Comparison of the efficacy of intranasal atomised dexmedetomidine versus intranasal atomised ketamine as a premedication for sedation and anxiolysis in children undergoing spinal dysraphism surgery: A randomized controlled trial.

BACKGROUND: Preoperative anxiety leads to adverse clinical outcomes and long-term maladaptive behavioural changes. The role of intranasal atomised dexmedetomidine and atomised ketamine as premedication to produce sedation and anxiolysis in paediatric neurosurgical patients has not been extensively studied. OBJECTIVE: To study the efficacy of intranasal atomised dexmedetomidine and intranasal atomised ketamine as premedication in producing sedation and facilitating smooth induction in children undergoing spinal dysraphism surgery. DESIGN: A prospective randomised double-blind trial. SETTING: A tertiary teaching hospital. PATIENTS: Sixty-four children aged 1 to 10 years undergoing spinal dysraphism surgery. METHODS: Children were randomised to receive intranasal atomised dexmedetomidine 2.5 µg kg -1 (Group D, n  = 32) and intranasal atomised ketamine 5 mg kg -1 (Group K, n  = 32) 30 min before surgery. OUTCOMES MEASURED: The primary outcome was to compare the level of sedation in both groups using the University of Michigan Sedation Score (UMSS). The secondary outcomes included an assessment of the ease of parental separation, intravenous cannulation and satisfactory mask acceptance along with perioperative vitals (heart rate, blood pressure and oxygen saturation). The incidence of emergence agitation and time to discharge were also noted. RESULTS: The degree of sedation was significantly better in Group D as compared to Group K at 20 min (UMSS, 1.55 ±â€Š0.51 versus 1.13 ±â€Š0.34, difference, -0.406; 95% CI, -0.621 to -0.191; P  = 0.0001) and 30 min (2.32 ±â€Š0.6 versus 1.94 ±â€Š0.50, difference, -0.374; 95% CI, -0.650 to -0.100; P  = 0.007). The ease of parental separation, venous cannulation and mask acceptance ( P  = 0.83, 0.418 and 0.100 respectively) were comparable in both groups. The heart rate was lower in group D at 10, 20 and 30 min post-drug administration but was clinically insignificant. The incidence of emergence agitation and time to discharge was also similar with no adverse events reported. CONCLUSION: Intranasal atomised dexmedetomidine produces greater sedation as compared to intranasal atomised ketamine with comparable ease of parental separation, venous cannulation and mask acceptance with no adverse effects.

Intermittent peri-tubal instillation of dexamethasone and ropivacaine on postoperative analgesia after percutaneous nephrolithotomy: A prospective randomized controlled trial.

OBJECTIVES: Percutaneous nephrolithotomy and placement of nephrostomy tube are performed for renal stones >2 cm in diameter. Attempts have been made to infiltrate local anesthetics with or without adjuvants into the surgical site to reduce pain. We hypothesized that there would be a significant prolongation of the analgesic effect of local anesthetic instillation along the nephrostomy tube due to the adjuvant dexamethasone. METHODS: After ethical approval and Clinical Trials Registry - India registration (CTRI/2020/03/024332), 64 American Society of Anesthesiologists classification 1 and 2 adult patients were enrolled in this randomized double-blinded prospective study divided into Group R-received 20 mL 0.2% Ropivacaine and Group R + D-received 20 mL 0.2% Ropivacaine with dexamethasone 8 mg, injected through a multi-lumen wound infiltration catheter. RESULTS: The demographic profile of patients was similar in both groups. The mean duration of analgesia was longer in Group R + D (21.3 ± 2.1 hrs) versus Group R (10 ± 1.9 hrs, P = 0.001). The mean numeric rating scale scores of Group R + D were significantly lower at all time intervals (P = 0.001). Also, the cumulative dose of ropivacaine and the total use of fentanyl postoperatively in Group R was much higher (70 ± 10.4 vs 56 ± 8.9 µg, P = 0.02). The C-reactive protein levels were significantly lower in Group R + D (13.8 ± 1.5 vs 23.1 ± 1.2 mg/L, P = 0.001 and 16.5 ± 1.3 vs 28.5 ± 1.7 mg/L, P = 0.001, at 24 and 48 hrs, respectively). CONCLUSION: We conclude that dexamethasone can be used as a suitable adjuvant to intermittent local anesthetic infiltration after percutaneous nephrolithotomy with a nephrostomy tube for the prolongation of analgesia.

Lung function and breathing patterns in hospitalised COVID-19 survivors: a review of post-COVID-19 Clinics.

INTRODUCTION: There is relatively little published on the effects of COVID-19 on respiratory physiology, particularly breathing patterns. We sought to determine if there were lasting detrimental effect following hospital discharge and if these related to the severity of COVID-19. METHODS: We reviewed lung function and breathing patterns in COVID-19 survivors > 3 months after discharge, comparing patients who had been admitted to the intensive therapy unit (ITU) (n = 47) to those who just received ward treatments (n = 45). Lung function included spirometry and gas transfer and breathing patterns were measured with structured light plethysmography. Continuous data were compared with an independent t-test or Mann Whitney-U test (depending on distribution) and nominal data were compared using a Fisher's exact test (for 2 categories in 2 groups) or a chi-squared test (for > 2 categories in 2 groups). A p-value of < 0.05 was taken to be statistically significant. RESULTS: We found evidence of pulmonary restriction (reduced vital capacity and/or alveolar volume) in 65.4% of all patients. 36.1% of all patients has a reduced transfer factor (TLCO) but the majority of these (78.1%) had a preserved/increased transfer coefficient (KCO), suggesting an extrapulmonary cause. There were no major differences between ITU and ward lung function, although KCO alone was higher in the ITU patients (p = 0.03). This could be explained partly by obesity, respiratory muscle fatigue, localised microvascular changes, or haemosiderosis from lung damage. Abnormal breathing patterns were observed in 18.8% of subjects, although no consistent pattern of breathing pattern abnormalities was evident. CONCLUSIONS: An "extrapulmonary restrictive" like pattern appears to be a common phenomenon in previously admitted COVID-19 survivors. Whilst the cause of this is not clear, the effects seem to be similar on patients whether or not they received mechanical ventilation or had ward based respiratory support/supplemental oxygen.

Effects of low- and high-pressure carbon dioxide pneumoperitoneum on intracranial pressure during laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic surgeries are a risk factor for raised intracranial **pressure and neurological complications. Even though rare, the consequences may be severe. METHODS: One hundred and one patients of laparoscopic cholecystectomy were enrolled and were randomized into two groups: low-pressure 8 mm Hg (Group A) and high-pressure 14 mm Hg (Group B) carbon dioxide pneumoperitoneum during surgery. Fifty patients were in group A and 51 patients were in group B. Intracranial pressure was measured by measuring the optic nerve sheath diameter (ONSD) using ultrasound examination. Baseline ONSD was recorded followed by ONSD recording at various intervals: at the induction of anesthesia; 30 min, 45 min, at the end of surgery; and 30 min post surgery. RESULTS: The groups were comparable in terms of demographics and comorbidities. The mean age of group A was 45 years and for group B it was 45.75 years. Most common indication for surgery was symptomatic gall stone disease. Baseline ONSD in group A was 0.427 ± 0.0459 mm, whereas it was 0.412 ± 0.0412 mm in group B. There was a significant rise of ONSD (p < 0.05) 30 min after induction of pneumoperitoneum and up to 30 min post anesthesia. In the low-pressure group 7 (14%) patients had a significant rise of ICP, whereas in the high-pressure group 20 (39%) patients had a significant rise of ICP (p < 0.05). CONCLUSIONS: High-pressure pneumoperitoneum causes significant rise in intracranial pressure in comparison to low-pressure pneumoperitoneum during laparoscopic cholecystectomy, which can be monitored by ONSD measurement by ultrasound examination and is totally non-invasive.

No Traces of SARS-CoV-2 In Wounds of COVID-19 Positive Patients: A Pilot Study.

Background This study was performed to investigate the presence of SARS-CoV-2 virus in wounds of COVID-19 positive patients. Methods This is a single-center observational study. COVID-19 patients with wounds (traumatic/infective/surgical) were included in this study. Preoperative, intraoperative, or postoperative specimens were collected and analyzed with real-time reverse transcriptase polymerase chain reaction (rRT-PCR) to know the presence of the virus. Results A total of eight patients were included in this study. Eleven samples were collected (seven wound swabs, two peritoneal fluids, and two tissue specimens) and analyzed. None of the samples from the wound tested positive for the virus while they were tested positive for nasal swab taken simultaneously or within 3 days prior. Conclusion The wounds of COVID-19 patients are considered negative and can be managed with routine wound precautions.

Elucidating the Structural Composition of an Fe-N-C Catalyst by Nuclear- and Electron-Resonance Techniques.

Fe-N-C catalysts are very promising materials for fuel cells and metal-air batteries. This work gives fundamental insights into the structural composition of an Fe-N-C catalyst and highlights the importance of an in-depth characterization. By nuclear- and electron-resonance techniques, we are able to show that even after mild pyrolysis and acid leaching, the catalyst contains considerable fractions of α-iron and, surprisingly, iron oxide. Our work makes it questionable to what extent FeN4 sites can be present in Fe-N-C catalysts prepared by pyrolysis at 900 °C and above. The simulation of the iron partial density of phonon states enables the identification of three FeN4 species in our catalyst, one of them comprising a sixfold coordination with end-on bonded oxygen as one of the axial ligands.

Treating Hallucinations and Delusions Associated With Parkinson's Disease Psychosis.

PURPOSE OF REVIEW: We discuss features of Parkinson's disease psychosis (PDP) including symptomology and pathophysiology. Treatment options, including non-pharmacologic strategies, dose reduction of offending agents, and the addition of non-dopaminergic antipsychotics, are addressed. The efficacy of second-generation antipsychotics and novel agents is examined. RECENT FINDINGS: Pimavanserin, a 5-HT2A/C receptor inverse agonist with no other receptor activity, has shown efficacy and tolerability and is now FDA approved for PDP treatment. Research into novel targets is ongoing. PDP is a morbid complication of Parkinson's disease with complex incompletely understood mechanisms. Treatment is directed towards mitigation of psychosis without worsening of motor features.

Comparison of a Novel Score "NOD-ACLF" to Other Established Prognostic Scores for Prediction of Mortality in APASL-ACLF Patients: A Cohort Study from a Tertiary Care Center of North India.

Background: Commonly used prognostic scores for acute on-chronic liver failure (ACLF) have complex calculations. We tried to compare the simple counting of numbers and types of organ dysfunction to these scores, to predict mortality in ACLF patients. Methods: In this prospective cohort study, ACLF patients diagnosed on the basis of Asia Pacific Association for Study of the Liver (APASL) definition were included. Severity scores were calculated. Prognostic factors for outcome were analysed. A new score, the Number of Organ Dysfunctions in Acute-on-Chronic Liver Failure (NOD-ACLF) score was developed. Results: Among 80 ACLF patients, 74 (92.5%) were male, and 6 were female (7.5%). The mean age was 41.0±10.7 (18-70) years. Profile of acute insult was; alcohol 48 (60%), sepsis 30 (37.5%), variceal bleeding 22 (27.5%), viral 8 (10%), and drug-induced 3 (3.8%). Profiles of chronic insults were alcohol 61 (76.3%), viral 20 (25%), autoimmune 3 (3.8%), and non-alcoholic steatohepatitis 2 (2.5%). Thirty-eight (47.5%) were discharged, and 42 (52.5%) expired. The mean number of organ dysfunction (NOD-ACLF score) was ->4.5, simple organ failure count (SOFC) score was >2.5, APASL ACLF Research Consortium score was >11.5, Model for End-Stage Liver Disease-Lactate (MELD-LA) score was >21.5, and presence of cardiovascular and respiratory dysfunctions were significantly associated with mortality. NOD-ACLF and SOFC scores had the highest area under the receiver operating characteristic to predict mortality among all these. Conclusion: The NOD-ACLF score is easy to calculate bedside and is a good predictor of mortality in ACLF patients performing similar or better to other scores.

As the World Struggles With the COVID-19 Pandemic, Another Emergency Threat Arrives on the Horizon, the Monkeypox: A Systematic Review.

The whole world got threatened by COVID-19, which made a significant loss in various sectors and pushed the world into a deep valley. Now a new threat, the emerging outbreak of monkeypox is rapidly spreading across the globe and is currently being observed in more than 110 countries with 79,473 confirmed cases and 50 deaths. Data were collected from PubMed, EMBASE, MEDLINE, Cochrane, Scopus database, African Journals OnLine, internet library sub-Saharan Africa, and Google Scholar. Most data were taken from the democratic Republic of Congo, the Central African Republic, Cameroon, the Republic of Congo, Liberia, Nigeria, the US, and the UK. Case reports, outbreak investigations, epidemiological studies, and surveillance studies were reviewed to find epidemiological details about the outbreak. A total of 50 peer-reviewed articles and 20 grey literature articles, including 9050 cases, were identified for data extraction. Our systematic review revealed that the group most affected is male (95.5%), with a median age of 33.8 years. A total of 55% of the transmission was sexually transmitted. The most commonly reported symptoms such as vesicular-pustular rashes (97.54%), fever (55.25%), inguinal lymphadenopathy (53.6%), exanthema (40.21%), fatigue, headache, asthenia (26.32%), myalgia (16.33%), vesicles and ulcers (30.61%) in the anogenital regions were some of the significant findings. The case fatality rate was observed to be up to 8.65%. The most affected country was the USA, which has the most fatalities in younger ages involved in homosexuality, suffering from HIV or sexually transmitted diseases (STDs).

Obstructive Sleep Apnea in Hypertension.

Introduction About one-half of patients who have essential hypertension have obstructive sleep apnea (OSA), and about one-half of patients who have obstructive sleep apnea have essential hypertension. OSA can cause even resistant hypertension if left untreated. These two entities often co-exist and are seen as a continuum of the same process. Eighty percent to 90% of OSA cases are undiagnosed mostly because of a lack of awareness. Material and methods This was a cross-sectional study done over a period of one year in a tertiary care hospital. After taking informed consent, 179 hypertensive patients of >18 years were included in the study. All patients were screened for OSA by the STOP-BANG questionnaire. Patients having scores of ≥3 were subjected to overnight polysomnography to confirm the diagnosis of OSA (AHI ≥5). Patients with a STOP-BANG score ≤2 or score ≥3 with AHI <5, were considered non-OSA. Results More than half (53.1%) of the patients enrolled in the study had OSA. Their age ranged from 18 to 78 years and the mean age was 52.07±11.40 years. The mean age of OSA cases was found to be slightly higher than that of non-OSA. The majority of OSA cases were males (73.7%). There was an increase in the prevalence, as well as the severity of OSA, with an increase in BMI. Most of the cases had snoring and a history of tiredness. Triglyceride (TG) and low-density lipoprotein (LDL) levels of the OSA group were found to be significantly higher and high-density lipoprotein (HDL) levels were significantly lower than that of the non-OSA group. Conclusion More than half of our hypertensive patients had OSA. These two conditions often co-exist and are known as a dangerous pair. Physicians ought to have increased suspicion for early diagnosis and treatment to improve cardiovascular outcomes, reduce road traffic accidents, and improve quality of life.

Comparison of Intraoperative Low-Dose Ketodex and Fentanyl Infusion for Postoperative Analgesia In Spine Surgery: A Prospective Randomized Double-Blind Study.

STUDY DESIGN: Prospective randomized double-blind study. PURPOSE: To assess the analgesic effects of the combination of a low-dose ketamine and dexmedetomidine (ketodex) infusion and compare it with that of fentanyl for postoperative analgesia after spine surgeries. OVERVIEW OF LITERATURE: Adequate pain management following spine surgeries is crucial. Approximately 57% of patients experience inadequate pain control in the first 24 hours following elective spine surgery, which is attributable to the extensive soft tissue and muscle damage. METHODS: The study included 60 patients graded American Society of Anesthesiologists I and II and scheduled for thoracolumbar spine surgery involving >3 vertebral levels. The patients were divided into two groups: group KD (ketodex) and group F (fentanyl). The primary objective was to compare the postoperative analgesic requirements among the groups. The secondary objectives included a comparison of the intraoperative anesthetic requirements, postoperative pain scores, hemodynamic parameters, side effects of the study drugs, and the duration of post-anesthesia care unit stay of both the groups. RESULTS: Ketodex use prolonged the mean time to first rescue analgesia (22.00±2.30 hours vs. 11.69±3.02 hours, p <0.001) and reduced the requirement of rescue analgesics in the first 24 hours postoperatively compared to fentanyl use (70.00±8.16 µg vs. 113.31±36.65 µg, p =0.03). The intraoperative requirement of desflurane was comparable between the groups (p >0.05). The postoperative pain scores were significantly lower in the group KD than in group F at most timepoints (p <0.05). Patients in group KD had a shorter post-anesthesia care unit stay than group F did (p <0.001). CONCLUSIONS: Low-dose ketodex could be a safe substitute for fentanyl infusion when employed as an anesthetic adjuvant for patients undergoing thoracolumbar spine surgeries involving >3 vertebral levels to achieve prolonged analgesia without any opioidrelated side effects.

Study of pattern and outcome of acute poisoning cases at tertiary care hospital in North India.

Introduction: The WHO 2021 data estimate that 2 million lives and 53 million disability-adjusted life-years were lost in 2019 due to exposures to selected chemicals. It is important to know the pattern and outcome of acute poisoning cases for proper planning, prevention and management. Knowing the pattern will also help in designing training modules for primary care physicians to make them aware about newer poisons and their management. Awareness regarding newer poisons consumed is necessary for early identification, initial management and timely referral to higher centres by primary care physicians. This study was performed to see the pattern and outcome of acute poisoning cases in North Indian population and various factors related to outcome. Materials and Methods: This study was conducted in department of medicine of a teaching institute in North India after approval by the Institutional Review Board. Patients admitted in the department during the study and fulfilling the inclusion criteria were enrolled in the study after obtaining consent. Results: A total of 417 patients with poisoning were recruited in the study. Out of 417 patients, majority were males (59.5%). Maximum number of patients were in the age group of 21-30 years (33.8%), and rural population (79.9%) was found to be more affected. Most of the patients were students and private employees. Most common types of poisoning were snakebite (n = 109, 26.1%), organophosphate (n = 49, 11.8%) and aluminium phosphide (n = 39, 9.3%). Out of 417 patients, 349 (83.69%) improved, while 68 (16.3%) expired. Requirement of ventilatory support was most commonly associated with aluminium phosphide poisoning (30.12%) followed by organophosphate poisoning (24.1%). Conclusion: Poisoning was more common in young males and more prevalent in rural population. Pesticides and snakebite were major causes of poisoning. Among suicidal cases, family conflict (problem/altercation with family members/marital discord) was main reason for the consumption of poison. There is need for creation of poison information centre along with separate toxicological units in tertiary care hospitals.

The Severity of COVID 19 Pneumonia in Vaccinated vs. Non-vaccinated Patients in the Second Wave: An Experience From a Tertiary Care Center in India.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by SARS CoV-2 that emerged in Wuhan, China, and has rapidly spread worldwide. The mortality rate of critically ill COVID-19 patients is high. OBJECTIVE: To assess the severity, different clinical symptoms, and comorbidities of COVID-19 pneumonia in vaccinated vs. non-vaccinated patients. METHODS: In this single-center, cross-sectional study, 142 patients with COVID-19 were enrolled. The clinical characteristics, comorbidities, severity, and outcomes were also assessed. RESULTS: Of the 142 patients, 92 (64.8%) were males, with a mean age of (56.00±14.81) years. Among them, 62 (43.7%) were aged above 60 years. Of these, 92 (64.7%) had comorbidities. The patients were divided into two groups: unvaccinated and those who received at least one dose of the vaccine within six months. The demographic characteristics of the two groups were similar except for gender. In the vaccinated group, most of the patients were males. Most patients in the non-vaccinated group had a severe illness, whereas most patients in the vaccinated group had mild to moderate disease. Only 26% of the vaccinated group experienced severe illness compared to 71.5% in the unvaccinated group. In addition, the all-cause 30-day mortality in the non-vaccinated population was higher than that in the vaccinated population. However, this difference was not statistically significant (12.5% vs. 7.1%). On the contrary, there was no difference in the length of the intensive care unit or total hospital stay between the two groups. CONCLUSION: Severe COVID-19 had the worst outcome in the unvaccinated patients. Most partially vaccinated patients got infected before developing immunity, and a small percentage of completely immunized patients who were infected were likely non-responders. Receiving at least one vaccination dose significantly reduced illness severity.

Quantitative Assessment of Nitrous Oxide Levels in Room Air of Operation Theaters and Recovery Area: An Observational Study.

BACKGROUND: Nitrous oxide has been used during surgical anesthesia for many years. However, information about occupational exposure and related risks due to N2O exposure to the health care personnel in India are still poorly understood. Here, we measured the residual N2O levels during the working time of operation theatre room air in our tertiary care hospital. MATERIAL AND METHODS: The air samples were collected from different anesthesia exposure zones on different days for quantitative analysis of available N2O in the room air in respective areas. Nitrous oxide concentrations in the ambient air were also measured to compare outdoor and indoor levels. OBSERVATIONS AND RESULTS: Nitrous oxide mixing ratios were found to be 65.61 ± 0.05 ppm, 281.63 ± 0.43 ppm, and 165.42 ± 0.42 ppm in elective surgical theatres of the hospital on three different days whereas in emergency operation theatres of the same hospital levels of N2O were 166.75 ± 0.07 ppm, 510.19 ± 0.30 ppm and 2443.92 ± 0.64 ppm during same period. In elective pediatric surgical theatres levels of N2O were found to be 1132.55 ± 0.70 ppm and 362.21 ± 0.13 ppm on two days of reading respectively. Outdoor levels of N2O in contrast found 0.32 ± 0.01 ppm and was lower by a factor of 1000. CONCLUSION: We observed the very high ambient concentration of N2O in the surgical theatre's environment (up to 2443 ppm) and recovery areas (up to 50 ppm). It was 5 to 50 times higher ambient concentration of N2O than REL in OT area and 200-7000 times higher ambient concentration of N2O than outdoor ambient air in all surgical theaters other than CTVS OTs.

Clinical and biochemical profile of scrub typhus patients at a tertiary care hospital in Northern India.

BACKGROUND: Scrub typhus is a neglected rickettsial disease in India. Every year, we are facing outbreaks of Scrub typhus after Monsoon season. Patients present with a wide clinical spectrum ranging from pyrexia of unknown origin to multiple organ dysfunction. Some of these clinical features overlap with presentation of other tropical infections prevalent in Indian subcontinent, which leads to diagnostic dilemma and delay in diagnosis. Hence, we planned this study to know the demographic, clinical and biochemical profile of scrub typhus patients. METHODS: This was an observational study conducted in department of Medicine, King George's Medical University Lucknow, India a leading tertiary care hospital of Northern India. All scrub typhus patients were evaluated by detailed history, examination and laboratory tests. RESULTS: We enrolled 52 patients in our study. The mean age of the patients was 35.17 ± 16.90 years with majority (82.7%) of patients from rural background. All the patients had fever with an average duration of 9.6 ± 2 days. Most of the patients developed hepatitis (69.2%) followed by acute encephalitis syndrome (47%), acute kidney injury (23.1%) and acute respiratory failure (19.2%). Eschar was found in 11 patients (21.2%). CONCLUSION: Scrub typhus is often misdiagnosed or diagnosed late due to its wide clinical spectrum overlapping with clinical presentation of other commonly prevalent tropical diseases. One should always consider the differential diagnosis of scrub typhus while evaluating a young febrile patient of rural background, with features of single or multiple organ dysfunction and laboratory findings of leucocytosis, thrombocytopenia and elevation of transaminases.

Consensus clinical management guidelines for Alström syndrome.

Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity. ALMS has an estimated incidence of 1 case per 1,000,000 live births and ethnically or geographically isolated populations have a higher-than-average frequency. The rarity and complexity of the syndrome and the lack of expertise can lead to delayed diagnosis, misdiagnosis and inadequate care. Multidisciplinary and multiprofessional teams of experts are essential for the management of patients with ALMS, as early diagnosis and intervention can slow the progression of multi-organ dysfunctions and improve patient quality of life.These guidelines are intended to define standard of care for patients suspected or diagnosed with ALMS of any age. All information contained in this document has originated from a systematic review of the literature and the experiences of the authors in their care of patients with ALMS. The Appraisal of Guidelines for Research & Evaluation (AGREE II) system was adopted for the development of the guidelines and for defining the related levels of evidence and strengths of recommendations.These guidelines are addressed to: a) specialist centres, other hospital-based medical teams and staffs involved with the care of ALMS patients, b) family physicians and other primary caregivers and c) patients and their families.

3D-QSAR studies of triazafluorenone inhibitors of metabotropic glutamate receptor subtype 1.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 46 triazafluorenone derivatives, inhibiting metabotropic glutamate receptor subtype 1 (mGluR1). It includes molecular field analysis (MFA) and receptor surface analysis (RSA). The QSAR model was developed using 35 compounds and its predictive ability was assessed using a test set of 11 compounds. The predictive 3D-QSAR models have conventional r(2) values of 0.908 and 0.798 for MFA and RSA, respectively; while the cross-validated coefficient r(cv)(2) values of 0.707 and 0.580 for MFA and RSA, respectively. The results of 3D-QSAR methodologies provide a powerful tool directed to the design of novel and selective triazafluorenone inhibitors.

Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: a comprehensive review of the literature.

Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure. Our analysis supports the utility of MIP for the early evaluation of respiratory muscle strength, especially of the diaphragm, in patients with NMD and as a surrogate endpoint in clinical trials of therapies for NMD.

Retrospective analysis of prognostic factors in dengue infected patients with intracranial bleed.

BACKGROUND: Dengue is one of the most common mosquito-transmitted arboviral disease of tropical and a few subtropical areas in the world. It is estimated that approximately 100 million cases occur per year and approximately 2.5 billion people are at risk of developing dengue infection. Hemorrhagic complications causing encephalopathy are quite rare but fatal consequences of this deadly disease. This study was conducted to discuss the prognostic factors in the management of intracranial hemorrhage in dengue infected patients. METHODS: This retrospective study was conducted in the neurosurgery department of our tertiary healthcare centre. Duration of the study was 1 year, and 18 patients who presented with intracranial bleed and required neurosurgical care were included in this study. All patients had deranged coagulation profile and were thrombocytopenic. All the patients were given platelet concentrates for correction of thrombocytopenia. Eight of these patients had deterioration in their neurological status, and 6 of them underwent surgery. RESULTS: Out of 18 patients, 12 (66.66%) were managed conservatively, including one case of cervical extradural hemorrhage. Five patients who were conservatively managed died because they had deep-seated bleed and rapid deterioration. The remaining 7 patients who were managed conservatively improved well with few residual deficits. Six (33.33%) patients who underwent surgery had excellent outcome with one case of mortality. CONCLUSION: Very high index of suspicion is required in dengue infected patients for neurological complications, especially during the convalescence period. Special attention should be given to those patients who have altered sensorium, and should not be misinterpreted as fever delirium or toxic encephalopathy. It requires immediate attention and further neurological investigation (including thorough clinical examination). Timely diagnosis using a computed tomography scan and early neurosurgical intervention after rapid correction of thrombocytopenia can save many lives.

Oxidative stress in hemodialysis--postdialytic changes.

BACKGROUND: There is evidence for production of free oxygen radicals during hemodialysis. Hemodialysis is an intervention that is intermittent and is usually undertaken once in two or three days. It is known that the free oxygen radicals are short lived. Hence, it is necessary to know how long the effects of this oxidative stress are seen in the postdialytic period and whether they are carried over to the next dialysis. Review of the literature showed that there is no information in this area. Hence, this study was undertaken in order to learn whether oxidative stress due to a dialysis session is carried over to next dialysis session or not. METHODS: The effects were studied after four different types of membrane and dialysate--Polysulphone-Bicarbonate (PB), Polysulphone-Acetate (PA), Cuprophan-Acetate (CA) and Cuprophan-Bicarbonate (CB). Two consecutive dialysis sessions were studied to know the effect of re-use of the membrane. For each dialysis session, blood samples were collected at 0 (immediately prior to dialysis or preHD), 4 (immediate postdialysis), 6, 12, 24 and 48 hours (start of next session). Lipid peroxides, SOD and GP were determined in erythrocytes. Vitamins A and E and lipid peroxides were estimated in plasma. RESULTS: In the postdialytic phase there was an increase in plasma lipid peroxide levels. Plasma vitamin E levels increased significantly in all groups after first use dialysis, whereas the increase found after re-use dialysis was not statistically significant. Erythrocyte lipid peroxide levels showed a significant decrease. No significant changes were observed in the plasma vitamin A, erythrocyte SOD and GP levels. There was no significant change in any of the parameters between preHD and either 48-hour or 96-hour samples in all groups studied. CONCLUSIONS: Our results show that there is no carry-over of oxidative stress produced by dialysis to the next session regardless of the type of dialysis.