Impact of weight gain with dolutegravir on antiretroviral adherence and viral suppression in four African countries.

OBJECTIVE: We hypothesized that total body weight (TBW) gain after switching antiretroviral therapy (ART) regimen to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) may negatively impact ART adherence and viral load (VL) and therefore sought to examine these associations. METHODS: The ongoing African Cohort Study (AFRICOS) enrols people with HIV at 12 facilities in Kenya, Nigeria, Tanzania and Uganda supported by The US President's Emergency Plan for AIDS Relief. Among ART-experienced participants who switched to TLD, we used multivariable multinomial logistic regression to examine associations between pre-/post-TLD changes in percentage TBW (≥5% gain, <5% change, ≥5% loss) and changes in self-reported ART adherence (0, 1-2, ≥3 days missed doses in past 30 days) and VL [(<50 copies/mL (undetectable), 50-999 copies/mL (detectable, but suppressed), ≥1000 copies/mL (unsuppressed)]. RESULTS: Among 1508 participants, median time from starting TLD to follow-up was 9 months (interquartile range: 7-11). Overall, 438 (29.1%) participants experienced a TBW gain ≥5%, which was more common among females than among males (32.2% vs 25.2%, p = 0.005) and participants switching from efavirenz [32.0% vs nevirapine (19.9%) and boosted protease inhibitor (20.0%); p < 0.001]. Compared with a TBW change <5% [950 (63.0%) participants], TBW gain ≥5% was not significantly associated with more days with missed ART doses [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI): 0.48-1.23] or VL becoming detectable and/or unsuppressed (aOR = 0.69, 95% CI: 0.41-1.16). CONCLUSIONS: Although a substantial proportion of participants experienced weight gain after switching to TLD, we did not identify a significant impact on adherence or virological outcomes.

Quantification of multidrug-resistant M. tuberculosis bacilli in sputum during the first 8 weeks of treatment.

SETTING: Mulago Hospital, Kampala, Uganda.OBJECTIVE: To quantify Mycobacterium tuberculosis in sputum during the first 8 weeks of pulmonary multidrug-resistant TB (MDR-TB) treatment.DESIGN: We enrolled consecutive adults with pulmonary MDR-TB treated according to national guidelines. We collected overnight sputum samples before treatment and weekly. Sputum samples were cultured on Middlebrook 7H11S agar to measure colony-forming units per mL (cfu/mL) and in MGIT™ 960™ media to measure time to detection (TTD). Linear mixed-effects regression was used to estimate the relational change in log10 cfu/mL and TTD.RESULTS: Twelve adults (median age: 27 years) were enrolled. Half were women, and two-thirds were HIV-positive. At baseline, median log10 cfu/mL was 5.1, decreasing by 0.29 log10 cfu/mL/week. The median TTD was 116.5 h, increasing in TTD by 36.97 h/week. The weekly change was greater in the first 2 weeks (-1.04 log10 cfu/mL/week and 120.02 h/week) than in the remaining 6 weeks (-0.17 log10 cfu/mL/week and 26.11 h/week).CONCLUSION: Serial quantitative culture measures indicate a slow, uneven rate of decline in sputum M. tuberculosis over 8 weeks of standardized pulmonary MDR-TB treatment.

Transitioning women to first-line preferred TLD regimen is lagging in Sub-Saharan Africa.

INTRODUCTION: In 2019, the World Health Organization (WHO) recommended tenofovir disoproxil fumarate-lamivudine-dolutegravir (TLD) as the preferred first line regimen for adults and adolescents regardless of childbearing status. Nevertheless, final eligibility is determined by local policies which may vary from WHO recommendations. We examined TLD transition by gender across five PEPFAR-supported HIV care programs in sub-Saharan Africa. METHODS: The African Cohort Study (AFRICOS) enrolls people living with HIV (PLWH) engaged in care in Uganda, Kenya (South Rift Valley and Kisumu West), Tanzania and Nigeria. PLWH with at least one study visit after the country introduced TLD were included. We generated Kaplan-Meier (KM) curves to compare TLD transition by gender from 1) time countries' introduction of TLD and 2) time of TLD eligibility according to local policies. RESULTS: Among 2.476 participants enrolled through September 2021 at 4 sites in sub-Saharan Africa and eligible to transition to TLD, fewer women (68%) compared to men (80%, p < 0.001) were taking TLD. Kaplan-Meier analysis showed time to transition varied by site, with women in Tanzania transitioning at the same rate as men. In Nigeria, women initially had a slower transition but caught up to men. After adjusting for local policies, women[1] in Kisumu West transitioned at the same rate as men. In South Rift Valley and Uganda, women were less likely to be transitioned. CONCLUSIONS: Despite TLD being the WHO's preferred regimen since 2019, transition of women to potentially lifesaving TLD has been slower than men at certain clinical sites even after accounting for local eligibility criteria.

Implementing TB preventive treatment within differentiated HIV service delivery models in global programs.

Global HIV program stakeholders, including the US President's Emergency Plan for AIDS Relief (PEPFAR), are undertaking efforts to ensure that eligible people living with HIV (PLHIV) receiving antiretroviral treatment (ART) receive a course of TB preventive treatment (TPT). In PEPFAR programming, this effort may require providing TPT not only to newly diagnosed PLHIV as part of HIV care initiation, but also to treatment-experienced PLHIV stable on ART who may not have been previously offered TPT. TPT scale-up is occurring at the same time as a trend to provide more person-centered HIV care through differentiated service delivery (DSD). In DSD, PLHIV stable on ART may receive less frequent clinical follow-up or receive care outside the traditional clinic-based model. The misalignment between traditional delivery of TPT and care delivery in innovative DSD may require adaptations to TPT delivery practices for PLHIV. Adaptations include components of planning and operationalization of TPT in DSD, such as determination of TPT eligibility and TPT initiation, and clinical management of PLHIV while on TPT. A key adaptation is alignment of timing and location for TPT and ART prescribing, monitoring, and dispensing. Conceptual examples of TPT delivery in DSD may help program managers operationalize TPT in HIV care.

Les parties prenantes du programme mondial VIH, notamment le plan américain PEPFAR (US President's Emergency Plan for AIDS Relief), entreprennent des efforts afin de s'assurer que les personnes vivant avec le VIH (PLVIH), éligibles, recevant un traitement antirétroviral (TAR), reçoivent également un traitement préventif TB (TPT). Dans la programmation PEPFAR, cet effort pourrait nécessiter de fournir le TPT non seulement aux PLVIH nouvellement diagnostiquées dans le cadre de l'initiation de la prise en charge du VIH, mais également aux PLVIH stables déjà traités par TAR à qui on n'aurait pas encore offert le TPT. L'expansion du TPT survient au même moment comme une tendance à offrir une prise en charge du VIH davantage centrée sur la personne à travers une prestation de services différenciée (DSD). Dans la DSD, les PLVIH stables sous TAR bénéficient d'un suivi clinique moins fréquent ou sont soignés hors du modèle traditionnel en structures de santé. Le décalage entre la prestation traditionnelle du TPT et la prestation de soins dans des DSD innovantes peut nécessiter des adaptations aux pratiques de prestation du TPT pour les PLVIH. Ces adaptations incluent des éléments de planification et d'opérationnalisation du TPT dans la DSD, comme la détermination de l'éligibilité au TPT et sa mise en route et la prise en charge clinique des PLVIH sous TPT. Une adaptation majeure est l'alignement en termes de temps et de lieu pour la prescription, le suivi et la délivrance du TPT et du TAR. Des exemples conceptuels de délivrance du TPT dans la DSD aideraient les gestionnaires de programme à rendre opérationnel le TPT au sein de la prise en charge du VIH.

Los interesados directos del Programa Mundial del VIH, incluido el Plan de Emergencia del Presidente (de los Estados Unidos) para el Alivio del Sida (PEPFAR), emprenden ahora esfuerzos encaminados a garantizar que las personas con infección por el VIH (PLVIH), que siguen un tratamiento antirretrovírico (TAR) y que reúnen las condiciones, reciban un ciclo de tratamiento preventivo de la TB (TPT). En la programación del PEPFAR esta iniciativa puede necesitar la provisión de TPT no solo a las personas con un diagnóstico reciente de infección por el VIH, como parte del inicio de la atención del VIH, sino también a las PLVIH, con experiencia de tratamiento y que se encuentran estables recibiendo el TAR, a quienes tal vez no se haya propuesto antes el TPT. La ampliación del TPT ocurre de manera simultánea con la tendencia a ofrecer una atención del VIH más centrada en la persona mediante la prestación diferenciada de servicios (DSD). En la DSD, las PLVIH, estables con el TAR, pueden tener encuentros de seguimiento clínico menos frecuentes o recibir atención por fuera del modelo tradicional en los consultorios. La discordancia entre la provisión tradicional del TPT y la prestación de atención en el marco innovador de la DSD exige adaptaciones de las prácticas de prestación del TPT a las PLVIH. Las adaptaciones incluyen componentes de planeación y puesta en práctica del TPT en la DSD, como la determinación de los criterios para recibir el TPT, el inicio del mismo y el manejo clínico de las PLVIH mientras reciben el TPT. Una adaptación primordial es la coordinación del ritmo y el lugar de prescripción, supervisión y suministro del TPT y el TAR. La presentación de ejemplos teóricos de provisión del TPT en el marco de la DSD puede ayudar a los gerentes de programas a poner en práctica el TPT en la atención del VIH.

Addressing advanced HIV disease and mortality in global HIV programming.

INTRODUCTION: The US President's Emergency Plan for AIDS Relief (PEPFAR) was launched to increase access to antiretroviral treatment (ART) among people living with HIV (PLHIV) and to prevent new HIV infections globally. As new infections have decreased in many PEPFAR-supported countries, PEPFAR is increasingly focusing on understanding and decreasing mortality among PLHIV, specifically by addressing advanced HIV disease (AHD) and its attendant opportunistic infections (OIs). Several developments in identifying AHD, in preventing, diagnosing, and treating selected OIs, and in PEPFAR's support for mortality surveillance make this an opportune moment for PEPFAR to address HIV-related mortality. DISCUSSION: AHD upon diagnosis or re-engagement in HIV care is not uncommon, and it substantially increases risk of death from OIs. The World Health Organization provides evidence-based guidelines for a package of interventions for preventing, diagnosing, and treating common OIs, including tuberculosis (TB), cryptococcal meningitis, and severe bacterial infections. PEPFAR facilitates implementation of these guidelines. To identify PLHIV with low CD4, PEPFAR plans to support expanded access to CD4 testing, including a point-of-care assay that differentiates CD4 cell count as a binary of greater than or less than 200 cells/µL. To prevent AHD-related mortality, PEPFAR supports rapid ART initiation with integrase inhibitor-based regimens and implementation and documentation of TB preventive treatment. To diagnose selected OIs, PEPFAR is implementing urine lateral flow lipoarabinomannan use to identify TB among PLHIV who have a CD4 cell count < 200 cells/µL. To treat selected OIs, PEPFAR has focused on improving patient-centered care in TB/HIV co-infection services and scaling up implementation of new drug regimens for cryptococcal meningitis. To better understand mortality, PEPFAR has introduced an indicator, TX_ML, to routinely and systematically categorize outcomes, including deaths, among PLHIV on ART. CONCLUSIONS: PEPFAR is increasing its efforts to identify AHD; to prevent, diagnose, and treat OIs; and to track mortality in its programs. These ongoing efforts, done in collaboration with other stakeholders, seek to decrease mortality among PLHIV.

Tuberculosis Preventive Treatment Scale-Up Among Antiretroviral Therapy Patients - 16 Countries Supported by the U.S. President's Emergency Plan for AIDS Relief, 2017-2019.

Tuberculosis (TB) is the leading cause of death among persons living with human immunodeficiency virus (HIV) infection. In 2018, an estimated 251,000 persons living with HIV infection died from TB, accounting for one third of all HIV-related deaths and one sixth of all TB deaths (1). TB preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV infection without active TB disease (i.e., adults with a negative clinical symptom screen for cough, fever, night sweats, or weight loss; and children with a negative clinical screen for cough, fever, contact with a person with TB, or poor weight gain) and either without* a tuberculin skin test result or with a known positive result (2). TPT decreases morbidity and mortality among persons living with HIV infection, independent of antiretroviral therapy (ART) (3); however, in 2017, fewer than 1 million of the estimated 21.3 million ART patients started TPT worldwide. Most patients receiving TPT were treated with 6 months of daily isoniazid (1,4). This report summarizes data on TB symptom screening and TPT initiation and completion among ART patients in 16 countries supported by the U.S. President's Emergency Plan for AIDS† Relief (PEPFAR) during April 1, 2017-March 31, 2019. During this period, these 16 countries accounted for approximately 90% of PEPFAR-supported ART patients. During April 1, 2017-September 30, 2018, TB symptom screening increased from 54% to 84%. Overall, nearly 2 million ART patients initiated TPT, and 60% completed treatment during October 1, 2017-March 31, 2019. Although TPT initiations increased substantially, completion among those who initiated TPT increased only from 55% to 66%. In addition to continuing gains in initiation, improving retention after initiation and identifying barriers to TPT completion are important to increase TPT scale-up and reduce global TB mortality.

Decline in Dental Fluorosis Severity during Adolescence: A Cohort Study.

Dental fluorosis occurs from overingestion of fluoride during tooth formation. However, there is little evidence in the literature on whether or how fluorosis prevalence and severity change over time after tooth eruption. Permanent dentition dental examinations were conducted at ages 9, 13, 17, and 23 as part of the Iowa Fluoride Study, which has followed a cohort from birth. Fluorosis was assessed using the Fluorosis Risk Index (FRI) and Russell's criteria for differential diagnosis. Measures of fluorosis severity at the person and tooth level were calculated: second highest FRI score at the person level (the maximum FRI score for each tooth was determined and the tooth with the second highest maximum FRI score was used) and highest FRI score at the tooth level. At both the person and tooth levels, a decline in mild to moderate fluorosis severity was observed across adolescence and young adulthood. Across each pair of adjacent examinations at the person level, for participants with a baseline second highest FRI of 0, most participants stayed at 0 (82% to 91%). Many participants with a baseline second highest FRI of 1 had a follow-up score of 0 (47% to 54%), while about a third had a follow-up score of 1 (34% to 38%), and a lower percentage had an increase to a score of 2 (9% to 15%). For participants with baseline second highest FRI score of 2, between 25% and 44% of participants had follow-up FRI scores each of 0, 1, and 2. Similar patterns were observed at the tooth level. These results were consistent with most of the existing, limited literature. Overall, fluorosis severity, which was initially mild to moderate, tended to decline during adolescence and young adulthood. Additional study of how this trend affects esthetic perceptions of fluorosis is warranted.

Evaluating thoracolumbar spine response during simulated underbody blast impact using a total human body finite element model.

In a study of spine injuries in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) from 2001-09, spinal fractures sustained by mounted soldiers accounted for 26% of all injuries, and of that, 43% were caused by explosions [1]. The thoracolumbar region is the most vulnerable area of the spine [2], and injuries are often incapacitating, making egress from vehicles difficult. Injury prediction from such events continues to remain a challenge due to the limited availability of studies specifically focused on underbody blasts (UBB) and criteria on related injuries. This study focuses on developing and validating the spine response of an updated 50th percentile male Global Human Body Models Consortium (GHBMC) Finite Element (FE) model using instrumented post-mortem human subject (PMHS) laboratory tests under two unique conditions. The model was validated against response corridors created using scaled thoracic (T12, T8, T5, T1) and sacrum (S1) spine Z-axis accelerations obtained from WSU whole-body PMHS tests. The scores for the updated spine model ranged from 0.557 - 0.756 for condition 1 (Seat- 4 m/s in 10 ms; Floor- 6 m/s in 5 ms) and 0.639-0.849 for condition 2 (Seat- 4 m/s in 55 ms; Floor- 8 m/s in 2 ms). The PMHS tests sustained spinal injuries in the thoracolumbar region. The validated model indicates high stress and strain concentrations at the same locations, providing an explanation for the fractures sustained in the PMHS tests.

Initiation of anti-tuberculosis treatment in children following gastric aspirate testing, Botswana, 2008-2012.

SETTING: Diagnosing pediatric tuberculosis (TB) is difficult; to improve diagnosis, gastric aspiration (GA) was performed in 121 Botswana health facilities. OBJECTIVE: To describe treatment initiation and outcomes in children with a positive GA result and those treated empirically. METHODS: Children with smear or culture-positive GA or those clinically diagnosed were referred for anti-tuberculosis treatment. Treatment initiation and outcomes were assessed from February 2008 to December 2012 using name-based matching algorithms of the GA database; treatment initiation was captured in the electronic TB registry. Analyses included descriptive statistics and regression models. RESULTS: GA was conducted in 1268 children. Among these, 121 (9.5%) were GA-positive; and treatment was initiated in 90 (74.3%). An additional 137 (11.9%) were treated empirically. More than a third (36.4%) had known human immunodeficiency virus status (positive or negative); this was significantly associated with TB treatment initiation (adjusted odds ratio [aOR] 1.8, 95%CI 1.3-2.5); P < 0.05). Among the 90 children with a positive GA result, nearly all either completed treatment (78.9%) or were on treatment (20.0%) at the time of data collection. CONCLUSION: We could not find documentation of treatment for more than a quarter of the children with laboratory-confirmed TB, an important gap that calls for further examination. The failure to initiate prompt treatment requires investigation and urgent action.

Policies, practices and barriers to implementing tuberculosis preventive treatment-35 countries, 2017.

BACKGROUND: Tuberculosis preventive treatment (TPT) reduces the development of tuberculosis (TB) disease and mortality in people living with human immunodeficiency virus (HIV) infection. Despite this known effectiveness, global uptake of TPT has been slow. We aimed to assess current status of TPT implementation in countries supported by the US President's Emergency Plan for AIDS Relief (PEPFAR).METHODS: We surveyed TB-HIV program staff at US Centers for Disease Control and Prevention (CDC) country offices in 42 PEPFAR-supported countries about current TPT policies, practices, and barriers to implementation. Surveys completed from July to December 2017 were analyzed.RESULTS: Of 42 eligible PEPFAR-supported countries, staff from 35 (83%) CDC country offices completed the survey. TPT was included in national guidelines in 33 (94%) countries, but only 21 (60%) reported nationwide programmatic TPT implementation. HIV programs led TPT implementation in 20/32 (63%) countries, but TB programs led drug procurement in 18/32 (56%) countries. Stock outs were frequent, as 21/28 (75%) countries reported at least one isoniazid stock out in the previous year.CONCLUSION: Despite widespread inclusion of TPT in guidelines, programmatic TPT implementation lags. Successful scale-up of TPT requires uninterrupted drug supply chains facilitated by improved leadership and coordination between HIV and TB programs.

Epidemiology of injury patterns for 4- to 10-year-olds in side and oblique impacts.

OBJECTIVES: With regard to the pediatric population involved in vehicle side impact collisions, epidemiologic data can be used to identify specific injury-producing conditions and offer possible safety technology effectiveness through population-based estimates. The objective of the current study was to perform a field data analysis to investigate injury patterns and sources of injury to 4- to 10-year-olds in side and oblique impacts to determine the potential effect of updated side impact regulations and airbag safety countermeasures. METHODS: The NASS-CDS, years 1991 to 2014, was analyzed in the current study. The Abbreviated Injury Scale (AIS) 2005-Update 2008 was used to determine specific injuries and injury severities. Injury distributions were examined by body region as specified in the AIS dictionary and the Maximum AIS (MAIS). Children ages 4 to 10 were examined in this study. All occupant seating locations were investigated. Seating positions were designated by row and as either near side, middle, or far side. Side impacts with a principal direction of force (PDOF) between 2:00 and 4:00 as well as between 8:00 and 10:00 were included. Restraint use was documented only as restrained or unrestrained and not whether the restraint was being used properly. Injury distribution by MAIS, body region, and source of injury were documented. Analysis regarding occupant injury severity, body region injured, and injury source was performed by vehicle model year to determine the effect of updated side impact testing regulation and safety countermeasures. Because the aim of the study was to identify the most common injury patterns and sources, only unweighted data were analyzed. RESULTS: Main results obtained from the current study with respect to 4- to 10-year-old child occupants in side impact were that a decrease was observed in frequency of MAIS 1-3 injuries; injuries to the head, face, and extremities; as well as injuries caused by child occupant interaction with the vehicle interior and seatback support structures in 1998 model year passenger cars and newer. CONCLUSIONS: Results from this study could be useful in design advances of pediatric anthropomorphic test devices, child restraints, as well as vehicles and their safety countermeasure systems.

TB preventive therapy for people living with HIV: key considerations for scale-up in resource-limited settings.

Tuberculosis (TB) is the leading cause of death for persons living with the human immunodeficiency virus (PLHIV). TB preventive therapy (TPT) works synergistically with, and independently of, antiretroviral therapy to reduce TB morbidity, mortality and incidence among PLHIV. However, although TPT is a crucial and cost-effective component of HIV care for adults and children and has been recommended as an international standard of care for over a decade, it remains highly underutilized. If we are to end the global TB epidemic, we must address the significant reservoir of tuberculous infection, especially in those, such as PLHIV, who are most likely to progress to TB disease. To do so, we must confront the pervasive perception that barriers to TPT scale-up are insurmountable in resource-limited settings. Here we review available evidence to address several commonly stated obstacles to TPT scale-up, including the need for the tuberculin skin test, limited diagnostic capacity to reliably exclude TB disease, concerns about creating drug resistance, suboptimal patient adherence to therapy, inability to monitor for and prevent adverse events, a 'one size fits all' option for TPT regimen and duration, and uncertainty about TPT use in children, adolescents, and pregnant women. We also discuss TPT delivery in the era of differentiated care for PLHIV, how best to tackle advanced planning for drug procurement and supply chain management, and how to create an enabling environment for TPT scale-up success.

Warmer weather as a risk factor for hospitalisations due to urinary tract infections.

The incidence of urinary tract infections (UTIs) is seasonal, and this seasonality may be explained by changes in weather, specifically, temperature. Using data from the Nationwide Inpatient Sample, we identified the geographic location for 581 813 hospital admissions with the primary diagnosis of a UTI and 56 630 773 non-UTI hospitalisations in the United States. Next, we used data from the National Climatic Data Center to estimate the monthly average temperature for each location. Using a case-control design, we modelled the odds of a hospital admission having a primary diagnosis of UTI as a function of demographics, payer, location, patient severity, admission month, year and the average temperature for the admission month. We found, after controlling for patient factors and month of admission, the odds of a UTI diagnosis increased with higher temperatures in a dose-dependent manner. For example, relative to months with average temperatures of 5-7.5 °C, an admission in a month with an average temperature of 27.5-30 °C has 20% higher odds of a primary diagnosis of UTI. However, in months with extremely high average temperatures (above 30 °C), the odds of a UTI admissions decrease, perhaps due to changes in behaviour. Thus, at a population level, UTI-related hospitalisations are associated with warmer weather.

Examining caries aetiology in adolescence with structural equation modelling.

OBJECTIVES: This analysis examines the aetiology of caries development in adolescents using structural equation modelling to identify behavioural mediators of the relationship between socioeconomic status (SES) and caries incidence, and to investigate the role of sex on caries-preventive behaviour and caries. METHODS: This analysis was based on data from the Iowa Fluoride Study, a longitudinal study of a birth cohort. We hypothesized that socioeconomic status earlier in life has a direct effect on caries development and an indirect effect from improved behavioural variables-dental visit attendance, toothbrushing frequency and percentage of beverage intake consisting of sugar-sweetened beverages-and that sex also plays a role in behavioural variables, as well as caries. A structural equation model was developed based on these hypotheses, and direct and indirect standardized path coefficients were calculated, as well as their standard errors. RESULTS: Based on our proposed model, SES at birth significantly influences SES during adolescence, but not adolescent behaviours. The effect of SES during adolescence on caries in the permanent dentition is mediated by adolescent behaviours. Female participants have worse caries than male participants, despite lower self-reported percentages of sugar-sweetened beverage intake and more frequent brushing and dental attendance. CONCLUSIONS: This analysis models the relationships among known causal factors for caries and suggests that the role of SES in caries may not be as important as previously thought and different behaviours that affect oral health between males and females as well as differences in caries between the sexes could begin during adolescence. These findings could help improve caries prevention programmes for adolescents.

'Aussie Normals': an a priori study to develop reference intervals in a healthy Australian population using the Beckman Coulter LH 750 Haematology Analyser as candidates for harmonised values.

Reference limits or intervals are important benchmarks or tools that help the clinician to distinguish between a result that is most likely to lie within a 'healthy' or diseased category. It has been suggested that a review of haematology reference intervals is long overdue. In this study we report on our findings for analytes routinely measured in a complete blood count (CBC) performed on the Beckman Coulter LH 750 analyser and an additional comparative study using the Beckman Coulter LH 750, the Sysmex XN and Abbott Sapphire. The results from the comparative study indicate that bias would not prevent harmonisation of reference intervals for these common haematology parameters. The results offered by the Aussie Normals study represent good candidates as the basis for harmonisation reference intervals.

Evaluation of Automated Molecular Testing Rollout for Tuberculosis Diagnosis Using Routinely Collected Surveillance Data - Uganda, 2012-2015.

In 2012, Uganda introduced the use of GeneXpert MTB/RIF (Cepheid, Sunnyvale CA), a sensitive, automated, real-time polymerase chain reaction-based platform for tuberculosis (TB) diagnosis, for programmatic use among children, adults with presumptive human immunodeficiency virus (HIV)-associated TB, and symptomatic persons at risk for rifampicin (RIF)-resistant TB. The effect of using the platform's Xpert MTB/RIF assay on TB care and control was assessed using routinely collected programmatic data; in addition, a retrospective review of district quarterly summaries using abstracted TB register data from purposively selected facilities in the capital city of Kampala was conducted. Case notification rates were calculated and nonparametric statistical methods were used for analysis. No statistically significant differences were observed in case notification rates before and after the Xpert MTB/RIF assay became available, although four of 10 districts demonstrated a statistically significant difference in bacteriologically confirmed TB. Once the GeneXpert MTB/RIF platform is established and refined, a more comprehensive evaluation should be conducted.

Multidrug-resistant tuberculosis in Bangladesh: results from a sentinel surveillance system.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to successful TB control. The 2010-2011 Bangladesh Drug Resistance Survey (DRS) showed MDR-TB prevalence to be 7% overall, 1.4% in new and 28.5% in previously treated patients. We aimed to determine the rate of MDR-TB in selected sentinel sites in Bangladesh. METHODS: Fourteen hospitals from the seven divisions in Bangladesh were selected as sentinel surveillance sites. Newly registered TB patients were systematically enrolled from August 2011 to December 2014. Sputum specimens were processed for culture and drug susceptibility testing by the proportion method using Löwenstein-Jensen medium. RESULTS: Specimens from 1906 (84%) of 2270 enrolled patients were analysed. Isolates from 61 (3.2%) were identified as having MDR-TB. The proportion of MDR-TB was 2.3% among new and 13.8% among previously treated TB patients (P < 0.001). The overall proportion of MDR-TB was 3.2%:3.5% in males and 2.3% in females; by age, the MDR-TB rate was highest (5.2%) in those aged 65 years. CONCLUSIONS: The high proportion of MDR-TB among new patients found in this sentinel surveillance significantly differs from that reported in the DRS. While the sentinel surveillance sites were not designed to be nationally representative, it is worrying to observe a higher number of MDR-TB cases among new patients.

Biofidelity assessment of the 6-year-old ATDs in lateral impact.

OBJECTIVES: The objective of this study was to assess and compare the current lateral impact biofidelity of the shoulder, thorax, abdomen, and pelvis of the Q6, Q6s, and Hybrid III (HIII) 6-year-old anthropomorphic test devices (ATDs) through lateral impact testing. METHODS: A series of lateral impact pendulum tests, vertical drop tests, and Wayne State University (WSU) sled tests was performed, based on the procedures detailed in ISO/TR 9790 (1999) and scaling to the 6-year-old using Irwin et al. ( 2002 ). The HIII used in this study was tested with the Ford-designed abdomen described in Rouhana ( 2006 ) and Elhagediab et al. ( 2006 ). The data collected from the 3 different ATDs were filtered using SAE J211 (SAE International 2003 ), aligned using the methodology described by Donnelly and Moorhouse ( 2012 ), and compared for each body region tested (shoulder, thorax, abdomen, and pelvis). The biofidelity performance in lateral impact for the 3 ATDs was assessed against the scaled biofidelity targets published in Irwin et al. ( 2002 ), the abdominal biofidelity target suggested in van Ratingen et al. ( 1997 ), and the biofidelity targets published in Rhule et al. ( 2013 ). Regional and overall biofidelity rankings for each of the 3 ATDs were performed using both the ISO 9790 biofidelity rating system (ISO/TR 9790 1999) and the NHTSA's external biofidelity ranking system (BRS; Rhule et al. 2013 ). RESULTS: All 3 6-year-old ATD's pelvises were rated as least biofidelic of the 4 body regions tested, based on both the ISO and BRS biofidelity rating systems, followed by the shoulder and abdomen, respectively. The thorax of all 3 ATDs was rated as the most biofidelic body region using the aforementioned biofidelity rating systems. The HIII 6-year-old ATD was rated last in overall biofidelity of the 3 tested ATDs, based on both rating systems. The Q6s ATD was rated as having the best overall biofidelity using both rating systems. CONCLUSIONS: All 3 ATDs are more biofidelic in the thorax and abdomen than the shoulder and pelvis, with the pelvis being the least biofidelic of all 4 tested body regions. None of the 3 tested 6-year-old ATDs had an overall ranking of 2.0 or less, based on the BRS ranking. Therefore, it is expected that none of the 3 ATDs would mechanically respond like a postmortem human subject (PMHS) in a lateral impact crash test based on this ranking system. With respect to the ISO biofidelity rating, the HIII dummy would be considered unsuitable and the Q-series dummies would be considered marginal for assessing side impact occupant protection.

Tuberculosis screening outcomes for newly diagnosed persons living with HIV, Nyanza Province, Kenya, 2009.

SETTING: Fifteen human immunodeficiency virus (HIV) clinics in Nyanza Region, Western Kenya. OBJECTIVE: To describe routine tuberculosis (TB) screening and diagnostic practices among newly enrolled people living with HIV (PLHIV) prior to the implementation of World Health Organization recommended TB intensified case finding. DESIGN: Retrospective chart abstraction of PLHIV aged ⩾7 years who were newly enrolled in HIV care in July and August 2009, and who had not received antiretroviral treatment in the preceding 2 years or been diagnosed with TB in the previous year. Factors associated with evidence of TB diagnostic evaluation among symptomatic PLHIV were assessed. RESULTS: Of 1020 patients included in the analysis, 995 (98%) were screened for TB at enrolment and 613 (62%) reported TB symptoms. Ninety-six (16%) patients with symptoms had evidence of referral for TB diagnostic evaluation, including patients at large clinics, those with advanced HIV disease and those reporting multiple TB symptoms. Among the 43 (45%) with documented evaluation results, 26 (60%) were diagnosed with TB. CONCLUSION: Although most PLHIV were screened for TB, very few underwent an evaluation, and the proportion diagnosed with TB was very low. Efforts to improve TB screening should focus on standardizing the intensified case finding algorithm and linkage to, and adequate infrastructure for, TB diagnostic evaluation.

Characterization of degenerative human facet joints and facet joint capsular tissues.

OBJECTIVE: Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue. These alterations in FJC tissues in pain stimulation were also assessed. DESIGN: FJs were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no history of back pain. Histological analyses of the FJs were performed. Cytokine antibody array and quantitative real-time polymerase chain reaction (qPCR) were used to determine the production of inflammatory cytokines, and western blotting analyses (WB) were used to assay for cartilage-degrading enzymes and pain mediators. Ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues was also performed. RESULTS: Increased neovascularization, inflammatory cell infiltration, and pain-related axonal-promoting factors were observed in degenerative FJCs surgically obtained from symptomatic subjects. Increased VEGF, (NGF/TrkA), and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs. Results from ex vivo co-culture of the DRG and FJC tissue demonstrated that degenerative FJCs increased the expression of inflammatory pain molecules in the sensory neurons. CONCLUSION: Degenerative FJCs possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.