil to know the role of inflammation on the pharmacokinetics of phenacetin and formation of its active metabolite (paracetamol) by CYP1A2 in wistar albino rats, weighing about 200-250 g that were randomly divided into two groups consisting six in each group. Rats in group I (control) received phenacetin (150 mg kg(-1), PO) where as group II received phenacetin 12 h after induction of inflammation by turpentine oil (0.4 mL, i.m). Blood samples were collected from retro orbital plexus at pre-determined time intervals prior to and at 0.166, 0.33, 0.67, 1.5, 2, 4, 8 and 12 h post-administration of phenacetin. Plasma was separated and analyzed for phenacetin and its metabolite paracetamol by HPLC assay. Based on plasma concentrations of phenacetin and its metabolite paracetamol, the pharmacokinetic parameters were determined by compartmental methods. C(max) of phenacetin was significantly (p < 0.01) decreased to 19.50 ± 2.74 µg mL(-1) in inflamed conditions compared to 38.13 ± 2.20 µg mL(-1) obtained in normal rats. Except, for significant (p < 0.001) increase in volume of distribution at steady state (V(dss)) from 2.87 ± 0.37 to 8.03 ± 1.26 L kg(-1) and increased the rate of absorption with shorter absorption half-life (t(1/2ka)) for phenacetin in inflammation. None of the pharmacokinetic parameters of either phenacetin or its metabolite paracetamol were affected. It can be concluded that turpentine oil induced inflammation has no role on the activity of CYP1A2 in rats, as the plasma concentrations and pharmacokinetic parameters of paracetamol were found unaltered.

AN AUDIT OF THE CURRENT PRACTICES OF AIRWAY MANAGEMENT IN PATIENTS UNDERGOING SURGERY FOR ATLANTO-AXIAL DISLOCATION IN A SINGLE INSTITUTION.

BACKGROUND: Patients with atlanto axial dislocation (AAD) undergo stabilisation procedures under general anesthesia. Airway management in these patients is difficult as cervical spine movements during laryngoscopy can worsen spinal cord damage. Though multiple airway devices are used to intubate the trachea of these patients, there is no evidence of superiority of one technique over another. This retrospective study was designed to audit the practice of airway management during surgery for AAD over a 5 year period, starting from 2006 till 2011. METHODS: Patients' demographics, airway intervention techniques, types of surgical procedures, postoperative neurological and respiratory deterioration were recorded from the case files. Association between the types of airway interventions and the postoperative neurological and respiratory deterioration were analysed. RESULTS: One hundred and six patients underwent surgery for AAD during the study period. Sixty one percent of the patients were intubated with the help of a fiberoptic bronchoscope (FOB) and among them 15% received general anesthesia to facilitate FOB. Eighteen patients developed neurological deterioration and 15 patients developed respiratory weakness requiring ventilation postoperatively. Congenital AAD patients had higher chances for extubation at the end of surgery when intubated using FOB (p = 0.007). Among the AAD patients, female gender had significantly higher incidence of neurological deterioration compared to males. CONCLUSION: In the current audit, there was no correlation between the perioperative variables and postoperative respiratory and neurological deterioration. Most of the respiratory problems occurred between 2-5 postoperative days stressing the need for extended intensive postoperative monitoring of these patients.

Exploring the potential of neem and tamarind gum as release retardants: Design and statistical optimisation of vildagliptin extended release matrix systems using D-optimal quadratic mixture design.

Exploring the significant role of natural polymers in developing drug delivery systems has been a promising area of research interest. The current investigation uses a D-optimal quadratic mixture design to design and evaluate neem and tamarind gum-based vildagliptin extended-release matrix tablets. Studying the combination effect of gums is one of the major objectives. Initial screening studies were performed to select the factors and their levels. The variables selected at different levels in mg/tablet are neem gum, tamarind gum, polyvinylpyrrolidone, and lactose monohydrate. Based on the screening experiments with both gums, the polymer content of 165 mg was chosen as the highest level in the DOE. Nineteen runs were generated to screen the desired parameters as responses. The total weight of the formulation was kept constant at 275 mg. Time (hours) required for 50 %, 90 % and 100 % of drug release and tablet hardness were selected as the responses for each run. The wet granulation method was adopted, and the critical variables were optimised using the design of experiments following Design Expert software. Statistical analysis was conducted, and the optimised formulations were prepared and evaluated to compare with the predicted responses. Stability studies were performed for the optimised batches. Results indicated that the prepared batches met the compendial limits and confirmed the application of neem and tamarind gum in the development of extended-release tablets of vildagliptin for 24 h. An optimised formulation comprising of 16.52 mg of neem gum and 148.48 mg of tamarind gum with a hardness of 7.5-8.5 kp produced 50 %, 90 % and 100 % drug release in 12, 22 and 25 h.

Cracking the Code of Lumpy Skin Disease: Identifying Causes, Symptoms and Treatment Options for Livestock Farmers.

The novel bovine viral infection known as lumpy skin disease is common in most African and Middle Eastern countries, with a significant likelihood of disease transfer to Asia and Europe. Recent rapid disease spread in formerly disease-free zones highlights the need of understanding disease limits and distribution mechanisms. Capripox virus, the causal agent, may also cause sheeppox and Goatpox. Even though the virus is expelled through several bodily fluids and excretions, the most common causes of infection include sperm and skin sores. Thus, vulnerable hosts are mostly infected mechanically by hematophagous arthropods such as biting flies, mosquitoes, and ticks. As a result, milk production lowers, abortions, permanent or temporary sterility, hide damage, and mortality occur, contributing to a massive financial loss for countries that raise cattle. These illnesses are economically significant because they affect international trade. The spread of Capripox viruses appears to be spreading because to a lack of effectual vaccinations and poverty in rural areas. Lumpy skin disease has reached historic levels; as a consequence, vaccination remains the only viable option to keep the illness from spreading in endemic as well as newly impacted areas. This study is intended to offer a full update on existing knowledge of the disease's pathological characteristics, mechanisms of spread, transmission, control measures, and available vaccinations.

Evaluation of skin cancer chemoprevention potential of sunscreen agents using the Epstein-Barr virus early antigen activation in vitro assay.

In our continuing search for novel cancer chemopreventive compounds of natural and synthetic origin, we have evaluated 14 commonly used ultraviolet (UV) sunscreen agents (designated UV-1 to UV-14) for their skin cancer chemoprevention potential. They belong to 8 different chemical categories: aminobenzoate (UV-5, UV-7, UV-8 and UV-14), benzophenone (UV-1, UV-2, UV-3 and UV-13), benzotriazole (UV-10), benzyloxyphenol (UV-9), cinnamate (UV-6), quinolone (UV-4), salicylate (UV-11) and xanthone (UV-12). In the in vitro assay employed, the sunscreens were assessed by their inhibition of the Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in human lymphoblastoid Raji cells. All sunscreens tested were found to exhibit anti-tumour promoting activity: listed in decreasing order, moderate (UV-11, UV-2, UV-7, UV-12, UV-3, UV-9 and UV-14) to weak (UV-1, UV-6, UV-8, UV-16, UV-5, UV-4 and UV-10) with octyl salicylate (UV-11) as the most potent and drometrizole (UV-10) as the least potent among the compounds evaluated. A plausible relationship between the antioxidant property of sunscreens and their ability to promote anti-tumour activity was noted. The results call for a comprehensive analysis of skin cancer chemoprevention potential of currently used UV sunscreen agents around the globe to identify those with the best clinical profile.

Incidence, predictors, and impact of acute post-operative pain after cranial neurosurgery: A prospective cohort study.

Objectives: Pain is common after craniotomy. Its incidence and predictors in developing nations are not adequately studied. We aimed to assess the incidence, predictors, and impact of acute post-operative pain after intracranial neurosurgeries. Materials and Methods: This prospective observational study was conducted in adult patients undergoing intracranial neurosurgeries. After patient consent, ethics committee approval, and study registration, we assessed the incidence of post-operative pain using numerical rating scale (NRS) score. Predictors and impact of pain on patient outcomes were also evaluated. Results: A total of 497 patients were recruited during 10-month study period. Significant (4-10 NRS score) post-operative pain at any time-point during the first 3 days after intracranial neurosurgery was reported by 65.5% (307/469) of patients. Incidence of significant pain during the 1st post-operative h, on the 1st, 2nd, and 3rd post-operative days was 20% (78/391), 50% (209/418), 38% (152/401), and 24% (86/360), respectively. Higher pre-operative NRS score and pain during the 1st h post-operatively, predicted the occurrence of pain during the first 3 days after surgery, P = 0.003 and P < 0.001, respectively. Pain was significantly associated with poor sleep quality on the first 2 post-operative nights (P < 0.001). Patient satisfaction score was higher in patients with post-operative pain, P = 0.002. Conclusion: Every two in three patients undergoing elective intracranial neurosurgery report significant pain at some point during the first 3 postoperative days. Pre-operative pain and pain during 1st post-operative h predict the occurrence of significant post-operative pain.

Organ-preserving surgery for penile cancer: description of techniques and surgical outcomes.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Organ-preserving surgeries for penile cancer have been described to reduce the morbidity associated with traditional operations. Patients derive better functional outcomes from penile-preserving surgery, although local recurrence rates can be higher. Excellent results can be obtained at large-volume centres. With close follow-up, local recurrences can be identified and treated promptly (often with further local excision). OBJECTIVE: • To describe the outcomes of organ-preserving surgery for penile cancer at a UK tertiary referral centre. PATIENTS AND METHODS: • Patients at Sunderland Hospital (UK) between 2001 and 2008 who had squamous cell tumours limited to the glans penis underwent penile-preserving surgery including total glansectomy and glanuloplasty, partial glansectomy, glans relining and distal penectomy with glans reconstruction. • Recurrence rates, cosmetic and functional outcomes were recorded. RESULTS: • In all, 65 patients were identified with a median follow-up of 40 months. Local recurrence was present in four patients (6%) despite 72% having intermediate or poorly differentiated tumours and 30% with T2 disease. • Complications included partial graft loss (1.5%), graft contractures (4.5%) and meatal stenosis (7.5%). • In all, 5% were deemed to have poor cosmetic outcome and 85% described good erections at 1 year after surgery. CONCLUSION: • Penile-preserving surgery can achieve good penile cancer control with minimal morbidity and reduced psychosexual side-effects.

Good airway reflexes and normal sensorium do not assure safe tracheal extubation in patients with cerebral hemispheric pathology.

Following brain injury, return of consciousness and cough reflex are presumed to be associated with safe airway. We describe two patients who had a normal cough reflex, but impaired swallowing, which led to prolonged hospital stay. This report highlights the dissociation between the cough reflex and swallowing function in such patients.