Clusters based on demography, disease phenotype, and autoantibody status predicts mortality in lupus: data from Indian lupus cohort (INSPIRE).

OBJECTIVES: SLE is associated with significant mortality, and data from South Asia is limited. Thus, we analysed the causes and predictors of mortality and hierarchical cluster-based survival in the Indian SLE Inception cohort for Research (INSPIRE). METHODS: Data for patients with SLE was extracted from the INSPIRE database. Univariate analyses of associations between mortality and a number of disease variables were conducted. Agglomerative unsupervised hierarchical cluster analysis was undertaken using 25 variables defining the SLE phenotype. Survival rates across clusters were assessed using non-adjusted and adjusted Cox proportional-hazards models. RESULTS: Among 2072 patients (with a median follow-up of 18 months), there were 170 deaths (49.2 deaths per 1000 patient-years) of which cause could be determined in 155 patients. 47.1% occurred in the first 6 months. Most of the mortality (n = 87) were due to SLE disease activity followed by coexisting disease activity and infection (n = 24), infections (n = 23), and 21 to other causes. Among the deaths in which infection played a role, 24 had pneumonia. Clustering identified four clusters, and the mean survival estimates were 39.26, 39.78, 37.69 and 35.86 months in clusters 1, 2, 3 and 4, respectively (P < 0.001). The adjusted hazard ratios (HRs) (95% CI) were significant for cluster 4 [2.19 (1.44, 3.31)], low socio-economic-status [1.69 (1.22, 2.35)], number of BILAG-A [1.5 (1.29, 1.73)] and BILAG-B [1.15 (1.01, 1.3)], and need for haemodialysis [4.63 (1.87,11.48)]. CONCLUSION: SLE in India has high early mortality, and the majority of deaths occur outside the health-care setting. Clustering using the clinically relevant variables at baseline may help identify individuals at high risk of mortality in SLE, even after adjusting for high disease activity.

Intracranial Aneurysm Biomarker Candidates Identified by a Proteome-Wide Study.

The scientific basis of intracranial aneurysm (IA) formation, its rupture and further development of cerebral vasospasm is incompletely understood. Aberrant protein expression may drive structural alterations of vasculature found in IA. Deciphering the molecular mechanisms underlying these events will lead to identification of early detection biomarkers and in turn, improved treatment outcomes. To unravel differential protein expression in three clinical subgroups of IA patients: (1) unruptured aneurysm, (2) ruptured aneurysm without vasospasm, (3) ruptured aneurysm who developed vasospasm, we performed untargeted quantitative proteomic analysis of aneurysm tissue and serum samples from three subgroups of IA patients and control subjects. Candidate molecules were then validated in a larger cohort of patients using enzyme-linked immunosorbent assay. A total of 937 and 294 proteins were identified from aneurysm tissue and serum samples, respectively. Several proteins that are known to maintain structural integrity of vasculature were found to be dysregulated in the context of aneurysm. ORM1, a glycoprotein, was significantly upregulated in both tissue and serum samples of unruptured aneurysm patients. We employed a larger cohort of subjects (n = 26) and validated ORM1 as a potential biomarker for screening of unruptured aneurysms. Samples from ruptured aneurysms with vasospasm showed significant upregulation of MMP9, a protease, compared with ruptured aneurysms without vasospasm. We validated MMP9 as a potential biomarker for vasospasm in a larger cohort (n = 52). This study reports the first global proteomic analysis of the entire clinical spectrum of IA. Furthermore, this study suggests ORM1 and MMP9 as potential biomarkers for unruptured aneurysm and cerebral vasospasm, respectively.

Dating of Acute and Subacute Subdural Haemorrhage: A Histo-Pathological Study.

INTRODUCTION: Microscopic study of the organization of the Subdural Haemorrhage (SDH) verified against the time period can help us in the determination of its age which has serious medico-legal implications. Very few studies concerning the dating of SDH are present in the literature. AIM: This study was conducted for dating the early subdural haemorrhage by routine histopathological stains. MATERIALS AND METHODS: A prospective analytical study was conducted during July 2009 to December 2010. A total of 100 cases (50 males and 50 females) fulfilling the inclusion and exclusion criteria were included in this study. Routine histopathological staining of the subdural haematoma was done. RESULTS: Correlation between the frequency of a given histomorphological phenomenon and the length of the Post-Traumatic Interval (PTI) was evidential. All the histomorphological features, when correlated with PTI groups, were found to be statistically significant, except for Polymorphonuclear Leukocytes (PMN). CONCLUSION: We concluded that routine histopathology was reliable in the dating of early subdural haemorrhages.

Sinonasal Anatomical Variants: CT and Endoscopy Study and Its Correlation with Extent of Disease.

To evaluate the incidence of anatomical variations in sinonasal area by nasal endoscopy and CT scan paranasal sinuses and to correlate the anatomical variations in sinonasal area with extent of disease. The present study was conducted on 40 patients of chronic sinusitis. All the patients underwent CT scan paranasal sinus axial and coronal view and nasal endoscopy. The most common anatomical variations were agger nasi cells (80 %), deviated nasal septum (72.5 %) and concha bullosa (47.5 %). Other anatomical variations seen in sinonasal region were uncinate process variations, paradoxical middle turbinate, haller cells, accessory ostia of maxillary sinus, multiseptated sphenoid. Osteomeatal unit (87.5 %) and maxillary sinuses (87.5 %) were the most commonly involved which was followed by anterior ethmoids (70 %), posterior ethmoids (50 %), frontal sinuses (32.5 %) and the sphenoids (20 %). Considering the results obtained, we believe that anatomical variations may increase the risk of sinus mucosal disease. We therefore, emphasize the importance of a careful evaluation of CT study in patients with persistent symptoms of chronic rhinosinusitis.

Dating of Early Subdural Haematoma: A Correlative Clinico-Radiological Study.

INTRODUCTION: Determination of post-traumatic interval remains one of the foremost important goals of any forensic investigation related to human crimes. The estimation of time since injury in cases of subdural haemorrhage has been studied only by a few investigators on the histological and radiological front. AIM: The purpose of this study was to determine the post-traumatic interval of Subdural Haemorrhage (SDH) based on Hounsfield Unit measurements (HU) on Computed Tomography (CT) in surviving victims of head injury. MATERIALS AND METHODS: The study included a total of 100 cases of closed head injury with subdural haemorrhage. The Post-traumatic Time Interval (PTI) varied from 0.5 hours to a maximum of 249 hours, with a mean of 54.2 hours. RESULTS: Statistically significant results were obtained between the HU measurements of the SDH and the post-traumatic intervals and were found to be statistically significant. A rough attempt was made to determine the effect of haematoma volume on attenuation and was found out to be statistically insignificant. CONCLUSION: The density of the subdural haematoma decreases with increase in the post-traumatic interval that concurs with the limited number of studies being conducted in the past. We concluded that further sorting of cases could be done according to its age with additional research and uniformity in the methodology.

Alcohol and Drug Use in Injured Drivers - An Emergency Room Study in a Regional Tertiary Care Centre of North West India.

BACKGROUND: Statistics show an increasing proportion of alcohol and drug use in drivers in more recent times throughout the world. It has been found that among the various human factors, alcohol consumption, using drugs and subsequent driving on the roads are major risk factors. Traffic regulations in India penalises drivers who drive beyond permissible alcohol limit of 30 mg%. Consumption of psychoactive drugs such as opioid, cannabis and benzodiazepines has been reported mainly among youngsters. Hardly any data is available in Indian context particularly from North-West Zone of India. STUDY OBJECTIVE: To study the pattern of alcohol, opioid, cannabis and benzodiazepines use in injured drivers presenting to a designated trauma centre in Chandigarh zone of North-West India. MATERIALS AND METHODS: Consenting injured drivers who presented to the trauma centre in Chandigarh from September 2013 to January 2014 were included. Urine samples collected from the subjects were screened for abusive drug exposure (opioid, cannabis and benzodiazepines) and alcohol using commercial bedside urine immunoassay kits. In urine alcohol positive cases blood samples were collected and analysed for alcohol concentration using standard gas chromatography. Retrograde extrapolation method was used to assess BAC at the time of accident. RESULTS: A total of 200 injured drivers were included in this study. We found substance consumption in 54.5% of drivers and alcohol (40.5%) was the most prevalent substance consumed followed by opiates (13%), cannabis (7%) and benzodiazepines (7%). More than one substance was shown in urine of 11.5% of drivers. Among 81 alcohol positive screening cases, the quantitative analysis was successfully done for 76 cases. Except one, all cases showed BAC value more than 30 mg% which is the legal limit for driving any vehicle in India. The values of alcohol concentration in blood at the time of accident were in the range of 20 to 391 mg%. CONCLUSION: This study has shown that drivers are consuming not only alcohol but other psychoactive drugs also. Indian traffic regulatory authorities are penalising drunk drivers by doing road side breath alcohol testing with no protocols for drug screening. Appropriate measures should be adopted to screen traffic offenders for psychoactive drugs also.

Lorazepam: a weapon of offence.

The use of knock out drugs for perpetuation of crime has significantly increased in recent years. These drug facilitated crimes mainly involve robbery and sexual offences. Most of the drugs employed for these purposes affect the nervous system and bring a state of incapacitation and amnesia. The miscreants exploit these properties of drugs to commit such crimes. The unsuspecting travellers on public transport vehicles and women in disco parties are most vulnerable to such crimes. The unrestricted and unregulated sale of prescription drugs and general ignorance of such incidents is a challenge that needs to be addressed promptly.

AATF RNome has the potential to define post mortem interval.

Keeping in view the fact that the circadian rhythm governs human behavioral characteristics, metabolism and body function, the present study was directed to explore whether or not there exists any cooperativity between AATF RNome (comprising AATF mRNA and its encoded microRNA miR-2909) rhythmicity and post mortem interval (PMI). Such a study unambiguously revealed that circadian rhythm exhibited by AATF RNome has a direct correlation with PMI in Balb/c mice. AATF RNome has the potential to act as biomarker for PMI with reasonably good accuracy and hence may turn out to be of crucial importance in forensic investigation.

Self inflicted human teeth bites: a case report.

Human infighting has been a part of our civilization since times immemorial. These incidences may go unnoticed or may attract attention of law enforcing agencies depending upon the severity of the offence. Though weapons are generally employed to inflict injuries, rare cases have been reported in literature where human teeth have been used to serve this purpose. Human bites may be self inflicted or self suffered in connivance with others to level an allegation against an adversary. We are presenting here such a case where such injuries were produced to bring a false charge against a neighbor.

Prospective study of 'otological injury secondary to head trauma'.

The aim of study was to evaluate etiological factors, types of skull fracture and associated hearing loss in 50 cases of head injury. This was prospective study involving 50 cases of head injury. Each patient will be subjected to detailed history, otological and neuro otological examination, radiological study followed by audiological assessment by pure tone audiometry. Road traffic injuries were the most frequent cause of injuries in our patients comprising 64% of the total, personal accidents/domestic falls, assaults and agriculture and related injuries were responsible for 8% of the total injuries each. Other causes of the injuries were sports injuries (6%), industrial accidents (4%) and fire arm injuries (2%). Out of the 9 patients having temporal bone fracture 7 cases (78%) had longitudinal fracture and 2 cases (22%) had transverse fracture. Out of the 21 patients having hearing loss, 5 patients (23.8%) had conductive hearing loss, 9 patients (42.86%) had mixed hearing loss and 7 patients (33.34%) had sensorineural hearing loss. Facial nerve palsy was present in 2 patients (28%) among longitudinal fracture cases and 1 patient (50%) among transverse fracture cases. Motor Vehicular accident (MVA) are still the commonest cause of injuries compared to the other mode of injury. Patients with longitudinal fracture showed conductive and mixed loss and patients with transverse fracture showed sensorineural hearing loss. Incidence of facial nerve paralysis was more with transverse fracture cases than with longitudinal fracture cases.

Effect of aceclofenac on pharmacokinetic of phenytoin.

Aceclofenac is presently most commonly prescribed analgesic for chronic pain and inflammatory conditions. In clinical practice, phenytoin and aceclofenac are used in a chronic condition of generalized seizure with concomitant chronic pain. Hence there are chances of drug-drug interaction because modulations of isoenzymes involved in metabolism of phenytoin and aceclofenac are CYP2C9/10 and CYP2C19. It is important to maintain the therapeutic level of phenytoin in plasma for effective control of seizure. So, the aim of the study was to determine the effect of aceclofenac on the pharmacokinetics of phenytoin in rabbits. In a parallel design study, phenytoin 30 mg/kg/day per oral was given daily for seven days. On day 7, blood samples were taken at various time intervals between 0-24 hours. In aceclofenac group, phenytoin was administered for seven days as above. On day 8, aceclofenac 14 mg/kg along with phenytoin 30 mg/kg/day was administered and blood samples drawn as above. Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated. In aceclofenac group, there was decrease in t½el than phenytoin group significant changes were observed in the pharmacokinetic parameters in aceclofenac treated group. These results suggest that aceclofenac alter the pharmacokinetics of phenytoin. Confirmation of these results in human studies will warrant changes in phenytoin dose or frequency when aceclofenac is co-administered with it.

Community based estimation of extent and determinants of cost of injuries in a north Indian city.

BACKGROUND AND OBJECTIVES: Very few community based studies on the economic impact of injuries are available from India. Being based on secondary data sources these underestimate the true burden. Current study aimed to ascertain the incidence and economic impact of injuries in an Indian city. MATERIALS AND METHODS: Details of injury events during the reference period were elicited in the study population through a community based survey in 2008. The severity of injury was categorized on the basis of need and duration of hospitalization. Direct and productivity costs were assessed for each event of injury. RESULTS: Out of 230 households contacted 212 participated in the study. Overall, 985 people were interviewed. The overall incidence of injury was 48.73/1000 population, Road traffic injuries (RTIs) were the leading cause (35%) of injury, followed by the falls (17%), contact with hot substances (13%), inanimate mechanical force (13%), animate mechanical force (8%), assault (8%) and others (6%). The ratio of fatal: severe non-fatal: mild injuries were 1:14:33. The total direct cost (DC) incurred was Rs. 310,951.67, contributed by medical (44%), surgical (21%), legal (15%), cost of informal care (10%). The total productivity cost of injuries was Rs. 416,700, contributed by mortality cost of Rs. 336,000 (81%) and morbidity cost of Rs. 807,00 (19%). CONCLUSIONS: For every case of fatal injury, there were 14 cases of severe hospitalized injuries and 33 cases of mild injuries. RTIs were the commonest. Injuries had sizeable direct and indirect cost on the society.

Isolated Sphenoid Pyocele with Thornwaldt's Cyst of Nasopharynx.

Isolated sphenoid sinusitis (ISS) is a rare entity. ISS accounts for about 1-2% of all sinus infections. Isolated sphenoid sinus involvement may include mucoceles, pyoceles and isolated mycotic infections. We report a case of isolated sphenoid pyocele in a 35 year-old female who presented in August 2007 with frontal and occipital headache, post nasal discharge and bilateral nasal obstruction for 6 years. CT scan showed isolated right sphenoid sinusitis. Diagnostic nasal endoscopy showed a streak of post nasal discharge on right side above the torus tubaris confirming right sphenoiditis. A cyst in the nasopharynx was incidentally detected which was confirmed by fluid aspiration to be Thornwaldt's cyst (TC). TCs have reported prevalence of 0.2-5% and though most are asymptomatic their location renders them vulnerable to infection. Sphenoidotomy was done and the cyst in the nasopharynx was removed and marsupialised. Postoperative course was uneventful.

Adverse reproductive and child health outcomes among people living near highly toxic waste water drains in Punjab, India.

BACKGROUND: Environmental influence plays a major role in determining health status of individuals. Punjab has been reported as having a high degree of water pollution due to heavy metals from untreated industrial effluent discharge and high pesticide consumption in agriculture. The present study ascertained the association of heavy metal and pesticide exposure on reproductive and child health outcomes in Punjab, India. METHODS: A cross-sectional community-based survey was conducted in which 1904 women in reproductive age group and 1762 children below 12 years of age from 35 villages in three districts of Punjab were interviewed on a semistructured schedule for systemic and general health morbidities. Medical doctors conducted a clinical examination and review of records where relevant. Out of 35 study villages, 25 served as target (exposed) and 10 as non-target (less exposed or reference). Effluent, ground and surface water, fodder, vegetables and milk (bovine and human) samples were tested for chemical composition, heavy metals and pesticides. RESULTS: Spontaneous abortion (20.6 per 1000 live births) and premature births (6.7 per 1000 live births) were significantly higher in area affected by heavy metal and pesticide pollution (p<0.05). Stillbirths were about five times higher as compared with a meta-analysis for South Asian countries. A larger proportion of children in target area were reported to have delayed milestones, language delay, blue line in the gums, mottling of teeth and gastrointestinal morbidities (p<0.05). Mercury was found in more than permissible limits (MPL) in 84.4% samples from the target area. Heptachlor, chlorpyriphos, beta-endosulfan, dimethoate and aldrin were found to be more than MPL in 23.9%, 21.7%, 19.6%, 6.5% and 6.5% ground water samples respectively. CONCLUSION: Although no direct association could be established in this study, heavy metal and pesticide exposure may be potential risk factors for adverse reproductive and child health outcomes.

Cardiac abnormalities in acute organophosphate poisoning.

BACKGROUND: Potentially lethal cardiac complications can occur in patients with acute organophosphate poisoning (OPP) and may be overlooked. PATIENTS AND METHODS: Thirty-six patients with acute OPP were studied. Clinical features and the nature of compound involved were recorded. The QT interval was plotted against heart rate to determine the risk for Torsades de Pointes using the Fossa nomogram. Echocardiography was undertaken in 29 patients. Twenty-four-hour Holter monitoring was performed on day 1 in five patients. Thirteen died. Necropsy was performed and hearts were studied both grossly and microscopically. RESULTS: Gross examination of the heart in 13 cases revealed cardiac discoloration or blotchiness in 12, patchy pericarditis in six, auricular thrombus in six, right ventricular hypertrophy in four, and dilatation in three. On histopathology, all 13 cases had myocardial interstitial edema and vascular congestion, eight had patchy interstitial inflammation, two had patchy myocarditis, and six had a mural thrombus. Sinus tachycardia was the most common electrocardiographic abnormality. The others were corrected QT interval prolongation, ST-T changes, U waves, and ventricular premature contractions. Echocardiography in 29 patients showed minor abnormalities in 10. On Holter monitoring, episodic tachycardia and ST-T changes were observed in four, QT prolongation in three, and episodic bradycardia in two. CONCLUSIONS: Patchy myocardial involvement as a result of direct cardiac toxicity could be one of the factors responsible for serious cardiac complications. As myocardial involvement is patchy, it may not be manifest clinically or on echocardiography. Continuous cardiac monitoring should be undertaken to detect dynamic cardiac changes.

Acute pesticide poisoning: 15 years experience of a large North-West Indian hospital.

INTRODUCTION: Acute pesticide poisoning is an important cause of morbidity and mortality in developing countries. Better preventive and management strategies can be developed if the incidence and pattern of acute poisoning are known. METHODS: This retrospective study covered 15 years (1990 to 2004). The case records of all cases admitted with acute poisoning during these years were reviewed and the results compared to earlier studies. RESULTS: A total of 2884 patients with acute poisoning were admitted during the study period (1918 men). The mean age was 27.8 years (range 13 to 82 years). The commonest agents were anticholinesterases (35.1%) and aluminum phosphide (26.1%). A seasonal variation in anticholinesterase poisoning was observed (most cases occurring July to September) but not for aluminum phosphide. No difference in mortality was observed over different months for different agents. Maximum case fatality ratio was due to aluminum phosphide exposures followed by anticholinesterase agents. The case fatality ratios for aluminum phosphide and organophosphate poisonings declined since 2000 despite an increase in aluminum phosphide exposures. The decline in aluminum phosphide mortality may be due to limited availability of 3 gm tablets and improved intensive care. CONCLUSIONS: Though incidence of acute pesticide poisoning increased over decades, there has been a decline in mortality for both aluminum phosphide and anticholinesterases. There is still need for measures like integrated pesticide management, development of safer aluminum phosphide formulations, and training of farmers in spraying techniques.

Extent and determinants of cost of road traffic injuries in an Indian city.

BACKGROUND: Studies aimed at estimating losses that are incurred as a result of road traffic injuries (RTIs), especially at the family level, are very limited. AIMS: To ascertain the direct and productivity costs of road traffic injuries and their determinants. SETTINGS AND DESIGN: This study was a cross-sectional survey of all the road traffic crashes recorded by traffic police during 2004 in Chandigarh, a modern planned city of north India. MATERIAL AND METHODS: All road traffic crashes recorded by the traffic police during the year 1st January to 31st December 2004 were included in the study. The houses of all the victims were visited. The direct costs included the immediate medical costs (i.e., emergency and hospital care, follow-up care, medicines and appliances, doctor bills, etc.), and nonmedical costs (transportation, property damage cost, etc.). STATISTICAL ANALYSIS: Work productivity and activity questionnaire (WPAI-SHP), the health and labor questionnaire (HLQ) and Human Capital Method were used for estimating the productivity costs. Percentage, mean, standard deviation of the outcome parameters were calculated. RESULTS: Of the 121 crash victims listed, 95 agreed to participate in the study. The net direct costs incurred were Rs. 8,55,644 ($19,991). The vehicle repair costs constituted more than half of such cost. Surgery, which was conducted in 28 cases, constituted 14.5% of the direct costs. The total productivity cost incurred was Rs. 8,06,24,530 ($1,883,750). Costs incurred due to premature mortality constituted over 99% of these productivity losses suffered by society. Lost wages due to the crash constituted less than 1% [Rs. 1,40,230 ($3276)] of the total productivity loss. CONCLUSIONS: Road traffic injuries are a significant financial drag on the society. The productivity costs far outweigh the direct costs. Premature mortality, vehicle damage and medical costs constituted the major share of the cost of RTIs.

Determination of age from pubic symphysis: an autopsy study.

The present study was conducted on three hundred and thirty-six cases brought for autopsy to the Department of Forensic Medicine, Government Medical College, Amritsar, Punjab, India, during the period 2000-2002. Pubic bones of either sex were analysed according to Todd's method (1920; 1921a,b,c) as modified by McKern and Stewart (1957) to assess and compare the known age of the corpses. Cases belonged to both sexes, i.e. 79.46% males and 20.54% females. All the cases were above the age of 17 years. No difference was noted in the scoring of right and left pubic bones. The age estimation from different components in males and females up to the total score of 10 (23-28 years) was +/- 6, whereas above a score of 10 the estimated age was +/- 12 in males and +/- 9 in females. The age range given for scores of 14 and 15, which were 29+ and 36+ respectively, did not account for variability of age after 40 years. Therefore, the age assessment from pubic bones in the fourth decade age group and beyond is not reliable which is in variance to the study by McKern and Stewart (1957).

Estimation of postmortem interval from human pericardial fluid electrolytes concentrations in Chandigarh zone of India: log transformed linear regression model.

Estimation of postmortem interval from changes in postmortem pericardial fluid electrolytes concentration is the topic of discussion in the study. Querido [Querido D. Double logarithmic, linear relationship between plasma sodium/potassium concentration ratio and postmortem interval during the 6-96h postmortem period in rats. Forensic Sci Int 1990;44:125-34; Querido D. Linearization of the relationship between postmortem plasma chloride concentration and postmortem interval in rats. Forensic Sci Int 1990;45:117-27] and Singh et al. [Singh D, Prashad R, Parkash C, Bansal YS, Sharma SK, Pandey AN. Linearization of relationship between serum sodium, potassium concentration, their ratio and time since deaths in Chandigarh zone of north west India. Forensic Sci Int 2002;130:107; Singh D, Prashad R, Parkash C, Sharma SK, Pandey AN. Double logarithmic linear relationship between plasma chloride concentration and time since death in humans in Chandigarh zone of north west India. Legal Med 2003;5:49-54] had demonstrated a highly significant double logarithmic linear relationship between the time since death and the plasma sodium/potassium ratio as well as with plasma chloride concentration in Wistar rats and human, respectively. In view of these facts, the present study was carried out to substantiate this propensity in this transcellular extension of blood plasma. Electrolytes analysis in postmortem pericardial fluid obtained from 311 subjects revealed that correlation of time since deaths with potassium, sodium/potassium ratio and phosphorus was highly significant (p<0.001) during 2.5-58h of deaths. Not withstanding, time since death although modulated by ambient temperature could be predicted by log transformed multiple regression equation derived from the combination of potassium, chloride and phosphorus electrolytes concentration with standard error (SE) of prediction (in log hours) of 0.1840h and by double logarithmic model with SE (in log hours) of 0.1959, 0.2068 and 0.2088h from potassium, sodium/potassium ratio and phosphorus electrolytes, respectively.