Study of cerebrospinal fluid levels of lactate, lactate dehydrogenase and adenosine deaminase in the diagnosis and outcome of acute meningitis.

BACKGROUND: Meningitis is a serious clinical health issue in most developing countries. Late diagnosis and treatment result in significant morbidity and mortality. This research aims to study the utility of CSF lactate, lactate dehydrogenase (LDH), and adenosine deaminase (ADA) as diagnostic markers in acute meningitis, and to differentiate among varied aetiologies of acute meningitis and their outcomes. METHOD: A cross-sectional observational case-control study was conducted in 30 patients of suspected meningitis of varied aetiologies and 30 controls without any pre-existing neurological disorder and who underwent lumbar puncture during spinal anesthesia. A fresh CSF sample was collected in a heparinized vial following an aseptic lumbar puncture. The levels of lactate, LDH and ADA were estimated and recorded. RESULT: CSF lactate was significantly elevated in bacterial meningitis (BM) and cryptococcal meningitis, with 100% sensitivity when compared to controls. Elevated LDH was found only in BM, hence elevated LDH levels may strongly signify bacterial etiology. Significantly elevated ADA levels were noted in tuberculous meningitis. Significantly elevated levels of lactate and ADA were suggestive of slower clinical recovery and a prolonged hospital stay (p < 0.001). CONCLUSION: Estimation of CSF lactate, LDH, and ADA levels is a rapid, inexpensive and simple procedure and can play a major role in the early differentiation of bacterial, viral, tuberculous, and fungal meningitis. This would facilitate the initiation of appropriate treatment as early as possible, thereby decreasing mortality and complications.

Rash Decisions in Neurology: A Case Report of Brachioradial Pruritus Secondary to Cervical Intramedullary Lesion.

Brachioradial pruritus (BRP) is an enigmatic condition often encountered by dermatologists and passed off as a benign itch. It is an "idiopathic" pruritus, presenting as severe itching on the radial aspect of the elbow. The physical examination may be unremarkable except for mild pruritic lesions. Hence, the patient is treated with local applications of sunscreens, anti-inflammatory agents, anti-histamines and steroids, most of which prove to be ineffective. Dermatomal localization of localization of pruritis has suggested cervical myeloradiculopathy as a novel aetiology and this has been elucidated in recent studies. Here we report a young man, who presented with brachioradial pruritus and was diagnosed to have a C6-7 intramedullary cervical cord lesion.

Longitudinally Extensive Transverse Myelitis with Aquaporin-4 Antibody Positivity in Renal Cell Carcinoma: Rare Occurrence.

The occurrence of longitudinally extensive transverse myelitis (LETM) in an elderly patient should evoke search for underlying systemic malignancy. Intramedullary spinal cord metastases and paraneoplastic myelopathy are the most common etiology for LETM in patients with systemic malignancy. The occurrence of LETM in association with renal cell carcinoma with aquaporin-4 (AQP4) antibody positivity has not been reported. We report an elderly woman who presented with acute paraplegia and was diagnosed as having LETM with AQP4 positivity and renal cell carcinoma.

Factors contributing to disparities in mortality among patients with non-small-cell lung cancer.

Historically, non-small-cell lung cancer (NSCLC) patients who are non-white, have low incomes, low educational attainment, and non-private insurance have worse survival. We assessed whether differences in survival were attributable to sociodemographic factors, clinical characteristics at diagnosis, or treatments received. We surveyed a multiregional cohort of patients diagnosed with NSCLC from 2003 to 2005 and followed through 2012. We used Cox proportional hazard analyses to estimate the risk of death associated with race/ethnicity, annual income, educational attainment, and insurance status, unadjusted and sequentially adjusting for sociodemographic factors, clinical characteristics, and receipt of surgery, chemotherapy, and radiotherapy. Of 3250 patients, 64% were white, 16% black, 7% Hispanic, and 7% Asian; 36% of patients had incomes <$20 000/y; 23% had not completed high school; and 74% had non-private insurance. In unadjusted analyses, black race, Hispanic ethnicity, income <$60 000/y, not attending college, and not having private insurance were all associated with an increased risk of mortality. Black-white differences were not statistically significant after adjustment for sociodemographic factors, although patients with patients without a high school diploma and patients with incomes <$40 000/y continued to have an increased risk of mortality. Differences by educational attainment were not statistically significant after adjustment for clinical characteristics. Differences by income were not statistically significant after adjustment for clinical characteristics and treatments. Clinical characteristics and treatments received primarily contributed to mortality disparities by race/ethnicity and socioeconomic status in patients with NSCLC. Additional efforts are needed to assure timely diagnosis and use of effective treatment to lessen these disparities.

Decompressive surgery in malignant cerebral venous sinus thrombosis: what predicts its outcome?

Cerebral venous sinus thrombosis (CVST) is common in Asians, accounting for 15% of all strokes in the young. CVST causing malignant cerebral oedema with brain herniation and death are referred as malignant CVST. This study was aimed at evaluating the outcome of patients and factors predicting the outcome with malignant CVST after decompressive surgery. It was a retrospective, observational, single centre, hospital-based and cross-sectional study. Records of patients with malignant CVST who had decompressive surgery were analysed. Over 5 years (2010-2015), 30 patients (15 men and 15 women) underwent decompressive surgery. In univariate analysis, age more than 50 years (p = 0.05); presence of midline shift of more than 10 mm (p = 0.03) and total effacement of basal cisterns (p = 0.01) had significant correlation with poor outcome. On multivariate analysis, presence of midline shift of more than 10 mm (p = 0.01) was a significant predictor of poor outcome. Decompressive surgery is a life saving therapeutic intervention in patients with malignant CVST and more than two-thirds of patient shows favourable outcome. Age more than 50 years, midline shift >10 mm and total effacement of basal cisterns determine poor outcome following decompressive surgery.

Odorless inhalant toxic encephalopathy in developing countries household: Gas geyser syndrome.

BACKGROUND: Liquefied petroleum gas geysers are used very frequently for heating water in developing countries such as India. However, these gas geysers emit various toxic gases; one among them is colorless, odorless carbon monoxide (CO). In the past few years, there were reports of unexplained loss of consciousness in the bathroom. However, the exact cause for these episodes has been recognized as toxic encephalopathy due to toxic gases inhalation mainly CO. OBJECTIVE: To analyze the clinical profile and outcome of patients brought with loss of consciousness in the bathroom while bathing using gas geyser. MATERIALS AND METHODS: Case records of patients with the diagnosis of gas geyser syndrome from 2013 to 2015 were retrieved and analyzed. Twenty-four cases were identified and included in the study. This was a retrospective, descriptive study. RESULTS: Twenty-four patients were brought to our Emergency Department with loss of consciousness in the bathroom while bathing. Twenty-one cases had loss of consciousness during bathing and recovered spontaneously. Two cases were found dead in the bathroom and were brought to the Department of Forensic Medicine for postmortem. One case was brought in deep altered state of consciousness and succumbed to illness within 1 week. CONCLUSION: Awareness regarding CO intoxication due to usage of ill-fitted, ill-ventilated gas geyser is necessary as they are entirely preventable conditions.

Mometasone furoate nasal spray in the treatment of nasal polyposis in Chinese patients: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Although mometasone furoate nasal spray (MFNS) has demonstrated efficacy in nasal polyposis (NP) in Western populations, data in Asian populations is limited. METHODS: This randomized, double-blind study evaluated MFNS 200 µg twice per day (BID) vs placebo in Chinese adults with bilateral nasal polyps (graded as 1, 2, or 3 by the investigator). A 14-day placebo run-in period was followed by a 16-week treatment period with MFNS 200 µg BID vs placebo (1:1 ratio). The co-primary endpoints were change from baseline in nasal congestion/obstruction averaged over the first 4 weeks of treatment and change from baseline in the total polyp size score (sum of scores from the left and right nasal fossa) at week 16. Secondary endpoints included other sinonasal symptoms scores and safety outcomes such as monitoring laboratory measurements, vital signs, and adverse events (AEs). RESULTS: There were 748 patients randomized, 375 received MFNS 200 µg BID and 373 received placebo. The between-treatment difference in least squares (LS) mean change from baseline in nasal congestion/obstruction over 4 weeks of treatment was -0.14 (95% confidence interval [CI], -0.22 to -0.06) for MFNS vs placebo (p = 0.0007). The between-treatment difference in LS mean change from baseline in total polyp size score at week 16 was -0.30 (95% CI, -0.45 to -0.15) for MFNS vs placebo (p < 0.0001). Serious AEs were rare (0.5% and 0.8% in MFNS and placebo groups, respectively) and considered not drug-related. There were significantly more AEs of epistaxis with MFNS vs placebo (p = 0.009). CONCLUSION: This study demonstrated that MFNS was effective and well tolerated in this population of adult, Chinese patients with NP.

Extraparenchymal (Racemose) Neurocysticercosis and Its Multitude Manifestations: A Comprehensive Review.

Neurocysticercosis is an infection of the central nervous system caused by the larval form of the pork tapeworm Taenia solium. In the brain it occurs in two forms: parenchymal and extraparenchymal or racemose cysts. The clinical presentation of racemose cysts is pleomorphic, and is quite different from parenchymal cysticercosis. The clinical diagnosis of racemose cysts is quite challenging, with neuroimaging being the mainstay. However, the advent of newer brain imaging modalities has made a more accurate diagnosis possible. The primary focus of this article is racemose neurocysticercosis and its multitude manifestations, and includes a discussion of the newer diagnostic modalities and treatment options.

Evaluation of etoricoxib in patients undergoing total knee replacement surgery in a double-blind, randomized controlled trial.

BACKGROUND: Optimal postoperative pain management is important to ensure patient comfort and early mobilization. METHODS: In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients ≥18 years of age who had pain at rest ≥5 (0-10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively. Co-primary endpoints included Average Pain Intensity Difference at Rest over Days 1-3 (0- to 10-point NRS) and Average Total Daily Dose of Morphine over Days 1-3. Pain upon movement was evaluated using Average Pain Intensity Difference upon Knee Flexion (0- to 10-point NRS). The primary objective was to demonstrate analgesic superiority for the etoricoxib doses vs. placebo; the secondary objective was to demonstrate that the analgesic effect of the etoricoxib doses was non-inferior to ibuprofen. Adverse experiences (AEs) including opioid-related AEs were evaluated. RESULTS: The least squares (LS) mean (95% CI) differences from placebo for Pain Intensity Difference at Rest over Days 1-3 were -0.54 (-0.95, -0.14); -0.49 (-0.89, -0.08); and -0.45 (-0.85, -0.04) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.05 for etoricoxib vs. placebo). Differences in LS Geometric Mean Ratio morphine use over Days 1-3 from placebo were 0.66 (0.54, 0.82); 0.69 (0.56, 0.85); and 0.66 (0.53, 0.81) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.001 for etoricoxib vs. placebo). Differences in LS Mean Pain Intensity upon Knee Flexion were -0.37 (-0.85, 0.11); -0.46 (-0.94, 0.01); and -0.42 (-0.90, 0.06) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. Opioid-related AEs occurred in 41.8%, 34.7%, 36.5%, and 36.3% of patients on placebo, etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. CONCLUSIONS: Postoperative use of etoricoxib 90 and 120 mg in patients undergoing total knee replacement is both superior to placebo and non-inferior to ibuprofen in reducing pain at rest and also reduces opioid (morphine) consumption. CLINICAL TRIAL REGISTRATION: NCT00820027.

Overview of accountable care organizations for oncology specialists.

Accountable care organizations (ACOs) are poised to become major components of health care delivery in the United States. The practice of oncology, often laden with high charges, is likely to undergo major shifts as ACOs become widespread. In this article, we review the economic factors leading to the growth of ACOs and discuss some elements of the current ACO model proposed in the Affordable Care Act. Oncology specialists-in medicine, surgery, and radiation oncology-will have important roles in determining the place of specialty care in an ACO framework and will have to take the lead in educating patients, primary care physicians, and administrators on the value propositions related to their activities. We also describe how oncology specialists may participate in the model to ensure success for physicians and patients.

Effect of montelukast for treatment of asthma in cigarette smokers.

OBJECTIVE: Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma. METHODS: Patients (ages 18-55 years, with asthma [≥1 year], FEV1 of 60% to 90% of predicted value, airway reversibility [≥12%], and self-reported active smoking [≥0.5 to ≤2 packs per day]) were randomized (after a 3-week, single-blind, placebo, run-in period) to 1 of 3 parallel, 6-month, double-blind treatment arms. The primary efficacy end point was the percentage of days with asthma control during treatment. Adverse experiences (AEs) were also evaluated. RESULTS: There were 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. The mean percentage of days with asthma control over 6 months of treatment was 45% (montelukast, P < .05 vs placebo), 49% (fluticasone, P < .001 vs placebo), and 39% (placebo); the difference between montelukast and fluticasone was not significant (P = .14). Patients with a smoking history of ≤11 pack years (the median value) tended to show more benefit with fluticasone, whereas those with a smoking history of >11 pack years tended to show more benefit with montelukast. AEs occurred in similar proportions among treatment groups. CONCLUSIONS: In a population of asthmatic patients actively smoking cigarettes, both 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo.

Evaluation of safety, pharmacokinetics, and efficacy of vorinostat, a histone deacetylase inhibitor, in the treatment of gastrointestinal (GI) cancer in a phase I clinical trial.

BACKGROUND: Control of epigenetic changes using histone deacetylase inhibitors (HDACi) is thought to be a promising target in therapy of gastrointestinal (GI) cancer. In this study, we evaluated the safety, pharmacokinetics, and efficacy of two dosing regimens of vorinostat, an oral HDACi, in patients with GI tumors. METHODS: Patients received either vorinostat 300 mg bid for 3 consecutive days followed by 4 rest days per cycle (n = 10) or vorinostat 400 mg qd for 21 consecutive days per cycle (n = 6). Pharmacokinetic parameters were assessed for the first treatment cycle. Efficacy was determined through evaluation of tumors and assessment of treatment response. RESULTS: The median treatment duration of 300 mg bid was 52.0 days and of 400 mg qd was 51.5 days. The most common drug-related adverse events were anorexia, nausea, fatigue, and hyperglycemia. Two patients taking 400 mg qd had dose-limiting toxicities (DLTs) of thrombocytopenia. No patients taking 300 mg bid experienced DLT. Five patients taking 300 mg bid and 2 patients taking 400 mg qd maintained stable disease for >8 weeks, with the maximum duration of 245 days. Mean drug exposure (±SD) was generally higher with 400 mg qd (area under the curve [AUC(0-∞)] of 7.75 ± 2.79 µM h on Day 1 post-dose) compared with 300 mg bid (AUC(0-∞) of 3.94 ± 1.56 µM h on Day 1 post-dose). CONCLUSIONS: Vorinostat 300 mg bid for 3 consecutive days followed by 4 days of rest was better tolerated in patients with GI cancer than a higher once daily dose. Additionally, there were patients in both groups who achieved stable disease, most maintaining it for longer than 8 weeks, suggesting vorinostat as a possible active agent in the treatment of GI cancer.

Evaluation of multiday analgesia with etoricoxib in a double-blind, randomized controlled trial using the postoperative third-molar extraction dental pain model.

OBJECTIVE: To evaluate the analgesic effects of etoricoxib and comparator agents on the second and third days after oral surgery. METHODS: There were 588 patients initially randomized to placebo (n=46), etoricoxib 120 mg once daily (n=97), etoricoxib 90 mg once daily (n=191), ibuprofen 600 mg every 6 hours (n=192), and acetaminophen 600 mg/codeine 60 mg (A/C) every 6 hours (n=62) after third-molar extraction (≥2, ≥1 impacted) in a double-blind controlled trial. Patients were allowed flexible dosing on days 2 and 3; 46, 96, 190, 192, and 56 patients on placebo, etoricoxib 120 mg, etoricoxib 90 mg, ibuprofen, and A/C, respectively, continued to Day 2 of the study. Outcomes included Average and Worst Recall Pain Assessments (0 to 10 scale) and Global Assessments of Study Medication (0 to 4 scale). Rescue medication (acetaminophen 325 mg up to 4 times daily) usage was evaluated. Adverse experiences were collected and evaluated. RESULTS: Average Pain Recall scores were lower than placebo for all active treatments on Day 2 but only for etoricoxib 120 and 90 mg on Day 3. Worst Pain Recall scores were lower than placebo for only etoricoxib 120 and 90 mg on Day 2; all treatment groups were similar on day 3. Rescue medicine was used on day 2 in 57% of placebo patients, whereas use in active treatments ranged from 18% to 23%; for Day 3, rescue was used in 22% of placebo patients, whereas use in active treatments ranged from 14% to 20%. Differences in mean Patient's Global Assessment of Study Medication scores were significant for etoricoxib versus placebo (P<0.001) and for etoricoxib versus A/C (P<0.010). Nausea and vomiting were among the most common adverse events with higher frequency in the A/C group. CONCLUSIONS: Pain control was most favorable for the etoricoxib doses and ibuprofen. Global Assessments of Study Medication continued to differentiate the treatments and demonstrated greater efficacy for etoricoxib on Days 2 and 3 compared with placebo and A/C (NCT00694369).

Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy: a double-blind, randomized, placebo-controlled phase III study.

OBJECTIVE: To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively. RESEARCH DESIGN AND METHODS: In this double-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n = 144), etoricoxib 90 mg/day (n = 142), or etoricoxib 120 mg/day (n = 144). Average Pain Intensity at Rest over days 1-3 (0- to 10-point numerical rating scale [NRS]) was the primary efficacy endpoint. Secondary endpoints included Average Pain Intensity upon Sitting, Standing, and Walking over days 1-3 (0- to 10-point NRS) as well as Average Total Daily Dose of Morphine over days 1-3. CLINICAL TRIAL REGISTRATION: This trial is registered on www.clinicaltrials.gov (NCT00788710). RESULTS: The least squares (LS) means (95% CI) for the primary endpoint were 3.26 (2.96, 3.55); 2.46 (2.16, 2.76); and 2.40 (2.11, 2.69) for placebo, etoricoxib 90 mg, and etoricoxib 120 mg, respectively, significantly different for both etoricoxib doses versus placebo (p < 0.001). Patients on etoricoxib 90 mg and 120 mg required ~30% less morphine per day than those on placebo (p < 0.001), which led to more rapid bowel recovery in the active treatment groups by ~10 hours vs. placebo. A greater proportion of patients on etoricoxib (10-30% greater than placebo) achieved mild levels of pain with movement, defined as pain ≤3/10. LIMITATIONS: A key limitation for this study was that movement-evoked pain measurements were not designated as primary endpoints. CONCLUSION: In patients undergoing total abdominal hysterectomy, etoricoxib 90 mg and 120 mg dosed preoperatively and then continued postoperatively significantly reduces both resting and movement-related pain, as well as reduced opioid (morphine) consumption that led to more rapid bowel recovery.

The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: results of a 4-week, double-blind, randomized, controlled trial.

BACKGROUND: Metastatic bone disease (MBD) is a frequent complication in patients with breast cancer and is associated with significant morbidity. This study assessed the pharmacokinetics, efficacy, and safety of odanacatib, a selective Cat K inhibitor, in reducing markers of bone resorption in women with breast cancer and MBD. PATIENTS AND METHODS: Women with breast cancer and MBD were randomized 2:1 (double-blind) to oral odanacatib 5 mg daily for 4 weeks or intravenous (I.V.) zoledronic acid (ZA) 4 mg given once at study initiation. Plasma samples were collected for pharmacokinetic analysis. Bone resorption was assessed by measuring urinary N-telopeptide of type I collagen corrected for creatinine (uNTx; primary objective, pmol BCE/µmol creatinine). Adverse events (AEs) were monitored throughout the 4-week study and up to 14 days after last dose. RESULTS: A total of 43 patients (mean age, 60 years) received odanacatib (n = 29) or ZA (n = 14); 40 patients completed 4 weeks of treatment. The mean percent change in uNTx values at week 4 was -77% (95% CI, -82 to -71; odanacatib) and -73% (95% CI, -80 to -62; ZA). Mean (standard deviation) plasma concentration of odanacatib was 511.7 (202.9) nM; the range was 63.7-844.8 nM. The most common AEs were nausea, vomiting, headache, and bone pain, which were generally not attributed to study drug. CONCLUSION: Odanacatib suppressed uNTx similarly to ZA after 4 weeks of treatment in women with breast cancer and MBD. Odanacatib was generally safe and well tolerated. These results suggest that Cat K inhibition is a potentially important, novel therapeutic approach for treating MBD.