Characteristics of and treatment outcomes in rifampicin-intolerant patients.

BACKGROUND: Rifampicin (RIF) is considered the backbone of TB treatment, but adverse effects often limit its use. METHODS: This retrospective cohort study examined patients treated for TB disease at our institution, and compared those who received RIF to those who were intolerant to RIF. RESULTS: A total of 829 patients were included. Seventy-six patients (9%) were intolerant to RIF. Patients with RIF intolerance were significantly older (median age: 67 years, IQR 50-78 vs. 48 years, IQR 31-70; P < 0.0001), and were more likely to be female (57% vs. 41%; P = 0.01) and have concurrent diabetes mellitus (37.3% vs. 19%; P < 0.0001) compared to those who tolerated RIF. RIF intolerance was most commonly due to transaminitis (25%), cytopenia (14.5%), rash (17.1%) and gastro-intestinal intolerance (7.8%). Twenty patients were subsequently challenged with rifabutin, and this was successful in 70%. The mean treatment duration was significantly longer in patients who were intolerant to RIF (335 vs. 270 days; P < 0.001). There was no significant difference in treatment outcomes. CONCLUSION: RIF intolerance is more common in older patients, females, and those with concurrent diabetes mellitus. Patients who could not tolerate RIF had a longer duration of therapy, but no difference in treatment outcomes. When attempted, rifabutin was well tolerated in most patients with a previous RIF-related adverse event.

CONTEXTE: La rifampicine (RIF) est généralement considérée comme le pilier du traitement de la TB, cependant, ses effets indésirables limitent fréquemment son utilisation. MÉTHODES: Dans cette étude de cohorte rétrospective nous avons examiné les patients traités pour la TB dans notre institution et avons comparé ceux qui ont reçu la RIF à ceux qui n'ont pas pu la tolérer. RÉSULTATS: Au total, 829 patients ont été inclus. Soixante-seize patients (9%) étaient intolérants au RIF. Les patients intolérants au RIF étaient significativement plus âgés (âge médian : 67 ans, IQR 50­78 vs. 48 ans, IQR 31­70 ; P < 0,0001), et étaient plus susceptibles d'être des femmes (57% vs. 41% ; P = 0,01) et d'avoir un diabète sucré concomitant (37,3% vs. 19% ; P < 0,0001) par rapport à ceux qui toléraient le RIF. L'intolérance au RIF était principalement due à une transaminite (25%), une cytopénie (14,5%), une éruption cutanée (17,1%) et une intolérance gastro-intestinale (7,8%). Vingt patients ont ensuite été soumis à un test de provocation à la rifabutine, avec un taux de succès de 70%. La durée moyenne du traitement était significativement plus longue chez les patients intolérants au RIF (335 vs. 270 jours ; P < 0.001). Aucune différence significative n'a été observée dans les résultats du traitement. CONCLUSION: L'intolérance au RIF est plus courante chez les patients plus âgés, les femmes et les patients atteints de diabète sucré. Les patients qui n'ont pas pu tolérer le RIF ont suivi un traitement plus long, mais cela n'a pas entrainé de différence dans les résultats du traitement. Lorsqu'elle a été tentée, la rifabutine a été bien tolérée par la plupart des patients ayant déjà présenté un effet indésirable lié au RIF.

A mathematical model of COVID-19 transmission.

Disease transmission is studied through disciplines like epidemiology, applied mathematics, and statistics. Mathematical simulation models for transmission have implications in solving public and personal health challenges. The SIR model uses a compartmental approach including dynamic and nonlinear behavior of transmission through three factors: susceptible, infected, and removed (recovered and deceased) individuals. Using the Lambert W Function, we propose a framework to study solutions of the SIR model. This demonstrates the applications of COVID-19 transmission data to model the spread of a real-world disease. Different models of disease including the SIR, SIRmp and SEIRρqr model are compared with respect to their ability to predict disease spread. Physical distancing impacts and personal protection equipment use are discussed with relevance to the COVID-19 spread.

A community-based cross-sectional study to assess the prevalence of post-partum depression: Why are the mothers depressed?

Introduction: Post-partum depression can have adverse long term effects. For the mother, the episode can be the precursor of chronic recurrent depression. For her children her on going depression can contribute to emotional, cognitive and interpersonal problems in their later life. In the present study, we aimed to identify the incidence of depression in post-partum period and explore the underlying etiological factors responsible for the same. Materials and Methods: A cross sectional study was conducted on 250 post- natal mothers covered under UHTC, Tripuri, Patiala. The data collection was done through one to one interview technique with mental evaluation done by Edinburgh Postnatal Depression Scale instrument. Based upon the results, the cases were classified either as normal or presence of psychiatric morbidity. Psychiatry referral was provided to those requiring it. Association of post-partum depression with various socio-demographic and medical correlates was then sought through statistical analysis. Results: Post-partum depression was observed in 82 out of 250 females (32.8%). On univariable analysis family income, illiteracy, history of depression, caesarean section, death in family, were significantly associated with post-partum depression. On multi-variable analysis, poverty, female gender of baby, domestic violence and were observed as true predictors of depression in post-partum period (p<0.05). Conclusion: Depression was prevalent among almost one-third of postnatal females. Poverty, Cesarean section, domestic violence and poor spousal support have been identified as major contributors towards psychiatric morbidities. Taking care of these largely modifiable risk factors can prevent development of postpartum depression.

The incidence and importance of anaemia in patients undergoing cardiac surgery in the UK - the first Association of Cardiothoracic Anaesthetists national audit.

The importance and variability of pre-operative anaemia in cardiac surgical patients across the UK is not known, and there is debate about its association with patient outcomes. The Association of Cardiothoracic Anaesthetists carried out its first national audit on anaemia and transfusion, and analysed data from 19,033 patients operated on in 12 cardiac surgical centres between 2010 and 2012; 5895 (31%) had pre-operative anaemia. Centre-specific prevalence of anaemia varied from 23% to 45%; anaemia was associated with older patients, diabetes and surgical risk (EuroSCORE). Nevertheless, controlling for these factors, regional variation remained an independent effect (p < 0.001). Multivariable analysis demonstrated an independent association of anaemia with transfusion (odds ratio (95% confidence interval) 2.75 (2.55-2.95), p < 0.001), mortality (1.42 (1.18-1.71), p < 0.001) and hospital stay (geometric mean ratio (95% confidence interval) 1.15 (1.13-1.17), p < 0.001). Haemoglobin concentration per se was also independently associated with worse outcomes; a 10 g.l(-1) decrease in haemoglobin was associated with a 43% increase (95% confidence interval 40-46%) in the odds of transfusion and a 16% increase (95% confidence interval 10-22%) in the odds of mortality (both p < 0.001). This large UK-wide audit has demonstrated marked regional variation in both anaemia and transfusion, with a consistently high incidence of both. The independent association between pre-operative anaemia and worse outcomes in UK practice has also been confirmed, and robust prospective study of anaemia treatment before cardiac surgery is required; these data will assist in designing such trials.

Complete genome characterization of a East European Type 1 subtype 3 porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome (PRRS) is a swine disease of major economic importance that causes reproductive and respiratory problems in pigs. PRRSV strains are divided into European (Type 1) and North-American (Type 2) genotypes. Within the European PRRSV genotype, three subtypes have been delineated. Full genome sequences for North American and European subtype 1 strains have been described. Here, the first complete genomic characterization of a European subtype 3 strain (Lena) is described. Amplification of Orf1a and Orf1b fragments was achieved using a set of degenerate oligonucleotides. Using RT-PCR with Lena-specific primers, the full length sequence (15001 nt) was obtained. Alignment of Lena with European subtype 1 reference strain Lelystad showed variation over the entire length (84% identity/89% similarity at amino acid level) with the most variation in Orf1a (Nsp2/NSP2) with a deletion of 29 amino acids. Phylogenetic relationships using different Orfs supported Lena's genetic distinction from European subtype 1 strains. The availability of the European subtype 3 PRRSV full genome may be important for the understanding of PRRSV evolution and the more pronounced pathogenic nature of Lena.

Patch repair is an independent predictor of morbidity and mortality in congenital diaphragmatic hernia.

BACKGROUND: Infants with congenital diaphragmatic hernia (CDH) have variable outcomes. There is a considerable potential benefit in being able to predict perinatally, which infants have severe hypoplasia and are thus more likely to die or survive with significant morbidity. We examine the relationship between a need for patch repair of CDH (PR) and outcome, using a national database. METHODS: Baseline characteristics of patients undergoing PR or non-patch repair (NPR) were compared. Multivariate analysis was performed to determine the association of PR with mortality and morbidity independent of other known predictors. RESULTS: Baseline characteristics of PR and NPR infants were similar although those infants with PR had higher SNAP-II scores. PR was an independent predictor of mortality with an odds ratio of 17.1 (95%CI 2.0-149.2) and was independently associated with secondary outcome measures of morbidity, including the need for oxygen at discharge and the duration of ventilation. CONCLUSIONS: Infants requiring PR have significantly higher mortality and suffer greater morbidity than those undergoing NPR. This association is independent of other known predictors of mortality. Identifying prenatal features associated with this high risk group would be of great clinical value.

Colour versus grey-scale display of images on high-resolution spectral OCT.

AIM: To determine whether colour or grey-scale images from high-resolution spectral optical coherence tomography (OCT) are superior in visualising clinically important details of retinal structures. METHODS: Patients with macular pathologies were imaged using spectral OCT (OTI, Toronto, Canada). Two reviewers independently analysed the retinal structures and pathologies and graded them on a four-point scale on the basis of the visibility. A third reviewer masked to the results then reviewed images where there was a different score for colour versus grey scale. RESULTS: Statistical analysis showed the grey-scale image to be significantly better in visualising the details of epiretinal membrane, photoreceptor and retinal pigment epithelium layer morphology than the colour scale image (p = 0.00088-0.0006). In 16.17% of eyes, the colour image led to the false impression of photoreceptor disruption. CONCLUSION: Grey-scale images are qualitatively superior to the colour-scale images on high-resolution spectral OCT. Colour images can be misleading, as the displayed colours are false colours, and the observer may see a dramatic change in colour and interpret that as a large change in the OCT reflectivity.

An FDA phase I clinical trial of quinacrine sterilization (QS).

OBJECTIVE: To review the significance of a United States Food and Drug Administration (FDA) approved Phase I clinical trial of a new use for an old drug, quinacrine. To discover whether ultrasound may have utility in quinacrine sterilization (QS). METHOD: This clinical trial began on 16 September 2000 at the Women's and Children's Hospital of Buffalo (WCHOB) in Buffalo, New York. Ten patients volunteered to have QS. These subjects were carefully followed with regularly scheduled examinations, including extensive laboratory blood tests. In addition, each patient had a trans-abdominal ultrasound examination six weeks or later past the date of the second insertion of quinacrine. The trial was completed on 30 April 2003. RESULTS: Laboratory results fell within normal limits, thus providing additional evidence to affirm the lack of toxic effects of QS. With ultrasound, we were able to see scars in both oviducts on all of our patients. One patient with a small scar as seen on ultrasound became pregnant. CONCLUSION: QS was found to be safe and effective. Ultrasound holds the promise of reducing the failure rate.

An FDA phase I clinical trial of quinacrine sterilization (QS).

OBJECTIVE: To review the significance of a United States Food and Drug Administration (FDA) approved Phase I clinical trial of a new use for an old drug, quinacrine. To discover whether ultrasound may have utility in quinacrine sterilization (QS). METHOD: This clinical trial began on 16 September 2000 at the Women's and Children's Hospital of Buffalo (WCHOB) in Buffalo, New York. Ten patients volunteered to have QS. These subjects were carefully followed with regularly scheduled examinations, including extensive laboratory blood tests. In addition, each patient had a trans-abdominal ultrasound examination six weeks or later past the date of the second insertion of quinacrine. The trial was completed on 30 April 2003. RESULTS: Laboratory results fell within normal limits, thus providing additional evidence to affirm the lack of toxic effects of QS. With ultrasound, we were able to see scars in both oviducts on all of our patients. One patient with a small scar as seen on ultrasound became pregnant. CONCLUSION: QS was found to be safe and effective. Ultrasound holds the promise of reducing the failure rate.

Oxy free radical system in heart failure and therapeutic role of oral vitamin E.

Twenty patients of heart failure and ten matched healthy controls were included in the trial. Out of these 20 patients of heart failure, 12 patients were also studied prospectively. Plasma levels of superoxide anion and malonyldialdehyde were increased while the levels of superoxide dismutase, catalase and glutathione reductase were decreased in patients of heart failure as compared to control subjects. The alteration in oxidative stress and antioxidant system did not correlate with the age and sex of patients or the etiology of heart failure. With the increasing severity of heart failure the malonyldialdehyde and superoxide anion increased significantly and catalase, glutathione reductase and superoxide dismutase levels decreased. The group of heart failure patients with ejection fraction < 40% (n = 7) exhibited significantly higher levels of malonyldialdehyde than those with an ejection fraction > 40% (n = 13). The superoxide anion and malonyldialdehyde levels were significantly higher in patients of heart failure in the pre-treatment state as compared to those in post-treatment state. Conversely catalase, glutathione reductase and superoxide dismutase were higher in the post-treatment period as compared to their values before treatment. The addition of vitamin E in doses of 400 mg once a day orally for 4 weeks significantly reduced the malonyldialdehyde and superoxide anion levels and produced an elevation of the antioxidant enzymes. Thus, there is an apparent normalisation of the indices of oxidative stress following treatment of heart failure and a markedly improved response on vitamin E supplementation which may be more beneficial.