Conflict of interest disclosure and interpretation – rest assured the medical professional in the audience is perceptive, alert and smart

INTRODUCTION:We present data from a systematic survey on conflict of interest (COI) disclosure and its interpretation by the doctors participating in continuing medical education (CME).METHODS:A brief 12 question online Google survey with multiple choice options (read, select, and click) was done among Indian practicing doctors using links shared through WhatsApp through the internet over a 72 h period.RESULTS:Of the 386 replies, 373 unique replies were eligible for evaluation. The majority found CME activities beneficial. About 73% of participants would watch out for bias, even if the speaker shows COI disclosure slide. The use of brand/trade names was considered as a flag for bias by the majority. About 99% wanted the speaker to show a final take home message slide. Cross verification of the data presented by comparing to published data was done in more than 75% of instances by only 25% of the participating doctors. A significantly higher number of doctors found bias when CME activities were being organized by the health-care industry as compared to programs of medical bodies/societies/organizations.DISCUSSION:COI considerations are given due to the importance of medical professionals. However, doctors are smart enough to understand the limitations of such disclosures and remain alert to ensure they are not influenced by any bias. Take home message slide gives the presenters opportunity to share their insights and allows the audience to make their own judgment on the impartiality of the data presented. The doctors are aware that bias could be more when CME activities are organized by healthcare industry and take appropriate precautions.CONCLUSION:COI is is given due importance by the medical professionals. COI disclosures are often incomplete. Doctors remain alert to ensure they are not influenced by biased presentations. Concluding take home message slide is unanimously recommended. Presentation bias is more when healthcare industry is directly organizing educational and promotional activities.

Our patient at risk from unauthorized, unapproved, illegally imported fake “generic medicines”

Introduction: We came across patients inquiring with oncologists about cheap copy medicines. These were of recently licensedinnovator drugs that should have been available from original company holding their patents. In fact these copy medicines weremanufactured in our neighboring countries and made available in India. We investigated further and this manuscript puts together thestartling information that we were able to find regarding the thriving grey market for fake generic medicines.

Comparison of nested-multiplex, Taqman & SYBR Green real-time PCR in diagnosis of amoebic liver abscess in a tertiary health care institute in India.

Background & objectives: Amoebiasis is a common parasitic infection caused by Entamoeba histolytica and amoebic liver abscess (ALA) is the most common extraintestinal manifestation of amoebiasis. The aim of this study was to standardise real-time PCR assays (Taqman and SYBR Green) to detect E. histolytica from liver abscess pus and stool samples and compare its results with nested-multiplex PCR. Methods: Liver abscess pus specimens were subjected to DNA extraction. The extracted DNA samples were subjected to amplification by nested-multiplex PCR, Taqman (18S rRNA) and SYBR Green real-time PCR (16S-like rRNA assays to detect E. histolytica/E. dispar/E. moshkovskii). The amplification products were further confirmed by DNA sequence analysis. Receiver operator characteristic (ROC) curve analysis was done for nested-multiplex and SYBR Green real-time PCR and the area under the curve was calculated for evaluating the accuracy of the tests to dignose ALA. Results: In all, 17, 19 and 25 liver abscess samples were positive for E. histolytica by nested-multiplex PCR, SYBR Green and Taqman real-time PCR assays, respectively. Significant differences in detection of E. histolytica were noted in the real-time PCR assays evaluated (P<0.0001). The nested-multiplex PCR, SYBR Green real-time PCR and Taqman real-time PCR evaluated showed a positivity rate of 34, 38 and 50 per cent, respectively. Based on ROC curve analysis (considering Taqman real-time PCR as the gold standard), it was observed that SYBR Green real-time PCR was better than conventional nested-multiplex PCR for the diagnosis of ALA. Interpretation & conclusions: Taqman real-time PCR targeting the 18S rRNA had the highest positivity rate evaluated in this study. Both nested multiplex and SYBR Green real-time PCR assays utilized were evaluated to give accurate results. Real-time PCR assays can be used as the gold standard in rapid and reliable diagnosis, and appropriate management of amoebiasis, replacing the conventional molecular methods.

Study on the safety profile of Latanoprost and Timolol in primary open angle glaucoma.

Background: Topical beta blockers, Timolol and the prostaglandin F2α analogue Latanoprost are the most common prescribed medications as first line therapy. Their safety profiles have to be compared to justify the same. The objectives of this study were to compare the safety profile of Latanoprost with that of Timolol in the treatment of primary open angle glaucoma. Methods: In this randomized open label 12-week study, 60 patients were randomized to receive either 0.005% of Latanoprost once daily in the evening or 0.5% of Timolol twice daily. Their safety was concluded by monitoring their adverse effects during follow-up visits at 2, 4, 6, and 12 weeks. Results: Bradycardia was seen only in Timolol group whereas ocular adverse effects such as periocular pigmentation, the growth of eyelashes, and conjunctival hyperemia were seen only in Latanoprost group. Ocular discomfort was present equally in both the groups. Foreign body sensation was seen in both the groups, but it was more frequent in Latanoprost group. The blurring of vision was predominantly seen in Timolol group. Corneal anesthesia was seen in one of the patients on Timolol. Conclusions: The incidence of adverse effects was not significantly different between Latanoprost and Timolol therapy. Both had favorable safety profiles. However, Latanoprost has safer systemic side effects profile when compared to Timolol.

Clinical rabies: is cure possible.

Rabies is a fatal disease in humans and till date survivors of the disease after the clinical onset of the illness are rare. The approach to management of rabies is usually palliative. In rare cases of paralytic rabies a trial for cure has been tried. No single therapeutic agent is likely to be effective, but a combination of specific therapies could be considered, including rabies vaccine, rabies immunoglobulin, monoclonal antibodies, ribavirin, interferon alpha, ketamine etc. the only reported cases in literature were with rare success of the Milwaukee protocol. This is the case report of a 45 year old male who presented with clinical rabies and was started on the trial. Has the treatment had any benefit is to be debated and further options discussed.

In vitro study on the efficacy of zinc oxide and titanium dioxide nanoparticles against metallo beta-lactamase and biofilm producing Pseudomonas aeruginosa.

Pseudomonas aeruginosa contributes to a multitude of infections exhibiting intrinsic resistance to numerous antibiotics. Metallo beta-lactamase and biofilm production is the most worrisome resistant mechanisms observed in P. aeruginosa. Emergence of antimicrobial resistance by pathogenic bacteria is a major health problem in recent years. Zinc oxide and titanium dioxide nanoparticles comprises of well-known inhibitory and bactericidal effects. The present study is designed to determine the efficacy of zinc oxide and titanium dioxide nanoparticles against metallo beta-lactamase and biofilm producing P. aeruginosa. A total of 51 non-repetitive P. aeruginosa isolates were obtained from Bioline laboratory, Coimbatore. Biofilm and metallo beta-lactamase production was tested by combined disc test and tissue culture plate method. Commercially available zinc and titanium dioxide nanoparticles were obtained and tested against two metallo beta-lactamase and biofilm producing isolates. Both the nanoparticles showed appreciable activity at all tested concentrations. Thus, it is concluded that ZnO and TiO2 nanoparticles may serve as a promising antibacterial agents in coming years.

Trends in the prevalence of Pulmonary Tuberculosis over a period of seven and half years in a rural community in south India with DOTS.

Setting: Tiruvallur district In Tamil Nadu where DOTS was implemented by the State Government as the tuberculosis control measure in 1999, and monitored by the National Institute for Research in Tuberculosis for over five years. Objective: To estimate trends in TB prevalence in a rural community with DOTS. Design: Surveys of pulmonary tuberculosis were undertaken in representative samples of subjects aged >15 years (N = 83,000 – 92,000), initially and after two and half, five and seven and half years of implementation of DOTS. Sputa were collected from those with abnormal radiograph and/or presence of chest symptoms, and examined by direct smear and culture. Results: The prevalence of culture-positive tuberculosis was 607, 454, 309 and 388 per 100,000 in the four surveys, and that of smear-positive tuberculosis was 326, 259, 168 and 180. In the first five years; annual decrease was 12.4% (95% CI 10.4 - 14.4%) for culture-positive tuberculosis, and 12.2% (95% CI 8.0–16.2) for smear-positive tuberculosis. This was, however, followed by a significant increase in the next two and half years. The average new smear-positive case-notification rate was 75 per 100,000 during first four years but declined to 49 in subsequent years. There were no methodological differences during this period and information on changes in socio-economic indicators and nutritional standards was unavailable. Conclusion: Despite the average annual success rate (78%) in this tuberculosis unit being lower than the expected rate of 85%, the implementation of DOTS was followed by a substantial decrease in the prevalence of pulmonary tuberculosis over the seven and half year period. Our findings suggest that sustaining the high effectiveness of DOTS programme needs vigilant supervision.

Emergence of drug resistant mutations after single dose nevirapine exposure in HIV-1 infected pregnant women in south India.

Background & objectives: Resistance to nevirapine (NVP) has been described with single dose preventive regimens in other populations. Our aim was to study the pattern and prevalence of HIV drug resistance (DR) at baseline (during pregnancy) and after delivery among antenatal women exposed to single dose NVP for prevention of parent to child transmission (PPTCT). Methods: HIV-infected, ART-naive primigravidae between 18-25 years of age, attending government antenatal clinics in Chennai, Vellore or Madurai were recruited. Drug resistance testing was carried out during pregnancy and after Sd-NVP treatment (one month after delivery) by Viroseq sequencing. HIV-1 testing by DNA PCR was done in newborns at 30 days. Results: Thirty one women were enrolled but only twenty six plasma specimens were analyzable (24 paired and two postnatal only). No major mutations were observed in any drug class at baseline though many polymorphisms were observed in both the reverse transcriptase and protease genes. Mutations to non-nucleoside reverse transcriptase inhibitors (NNRTI) were observed post-delivery in 33 per cent of women who were treated with Sd-NVP. None of the infants were HIV-positive. Interpretation & conclusions: Among pregnant ART-naïve women, baseline HIV drug resistance was not observed. A high rate of development of NNRTI class resistance among women treated with single-dose NVP was observed. Our results emphasize the need to implement more effective PPTCT regimens, minimizing emergence of drug resistance and thereby preserving long-term treatment options for HIV-infected women in India.

Fulminant hepatic failure in an infant with severe dengue infection.

Fulminant hepatic failure due to dengue infection is rare, although mild liver dysfunction is common. Here we report a fatal case of fulminant hepatitis in an infant infected with dengue 3 serotype. Attention must be given to the use of hepatotoxic drugs in some cases of dengue especially in infants.

Acute respiratory distress syndrome in pediatric intensive care unit.

Objective. To report causes, clinical feature and outcome of children with Acute Respiratory Distress Syndrome (ARDS). Methods. The case records of children admitted with ARDS from June 2003 to June 2006 were retrospectively reviewed and the data collected was analyzed. Results. A total of 17 children were diagnosed as ARDS during study period giving an incidence of 22.7/1,000 admissions. The mean (SD) age was 74.5 (56.32) mo [range 6 -144 mo]. Primary lung pathology contributed to a (53%) cases of ARDS while the rest (47%) had non pulmonary causes.There was not any significant different in mortality between these two groups. Similarly when infections and non infections conditions were considered separately there was no difference in survival. All children were ventilated using Pressure Controlled Ventilation. The mean (SD) duration of ventilation was 5.0 days [range 1-10 days]. The maximum PEEP (SD) used during the course of ventilation was 10 (3.37) cm H2O [range 7- 18], while the maximum PIP (SD) used was 31 (3.75) cm H2O (range 25-36). The overall mortality was 70%; highest in children less than 2 years of age. Majority of the children had shock as the most common comorbid factor and had a high mortality (73.3%). Conclusion. The high incidence and mortality of ARDS and the presence of a large proportion of potentially preventable accidents and poisoning cases in the study group underline the need for health education measures addressing preventive strategies among the rural population.

CCR2, MCP-1, SDF-1α & DC-sign gene polymorphisms in HIV-1 infected patients with & without tuberculosis.

Background & objectives: Variability in the clinical outcome of persons exposed to and infected with HIV-1 and tuberculosis (TB) is determined by multiple factors including host genetic variations. The aim of the present study was to find out whether chemokine, chemokine receptor and DC-SIGN gene polymorphisms were associated with susceptibility or resistance to HIV and HIV-TB in south India. Methods: CCR2 V64I (G/A), monocyte chemoattractant protein-1 (MCP-1) -2518 A/G, stromal cell derived factor-1α (SDF-1α) 3’UTR G/A and DC-SIGN gene polymorphisms were studied by polymerase chain reaction based methods in HIV-1 infected patients without TB (n=151), with pulmonary TB (PTB) (n=81) and extrapulmonary TB (n=31), 155 PTB patients without HIV and 206 healthy controls. Results: The genotype frequencies of CCR2 V64I, MCP-1 -2518 and DC-SIGN polymorphisms did not differ significantly between the study groups. A significantly increased frequency of GG genotype of SDF-1α polymorphism was observed among HIV+PTB+ patients compared to healthy controls (P=0.009, Pc=0.027). Interpretation & conclusions: Our data suggest that GG genotype of SDF-1α 3’UTR polymorphism may be associated with susceptibility to PTB in HIV-1 infected patients. A better understanding of genetic factors that are associated with TB could help target preventive strategies to those HIV patients likely to develop tuberculosis.

DOTS Reacdes Socially Marginalized Population in the Community a Study from a Rural Area of South India.

We report here that the Directly Observed Treatment, Short course (DOTS) is reaching all tuberculosis patients in the community irrespective of social classification based on the analysis from the tuberculosis prevalence survey and programme performance during 1999-2003 from a rural area in Tamilnadu, South India. New smear- positive cases treated under a DOTS programme were classified in two groups namely; scheduled caste living in colony and other population. The prevalence of smear- positive cases among the scheduled caste population was 1.9 times higher than the other population and this was reflected in the notification also. The successful treatment outcome was also similar in these two groups (75% and 78% respectively; overall 77%). From these findings it is concluded that people living in colony have equal access to DOTS as those in the village.

Assessment of long term status of sputum positive pulmonary TB patients successfully treated with short course chemotherapy.

Background: Long term status of pulmonary tuberculosis (PTB) patients treated with short course chemotherapy (SCC) regimens remains unknown. Objective: To assess the clinical, bacteriological, radiological status and health related quality of life (HRQoL) of PTB patients 14 -18 years after successful treatment with SCC. Methodology: In a cross-sectional study, cured PTB patients treated during 1986 – 1990 at the Tuberculosis Research Centre (TRC) were investigated for their current health status including pulmonary function tests (PFT). The St Georges respiratory questionnaire (SGRQ) was used to assess the HRQoL Results: The mean period after treatment completion for the 363 eligible participants was 16.5yrs (range 14-18 yrs, 84% coverage) ; 25 (7 %) had been re-treated and 52 (14%) died. Among the investigated, 58 (29%) had persistent respiratory symptoms; 170(86%) had radiological sequelae but none had active disease. Abnormal PFT was observed in 96 (65%) with predominantly restrictive type of disease in 66(45%). The SGRQ scores for activity and impact were high implying impairment in HRQoL. Conclusion: Assessment of long term status of cured PTB patients showed an impairment of lung functions and HRQoL highlighting the need to address these issues in the management of TB that may provide added value to patient care.

Incomplete immunological recovery following anti-tuberculosis.

Background & objectives: Mycobacterium tuberculosis infection has been shown to result in increased HIV replication and disease progression in HIV-infected individuals through increased immune activation. The objective of this study was to correlate plasma levels of immune activation markers with the presence of tuberculosis (TB) in HIV-infected and uninfected individuals, and to study the changes following anti-tuberculosis treatment. Methods: Plasma markers of immune activation - neopterin, beta-2-microglobulin (β2M) and soluble tumour necrosis factor alpha receptor type I (sTNFα-RI) were measured by ELISA in 42 HIV positive TB patients (HIV+TB+) undergoing a six-month course of TB chemotherapy. Thirty seven HIV+ persons without active TB, 38 TB patients without HIV infection, and 62 healthy volunteers served as controls. Results: Plasma levels of all three markers were elevated in HIV+ individuals, more so in those with active TB. When HIV+ individuals were further categorized based on CD4+ T cell counts, HIV+TB+ patients with CD4+ T cells counts < 200 cells/μl were found to have the highest levels at baseline with a steep fall in neopterin and sTNFα-RI during treatment, but in most instances the levels did not drop to normal. β2M levels remained persistently high despite completing TB treatment. Interpretation & conclusions: The fi ndings of the study suggest that both HIV and TB act synergistically to activate the host immune system. Although ATT was effective in clearing M. tuberculosis infection, a high proportion of HIV+ TB patients continued to have levels well above the normal range, indicating that underlying immune activation persists despite TB treatment. None of the markers were specific enough to be used to assess cure of TB.

Electrocardiographic and echocardiographic changes in perinatal asphyxia.

OBJECTIVE: To study the usefulness of cardiac enzymes in evaluating myocardial damage in perinatal asphyxia. METHODS: Thirty term babies with perinatal asphyxia and without any congenital malformations were selected as cases. They were compared with thirty healthy term babies without asphyxia. Myocardial dysfunction was evaluated using clinical, electrocardiography, echocardiography and cardiac enzymes i.e, troponin-T and CK-MB levels. RESULTS: Among the 30 cases 23 had evidence of myocardial involvement while one baby in the control group had ECG evidence compatible with cardiac involvement. Cardiac enzymes were significantly increased in babies with perinatal asphyxia. The mean level of C-troponin-T among cases and controls were 0.22+/-0.28 and 0.003+/-0.018 while CK-MB levels were 121+/-77.4 IU/L and 28.8 +/- 20.2 IU/L respectively. C-troponin-T had higher sensitivity and specificity compared to CK-MB levels. Moreover, C troponin-T levels correlated well with severity and outcome in babies with perinatal asphyxia. CONCLUSION: C-Tropopnin assay is useful in evaluating the severity of myocardial damage and outcome in perinatal asphyxia.

Pot method for storage & detection of acid-fast bacilli from sputum samples.

BACKGROUND & OBJECTIVES: Sputum acid-fast bacilli (AFB) microscopy services are not available in all health facilities. Alternative procedures are needed to transport sputum samples to the diagnostic centres for detection of AFB. The objective of the present study was to evaluate sputum smears made by pot-method with the direct smears made immediately after sputum collection by Ziehl-Neelsen (ZN) method. METHODS: Ninety three sputum samples from 49 pulmonary tuberculosis suspects were studied. Their direct smears (ZN smears) were stained by hot ZN method. The samples were then mixed with phenol ammonium sulphate basic fuchsin solution and stored at ambient conditions. The smears (pot smears), made on day 7, were then, decolourized and counter-stained for detection of AFB (pot method). The ZN and pot smears were read blind. After excluding 18 samples for various reasons, the results of pot and ZN smears of 63 samples from smear positive (2 of 3 direct smears were positive) and 12 from smear negative (3 of 3 direct smears were negative) patients were analysed. ZN method was the gold standard. RESULTS: Pot and ZN smears were positive in 61 of 63 samples from smear-positive patients and negative in 11 of 12 smear-negative patients (kappa = 0.87). The sensitivity and specificity of pot method were 96.8 and 91.7 per cent respectively. INTERPRETATION & CONCLUSION: Sputum samples can be stored for up to seven days in the sputum container with phenol ammonium sulphate basic fuchsin solution. However, a comprehensive study needs to be done confirm the accuracy of the pot method for storage and transportation of sputum to microscopy centres for detection of AFB.