2022 TB programme review in Pakistan: strengthening governance, with better patient diagnosis and treatment.

BACKGROUND: In Pakistan, 84% of healthcare is provided by the private sector. We conducted an epidemiological and programme review for TB to document progress and guide further efforts. METHODS: Surveillance and data systems were assessed before analysing epidemiological data. We reviewed the programme at federal, provincial and peripheral levels and compiled national data along with WHO estimates to describe the evolution of epidemiological and programme indicators. RESULTS: In 2021, of the estimated number of TB cases, 55% of overall cases and 18% of drug-resistant cases were diagnosed and treated respectively. The contribution of the private sector in case detection increased from 30% in 2017 to 40% by 2021. For newly diagnosed pulmonary TB cases, the overall proportion of confirmed cases was 52%. In 2021, testing for rifampicin resistance among confirmed cases was 66% for new and 84% for previously treated patients. The treatment success rate exceeded 90% for drug susceptible TB. The main challenges identified were a funding gap (60% in 2021-2023), fragmented electronic systems for data collection and suboptimal coordination among provinces. CONCLUSIONS: The main challenges prevent further progress in controlling TB. By addressing these, Pakistan could improve coverage of interventions, including diagnosis and treatment. Bacteriological confirmation using recommended diagnostics also requires further optimisation.

CONTEXTE: Au Pakistan, le secteur privé assure 84% des services de santé. Une étude épidémiologique et programmatique a été réalisée sur la TB afin de recueillir des informations sur les avancées réalisées et de guider les actions à venir. MÉTHODES: Les systèmes de surveillance et de données ont été évalués préalablement à l'analyse des données épidémiologiques. Nous avons examiné le programme aux niveaux fédéral, provincial et local et compilé les données nationales ainsi que les estimations de l'OMS afin de décrire l'évolution des indicateurs épidémiologiques et du programme. RÉSULTATS: En 2021, environ 55% de l'ensemble cas de TB et 18% des cas résistants aux médicaments ont été diagnostiqués et traités respectivement. La contribution du secteur privé dans la détection des cas est passée de 30% en 2017 à 40% en 2021. La proportion totale de cas confirmés pour les nouveaux diagnostics de TB pulmonaire s'élevait à 52%. En 2021, les tests de résistance à la rifampicine parmi les cas confirmés s'élevaient à 66% pour les nouveaux patients et de 84% pour les patients déjà traités. Le taux de réussite du traitement a dépassé 90% pour la TB sensible aux médicaments. Les défis majeurs comprennent un manque de financement (60% pour la période 2021­2023), des systèmes électroniques de collecte de données fragmentés et une coordination insuffisante entre les provinces. CONCLUSIONS: Les défis majeurs entravent les avancées dans la lutte contre la TB. En les mettant en évidence, le Pakistan pourrait améliorer la portée des interventions, y compris le diagnostic et le traitement. Il est également essentiel d'optimiser la confirmation bactériologique en utilisant les diagnostics recommandés.

Commitment, partnerships and operational research: three priorities for 11 EMR countries to achieve TB elimination.

BACKGROUND: In 2022, 11 of 22 Member States of the WHO Eastern Mediterranean Region (EMR) had an estimated TB incidence of <20 cases per 100,000 population. We assessed preparedness for elimination and provided recommendations to pursue the process. METHODS: We surveyed 11 EMR national TB programme managers and collected information on eight TB elimination framework domains using a close-ended data collection tool. We compiled, consolidated and validated data, including a virtual consultation before triangulating data with other sources. RESULTS: Implementation was sufficient (≥74%) for 5 of 8 domains, highest for TB infection management, TB preventive treatment, laboratory service, drug management, drug-resistant TB and TB-HIV collaboration (89%, 83% and 78%, respectively). Countries ranked lowest for commitment (73%), operational research and infection control (63%), and partnership/collaborations (41%). Five countries reached >80% when consolidating the responses, reaching sufficient from all domains. Two reached <50%. CONCLUSION: Key identified obstacles to TB elimination in EMR were insufficient commitment/financing, sub-optimal partnerships/collaborations and operational research calling for 1) all-stakeholder-inclusive, sustainably funded TB elimination plans, 2) cost-effective tools to exchange strategic information and build operational research capacity, and 3) improved collaboration.

CONTEXTE: En 2022, 11 des 22 États membres de la Région de la Méditerranée orientale de l'OMS avaient une incidence de la TB estimée à moins de 20 cas pour 100 000 habitants. Nous avons évalué l'état de préparation à l'élimination et formulé des recommandations pour poursuivre le processus. MÉTHODES: Nous avons interrogé 11 responsables de programmes nationaux de lutte contre la TB dans la région de la Méditerranée orientale et recueilli des informations sur huit domaines du cadre d'élimination de la TB à l'aide d'un outil de collecte de données à questions fermées. Nous avons compilé, consolidé et validé les données, y compris lors d'une consultation virtuelle, avant de les trianguler avec d'autres sources. RÉSULTATS: La mise en œuvre était suffisante (≥74%) pour 5 des 8 domaines, les plus élevés étant la gestion de l'infection tuberculeuse, le traitement préventif de la TB, les services de laboratoire, la gestion des médicaments, la TB pharmacorésistante et la collaboration TB-VIH (89%, 83% et 78%, respectivement). Les pays se sont classés au dernier rang pour l'engagement (73%), la recherche opérationnelle et la lutte contre l'infection (63%) et le partenariat/la collaboration (41%). Cinq pays ont atteint >80% lors de la consolidation des réponses, atteignant un niveau suffisant dans tous les domaines. Deux pays ont atteint un taux de réponse inférieur à 50%. CONCLUSION: Les principaux obstacles à l'élimination de la TB dans les pays de l'Union européenne sont un engagement/un financement insuffisant, des partenariats/collaborations sous-optimaux et une recherche opérationnelle nécessitant 1) des plans d'élimination de la TB incluant toutes les parties prenantes et bénéficiant d'un financement durable, 2) des outils rentables permettant d'échanger des informations stratégiques et de renforcer les capacités de recherche opérationnelle, et 3) une meilleure collaboration.

Vaccination in post-tuberculosis lung disease management: A review of the evidence.

INTRODUCTION AND OBJECTIVES: Post-tuberculosis lung disease (PTLD), as other chronic respiratory disorders, may have infectious complications; some of them can be prevented with vaccinations. So far, no document has discussed the potential role of vaccination in PTLD. Therefore, the objective of this review was to describe vaccination recommendations to prevent infections potentially capable of complicating PTLD. MATERIALS AND METHODS: A non-systematic review of the literature was conducted. The following keywords were used: tuberculosis, vaccination, vaccines and PTLD. PubMed/MEDLINE and Embase were used as the search engine, focusing on English-language literature only. RESULTS: We identified 9 vaccines potentially useful in PTLD. Influenza, pneumococcal and anti-COVID-19 vaccinations should be recommended. Patients with PTLD can also benefit from vaccination against shingles. Vaccination against pertussis is mainly relevant during childhood. Diphtheria, tetanus and measles vaccination are recommended for general population and should be considered in patients with PTLD not previously vaccinated. Tdap (Tetanus, diphtheria, and pertussis) booster should be repeated in every adult every ten years. Vaccination against BCG retains its importance during early childhood in countries where TB is endemic. CONCLUSIONS: Vaccination deserves to be considered among the strategies to prevent and/or mitigate PTLD complications. Further evidence is necessary to better understand which vaccines have the greatest impact and cost-benefit.

A systematic review of the costs of diagnosis for multidrug-resistant/extensively drug-resistant TB in different settings.

BACKGROUND: We performed an analysis of the cost and relative merits of different strategies for the diagnosis of multidrug-resistant/extensively drug-resistant TB (MDR/XDR-TB) in different settings.METHODS: We systematically reviewed the published evidence on cost/cost-effectiveness of rapid MDR/pre-XDR-TB and other methods for XDR-TB testing up to September 2022. PRISMA guidelines were followed. Collected data were analysed using Stata v17 software. Cost data were reported in USD ($) and summarised by mean, standard deviation, and range. Country income level was defined according to the World Bank country classification. Three simplified scenarios were also used to explore testing implications, based on low, intermediate and high TB incidence.RESULTS: Of 157 records, 25 studies were included with 24 reporting the cost of Xpert/RIF and two that evaluated the implementation of the MTBDRplus test. The total rapid test cost ranged from $12.41-$218, including $1.13-$74.60 for reagents/consumables and $0.40-$14.34 for equipment.CONCLUSION: The cost of MDR/XDR-TB diagnostics is lower in low resource settings. However, the cost-effective implementation of MDR/XDR-TB diagnostic algorithms requires careful consideration of local resources to avoid missed identification and the use of inappropriate regimen.

Strength of hip muscles and bradykinesia contribute to walking speed over a long distance, but not a short distance, in people with mild Parkinson's disease: An observational study.

BACKGROUND: Bradykinesia and postural instability contribute to walking limitations in people with Parkinson's disease (PD), but the contribution of muscle strength to walking speed has not been examined extensively. RESEARCH QUESTION: Does strength of the major lower limb muscles contribute to walking speed over short and long distances in people with PD? METHOD: na. DESIGN: A cross-sectional, observational study. PARTICIPANTS: 50 people with mild PD. OUTCOME MEASURES: Maximum isometric strength of the flexors and extensors of the lower limb was measured using hand-held dynamometry. Flexed posture, postural instability and bradykinesia were measured using the MDS-UPDRS part III. Walking speed was measured during the 10-m Walk Test and 6-min Walk Test. RESULTS: Univariate analysis revealed that age, bradykinesia, flexed posture, and hip, knee and ankle weakness were all significantly correlated with walking speed over short and long distances. Multiple regression analysis revealed that age, bradykinesia, flexed posture and weakness of the hip and knee muscles together accounted for 47% of the variance in walking speed over a short distance, with age (R2 = 0.11, p = 0.003) making a significant independent contribution. Age, bradykinesia, flexed posture and strength of the hip and knee muscles together accounted for 56% of the variance in walking speed over a long distance. Age (R2 = 0.12, p = 0.001), weakness of the hip muscles (R2 = 0.12, p = 0.001) and bradykinesia (R2 = 0.04, p = 0.04) made significant, independent contributions to the variance in walking speed over a long distance. SIGNIFICANCE: In people with mild PD, weakness of the hip muscles and bradykinesia only make a significant relative contribution to walking speed over a long distance. Therefore, in people with normal walking speed over a short distance the 6-min Walk Test could be measured to more effectively identify the impact of motor impairments on walking.

Management of childhood MDR-TB in Europe and Central Asia: report of a Regional WHO meeting.

BACKGROUND: As the WHO European Region has the highest proportion of multidrug-resistant TB (MDR-TB) among total incident TB cases, many children and adolescents are at risk of MDR-TB infection and disease.METHODS: We performed an electronic survey of clinicians and TB programme personnel who attended the 2020 Regional Consultation on child and adolescent TB organised by the WHO Regional Office. We characterised access to diagnostics and drugs, and practices in the prevention and management of child and adolescent MDR-TB.RESULTS: Children and adolescents are inconsistently represented in national guidelines and budgets; child-friendly drug formulations for MDR-TB treatment are insufficiently available in 57% of countries, and 32% of countries reported paediatric drug stock-outs. The novel drugs, bedaquiline and delamanid, are accessible by respectively 80% and 60% of respondent countries. Respondents were asked how many children were diagnosed with MDR-TB in 2019, and a comparison of this number to modelled estimates of incidence (to identify the case detection gap) and WHO notifications (to identify the case reporting gap) showed substantial differences in both comparisons.CONCLUSIONS: Better representation of this patient group in guidelines and budgets, greater access to drugs and improved reporting are essential to reach TB elimination in this Region.

Mesh-related complications and recurrence after ventral mesh rectopexy with synthetic versus biologic mesh: a systematic review and meta-analysis.

BACKGROUND: Ventral mesh rectopexy (VMR) is a widely accepted surgical treatment for rectal prolapse. Both synthetic and biologic mesh are used. No consensus exists on the preferred type of mesh material. The aim of this systematic review and meta-analysis was to establish an overview of the current literature on mesh-related complications and recurrence after VMR with synthetic or biologic mesh to aid evidence-based decision making in preferred mesh material. METHODS: A systematic search of the electronic databases of PubMed, Embase and Cochrane was performed (from inception until September 2020). Studies evaluating patients who underwent VMR with synthetic or biologic mesh were eligible. The MINORS score was used for quality assessment. RESULTS: Thirty-two studies were eligible after qualitative assessment. Eleven studies reported on mesh-related complications including 4001 patients treated with synthetic mesh and 762 treated with biologic mesh. The incidence of mesh-related complications ranged between 0 and 2.4% after synthetic versus 0-0.7% after biologic VMR. Synthetic mesh studies showed a pooled incidence of mesh-related complications of 1.0% (95% CI 0.5-1.7). Data of biologic mesh studies could not be pooled. Twenty-nine studies reported on the risk of recurrence in 2371 synthetic mesh patients and 602 biologic mesh patients. The risk of recurrence varied between 1.1 and 18.8% for synthetic VMR versus 0-15.4% for biologic VMR. Cumulative incidence of recurrence was found to be 6.1% (95% CI 4.3-8.1) and 5.8% (95% CI 2.9-9.6), respectively. The clinical and statistical heterogeneity was high. CONCLUSIONS: No definitive conclusions on preferred mesh type can be made due to the quality of the included studies with high heterogeneity amongst them.

Tuberculosis, COVID-19 and migrants: Preliminary analysis of deaths occurring in 69 patients from two cohorts.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

Tuberculosis surveillance in adolescents: what to learn from European Union/European Economic Area data?

OBJECTIVE: To describe tuberculosis (TB) characteristics in the adolescent 10-19 years age group that is often underrepresented in surveillance and studies despite the high global TB burden estimated for this group.SETTING AND DESIGN: We use the case-based data reported to the European Surveillance System (TESSy) from European Union (EU)/European Economic Area (EEA) countries between 2007 and 2016 to describe notification rates, TB characteristics and treatment outcomes among adolescent TB cases. We also compare TB characteristics in young adolescents (10-14 years) and older adolescents (15-19 years).RESULTS: For the period 2007 to 2016, 705 826 TB cases were reported to TESSy by 29 EU/EEA countries, 38 054 (5.4%) of which were adolescents. The overall EU/EEA notification rate among adolescents was 6.9 per 100 000 population, 3.5 among young adolescents and 10.1 among older adolescents. The two adolescent groups had differences regarding sex distribution, site of disease, sputum smear microscopy positivity, laboratory confirmation and treatment outcome.CONCLUSION: Younger and older adolescents should be analysed as separate groups when studying and reporting TB, particularly to inform better targeting of TB prevention and care interventions in the future, in order to improve outcomes.

People- and patient-centred care for tuberculosis: models of care for tuberculosis.

SETTING: The first pillar in the World Health Organisation's (WHO's) End TB strategy is 'Integrated, patient-centred tuberculosis (TB) care and prevention'. However, what are patient- and people-centred care, and why are they important for TB care and prevention? OBJECTIVE AND RATIONALE: To define the concept of patient-centred care, the rationale for it, and its evolution into people-centred care; and to explore evidence on whether people-centred approaches work for TB and present key areas where continuous efforts are needed to support their implementation. RESULTS: Based on the reasoning and the evidence presented, we propose four areas where further action is needed to ensure that people-centred TB care and prevention can achieve their potential: 1) reaching consensus on definitions and terminology; 2) strengthening research; 3) using and evaluating new technology; and 4) nurturing country leadership and advocacy. CONCLUSION: Integrated, people-centred TB care and prevention should be a guiding light for all those involved in the quest to eliminate TB. However, much still needs to be done to bridge the gaps between the potential and actual performance of national programmes.

Doxapram-mediated Increase in Cardiac Output Reduces Opioid Plasma Concentrations: A Pharmacokinetic/Pharmacodynamic-Pharmacokinetic/Pharmacodynamic Modeling Study in Healthy Volunteers.

Doxapram is an analeptic that induces ventilatory stimulation and increases blood pressure and cardiac output (CO). Its mechanism of action is the blockade of background K+ -channels expressed on type 1 carotid body cells. In the randomized controlled trial, the authors explored the role of the increase in CO by doxapram (plasma concentration (Cp) 1,000-3,500 ng/mL) on the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the potent opioid alfentanil (Cp 100-200 ng/mL). Population PK-PD analyses were performed on the doxapram PK-CO data and the alfentanil PK-antinociception data. The analyses showed that the doxapram-induced increase in CO explained the increase in alfentanil distribution and elimination clearances causing a significant reduction in plasma alfentanil Cp and antinociception. This novel approach in which one PK-PD model effectively drives another PK-PD model highlights the importance of physiological influences on PK and PD of a potent opioid with rapid onset of effect and low clinical margin of safety.

Nanocrystallinity and direct cross-linkage as key-factors for the assembly of gold nanoparticle-superlattices.

We report here how the crystallinity of AuNPs and the choice of binding sites of molecular cross-linkers control their aggregation. The combination of different binding moieties (N-oxides, ArF-I) and the reactivity of the particles' facets allow control over the organization and crystallinity of the AuNP assemblies.

When do patients prefer a direct oral anticoagulant over a vitamin K antagonist?

BACKGROUND: The reasons for patients to change their usual vitamin K antagonist (VKA) treatment to a direct oral anticoagulant (DOAC) are unexplored. METHOD: A random sample of 200 patients treated with VKAs for the indication of atrial fibrillation from the Thrombosis Service in Amsterdam was selected. A survey, using the treatment trade-off technique, was sent to participants. The trade-off included four scenarios: 1 (no need for laboratory controls); 2 (less bleeding); 3 (less interactions); 4 (more effective). RESULTS: Under scenario 1, 57% of the patients would have made the switch, with a further increase to 65% with scenario 2 (trend value, p = 0.006, 95% CI 1.11-1.85). In addition, in each scenario patients who were less satisfied with their current treatment were more likely to switch to a DOAC compared with satisfied patients. The variables duration of treatment, gender, age and educational level did not affect the preference for a DOAC. CONCLUSION: Patients considered no requirement for regular laboratory control and a lower risk of bleeding the most important arguments to switch to a DOAC.

Validation of a novel respiratory rate monitor based on exhaled humidity.

BACKGROUND: Postoperative monitoring of ventilation is largely restricted to the measurement of haemoglobin-oxygen saturation and respiratory rate (RR) derived from the ECG. measurement is inadequate when used with supplemental oxygen and ECG-derived RR is subject to artifacts. A new monitor measures RR by quantifying the humidity of exhaled air (respiR8(®)). METHODS: The accuracy of the system was tested using a breathing simulator. In healthy volunteers, the respiR8(®) monitor was compared with two other methods of measuring RR: capnometry and counting of thoracic breathing movements. The ability of the monitor to track changes in RR resulting from the infusion of 2.5 µg kg(-1) fentanyl was assessed and compared with RR measured from a validated flow measurement system. The RR in 50 postoperative patients measured with the respiR8(®) was compared with that derived from the ECG. RR values were compared by population-based Bland-Altman analyses. RESULTS: The respiR8(®) monitor was accurate in the range required in clinical practice. There was a close agreement between RR from respiR8(®), capnometry, and manual counting of respiratory movements without bias (limits of agreement ±1 bpm). The respiR8(®) monitor was well able to accurately track RR changes from fentanyl. In postoperative patients, RR from respiR8(®) and ECG had a bias of 1.7 (5.7) bpm due to greater RR values observed from the ECG due to artifacts. CONCLUSIONS: The respiR8(®) gives an accurate measurement of RR and is useful in postoperative care.

Is screening for renal anomalies warranted in neonates with isolated single umbilical artery?

AIM: To determine the prevalence of renal anomalies in patients with an isolated single umbilical artery (SUA). METHODS: We performed a retrospective study of all renal ultrasound examinations assessed at our centre between January 1998 and December 2008 in neonates with SUA with or without associated anomalies. RESULTS: Renal ultrasound examination was performed in 65 neonates with SUA (57 neonates with isolated SUA and 8 neonates with nonisolated SUA). The prevalence of renal anomalies in the group with and without isolated SUA was 2% (1/57) and 38% (3/8), respectively. Only one patient with isolated SUA had a mild renal abnormality without clinical consequences. CONCLUSIONS: The prevalence of renal anomalies in neonates with isolated SUA is low. We suggest that routine ultrasound screening for renal anomalies is not warranted in neonates with isolated SUA.