A headspace-gas chromatography method for isopropanol determination in warfarin sodium products as a measure of drug crystallinity

Coumadin® and several generic products of warfarin sodium (WS) contain the crystalline form (clathrate) in which WS and isopropanol (IPA) are associated in a 2:1 molar ratio. IPA is critical in maintaining the WS crystalline structure. Physicochemical properties of the drug and drug product may change when the crystalline drug transforms to amorphous form. A headspace-gas chromatography (HS-GC) method was developed and validated for IPA determination in the WS drug product. n-propanol (NPA) was used as internal standard and the method was validated for specificity, system suitability, linearity, accuracy, precision, range, limits of detection and quantification, and robustness. The method was specific, with good resolution between IPA and NPA peaks. Chromatographic parameters (retention time, IPA/NPA area ratio, tailing factor, theoretical plates, USP symmetry, capacity factor, selectivity and resolution) were consistent over three days of validation. The analytical method was linear from 2–200 µg mL–1 (0.1–10 % IPA present in the drug product). LOD and LOQ were 0.1 and 2 µg mL–1, respectively. Accuracy at low (2 µg mL–1) and high (200 µg mL–1) IPA concentrations of the calibration curve was 103.3–113.3 and 98.9–102.2 % of the nominal value, resp. The validated method was precise, as indicated by the RSD value of less than 2 % at three concentration levels of the calibration curve. The method reported here was utilized to determine accurately and precisely the IPA content in in-house formulations and commercial products. In summary, IPA determination by HS-GC provides an indirect measure of WS crystallinity in the drug product. Nevertheless, it should be confirmed by another analytical method since IPA from the drug substance is not distinguishable from IPA that may be present outside the drug crystals in a dosage form when prepared by wet granulation with IPA

Renal involvement in systemic lupus erythematosus in Pakistan

Objective: To find the prevalence of lupus nephritis, delineate its clinical, immunological and therapeutic characteristics and compare them with the data worldwide.PATIENTS AND Methods: Between 1985 and 2001, 198 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association (ARA) admitted to the hospital were studied by means of a retrospective review of their records.Results: Renal involvement was found in 89 (45%) patients. Biopsy showed lupus nephritis in 42 patients; there were 9 male and 33 females. Mean age at initial presentation was 27 years and mean duration of follow-up was 2 .3 years. The histological types (WHO Classification) were mainly class. 4 (n = 27), class 3 (n = 7) and class 5 (n = 6). Immunoflourescence showed a predominantly granular pattern of IgG, IgA and C3. Renal manifestations included renal failure (50%), microscopic hematuria (67%), active urine sediment (22%), and proteinuria (74%). Proteinuria was nephrotic range in 45% patients. Treatment was with combinations of prednisolone and cyclophosphamide (n = 13), prednisolone and azathioprine (n = 27). 19 patients received high dose methyl prednisolone (1 gm/day for 3 days). There was no difference in mortality rate between prednisolone and cyclophosphamide and prednisolone and azathioprine treatment groups. The overall mortality rate was 17% (n = 7). Mortality was higher in WHO class 4 and 5 as compared to class 2 and 3 (p \u3c 0.001).CONCLUSION: The prevalence of lupus nephritis in our population is an intermediate between Caucasians and other Asians. Certain clinical characteristics in our patients with lupus nephritis are different as compared to various other studies. Because of limited resources for treatment in developing countries, we believe that patients with lupus nephritis should be treated with improved ancillary medical therapies and more effective immunosuppressive regimens

Do clinical manifestations of Systemic Lupus Erythematosus in Pakistan correlate with rest of Asia?

Objective: Systemic Lupus Erythematosus (SLE) is known to be different among people with different racial, geographical and socio-economic back grounds. Asia has diverse ethnic groups broadly, Orientals in the East and Southeast Asia, Indians in South Asia and Arabs in the Middle East. These regions differ significantly from the Caucasians with reference to SLE. The purpose of this study was, therefore, to delineate the clinical pattern and disease course in Pakistani patients with SLE and compare it with Asian data.Methods: Patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association admitted at the Aga Khan University Hospital between 1986 and 2001 were studied by means of a retrospective review of their records. The results were compared with various studies in different regions of Asia.Results: Demographically, it was seen that SLE is a disease predominantly of females in their third decade, which is generally consistent with Asian data. There was less cutaneous manifestations, arthritis, serositis, haematological and renal involvement compared to various regions in Asia. The neurological manifestations of SLE, however, place Pakistani patients in the middle of a spectrum between South Asians and other Asian races.CONCLUSION: This study has shown that the clinical characteristics of SLE patients in our country may be different to those of other Asian races. Although our population is similar to South Asians, but clinical manifestations of our SLE patients are considerably different, suggesting some unknown etiology. Further studies are required to confirm the above results and to find statistically sounder associations

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Sixty-minute post-Synacthen serum cortisol level: a reliable and cost-effective screening test for excluding adrenal insufficiency compared to the conventional short Synacthen test

Introduction: Previous studies have indicated that most individuals reach peak cortisol levels in 60 minutes during the short Synacthen test (SST) done to exclude adrenal insufficiency. Therefore, measuring serum cortisol at only 60 minutes may suffice. This study was carried out to evaluate the significance of the 60-minute serum cortisol level in SST as a reliable and cost-effective screening test in comparison to the conventional SST.Methods: A cross-sectional study was conducted from January 2000 to September 2004, in which data was collected by reviewing medical records of all patients who underwent SST at the Aga Khan University Hospital, Karachi. A total of 236 patients suspected of having adrenal insufficiency were included. Values of serum cortisol at baseline, 30 and 60 minutes post-250 ug-injection Synacthen were recorded. The cortisol level was measured through fluorescence polarisation immunoassay. The cut-off value of 20 ug/dL was used to differentiate normal individuals from hypoadrenal individuals.Results: Out of 236 study participants, 93 (39 percent) were males and 143 (61 percent) were females. The mean age and standard deviation was 44.4 +/- 21 years. Cortisol concentration increased significantly from baseline to 30 minutes and 60 minutes after injecting Synacthen (p-value is less than 0.001 for each). The majority of the patients reached the cortisol peak of greater than 20 ug/dL (555 nmol/L) at 60 minutes. Normal responses were found in 148 patients (63.1 percent) at both 30 and 60 minutes, while 27 participants (12 percent) reached a peak greater than 20 ug/dL (555 nmol/L) at 60 minutes but were less than 20 ug/dL (555 nmol/L) at 30 minutes. In the deficient cases, SST showed abnormal responses in 60 cases (25 percent) at both 30 and 60 minutes. However, there was only one patient who reached a peak value of 21 ug/dL (589 nmol/L) at 30 minutes, which reduced to 17 ug/dL (485 nmol/L) at 60 minutes.CONCLUSION: This study showed that a 60-minute cortisol value during SST was reliable enough in identifying normal subjects for excluding adrenal insufficiency, and was equally effective in identifying abnormal cases, as compared to values at both 30 and 60 minutes. It is therefore suggested that a single 60-minute post-Synacthen serum cortisol level may suffice, as compared to the conventional SST. This is also significant as a cost-effective measure, especially in third world countries where cost is a major issue for diagnosing and treating patients

Phytodiversity Conservation through Evaluation of Nematicidal Properties of Latex Bearing Plants against Meloidogyne javanica

The antagonistic effect of five organic additives (fresh chopped leaves) of various latex bearing plant species were applied against Meloidogyne javanica in bottlegourd. The two doses (50&100g) of organic additives were treated with 1 kg soil separately, filled in pots under a glasshouse trial to determine nematicidal effect against root-knot infections. All treatments stimulated plant height, fresh & dry weight, and chlorophyll content compared to untreated inoculated plants. Plants treated with fresh chopped leaves of Calotropis procera (100g) were the best among all. The use of organic additives is ecofriendly and does not harm soil biota. It is an alternative to conserve the phytodiversity through phytochemicals without causing any pollution and hazardous effect