Objective assessment of handwriting in outpatient prescriptions of a tertiary care hospital

Background: Poor physician handwriting may lead to wrong comprehension and dispensing errors. This study was planned to objectively assess the quality of handwriting of doctors and their readability by physician, pharmacist and patient and to explore the impact of experience and familiarity of pharmacist on prescription readability.Methods: A 100 prescriptions were selected and were given to a pharmacist, a doctor and an educated lay person. They rated the readability of prescriptions on a scale of 1-10 and an average readability score was calculated. Prescriptions with average score 4 or less were subjected to analysis by a pharmacist working at the hospital dispensary (P1) and another pharmacist not working at hospital pharmacy (P2).Results: Average score of pharmacist, physician and lay person was 6.14, 5.2 and 3.14 respectively.  A total of 28 prescriptions, containing 93 medicines, had an average readability score of 4 or less. P1 was not able to comprehend one medicine while P2 could not comprehend 19 medicines out of these 93. The performance of both pharmacists was compared by diagnostic tests (EPI 6.04D). The sensitivity of P2 was 80% (95% CI 70.6-87.7), specificity and positive predictive value were 100, and negative predictive value was 5.3 (0.3-28.1).Conclusions: Familiarity of the pharmacist with the prescribing physicians’ handwriting is an important factor in comprehension of poorly legible prescriptions. This could limit the patients to pharmacists around the prescribers. Implementation of appropriate steps need to be assured to minimize the prescription errors

NUMBER NEEDED TO TREAT AS A TOOL FOR COST EFFECTIVENESS ANALYSIS: A CASE STUDY IN RENAL TRANSPLANTATION

Objective: To assess the utility of number needed to treat (NNT) as a tool for cost effectiveness analysis. Methods: Two monoclonal antibodies (MAbs), used for induction therapy viz basiliximab and daclizumab in renal transplantation, were identified. Pivotal placebo controlled clinical trials, mentioned in the innovator package inserts, were compared and analyzed for acute graft rejection and graft survival at 12 mo. NNT viz-a-vis cost was calculated and compared. Results: Daclizumab was comparable to basiliximab for acute graft rejection (NNT 10 vs. 9) but better for graft survival (20 vs. 25) at 12 mo, when used along with triple drug regimen (cyclosporine, azathioprine and corticosteroid). However, considering the cost of regimen for these drugs, in terms of NNT, basiliximab was more cost effective (INR 12,52,044 vs. 28,70,400 for acute rejection and INR 34,77,900 vs. 57,40,800 for graft survival). On the other hand, when these MAbs were used along with dual drug regimen (cyclosporine and corticosteroid), daclizumab was more cost effective for graft survival at 12 mo. The higher cost of daclizumab regimen (INR 2,87,040 vs. 1,39,116 for basiliximab) was offset by its substantially lower NNT (20 vs. 58-75 for one extra graft survival at 12 mo). Conclusion: This study demonstrates the utility of NNT in ascertaining relative effectiveness of treatment modalities that would help to formulate appropriate healthcare policies

Are acute infusion reactions after rituximab underreported?

Background: Rigorous premarketing trials may fail to capture safety issues associated with new drugs. This is more likely to happen in case of biopharmaceuticals. We take the case of rituximab, and anti CD20 monoclonal antibody, which was the first monoclonal antibody to get approval. This open label observational study was done with the objective of estimating the incidence of acute infusion reaction associated with rituximab infusion.Methods: The study population consisted of patients hospitalized for receiving rituximab, in day care centre(s) of a tertiary care hospital. Number and type of acute infusion reactions (AIR) were recorded on a case record form along with patient characteristics and medical history.Results: A total of 50 infusions were observed and all infusions were followed by at least one AIR. Total 71 AIRs were recorded among these 50 infusions (1.4 AIR per infusion). Non-Hodgkin’s lymphoma was the commonest indication for which patients were receiving rituximab. In a subset analysis, incidence of AIR was statistically lower in patients having received corticosteroids as premedication. However, brand of rituximab, gender of the patient and first or second cycle had no bearing on incidence of AIRs.Conclusions: AIRs are more common in real time clinical settings than what is reported. There is a need to formulate appropriate risk management plan depending on post marketing clinical data. Use of corticosteroids as premedication may be one such strategy. New drugs, esp biopharmaceuticals, may have unidentified/under reported safety issues and there is a need to undertake focussed pharmacovigilance endeavours to unravel them

Netarsudil: a novel intra-ocular pressure lowering agent

Optic disc health is an important indicator of visual functions. The first line of management to prevent/halt the damage to optic disc is to control responsible pathological condition, if identified. In absence of identifiable cause, the most validated approach is lowering of intra-ocular pressure (IOP). Individually, as well as combinations of currently available drugs are not fully effective in all patients of glaucoma in achieving desired IOP control. Hence, there is a need of newer alternatives which address this unmet need. Recently, a newer IOP lowering agent with a novel mechanism of action, netarsudil, has been approved by United States Food and Drug Administration (US-FDA) in December 2017. Netarsudil acts by inhibiting Rho-associated protein kinase resulting in lowering of overall tone of the contractible cells in trabecular meshwork thereby improving drainage of aqueous humor outflow and lowering of IOP. Though in its early days, this drug gives an armamentarium to ophthalmologists and physicians to control IOP in patients of open-angle glaucoma and ocular hypertension

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Greater concern about hypoglycemia in Type 2 diabetics is the need of the hour—findings from a prospective, single-center, observational study

Context: Hypoglycemia is a well-recognized adverse effect in the treatment of type 1 diabetes mellitus. For patients of type 2 diabetes mellitus (T2DM) on stabilized treatment with the current oral antidiabetic drugs, occurrence of hypoglycemia is considerably less well studied. The current study was undertaken to understand the extent of this problem in elderly Indian patients. Objectives: Primary Objective: Assessment of incidence of hypoglycemia in patients of T2DM on stable treatment. Secondary Objectives: 1. Estimation of incidence of episodes of severe hypoglycemia in patients. 2. Correlation of presence of hypoglycemia with treatment modality. Settings and Design: This study was conducted as an open label, single-center observational study at a multispecialty tertiary care hospital. Materials and Methods: The study participants consisted of 50 elderly confirmed patients of either gender suffering from T2DM undergoing treatment and follow-up in the hospital for at least 12 weeks. After a brief training session and enrolment, the patients were asked to report to study site every month for next 2 months. Parameters recorded were plasma glucose levels, HbA1c levels, treatment regimen, body mass index, possible hypoglycemic episode based on symptoms and self-monitoring of blood glucose, and quality of life based on questionnaire score. Statistical Analysis: Descriptive and other statistics were used to analyze the hypoglycemic episodes experienced by the patients for correlation with medicines and the effect of hypoglycemia on their quality of life. Results: Total of nine hypoglycemic episodes were recorded. Severe hypoglycemia did not occur in any patient. Patient on insulin reported significantly more hypoglycemia. Quality of life is not much different in patients using insulin in T2DM

CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BackgroundCyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.MethodsWithin the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated.ResultsHigh-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss.ConclusionThis study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC