PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Reliability of Sonoelastography in Ductal Carcinoma

The objective of the study was to evaluate the reliability of sonoelastography in ductal carcinoma in patients in primary and secondary health care settings. Google Scholar, PubMed, Medline, Medscape, Wikipedia and NCBI were searched in January 2018 for all original research and review articles to identify relevant studies. Two reviewers selected the articles independently for based on the title and abstract. The selection criteria were sonoelastography accuracy for diagnosing ductal carcinoma as index text, B-mode sonography, and micropure imaging; surgery and histologic findings were used as reference text; and benign and malignant breast abnormalities and ductal carcinoma were used as target conditions. Two reviewers extracted the data on selected study characteristics, and the results were used to construct the tables and figures. Fifteen studies on ductal carcinoma were found. The overall sensitivity of sonoelastography in diagnosing ductal carcinoma was 85.7%, and the specificity, 79.8%. On the basis of the literature review, it was concluded that sonoelastography has high sensitivity and specificity in diagnosing ductal carcinoma.     

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Three Cases of Comprehensive Dietary Therapy and Pharmacotherapy of Patients with Complex Obesity-related Diseases

The effect of weight loss with anorectic medications on sleep apnea, non-insulin-dependent diabetes, and steatohepatitis is illustrated in three cases from practice in a clinical nutrition setting. Prevention of obesity, a chronic disorder, is preferable, but when obesity becomes a major obstacle in the care of patients with respiratory, cardiovascular, and metabolic disorders and osteoarthritis, an intense course of weight reduction using anorectic medications under medical and dietetic guidance is essential for patients' survival and reduction of medical cost.     

Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid-registered MRI.

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA.     

Detection of Vi-negative Salmonella enterica serovar typhi in the peripheral blood of patients with typhoid fever in the Faisalabad region of Pakistan

The synthesis and transportation proteins of the Vi capsular polysaccharide of Salmonella enterica serovar Typhi (serovar Typhi) are encoded by the viaB operon, which resides on a 134-kb pathogenicity island known as SPI-7. In recent years, Vi-negative strains of serovar Typhi have been reported in regions where typhoid fever is endemic. However, because Vi negativity can arise during in vitro passage, the clinical significance of Vi-negative serovar Typhi is not clear. To investigate the loss of Vi expression at the genetic level, 60 stored strains of serovar Typhi from the Faisalabad region of Pakistan were analyzed by PCR for the presence of SPI-7 and two genes essential for Vi production: tviA and tviB. Nine of the sixty strains analyzed (15%) tested negative for both tviA and tviB; only two of these strains lacked SPI-7. In order to investigate whether this phenomenon occurred in vivo, blood samples from patients with the clinical symptoms of typhoid fever were also investigated. Of 48 blood samples tested, 42 tested positive by fliC PCR for serovar Typhi; 4 of these were negative for tviA and tviB. Three of these samples tested positive for SPI-7. These results demonstrate that viaB-negative, SPI-7-positive serovar Typhi is naturally occurring and can be detected by PCR in the peripheral blood of typhoid patients in this region. The method described here can be used to monitor the incidence of Vi-negative serovar Typhi in regions where the Vi vaccine is used.     

Antimicrobial susceptibility pattern of clinical isolates of Pseudomonas aeruginosa in a tertiary care hospital.

BACKGROUND AND PURPOSE: Pseudomonas aeruginosa is an important cause of morbidity and mortality in hospitalized, critically ill patients and patients with underlying medical conditions such as cystic fibrosis, neutropenia, and iatrogenic immunosuppression. The prevalence of multiresistant P. aeruginosa isolates has been increasing. The aim of this study was to determine the antimicrobial susceptibility patterns in P. aeruginosa strains isolated at a university teaching hospital in Kuala Lumpur, Malaysia. METHODS: The Laboratory Information System of the microbiology department was retrospectively reviewed to determine the susceptibility patterns of P. aeruginosa isolates to anti-pseudomonal antibiotics, from January to June 2005. Disk diffusion methods were employed and results were interpreted according to National Committee for Clinical Laboratory Standards guidelines. RESULTS: 505 clinical isolates of P. aeruginosa were tested. Major sources of these isolates included respiratory tract, wound, urine and blood. The rates of antimicrobial resistance of isolates were 6.73% to amikacin, 12.9% to gentamicin, 10.1% to netilmicin, 10.9% to ceftazidime, 11.3% to ciprofloxacin, 9.9% to imipenem, 10.8% to piperacillin, 9.4% to piperacillin-tazobactam and 0% to polymyxin B. Of the 505 isolates, 29 (5.74%) were found to be multidrug-resistant; these were most commonly isolated from respiratory tract specimens of patients in surgical units, followed by respiratory tract specimens in patients in medical units. CONCLUSIONS: The data in this study showed low rates of antibiotic resistance among P. aeruginosa isolates. Combinations of aminoglycosides plus beta-lactams or quinolones should be the appropriate choice for empirical therapy in P. aeruginosa infections. Active antibiotic susceptibility testing and surveillance should be continued in order to curtail the problem of antibiotic resistance.     

Using the literature in developing McGill's guidelines for interactions between residents and the pharmaceutical industry.

Evidence suggests that the pharmaceutical industry exerts a large influence on residents' education and practice. Yet existing guidelines by professional bodies do not cover the specifics of residents' interactions with the pharmaceutical industry. At the psychiatry residency program of the McGill University Health Center, the authors set out to systematically evaluate areas of concern for residents and to develop guidelines for use by residents during and outside their training. Areas of concern included educational activities, training, fundraising, and other specific resident-industry interactions. In 1998, a committee of residents and faculty systematically evaluated areas of concern and, based on a review of the literature and discussions with experts, in 2000 developed guidelines for use by McGill's psychiatry program residents. The process for guideline development and methods for their implementation in 2001 are described. Education and training of residents on resident-industry interactions were included early in the curriculum. Guidelines were developed to address limitations on fundraising activities; restriction of direct gifts to residents; the appropriateness and awarding of industry fellowships; and the handling of drug samples, meals, and other presentations to residents. While guidelines for residents are useful adjuncts for guiding residents' interactions with the pharmaceutical industry, the authors conclude that they need to be reinforced with education and sensitization by faculty.