Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial.

BACKGROUND: The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI). METHODS: The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status. RESULTS: 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001). CONCLUSION: In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.

Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Prevalence and Correlates of Injecting with Visitors from the United States Among People Who Inject Drugs in Tijuana, Mexico.

Cross-border infectious disease transmission is a concern related to drug tourism from the U.S. to Mexico. We assessed this risk among people who inject drugs (PWID) in Tijuana, Mexico. We measured the prevalence and identified correlates of injecting with PWID visiting from the U.S. among PWID in Tijuana using univariable and multivariable logistic regression. Of 727 participants, 18.5% injected during the past 6 months in Mexico with U.S. PWID described mostly as friends (63%) or acquaintances (26%). Injecting with U.S. PWID was independently associated with higher education [adjusted odds ratio (aOR) = 1.13/year], deportation from the U.S. (aOR = 1.70), younger age at first injection (aOR = 0.96/year), more lifetime overdoses (aOR = 1.08), and, in the past 6 months, backloading (aOR = 4.00), syringe confiscation by the police (aOR = 3.02) and paying for sex (aOR = 2.98; all p-values < 0.05). Nearly one-fifth of PWID in Tijuana recently injected with U.S. PWID, and their reported risk behaviors could facilitate cross-border disease transmission.

Validation of the GeneXpert® CT/NG Assay for use with Male Pharyngeal and Rectal Swabs.

OBJECTIVES: The GeneXpert® CT/NG (Cepheid, Sunnyvale, CA) assay is a point-of-care (POC) molecular diagnostic assay designed to rapidly test for the presence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC). However, the test is only approved for vaginal swabs, urine, and endocervical swabs. Here, we performed an evaluation of the GeneXpert® CT/NG assay to detect the presence of CT and GC on male pharyngeal and rectal swabs. METHODS: Men who have sex with men participating in an HIV and Sexually Transmitted Infection (STI) screening program providing consent were enrolled into the study. Participants were asked to self-collect two pharyngeal and two rectal swabs. One set was tested on site using GeneXpert® and the other was sent to a reference lab for molecular testing using the APTIMA® system (Hologic, San Diego, CA). RESULTS: A total of 570 swabs were collected from 144 patients. GeneXpert® detected 13/15 rectal swabs testing CT positive by the APTIMA® assay (relative sensitivity=88.2%), 1/2 pharyngeal swabs testing CT positive (relative sensitivity=50%), and 7/9 pharyngeal swabs testing NG positive (relative sensitivity =77.8%). No discordance was observed for rectal NG swabs. CONCLUSIONS: Although less sensitive than the APTIMA® assay for the molecular detection of NG and CT, GeneXpert®'s potential as a rapid POC diagnostic still make it a viable diagnostic test for STI screening. Molecular POC diagnostics, such as this, will allow more thorough screening of at risk individuals, and enhance the ability of clinics to provide same-day diagnosis and treatment.

A case cluster demonstrating the relationship between HLA concordance and virologic and disease outcomes in human immunodeficiency virus infection.

We present a detailed analysis of sexual HIV transmission from one source partner to two recipients. The HLA haplotypes between the source partner and one recipient were very similar with 7 out of 8 HLA alleles from four loci (HLA A, B, C and DRB) shared, while the other recipient shared only one allele. The immunologic outcomes between the two recipients differed dramatically, despite the absence of apparent virologic differences in their inoculums. We suggest that non-viral factors, which might be related to differences in the HLA profile, played a role in determining different CD4+ T-cells dynamics for these two recipients.

Comparison of the anticoagulant intensities of fondaparinux and enoxaparin in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS)-5 trial.

BACKGROUND: In the OASIS-5 trial, fondaparinux reduced major bleeding with similar short-term efficacy as enoxaparin but lowered death and stroke during long-term follow-up. The mechanism of lower bleeding and improved efficacy with fondaparinux is uncertain. METHODS AND RESULTS: We compared the anti-Xa concentration (reflecting drug levels), Xa clot time (reflecting anticoagulant effect) and endogenous thrombin potential (ETP; a global test of hemostatic function) in plasma samples collected 6, 24 and 72 h after the first dose of the study drug in 48 patients randomly assigned fondaparinux 2.5 mg day(-1) and 42 patients assigned enoxaparin 1 mg kg(-1) twice daily in the OASIS-5 trial. Patients assigned to fondaparinux compared with enoxaparin had a significantly lower mean anti-Xa level [0.52 IU mL(-1) (SD 0.22 IU mL(-1)) vs. 1.2 IU mL(-1) (SD 0.45 IU mL(-1)), P<0.0001] and Xa clot time [64.9 s (SD 17.7 s) vs. 111.8 s (SD 29.6 s), P<0.0001], and significantly higher ETP area under the curve (AUC) [386.7 mA (SD 51.5 mA) vs. 206.4 mA (SD 90.6 mA), P<0.001] at 6 h, and these differences remained evident at 24 and 72 h. There was significantly less variability of the results of anti-Xa levels, Xa clot time and ETP AUC for fondaparinux compared with enoxaparin at 6 h (P<0.001 for each comparison). CONCLUSION: Fondaparinux 2.5 mg day(-1) compared with enoxaparin 1 mg kg(-1) twice daily produces less variable anticoagulant effect and lower mean anticoagulant intensity. These results most likely explain the reduced risk of bleeding seen with fondaparinux compared with enoxaparin in the OASIS-5 trial and suggest that a lower intensity of anticoagulation than used in the past may be sufficient to prevent recurrent ischemic events and death in patients with ACS who are concurrently treated with aspirin and clopidogrel.

Radiotherapy: Basic Concepts and Recent Advances.

Radiation therapy (RT) is a clinical modality dealing with the use of ionizing radiations to treat malignant neoplasias (and occasionally benign diseases). Since its inception, the goal of RT has been to cure cancer locally without excessive side effects. The most important factors affecting the results of RT are the tumor type, its location and regional extent, the anatomic area of involvement and the geometric accuracy with which a calculated radiation dose is delivered. Although higher doses of radiation can produce better tumor control, the dosage which can be given is limited by the possibility of normal tissue damage. Approximately 60-65% of all cancer patients require RT as the sole treatment modality and / or in combination with surgery or chemotherapeutic drugs. There is a huge gap between demand and supply of radiotherapy facilities and infrastructure. Most of the oncocentres are located in urban areas in private sector and are beyond the reach of the common man.

Incidental findings in healthy control research subjects using whole-body MRI.

AIM: Magnetic resonance imaging (MRI) is a powerful clinical tool used increasingly in the research setting. We aimed to assess the prevalence of incidental findings in a sequential cohort of healthy volunteers undergoing whole-body MRI as part of a normal control database for imaging research studies. MATERIALS AND METHODS: 148 healthy volunteers (median age 36 years, range 21-69 years; 63.5% males, 36.5% females) were enrolled into a prospective observational study at a single hospital-based MRI research unit in London, UK. Individuals with a clinical illness, treated or under investigation were excluded from the study. RESULTS: 43 (29.1%) scans were abnormal with a total of 49 abnormalities detected. Of these, 20 abnormalities in 19 patients (12.8%) were of clinical significance. The prevalence of incidental findings increased significantly with both increasing age and body mass index (BMI). Obese subjects had a fivefold greater risk of having an incidental abnormality on MRI (OR 5.4, CI 2.1-14.0). CONCLUSIONS: This study showed that more than one quarter of healthy volunteers have MR-demonstrable abnormalities. There was an increased risk of such findings in obese patients. This has ethical and financial implications for future imaging research, particularly with respect to informed consent and follow-up of those with abnormalities detected during the course of imaging studies.

Diabetes Mellitus in India: The Modern Scourge.

India has a high prevalence of diabetes mellitus and the numbers are increasing at an alarming rate. In India alone, diabetes is expected to increase from 40.6 million in 2006 to 79.4 million by 2030. Studies have shown that the prevalence of diabetes in urban Indian adults is about 12.1%, the onset of which is about a decade earlier than their western counterparts and the prevalence of Type 2 diabetes is 4-6 times higher in urban than in rural areas. The risk factors peculiar for developing diabetes among Indians include high familial aggregation, central obesity, insulin resistance and life style changes due to urbanization. Screening for gestational diabetes and impaired glucose tolerance among pregnant women provides a scope for primary prevention of the disease in mothers as well as in their children. The problems of obesity and impaired glucose tolerance (IGT) (important predisposing factors) are not confined to adults alone but children are also increasingly getting affected. Most long standing macro and micro vascular complications are also more common among Indian diabetics as compared to other races and ethnic groups. A strong familial clustering of diabetic nephropathy among Indian Type 2 diabetics has also been noted. Clustering of cardiovascular risk factor like Syndrome X is common among urban Indians. The rising incidence of diabetes and its complications are going to pose a grave health care burden on our country. Timely effective interventions/measures and screening tests for complications at the time of diagnosis becomes imperative not only for early detection, but also to prevent progression to end stage disease. Screening for gestational diabetes among pregnant women would also go a long way in primary prevention of the disease. Life style changes/interventions and drugs like rosiglitazone are the current strategies that can prevent and/or delay the onset of diabetes. Simple interventional strategies like "Eat less, Eat on time and Walk more" can go a long way in preventing these chronic disorders among present as well as in the future generations.

Bioshock: Biotechnology and Bioterrorism.

In the recent past, the threat of a global bioterrorist attack has increased dramatically. In addition to the already existing microorganisms and techniques, the recent explosion in biotechnology has considerably added to the arsenal of the bioterrorist. Molecular technologies are now available which can be used by committed bioterrorist groups to manipulate and modify microorganisms so as to make them increasingly infectious, virulent or treatment resistant for causing maximum casualties. Infectious diseases which are likely to be used as bioweapons are Anthrax, Botulism, Plague, Smallpox and Brucella. Molecular techniques like immunoassays and nucleic acid amplification are now available to detect bioattacks. This article discusses the threat of bioterrorism. It also evaluates the molecular diagnostic methods and the future of early containment of a bioterrorist attack using molecular techniques.

Management of malaria: recent trends.

In the present day scenario of resurgence of infectious diseases, malaria compounded with problems of multi drug resistance, assumes paramount importance. A combination of artemisinine derivatives with other effective anti-malarial drug remains the most effective form of treatment against the falciparum malaria which is most lethal form of disease. Oral chloroquin in the dose of 25 mg base/kg over 48 hours is effective in infections due to P. vivax, P. ovale P. malariae and chloroquine sensitive P. Falciparum. For chloroquine resistant P. vivax and multidrug resistant falciparum malaria, a combination of Quinine with doxycycline or clindamycin for 5-7 days, Quinine with singlt dose sulfadoxine-pyrimethamine combination. Mefloquine with artemeter or artesunate for 3 days, artesunate with doxycycline or clindamycin for 7 days and Otovaquin with proguanil for 3 days have been found to be effective. Primiquin as a hypnozoticide for 5-10 days is mandatory for preventing relapse in cases of P. vivax, P. Ovale and P. malariae. Death due to complicated malaria can be as high as 75% if case diagnosis is delayed or the patient arrives late. The artemisinine based rectal suppositories can be very effective in home/village setting in patients who can not be given oral anti malarial, though not yet approved for use in our country. In ICU settings, properly administered loading dose of quinine has proved to be effective and safe in almost all therapeutic trials including our study on Indian patients. Frequent blood glucose monitoring is mandatory. Parentral artemisinine with oral mefloquine is an effective alternative to quinine based therapy. The cerebral malaria management in the ICU setting includes monitoring fluid and electrolyte balance so as to maintain a CVP of 5 cm of water and pulmonary arterial occlusive pressure at less than 15 mm of mercury. In renal failure haemofiltration is ideal. Mefloquine is safe in second and third trimester of pregnancy. Exchange transfusion, haemopheresis and plasmapheresis are new techniques in the treatment of gravely ill patients with PF malaria especially when parasitemia exceeds 10%.

Avian Flu - A Bird's Eye View.

Influenza A (H5N1) virus infects a variety of animals, birds and humans. Present ongoing epidemic of this deadly virus in poultry livestock and humans has had major economic and health repercussions. It causes a wide spectrum of clinical features in human beings ranging from mild respiratory tract infection to a fatal pneumonia leading to multi organ system failure. Diagnosis is mainly clinical, aided by lab features like lymphopaenia and non-specific chest X-ray findings. Diagnostic tests are being evolved for rapid and specific diagnosis. Management is mainly symptomatic. Newer and effective antivirals, i.e. amantadine, zanamivir etc are also being tried.

Delirium Tremens.

The varied clinical manifestations and management of 14 male patients with delirium tremens (DT) have been studied. Eight patients were initially hospitalised for diseases unrelated to ethanol abuse i.e. 2 each for gun shot wound, myocardial infarction and stroke, and one each for pneumonia and gastroenteritis. One patient was going through withdrawal because of prodrome of viral hepatitis before he was hospitalised for uncontrolled agitation and delirium. Two known cases of mild essential hypertension on dietary therapy reported for agitation, abnormal behaviour, a single episode of tonic clonic seizure and hypertensive encephalopathy as they could not/did not get alcohol for 3 days. Three patients presented denovo with DT without concomitant illness. The other features besides delirium and hallucinations were tremulousness in 10, tachycardia in 12, fever in 3, diaphoresis in 2 and tonic clonic seizures in 4 patients. The symptoms fluctuated markedly at short intervals and 2 patients did not have any features of sympathetic overactivity. Altered hepatic biochemical parameters and ketonuria with normal blood sugar were noted in 4 and one patients respectively. Other biochemical parameters including serum electrolytes were normal. CT scan brain done for 5 patients revealed subdural haematoma in one. Cerebro spinal fluid (CSF) and EEG findings were noncontributory. All made good recovery with heavy doses of intravenous vitamin B complex, glucose and oral benzodiazepine. Short course of haloperidol was used in 2 patients. Two patients developed pancreatitis during follow up. All patients made complete recovery, and 8 patients have been followed for 8 to 12 months without relapse. The reason for hospitalisation in such cases is often unrelated to alcohol abuse; hence a detailed history of alcoholism is mandatory to identify those at risk as well as for prompt treatment and decreasing the mortality.