eHealth in TB clinical management Margineanu, I; Louka, C; Akkerman, O ...
The international journal of tuberculosis and lung disease,
12/2022, Letnik:
26, Številka:
12
Journal Article
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The constant expansion of internet and mobile technologies has created new opportunities in the field of eHealth, or the digital delivery of healthcare services. This TB meta-analysis aims to examine ...eHealth and its impact on TB clinical management in order to formulate recommendations for further development.
A systematic search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework in PubMed and Embase of articles published up to April 2021. Screening, extraction and quality assessment were performed by two independent researchers. Studies evaluating an internet and/or mobile-based eHealth intervention with an impact on TB clinical management were included. Outcomes were organised following the five domains described in the WHO "Recommendations on Digital Interventions for Health System Strengthening" guideline.
Search strategy yielded 3,873 studies, and 89 full texts were finally included. eHealth tended to enhance screening, diagnosis and treatment indicators, while being cost-effective and acceptable to users. The main challenges concern hardware malfunction and software misuse.
This study offers a broad overview of the innovative field of eHealth applications in TB. Different studies implementing eHealth solutions consistently reported on benefits, but also on specific challenges. eHealth is a promising field of research and could enhance clinical management of TB.
New tools for diagnosis and treatment of rifampicin-resistant (RR-) and multidrug-resistant (MDR-) TB have become available in the last decade, including better tests confirming transmission.
To ...analyse transmission risks of MDR/RR-TB in the Netherlands.
Analysis of national data of patients with MDR/RR-TB notified in 2010-2019, including contact investigation and genotyping data.
Patients with MDR/RR-TB (
= 121) were more often female (adjusted odds ratio aOR 1.5), foreign-born, previously treated for TB (aOR 5.2) and co-infected with HIV (aOR 2.3) than patients with no MDR/RR-TB. Treatment outcomes were satisfactory, with at least 79% completing treatment. After additional whole-genome sequencing (WGS), five molecular clusters of 16 patients remained. Patients in three clusters could not be epidemiologically linked and were unlikely to have been infected in the Netherlands. The remaining eight (6.6%) patients with MDR/RR-TB belonged to two clusters, and were likely the result of transmission in the Netherlands. Among close contacts of patients with smear-positive pulmonary MDR/RR-TB, 13.4% (
= 38) had TB infection and 1.1% (
= 3) had TB disease. Only six contacts with TB infection were treated with a quinolone-based preventive treatment regimen.
MDR/RR-TB is effectively controlled in the Netherlands. Preventive treatment options could be considered more frequently in contacts clearly infected by an index patient with MDR-TB.
Background: Cold‐storage of platelets followed by rewarming induces changes in Glycoprotein (GP) Ibα‐distribution indicative of receptor clustering and initiates thromboxane A2‐formation. GPIbα is ...associated with 14‐3‐3 proteins, which contribute to GPIbα‐signaling and in nucleated cells take part in apoptosis regulation.
Objectives and methods: We investigated whether GPIbα‐clustering induces platelet apoptosis through 14‐3‐3 proteins during cold (4 h 0 °C)‐rewarming (1 h 37 °C).
Results: During cold‐rewarming, 14‐3‐3 proteins associate with GPIbα and dissociate from Bad inducing Bad‐dephosphorylation and activation. This initiates pro‐apoptosis changes in Bax/Bcl‐xL and Bax‐translocation to the mitochondria, inducing cytochrome c release. The result is activation of caspase‐9, which triggers phosphatidylserine exposure and platelet phagocytosis by macrophages. Responses are prevented by N‐acetyl‐d‐glucosamine (GN), which blocks GPIbα‐clustering, and by O‐sialoglycoprotein endopeptidase, which removes extracellular GPIbα.
Conclusions: Cold‐rewarming triggers apoptosis through a GN‐sensitive GPIbα‐change indicative of receptor clustering. Attempts to improve platelet transfusion by cold‐storage should focus on prevention of the GPIbα‐change.
Therapeutic drug monitoring (TDM) uses drug concentrations, primarily from plasma, to optimize drug dosing. Optimisation of drug dosing may improve treatment outcomes, reduce toxicity and reduce the ...risk of acquired drug resistance. The aim of this narrative review is to outline and discuss the challenges of developing multi-analyte assays for anti-tuberculosis (TB) drugs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) by reviewing the existing literature in the field. Compared to other analytical methods, LC-MS/MS offers higher sensitivity and selectivity while requiring relatively low sample volumes. Additionally, multi-analyte assays are easier to perform since adequate separation and short run times are possible even when non-selective sample preparation techniques are used. However, challenges still exist, especially when optimizing LC separation techniques for assays that include analytes with differing chemical properties. Here, we have identified seven multi-analyte assays for first-line anti-TB drugs that use various solvents for sample preparation and mobile phase separation. Only two multi-analyte assays for second-line anti-TB drugs were identified (including either nine or 20 analytes), with each using different protein precipitation methods, mobile phases and columns. The 20 analyte assay did not include bedaquiline, delamanid, meropenem or imipenem. For these drugs, other assays with similar methodologies were identified that could be incorporated in the development of a future comprehensive multi-analyte assay. TDM is a powerful methodology for monitoring patient's individual treatments in TB programmes, but its implementation will require different approaches depending on available resources. Since TB is most-prevalent in low- and middle-income countries where resources are scarce, a patient-centred approach using sampling methods other than large volume blood draws, such as dried blood spots or saliva collection, could facilitate its adoption and use. Regardless of the methodology of collection and analysis, it will be critical that laboratory proficiency programmes are in place to ensure adequate quality control. It is our intent that the information contained in this review will contribute to the process of assembling comprehensive multiplexed assays for the dynamic monitoring of anti-TB drug treatment in affected individuals.
Cold storage of platelets reduces bacterial growth and preserves their hemostatic properties better than current procedures do. However, storage at 0°C induces 14-3-3ζ-glycoprotein Ibα association, ...14-3-3ζ release from phospho-Bad, Bad activation and apoptosis.
We investigated whether arachidonic acid, which also binds 14-3-3ζ, contributes to coldinduced apoptosis.
Cold storage activated P38-mitogen-activated protein kinase and released arachidonic acid, which accumulated due to cold inactivation of cyclooxygenase-1/thromboxane synthase. Accumulated arachidonic acid released 14-3-3ζ from phospho-Bad and decreased the mitochondrial membrane potential, which are steps in the induction of apoptosis. Addition of arachidonic acid did the same and its depletion made platelets resistant to cold-induced apoptosis. Incubation with biotin-arachidonic acid revealed formation of an arachidonic acid-14-3-3ζ-glycoprotein Ibα complex. Indomethacin promoted complex formation by accumulating arachidonic acid and released 14-3-3ζ from cyclo-oxygenase-1. Arachidonic acid depletion prevented the cold-induced reduction of platelet survival in mice.
We conclude that cold storage induced apoptosis through an arachidonic acid-14-3-3ζ-glycoprotein Ibα complex, which released 14-3-3ζ from Bad in an arachidonic acid-dependent manner. Although arachidonic acid depletion reduced agonist-induced thromboxane A(2) formation and aggregation, arachidonic acid repletion restored these functions, opening ways to reduce apoptosis during storage without compromising hemostatic functions post-transfusion.
► CMP X and CMP Y are two novel and highly selective 5-HT6 receptor antagonists. ► CMP X and CMP Y improved scopolamine-induced deficits in tests for episodic memory. ► Donepezil and reference 5-HT6 ...antagonist GSK-742457 also improved performance. ► Co-adm. of CMP X, CMP Y with donepezil resulted in additive cogn. enhancing effects. ► 5-HT6 antagonists could have potential as adjunctive therapy to donepezil.
The 5-hydroxytryptamine6 (5-HT6) receptor has been suggested to play an important role in the regulation of memory and cognition. In the present study, our aim was to investigate whether the novel, selective 5-HT6 antagonists compound (CMP) X and CMP Y and the reference 5-HT6 antagonist GSK-742457 could ameliorate impairments in episodic memory in 3-months-old male Wistar rats. The acetylcholinesterase inhibitor (AChEI) donepezil (Aricept®, approved for symptomatic treatment of Alzheimer’s disease, AD) was used as a positive reference compound. First, effects of the 5-HT6 antagonists CMP X, CMP Y and GSK-742457 were investigated on object recognition task (ORT) performance in rats treated with the muscarinic antagonist scopolamine (0.1mg/kg, administered intraperitoneally, i.p., 30min before trial 1). Second, effects of the combination of suboptimal doses of 5-HT6 antagonists CMP X and CMP Y with the AChEI donepezil were studied, to determine whether the 5-HT6 antagonists show additive synergism with donepezil in the ORT. Finally, effects of CMP Y, GSK-742457 and donepezil were investigated on object location task (OLT) performance in rats treated with scopolamine.
Donepezil (1mg/kg, oral administration, p.o.), GSK-742457 (3mg/kg, i.p.), CMP X (3mg/kg, i.p.) and CMP Y (30mg/kg, p.o.), all ameliorated the scopolamine-induced deficits in object recognition. In the ORT, we have found that combined administration of subthreshold doses of CMP X (1mg/kg, i.p.) and CMP Y (10mg/kg, p.o.) with the AChEI donepezil (0.1mg/kg, p.o.), enhanced memory performance in Wistar rats with deficits induced by scopolamine. Donepezil (0.1mg/kg, p.o.) alone had no discernable effects on performance. This suggests additive synergistic effects of the 5-HT6 antagonists (CMP X and CMP Y) with donepezil on cognitive impairment. Finally, donepezil (1mg/kg, p.o.), GSK-742457 (10mg/kg, p.o.) and CMP Y (30mg/kg, p.o.) also reduced scopolamine-induced deficits in the OLT.
In conclusion, the 5-HT6 antagonists were found to clearly improve episodic memory deficits induced by scopolamine. In addition, co-administration of the 5-HT6 receptor antagonists CMP X and CMP Y with the AChEI donepezil to cognitively impaired rats also resulted in potentially additive enhancing effects on cognition. This suggests that these compounds could have potential as monotherapy, but also as adjunctive therapy in patients with AD treated with common treatments such as donepezil.
IntroductionGlobal multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and ...interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls.Methods and analysisPatients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0 and t=5 hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7 days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2 months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM.Ethics and disseminationEthical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal.Trial registration numberClinicalTrials.gov Registry (NCT03409315).
Parents of short children born SGA often report that their children have a serious lack of appetite and a low food intake. In this study we investigated food intake, by using a standardized 7-day ...food questionnaire, in 88 short SGA children before start of GH treatment. The intake was compared with the recommended daily intake (RDI) of age-matched children. We also compared the food intake of GH-treated children (n=62) with randomized controls (n=26) after 1 year of GH treatment. In addition, we evaluated the effect of food intake and GH treatment on body composition and serum levels of IGF-I, IGFBP-3 and leptin. Our study shows that caloric intake, fat and carbohydrate intake of short SGA children aged 5.9 (1.6) years was significantly lower compared to the RDI for age-matched children. One year of GH treatment resulted in a significant increase of caloric, fat, carbohydrate and protein intake compared to baseline. Compared to randomized controls, caloric, carbohydrate and protein intake increased significantly after 1 year of GH treatment. Short SGA children had significantly lower SDS scores for LBM, fat mass, skinfold (SF) and BMI compared to age-matched references. They also had significantly lower serum IGF-I, IGFBP-3 and leptin levels. GH treatment resulted in a significant increase of height, LBM, BMI, IGF-I and IGFBP-3 SDS and a significant decrease of SF SDS and leptin SDS. In conclusion, our study shows that short SGA children have indeed a lower food intake than age-matched controls. During GH treatment the food intake increased significantly compared to baseline in contrast to the randomized control group.
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