The TB Surge intervention: an optimized approach to TB case-finding in Nigeria.

INTRODUCTION: TB remains one of the leading causes of death in Nigeria, and despite progress in treatment coverage, a 56% gap in national case notifications remains. This gap is attributable in part to underdiagnosis due to missed cases in health facilities. The TB Surge intervention presented an opportunity to address barriers to optimal case detection in public health facilities. METHODS: KNCV Nigeria implemented the TB Surge intervention under the USAID-funded TB-LON Project in 1,041 public facilities from June 2020 to September 2022. Trained ad-hoc staff screened hospital attendees, linked identified presumptive TB cases to diagnosis and confirmed TB cases to treatment. Data were reported using the Commcare application. Robust project monitoring was used to address gaps. RESULTS: Of a total of 12,195,874 hospital attendees screened for TB, 729,369 identified as presumptive TB were tested and 65,029 TB cases were diagnosed; 8% of the TB cases were children. Overall TB yield was 9%. Medical ward service delivery point had the highest TB yield of 21%. The number needed to test was 11 and the number needed to screen was 188. CONCLUSION: The TB Surge intervention was of strategic importance in addressing missed cases and barriers to prompt TB diagnosis in health facilities.

INTRODUCTION: La TB reste l'une des principales causes de décès au Nigeria et, malgré les progrès réalisés en matière de couverture thérapeutique, il subsiste un écart de 56% dans la déclaration des cas à l'échelon national. Cet écart s'explique en partie par le sous-diagnostic dû aux cas manqués dans les centres de santé. L'intervention TB Surge a permis de lever les obstacles à la détection optimale des cas dans les centres de santé publique. MÉTHODES: KNCV Nigeria a mis en œuvre l'intervention TB Surge dans le cadre du projet TB-LON financé par l'USAID dans 1 041 centres publics de juin 2020 à septembre 2022. Le personnel ad hoc formé a dépisté les personnes présentes à l'hôpital, lié les cas de TB présomptifs identifiés au diagnostic et les cas de TB confirmés au traitement. Les données ont été communiquées à l'aide de l'application Commcare. Un suivi rigoureux du projet a permis de combler les lacunes. RÉSULTATS: Sur un total de 12 195 874 patients hospitalisés ayant fait l'objet d'un dépistage de la TB, 729 369 cas présumés de TB ont été testés et 65 029 cas de TB ont été diagnostiqués ; 8% des cas de TB étaient des enfants. Le rendement global de la TB était de 9%. Le point de prestation de services du service médical a enregistré le taux de TB le plus élevé (21%). Le nombre de tests nécessaires était de 11 et le nombre de dépistages nécessaires de 188. CONCLUSION: L'intervention TB Surge a été d'une importance stratégique pour traiter les cas non détectés et les entraves à un diagnostic rapide de la TB dans les centres de santé.

An International Study Evaluating Elemental Analysis.

Based on statistical analysis of CHN combustion results of 18 international service providers, it is determined that the ±0.4% deviation most commonly required by chemistry journals is not justified.

Carotid artery screening at the time of coronary artery bypass - Does it influence neurological outcomes?

OBJECTIVE: Patients undergoing coronary artery bypass graft (CABG) are recommended to undergo carotid duplex study in presence of risk factors. Aim of the study was to quantify the relationship between risk factors and presence of carotid disease and examine if screening influenced outcomes. METHODS: Over a four year period in a single institution, 4364 consecutive patients presenting for primary isolated CABG were enrolled to undergo carotid duplex scanning. Patients were grouped as no significant carotid artery stenosis (<50%), moderate stenosis (50%-70%) and severe stenosis (>70%). Sub group analysis of patients with severe carotid stenosis was performed. Sensitivity of risk factors thought to be associated with carotid disease was also assessed. RESULTS: Of the 4364 patients, 406 patients (9.3%) had moderate or severe carotid artery stenosis. 32 (7.88%) had bilateral disease. Age>65, hypertension, left main stem stenosis, peripheral vascular disease, and previous neurological injury were all associated with carotid artery disease (p<0. 01). Diabetes (p=0.06) and smoking (p=0.79) were not significant risk factors. In patients with moderate carotid artery stenosis there was no difference in the incidence of major 4 (0.98%) vs.18 (0.45%) p=0.14 or minor 8 (1.9%) vs. 56 (1.41%); p=0.38 neurological outcomes. However, severe carotid stenosis was associated with an increase in all-cause mortality but no increase in neurological events. CONCLUSIONS: In the presence of risk factors carotid screening identifies at risk population. Severe carotid stenosis was associated with increased all-cause mortality. However, moderate stenosis did not influence neurological outcomes or mortality in patients undergoing coronary artery bypass grafting.

Lumbar plexus block: Safe anesthesia for hip surgery.

General anesthesia and neuraxial blockade have their own advantages and disadvantages over each other when used for hip surgery. Single shot lumbar plexus block can be the choice of the anesthetic technique for postrenal transplant, immunocompromised, postspinal surgery patient to undergo dynamic hip screw surgery.

For protection from HIV-1 infection, more might not be better: a systematic analysis of HIV Gag epitopes of two alleles associated with different outcomes of HIV-1 infection.

A subset of women in the Pumwani Sex Worker Cohort, established in 1985 in Nairobi, Kenya, remains uninfected despite repeated high-risk exposure (HIV-exposed, seronegative [HESN]) through active sex work. This HESN phenotype is associated with several alleles of human leukocyte antigens (HLAs) and specific CD8(+) and CD4(+) T cell responses to HIV-1. The associations of HLA alleles with differential HIV-1 infection are most likely due to their different abilities to present antigen and the different immune responses they induce. The characteristics of epitopes of HLA alleles associated with different outcomes of HIV-1 infection might therefore point to a vital clue for developing an effective vaccine. In this study, we systematically analyzed HIV-1 clade A and D Gag CD8(+) T cell epitopes of two HLA class I alleles associated with different outcomes of HIV-1 infection. Binding affinity and off-rates of the identified epitopes were determined. Gamma interferon (IFN-γ) enzyme-linked immunospot (ELISpot) assays with patient peripheral blood mononuclear cells (PBMCs) validated the epitopes. Epitope-specific CD8(+) T cells were further phenotyped for memory markers with tetramer staining. Our study showed that the protective allele A*01:01 recognizes only three Gag epitopes. By contrast, B*07:02, the allele associated with susceptibility, binds 30 epitope variants. These two alleles differ most importantly in the spectrum of Gag epitopes they can present and not in affinity, off-rates, the location of the epitopes, or epitope-specific Tem/Tcm frequencies. The binding of more epitopes and strong IFN-gamma ELISpot responses are associated with susceptibility to HIV-1 infection, while more focused antigen recognition of multiple subtypes is protective. Rational vaccine design should take these observations into account.

Identification and characterization of HLA-A*0301 epitopes in HIV-1 gag proteins using a novel approach.

Identification of CTL epitopes correlated to immune protection is important for the development of vaccines that enhance T-cell mediated immune responses. The correlation of positively selected amino acids (PS) of HIV-1 with host HLA alleles can identify regions containing potential T-cell epitopes. However, the specific epitopes have to be identified and characterized using overlapping peptides through T-cell functional assays. In this study we used a new approach to identify and characterize potential epitopes in the gag region containing PS mutations that significantly correlated with HLA-A*0301. The iTopia Epitope Discovery System was used to rapidly screen a panel of peptides overlapping the regions containing PS mutations and the peptides identified were assessed for relative affinity and complex stability. The potential epitopes were then validated by interferon gamma (IFN-gamma) ELISpot assays with patient PBMCs. Using this approach we identified/confirmed the predicted HLA-A*0301 epitopes in two regions of gag containing PS mutations V7I and K403R, one previously reported and the other novel. Five of the seven peptides that bound to A*0301 contained the K403R mutation and corresponded to the documented LARNCRAPRK-A3 supertype epitope. Two epitope variants, RASVLSGGK and RASILSGGK containing the V7I mutation, were identified using the iTopia Epitope Discovery System, however only the consensus variant (RAK9C) was confirmed using the ELISpot assay and it represents a novel A*0301 epitope.

An integrative bioinformatic approach for studying escape mutations in human immunodeficiency virus type 1 gag in the Pumwani Sex Worker Cohort.

Human immunodeficiency virus type 1 (HIV-1) is able to evade the host cytotoxic T-lymphocyte (CTL) response through a variety of escape avenues. Epitopes that are presented to CTLs are first processed in the presenting cell in several steps, including proteasomal cleavage, transport to the endoplasmic reticulum, binding by the HLA molecule, and finally presentation to the T-cell receptor. An understanding of the potential of the virus to escape CTL responses can aid in designing an effective vaccine. To investigate such a potential, we analyzed HIV-1 gag from 468 HIV-1-positive Kenyan women by using several bioinformatic approaches that allowed the identification of positively selected amino acids in the HIV-1 gag region and study of the effects that these mutations could have on the various stages of antigen processing. Correlations between positively selected residues and mean CD4 counts also allowed study of the effect of mutation on HIV disease progression. A number of mutations that could create or destroy proteasomal cleavage sites or reduce binding affinity of the transport antigen processing protein, effectively hindering epitope presentation, were identified. Many mutations correlated with the presence of specific HLA alleles and with lower or higher CD4 counts. For instance, the mutation V190I in subtype A1-infected individuals is associated with HLA-B*5802 (P = 4.73 x 10(-4)), a rapid-progression allele according to other studies, and also to a decreased mean CD4 count (P = 0.019). Thus, V190I is a possible HLA escape mutant. This method classifies many positively selected mutations across the entire gag region according to their potential for immune escape and their effect on disease progression.

Transoesophageal echocardiography: a useful tool to diagnose entrapment of pulmonary artery catheter.

Placement of a pulmonary artery catheter during cardiac surgery is associated with various complications, one of which is entrapment. On the day following surgery unusual resistance was encountered while attempting to remove a pulmonary artery catheter from a patient who had undergone coronary artery bypass grafting. Entrapment of the catheter was confirmed by transoesophageal echocardiography, which demonstrated invagination of the free wall of the pulmonary trunk on gentle traction on the pulmonary artery catheter. Surgical exploration revealed that the catheter was transfixed by the suture used to close the pulmonary artery vent site. Surgical re-exploration and other potential complications related to catheter retrieval can be avoided if catheter entrapment is diagnosed intra-operatively. We suggest that a high index of clinical suspicion along with the use of intra-operative transoesophageal echocardiography is considered in situations where catheter entrapment is a possibility.

The effect of levetiracetam on essential tremor.

The effect of a single dose of 1,000 mg of levetiracetam on essential tremor was investigated in 24 patients in a double-blind, placebo-controlled trial. There was a significant reduction of hand tremor for at least 2 hours as measured by accelerometry and functional tests.

Biochemical Markers of Myocardial Injury during Coronary Artery Bypass Grafting with and without Cardiopulmonary Bypass.

Minimally invasive cardiac surgical techniques have been applied recently in the management of variety of cardiac lesions. Between December 1998 and February 1999, fifty patients underwent coronary artery bypass grafting (CABG) under two different techniques. In group A (twenty five patients), CABG was done under cardiopulmonary bypass (CPB) and in group B (twenty three patients), CABG was performed on a 'beating heart' without CPB. Serum concentration of cardiac specific enzymes CPZ-MB and Troponin-T were estimated in all the patients from pre-induction period to 72 hours after the bypass graft. Group A patients exhibited a significant (P<0.05) elevation in the CPK-MB and Troponin-T level as compared to group B. Our results show that the extent of myocardial damage following CABG is significantly less when the procedure is done on a 'beating heart'.