Clinical features and risk factors for death in acute undifferentiated fever: A prospective observational study in rural community hospitals in six states of India.

BACKGROUND: Acute undifferentiated fever (AUF) ranges from self-limiting illness to life-threatening infections, such as sepsis, malaria, dengue, leptospirosis and rickettsioses. Similar clinical presentation challenges the clinical management. This study describes risk factors for death in patients hospitalized with AUF in India. METHODS: Patients aged ≥5 y admitted with fever for 2-14 d without localizing signs were included in a prospective observational study at seven hospitals in India during 2011-2012. Predictors identified by univariate analysis were analyzed by multivariate logistic regression for survival analysis. RESULTS: Mortality was 2.4% (37/1521) and 46.9% (15/32) died within 2 d. History of heart disease (p=0.013), steroid use (p=0.011), altered consciousness (p<0.0001), bleeding (p<0.0001), oliguria (p=0.020) and breathlessness (p=0.015) were predictors of death, as were reduced Glasgow coma score (p=0.005), low urinary output (p=0.004), abnormal breathing (p=0.006), abdominal tenderness (p=0.023), leucocytosis (p<0.0001) and thrombocytopenia (p=0.001) at admission. Etiology was identified in 48.6% (18/37) of fatal cases. CONCLUSIONS: Bleeding, cerebral dysfunction, respiratory failure and oliguria at admission, suggestive of severe organ failure secondary to systemic infection, were predictors of death. Almost half of the patients who died, died shortly after admission, which, together with organ failure, suggests that delay in hospitalization and, consequently, delayed treatment, contribute to death from AUF.

The prevalence of vertebral fractures among Indian perimenopausal women and its association with ovarian biomarkers.

INTRODUCTION: There is dearth of data on prevalent vertebral fractures in perimenopausal women in India and limited literature on the utility of FSH, AMH and estradiol in evaluating bone health them. The objective was to study the prevalence of vertebral fractures (VF) and to assess the utility of FSH, estradiol and AMH in predicting them in Indian perimenopausal women MATERIALS AND METHODS: It was a cross-sectional study. Perimenopausal women aged 40-49 years underwent assessment for prevalent vertebral fractures, bone mineral density (BMD) and trabecular bone score (TBS). Utility of serum FSH, estradiol and AMH in predicting prevalent vertebral fractures was also assessed. RESULTS: A total of 300 perimenopausal women with mean (SD) age of 43.2 (2.8) years was recruited and 18% had moderate-severe VF. Mean (SD) serum AMH was lower in perimenopausal women with VF as compared to those without fractures [0.752 (0.594) vs 1.023 (0.704) P = 0.006]. AMH showed significant positive correlation with TBS (r = 0.3; P < 0.001) and BMD at the femoral neck (r = 0.2; P < 0.001) and lumbar spine (r = 0.3; P < 0.001).On ROC analysis, AMH demonstrated good performance in predicting prevalent VF with an AUC of 0.800 (95% CI 0.705-0.880) and a sensitivity of 85% and specificity of 60% at a cut-off of 1.12 ng/mL. On an exploratory multivariate logistic regression analysis, AMH significantly predicted prevalent fractures with an adjusted OR (OR) of 1.85 (95% CI: 1.03-3.00; P = 0.04). The performance of FSH and estradiol in predicting prevalent fractures was sub-optimal. CONCLUSION: About one-fifth of the study subjects had prevalent vertebral fractures. AMH may be a menstrual cycle independent biomarker and may reflect bone loss in perimenopausal women. Further prospective studies are needed to validate these findings.

Knowledge gap regarding osteoporosis among medical professionals in Southern India.

RATIONALE, AIMS, AND OBJECTIVES: Osteoporosis is a common health problem in India, which leads to significant morbidity and mortality in elderly individuals. Lack of knowledge and awareness among medical professionals is one of the important barriers in management of these patients. Therefore, this study was conducted to assess knowledge pertaining to diagnosis and treatment of osteoporosis among a group of Indian medical practitioners. METHODS: The study participants included 222 allopathic medical professionals, either graduate or postgraduate working in primary or secondary health care levels. They were assessed using a previously validated Fogelman's multiple choice questionnaire. Out of a total of 18 questions, four questions pertained to knowledge of diagnosis, three questions to treatment decisions, one question to assess knowledge regarding recommended dosage of vitamin D and calcium supplementation, five questions concerned medication use, and the rest to assess attitude and practices. The correct answers were converted into scores and expressed as percentages with a maximum of 100. RESULTS: The mean total score among them was 22.5%, which was quite low. Almost all of them had a score of less than 50%. Medical practitioners performed better in diagnosis-related questions, (19.4% answered all options correctly) than in medication knowledge (no correct response regarding side effects and 2% regarding contraindications). In treatment-related decisions, 37.4% answered correctly for duration of treatment, and 59% answered correctly for treatment goal. Only 1.4% of them were able to answer correctly regarding recommended calcium and vitamin D intake. Professional literature, conferences, and Continuing Medical Education (CME's) were regarded as the main sources of information on the subject by 40% of practitioners. CONCLUSION: This study showed suboptimal knowledge among a group of medical professionals regarding various aspects of diagnosis and management of osteoporosis, and it stipulates the need for escalating the efforts to improve their knowledge regarding various aspects of osteoporosis.

A rare cause of familial exogenous Cushing syndrome.

Exogenous steroid use is the most common cause of Cushing syndrome. With the use of glucocorticoids(GC) for a variety of diseases, the indiscriminate use of this group of drugs has increased. We present a family from which both children were brought with features suggestive of Cushing syndrome. On evaluation, they were found to have suppressed hypothalamic pituitary adrenal (HPA) axis, signifying steroid use from exogenous sources. On further evaluation by a psychiatrist, the mother who was on treatment for chronic depression confessed that she had bought dexamethasone tablets over the counter, and administered the same, mixed with fruit juices to her sons. The family was counselled regarding the consequences of chronic steroid abuse and the children were started on replacement doses of prednisolone. Certain features like posterior subcapsular cataract, glaucoma, avascular necrosis of femur and psychosis are specific to exogenous Cushing syndrome. Despite efforts to understand the effects of long-term steroid treatment on the HPA axis, it is not yet clear as to which patients will have prolonged HPA axis suppression. The time taken for the recovery of HPA axis remains variable. Also, HPA axis suppression due to exogenous steroids may present as acute adrenal crisis. Hence, it is important to start these patients on replacement dose of steroids and also educate them regarding the increased requirement of steroids during stress.

End-of-life decisions: A retrospective study in a tertiary care teaching hospital in India.

Background & objectives: In developing countries like India, there is a lack of clarity regarding the factors that influence decisions pertaining to life supports at the end-of-life (EOL). The objectives of this study were to assess the factors associated with EOL-care decisions in the Indian context and to raise awareness in this area of healthcare. Methods: This retrospectively study included all patients admitted to the medical unit of a tertiary care hospital in southern India, over one year and died. The baseline demographics, economic, physiological, sociological, prognostic and medical treatment-related factors were retrieved from the patient's medical records and analysed. Results: Of the 122 decedents included in the study whose characteristics were analyzed, 41 (33.6%) received full life support and 81 (66.4%) had withdrawal or withholding of some life support measure. Amongst those who had withdrawal or withholding of life support, 62 (76.5%) had some support withheld and in 19 (23.5%), it was withdrawn. The documentation of the disease process, prognosis and the mention of imminent death in the medical records was the single most important factor that was associated with the EOL decision (odds ratio - 0.08; 95% confidence interval, 0.01-0.74; P=0.03). Interpretation & conclusions: The documentation of poor prognosis was the only factor found to be associated with EOL care decisions in our study. Prospective, multicentric studies need to be done to evaluate the influence of various other factors on the EOL care.

Cerebrovascular injury in cryptococcal meningitis.

Background Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.

Acute undifferentiated fever in India: a multicentre study of aetiology and diagnostic accuracy.

BACKGROUND: The objectives of this study were to determine the proportion of malaria, bacteraemia, scrub typhus, leptospirosis, chikungunya and dengue among hospitalized patients with acute undifferentiated fever in India, and to describe the performance of standard diagnostic methods. METHODS: During April 2011-November 2012, 1564 patients aged ≥5 years with febrile illness for 2-14 days were consecutively included in an observational study at seven community hospitals in six states in India. Malaria microscopy, blood culture, Dengue rapid NS1 antigen and IgM Combo test, Leptospira IgM ELISA, Scrub typhus IgM ELISA and Chikungunya IgM ELISA were routinely performed at the hospitals. Second line testing, Dengue IgM capture ELISA (MAC-ELISA), Scrub typhus immunofluorescence (IFA), Leptospira Microscopic Agglutination Test (MAT), malaria PCR and malaria immunochromatographic rapid diagnostic test (RDT) Parahit Total™ were performed at the coordinating centre. Convalescence samples were not available. Case definitions were as follows: Leptospirosis: Positive ELISA and positive MAT. Scrub typhus: Positive ELISA and positive IFA. Dengue: Positive RDT and/or positive MAC-ELISA. Chikungunya: Positive ELISA. Bacteraemia: Growth in blood culture excluding those defined as contaminants. Malaria: Positive genus-specific PCR. RESULTS: Malaria was diagnosed in 17% (268/1564) and among these 54% had P. falciparum. Dengue was diagnosed in 16% (244/1564). Bacteraemia was found in 8% (124/1564), and among these Salmonella typhi or S. paratyphi constituted 35%. Scrub typhus was diagnosed in 10%, leptospirosis in 7% and chikungunya in 6%. Fulfilling more than one case definition was common, most frequent in chikungunya where 26% (25/98) also had positive dengue test. CONCLUSIONS: Malaria and dengue were the most common causes of fever in this study. A high overlap between case definitions probably reflects high prevalence of prior infections, cross reactivity and subclinical infections, rather than high prevalence of coinfections. Low accuracy of routine diagnostic tests should be taken into consideration when approaching the patient with acute undifferentiated fever in India.

Low dose versus high dose anti-snake venom therapy in the treatment of haematotoxic snake bite in South India.

Most of the studies on the appropriate dose of anti-snake venom (ASV) are from tertiary hospitals and the guidelines are unclear. Our observational study compared the outcomes of two prevalent treatment regimes for haematotoxic snake bite in a secondary care hospital in South India. The time to normalisation of whole blood clotting time, mortality and complications were not different between the groups. The average dose of ASV required in the low and high dose groups were 106 mL and 246 mL, respectively. Consequently, patients who received low dose ASV incurred approximately 50% less expense. Urticarial rashes were also significantly fewer in the low dose group.

Is Ross Syndrome an Autoimmune Entity? A Case Series of 11 Patients.

BACKGROUND: Ross syndrome is diagnosed by the presence of segmental anhidrosis, areflexia, and tonic pupils. Fewer than 60 cases have been described in literature so far. There have been reports of presence of antibodies in such patients, suggesting an autoimmune pathogenesis. METHODS: We describe the clinical profile in this case series of 11 patients with Ross syndrome and discuss the current status of autoimmunity in its pathogenesis and the management. RESULTS: Of the 11 patients with Ross syndrome there was an almost equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset of symptoms was 26 years. Patients took an average of 6 years to present to a tertiary center. Sixty-three percent of the patients presented with complaints of excessive sweating, whereas only 27% had complaints of decreased sweating over a particular area of the body. Only 45% of the patients had the complete triad of Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent reflexes. Eighty-nine percent of the patients had documented absent sympathetic skin response on electromyography. The various markers of autoimmunity were negative in all patients who were investigated for the same in this series. Ninety percent of the patients were managed conservatively. CONCLUSIONS: These findings suggest that, in Ross syndrome, generalized injury to ganglion cells or their projections are not purely autoimmune-mediated.

Validity of tuberculous pleuritis diagnosed in a resource-constrained setting in Dindigul district of Tamil Nadu.

CONTEXT: Majority of the Indians live in rural areas where resource constrained settings depend on cheaper and less invasive tests to diagnose extrapulmonary tuberculosis (TB). The decline in prevalence of TB in the country could affect the validity of the diagnosis. The aim was to measure validity of the pleural fluid study of proteins, lactate dehydrogenase (LDH), and cell counts in diagnosis of tuberculous pleuritis. MATERIALS AND METHODS: This was a cross-sectional study conducted in a 300 bedded secondary care hospital in rural Tamil Nadu. Exhaustive sampling was performed during April 2013 to March 2014. Pleural fluid study of 54 patients with exudative pleural effusion was conducted. Diagnosis was established by closed needle pleural biopsy. Receiver operator curves were plotted and area under curve (AUC) was calculated for various parameters. Sensitivity, specificity, and predictive values were calculated for different cut-off values of the parameter with significant AUC. RESULTS: Prevalence of tuberculous pleural effusion was 56% (95% confidence interval [95% CI] - 42.5-69.5%). Lymphocyte predominance in pleural fluid was the only valid test, and cut-off >80% had sensitivity of 70.0% (95% CI - 53.3-86.7%) and specificity of 70.8% (95% CI - 52.2-89.4%). Pleural fluid pH, protein or its ratio with serum protein, sugar, total leukocyte count, LDH or its ratio with serum LDH; erythrocyte sedimentation rate were not valid screening tests. CONCLUSIONS: Lymphocyte predominance > 80% can be used as a marker of tuberculous pleuritis. Since the prevalence of tuberculous pleuritis in India has come down considerably, newer tests need to be included to make a valid diagnosis.