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Introduction: FNAC has a pivotal role in the evaluation of breast lesions. Cytological grading systems are being utilized for the categorization of breast lesions. Modified Masood’s scoring System (MMSS) is used to improve the grading system for accurate pre-operative diagnosis. This study aims to assess the effectiveness and accuracy of the Modified Masood Scoring System for evaluating breast lesions and their correlation with histopathological diagnosis. Materials and Methods: This is a prospective study conducted in the Department of Pathology, MGM Medical College, Navi Mumbai which included 40 patients who presented with clinically palpable breast lump and were subjected to FNAC along with histopathological examination. The cytological smears were grouped into four categories according to MMSS. Correlation and concordance analysis between cytological categories and histopathological diagnosis was carried out. Observations and Results: The age of the patients ranged from 17 to 70 years with a mean age of 38.12 years, right-sided breast lesions were more common as compared to the left side. Of the total 40 cases, 27 cases were benign, and 13 cases were malignant on histopathology. The most common benign breast lesion was Fibroadenoma [Figure 1] and the malignant lesion was infiltrating duct carcinoma [Figure 2]. The sensitivity, specificity, Positive predictive value, Negative predictive value, and diagnostic accuracy were 76.9%, 100%, 100%, 90%, and 92.5% respectively. Conclusion: MMSS is simple, cost-effective, easily reproducible, reliable, and can be applied to FNAC aspirates to increase the diagnostic accuracy of Breast Lesions. [ABSTRACT FROM AUTHOR]

Background: FNAC is a simple, safe and cost-effective method and is one of the triple diagnostic triads along with clinical breast examination and radiology methods (mammography/ ultrasonography).Cytological diagnosis is very beneficial for the preoperative assessment of various breast lesions. The application of LBC technique along with conventional smear can strengthen the efficacy of diagnosing various breast lesions on FNAC. Aim: Comparison of liquid-based cytology versus conventional smears in fine needle aspiration cytology of breast lesions. Materials and Methods: A prospective study of 50 cases conducted over a period of 16 months included all female patients referred to the cytology department for FNAC. Two different passes were given, the first pass was used to prepare conventional smears and second pass was used for LBC smears. Results: Among 50 cases, 38 (76%) were benign and 12 (24%) were malignant. The commonest benign lesion was fibroadenoma and malignant lesion was Infiltrating Ductal Carcinoma. The difference between LBC and conventional smears was statistically significant pertaining to background blood debris (p < 0.00001), informative background (p = 0.0004) and cellular architecture (p = 0.0075) while it was not statistically significant for cellularity, mono layering, nuclear and cytoplasmic details The sensitivity, specificity, PPV, NPV and diagnostic accuracy of FNAC in both LBC and conventional smears were similar, being 80%, 100%, 100%, 95.23% and 96% respectively. Conclusion: LBC cannot replace conventional cytology but can be used as a supplement with the conventional method to minimize false negative cytology rate and to increase the diagnostic accuracy of breast lesions. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is the most prevalent infectious disease which is brought by the mycobacterium tuberculosis. In addition to the lung tissue, TB also affects the bone marrow. Significant haematological and coagulation abnormalities are associated with TB. Therefore the diagnosis, prognosis, and therapeutic response can also be indicated by these haematological and coagulation markers. These coagulation abnormalities can lead to stroke and DIC leading to increased mortality. Aims To evaluate the haematological and coagulation parameters in pulmonary tuberculosis patients. Methods and Materials: In this study a total of 50 patients with confirmed tuberculosis were chosen using purposive sampling. Four millilitres of venous blood were drawn while taking the necessary aseptic precaution. Sysmex XN 1000 6-part haematology analyser was used to perform hematologicalanalysis on two millilitres of ethylenediamine tetra acetic acid (EDTA)vacutainer tubes. Rest two millilitres of blood in sodium citrate vacutainer tube was used to perform coagulation parameters analysis on ACL elite pro coagulation analyser for measurement of D dimer and fibrinogen. Results Hemoglobin and other blood indices were marginally lower in both sexes compared to healthy controls. Patients with tuberculosis show significantly greater levels of white blood cells (WBC), platelets, D-dimer, and fibrinogen when compared to healthy controls. P-value < 0.05 indicated that these increases were statistically significant. [ABSTRACT FROM AUTHOR]

Introduction: Peripheral neuropathy is common in chronic kidney disease (CKD) and may be multifactorial in origin, resulting from uremia, hyperkalemia, and diabetes. Previous studies have suggested that magnesium plays a crucial role in chronic pain. Studies evaluating magnesium in neuropathy have demonstrated mixed results. Aims: To provide preliminary data on the effectiveness of transdermal magnesium in treating peripheral neuropathy related to CKD. Methods: Twenty participants with advanced CKD were enrolled from a major teaching hospital clinic in Sydney, Australia. Each participant was provided with a spray bottle containing magnesium chloride and instructed to apply five sprays to each limb affected by neuropathy daily for 12 weeks. Participants completed the Neuropathy Total Symptom Score-6 (NTSS-6) every 4 weeks during follow-up. Serum magnesium concentrations were measured at 4-week intervals. Results: Twenty participants were recruited, of which 14 completed the 12-week follow-up period. Mean age was 78.90 years, 80.00% were female and mean estimated glomerular filtration rate was 9.78 mL/min/1.73 m2. With intention to treat analysis (mean [95% confidence interval]), NTSS-6 was significantly reduced at weeks 8 (4.04 [2.43–5.65]) and 12 (4.26 [2.47–6.05]), compared with baseline (6.92 [5.29–8.55]), p < 0.05. Serum magnesium concentration did not change significantly during the study. Conclusion: This pilot study suggests that transdermal magnesium may be beneficial in reducing frequency and severity of peripheral neuropathic symptoms in patients with advanced CKD. Trial Registration: australianclinicaltrials.gov.au. Identifier: ACTRN12621000841875. Date first registered January 7, 2021. [ABSTRACT FROM AUTHOR]

The Australian Therapeutic Goods Administration's approved indications for prescription of gabapentinoids are refractory focal epilepsy and neuropathic pain. Use of gabapentinoids outside of the approved indications is common, but evidence for this is limited, especially for chronic nonspecific back pain and nonradicular leg pain. Some effects of gabapentinoids encourage their nonmedical use (e.g. euphoria, sedation, disinhibition). Widespread nonmedical use has increased the incidence of accidental and deliberate poisonings. Dependence may develop with chronic use of gabapentinoids and abrupt cessation may induce withdrawal symptoms. If the indication for continued use is unclear, gradual dose tapering as a means of deprescribing is recommended. Clinicians should consider the indication, patient characteristics and harm-benefit profile when prescribing gabapentinoids. Some people, such as those with kidney disease, have an increased risk of harm when using these drugs. [ABSTRACT FROM AUTHOR]

Aims: Buprenorphine is effective at reducing relapse to opioid misuse, morbidity and mortality in opioid‐dependent patients. Urine drug screening (UDS) to assess adherence is used routinely in opioid agonist treatment (OAT). The primary aim of this study was to determine factors which may be associated with a negative qualitative urine drug screen for buprenorphine in OAT patients. Methods: This prospective pilot study was conducted at a tertiary addiction medicine centre. Twenty participants on stable treatment underwent supervised administration of sublingual buprenorphine. Matched urine and blood samples were collected prior to and 2, 4 and 6 hours after buprenorphine administration. Qualitative urine drug screen results were obtained using gas chromatography–mass spectrometry (GC–MS), while quantitative blood and urine results were obtained using ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Results: Qualitative urine assay yielded a negative result for buprenorphine in 57% of tested samples. The median concentration of urinary buprenorphine was 167 mcg/L (range: 2–1730 mcg/L). Thirty percent of all blood samples did not detect buprenorphine (range 0–18 mcg/L). Positive qualitative urine drug screen results were associated with higher urine (343 mcg/L compared with 75 mcg/L; P <.05) and blood (4 mcg/L compared with 2 mcg/L; P <.05) buprenorphine concentrations. Median urine concentrations of buprenorphine were highest at 2 hours and were higher in participants receiving CYP3A4 inhibitors. Conclusion: Interpretation of qualitative urine drug screens to assess adherence in OAT is complex. Poor adherence with treatment cannot be assumed in patients returning a negative qualitative GC–MS urine drug screen. [ABSTRACT FROM AUTHOR]

We report a case of misdiagnosed tuberous sclerosis complex (TSC) in a patient without TSC gene variant presenting with bilateral renal angiomyolipomas and seizures in the context of strong family history of polycystic kidney disease. Clinical diagnosis of tuberous sclerosis complex was made and treatment with everolimus reduced size of renal angiomyolipomas. In this case, report we discuss the association between tuberous sclerosis complex and polycystic kidney disease and novel treatment for TSC. [ABSTRACT FROM AUTHOR]

Introduction: Dabigatran, a direct thrombin inhibitor, is 80% renally eliminated and demonstrates multi-compartmental pharmacokinetics. Idarucizumab is a monoclonal antibody that reverses dabigatran-induced anticoagulation and displays single compartment pharmacokinetics, with a smaller volume of distribution and shorter elimination half-life than dabigatran. These differences in pharmacokinetics mean that redistribution of dabigatran from peripheral compartments can occur after idarucizumab has been eliminated, resulting in rebound in the dabigatran plasma concentration and treatment failure. Clinical experience notes failure of a single idarucizumab 5 g dose to fully reverse coagulopathy in certain patients. Aims: To identify factors predisposing to an incomplete response to the standard idarucizumab 5 g dose. Methods: A systematic literature search in PubMed using terms "dabigatran" and "idarucizumab" covering 2015 to October 2019 identified 387 entries. Titles and abstracts were screened initially, followed by full text review and data extraction from 97 eligible articles. Data extracted included clinical information, dabigatran concentrations, coagulation results, idarucizumab dosage and patient outcomes. Pharmacokinetic simulations were conducted using a two-compartment model to predict the likelihood that acute or chronic kidney disease will contribute to an incomplete reversal of dabigatran-induced anticoagulation. Results: Of 240 published cases receiving idarucizumab, 33 reported dabigatran concentration rebound, within a median time of 22 h. From 231 cases reporting idarucizumab dose, 10 received repeated administration due to a rebound in dabigatran concentrations. Baseline dabigatran concentrations >228 ng/mL were more likely to experience a rebound post-idarucizumab to >30 ng/mL (detectable). For baseline dabigatran >488 ng/mL, the concentration rebounded to >75 ng/mL (therapeutic). The impact of kidney dysfunction on the effect of the recommended dose of idarucizumab: Idarucizumab is expected to neutralise a maximum plasma dabigatran concentration of 980 ng/mL, but most likely a lesser amount. Pharmacokinetic modelling suggests, for patients taking dabigatran 150 mg twice daily, an incomplete response to 5 g idarucizumab is predicted after approximately 72 h dosing when GFR less than 30 mL/min (25% of normal), and after 36 h with severely impaired renal function (GFR 6 mL/min; GFR 5% of normal). Acute dabigatran self-poisoning: Idarucizumab has neutralised dabigatran following deliberate self-poisoning with dabigatran in a limited number of cases, even in the absence of bleeding. There are insufficient data regarding the use of idarucizumab as part of standard supportive care in this context. Clinical use of idarucizumab in complex circumstances: The dilute thrombin time can be used to determine the dabigatran concentration, but other more standard coagulation assays are less precise. A normal aPTT largely excludes dabigatran. We suggest performing coagulation assays and dabigatran concentrations every 6 h for a minimum of 36 h after idarucizumab administration to detect a rebound in dabigatran. This is particularly necessary in patients with glomerular filtration rate <30 mL/min or those with a plasma dabigatran concentration exceeding approximately 500 ng/mL. If a rebound in dabigatran is noted, then repeat administration of idarucizumab 5 g can be considered for reversal of recurrent coagulopathy if clinically indicated. Conclusion: The use of idarucizumab for reversal of dabigatran is complex and requires consideration of clinical circumstances and laboratory investigations. Monitoring post-idarucizumab may be required in acute or chronic kidney disease to detect a rebound in dabigatran concentration and the need for additional doses of idarucizumab. [ABSTRACT FROM AUTHOR]

Proteinuria, in particular albuminuria, is a potentially significant modifiable risk factor for cardiovascular disease and the progression of kidney disease. Current treatment guidelines for albuminuria recommend a single renin-angiotensin-aldosterone inhibitor. This can be an ACE inhibitor or an angiotensin receptor antagonist. The routine use of combined renin-angiotensin-aldosterone inhibition for albuminuria is not supported by current evidence. Combination therapy is associated with higher rates of adverse events such as hyperkalaemia and progressive renal impairment. [ABSTRACT FROM AUTHOR]

Nausea and vomiting are common symptoms with many possible causes, including the adverse effects of drugs. If a drug is indicated, the cause guides the choice of antiemetic drug. The main antiemetic classes include antagonists of the serotonin, dopamine, histamine, muscarinic and neurokinin systems, corticosteroids and benzodiazepines. Some antiemetics appear more effective for specific indications. Serotonin and neurokinin antagonists, such as ondansetron and aprepitant, are highly effective in treating chemotherapy-induced nausea and vomiting. Metoclopramide and antihistamines are first-line options for nausea and vomiting in pregnancy. Serotonin antagonists and some dopamine antagonists, such as metoclopramide, can prolong the QT interval on the ECG. Dopamine antagonists can cause extrapyramidal adverse effects, particularly in children. [ABSTRACT FROM AUTHOR]

Background: Advanced physician training in clinical pharmacology lacks a continuing education programme. There is a need for continuing medical education but how to introduce and develop education remains unclear. Aims: The primary aim was to develop and implement a peer‐led, web‐based multiple choice question approach to continuing education in clinical pharmacology training across Australia and New Zealand. Secondary aims included determining, quality, difficulty, utility, relevance, user‐friendliness, sustainability and potential to form part of formal clinical pharmacology physician training. Methods: In February 2018, a survey of clinical pharmacology trainees identified topics for question development. Questions covering requested topics were developed and piloted in PeerWise between March and October 2018. Participants could rate quality and difficulty of questions using categorical rating scales and make free text comments. After questions were piloted, a survey using a 0–10‐point Likert scale and yes/no responses assessed utility, relevance, user‐friendliness, sustainability and formalisation potential. Results: Twenty‐four trainees were invited to participate. Nine (38%) of trainees completed the initial survey, 10 (42%) attempted questions and 7 (29%) completed the end survey. Median scores of 8.00 (IQR 6.50 – 9.00), 7.00 (IQR 6.50 – 7.50) and 8.00 (IQR 6.50 – 8.00) using a 0–10‐point Likert scale indicated trainees found this approach useful, relevant and user‐friendly. Five (71%) out of seven responding trainees felt this approach was sustainable and could be incorporated as part of formal clinical training. Conclusion: This study suggests that peer‐led multiple choice questions could form an enduring education modality which could be incorporated into clinical pharmacology training. [ABSTRACT FROM AUTHOR]

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole‐trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole‐trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole‐trimethoprim‐induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved. SUMMARY AT A GLANCE: A novel association between the sulfamethoxazole/trimethoprim and acute interstitial nephritis and nephrogenic diabetes insipidus is described in a patient treated with temozolomide for glioblastoma multiforme. Kidney biopsy confirmed acute tubular changes and the patient's kidney function improved with cessation of the drug. [ABSTRACT FROM AUTHOR]

Introduction: Urine drug screens (UDS) assist in clinical planning and assessment of adherence in opioid agonist treatment (OAT). Urine drug screens may also be used in criminal justice and child protection settings. Buprenorphine (BPN) UDS testing is complex. Immunoassay often does not detect BPN and gas chromatography-mass spectrometry (GC-MS) is needed. A limited understanding of testing can negatively influence UDS interpretation and clinical decision making., Objectives: The primary aim was to determine detection rates of BPN in UDS in participants on BPN or buprenorphine/naloxone (BNX) treatment. The secondary aim was to identify if comorbidities, sex, co-prescribed medications, or dosing site and observation were associated with BPN detection., Setting: Public outpatient clinic in a specialist addiction treatment service., Design/participants: In this retrospective observational study, records of clients on supervised BPN/BNX treatment between September 2017 and 2018 were reviewed., Measures: Data extracted included UDS results, age, sex, indication for BPN, frequency of observed doses, dose of BPN, dosing site, comorbid medical conditions, and medications., Results: One hundred and sixty-one medical records were reviewed. Ninety-seven (60 percent) underwent screening urine immunoassay. Of these 97, 51 (53 percent) had further GC-MS testing for BPN of which 22 (43 percent) did not detect BPN despite directly observed OAT. Co-prescription of medications known to interact with cytochrome P450 3A4 was associated with nondetection of BPN (p < 0.05). No significant association between median dose, dosing site, and observed dosing and BPN detection was identified., Conclusion: Urine drug testing for BPN is complex. Failure to detect BPN does not betoken nonadherence to treatment and is associated with co-prescription of drugs interacting with cytochrome P450 3A4.