Risk factors for early TB treatment interruption among newly diagnosed patients in Malaysia

TB treatment interruption has resulted in delayed sputum conversion, drug resistance, and a high mortality rate and a prolonged treatment course, hence leading to economic and psychosocial affliction. To date, there are limited studies investigating the physico-social risk factors for early treatment interruptions. This prospective multicenter cohort study aimed to investigate the risk factors for early treatment interruption among new pulmonary tuberculosis (TB) smear-positive patients in Selangor, Malaysia. A total of 439 participants were recruited from 39 public treatment centres, 2018–2019. Multivariate Cox proportional hazard analyses were performed to analyse the risk factors for early treatment interruption. Of 439 participants, 104 (23.7%) had early treatment interruption, with 67.3% of early treatment interruption occurring in the first month of treatment. Being a current smoker and having a history of hospitalization, internalized stigma, low TB symptoms score, and waiting time spent at Directly Observed Treatment, Short-course centre were risk factors for early treatment interruption. An appropriate treatment adherence strategy is suggested to prioritize the high-risk group with high early treatment interruption. Efforts to quit smoking cessation programs and to promote stigma reduction interventions are crucial to reduce the probability of early treatment interruption.

Effectiveness of Various Treatments for Sudden Sensorineural Hearing Loss—A Retrospective Study

(1) Background: A retrospective clinical study was conducted to compare the effectiveness of different pharmacological and non-pharmacological regimens for treating sudden sensorineural hearing loss (SSNHL). (2) Methods: Adult patients (n = 130) diagnosed with sudden sensorineural hearing loss (SSNHL) and hospitalized between 2015 and 2020 were enrolled in this study. Depending on the treatment regimen applied, patients were divided into five groups. Inclusion criteria were as follows: (i) hearing loss of sudden onset; (ii) hearing loss of at least 30 dB at three consecutive frequencies; (iii) unilateral hearing loss; (iv) age above 18 years. Exclusion criteria were as follows: (i) no follow-up audiogram; (ii) bilateral hearing loss; (iii) recognized alternative diagnosis such as tumor, disorder of inner ear fluids, infection or inflammation, autoimmune disease, malformation, hematological disease, dialysis-dependent renal failure, postdural puncture syndrome, gene-related syndrome, mitochondrial disease; and (iv) age below 18 years. (3) Results: Complete recovery was found in 14% of patients (18/130) and marked improvement was found in 6% (8/130), giving an overall success rate of 20%. The best results were obtained in the second group (i.e., patients given intratympanic glucocorticoid + prolonged orally administered glucocorticoid) where the success rate was 28%. In general, the older the patient, the smaller the improvement in hearing, a correlation that was statistically significant. (4) Conclusions: In treating SSNHL, the highest rate of hearing recovery—28%—was in the group of patients given intratympanic corticoid plus prolonged treatment with orally administered glucocorticoid.

Idiopathic multifocal choroiditis (MFC): aggressive and prolonged therapy with multiple immunosuppressive agents is needed to halt the progression of active disease. An offbeat review and a case series

Background and purpose Idiopathic multifocal choroiditis (MFC) is part of the group of choriocapillaritis entities. The clinical definition of the disease has evolved with time. The aim of this article was to undertake a review on MFC, on its present-day appraisal and nomenclature and we also report a series of patients with emphasis on the clinical presentation and the importance of vigorous immunosuppressive management. Methods A review of the literature and a retrospective case series study which was performed in the Centre for Ophthalmic Specialised care (COS), Lausanne, Switzerland. Patients diagnosed from 1994 to 2020 with idiopathic multifocal choroiditis (MFC) treated with multiple immunosuppressants were included. Exclusion criteria were insufficient follow up and cases not treated with vigorous immunosuppressive therapy. Imaging analysis included spectral domain optical coherence tomography (SD-OCT) / enhanced depth imaging OCT (EDI-OCT), OCT angiography (OCT-A). Fluorescein and Indocyanine angiography (FA, ICGA) before and after the instauration of treatment. Best corrected visual acuity (BCVA), intraocular pressure (IOP), routine ocular examination, laser flare photometry (LFP) were performed at presentation and follow-up. Immunosuppression comprised at minimum two among the following agents: prednisone, cyclosporine, azathioprine, mycophenolic acid or infliximab. Mean duration of therapy was calculated. Results 26 (52 eyes) of 2102 new patients (1.24%) were diagnosed with MFC. 25 (96%) patients were female and 1 (4%) was male. 43/52 (82%) eyes were myopic with a mean dioptre of − 5.87 ± 2.94, six (12%) eyes were hypermetropic with mean dioptres 2.0 ± 2.68 and three (6%) were emmetropic. 14/52 (27%) eyes had at least 1 anti-VEGF injection because of choroidal neovascularisation (CNVs), 1 eye had a phototherapy laser and 37/52 (71%) had no complication of CNVs during the follow-up. 5/26 (19%) fulfilled the inclusion criteria for our study. Mean age was 26.4 ± 9.3 years. Snellen best corrected visual acuity (BCVA) at presentation was 0.955+/-0.26. Mean follow up was 84+/-55 months. LFP at presentation was 6.34 ± 2.94 ph/ms. None of four patients with prolonged treatment and prolonged follow-up showed disease activity. One patient still under therapy after 4 months’ follow-up still showed an active neovascular membrane. Conclusion Treatment with multiple immunosuppressive agents was shown to stop the progression of the disease.

Personalisation of DAPT: from ‘bench’ to bedside

The ideal duration of antiplatelet therapy following percutaneous coronary intervention is a topic of much discussion within the cardiology community. Numerous contemporary studies have highlighted benefits of both shortened and prolonged treatment courses within particular patient cohorts. Despite this, there is a delay in seeing such individualised decisions being made within stretched healthcare systems. We aimed to highlight this issue and facilitate discussions on how we can bring this important research from ‘bench’ to ‘bedside’.

Application of Nanoemulsion in Tuberculosis Treatment

Tuberculosis is commonly called TB and considered to be the most contagious disease. This disease is caused by a causative agent known as Mycobacterium tuberculosis within the host body cells. Emergence incidence of XDR and MDR of tuberculosis are due to high dose intake and prolonged treatment of antibiotics. In this era, only one vaccine called as BCG is available which is ineffective against infected tuberculosis adults. Though several antibiotics have been produced to overcome drug resistance and even enhance the patient compliance towards treatment and reduce the treatment regimen, we require a novel strategy that can improve the potency of therapeutic synthetic drugs. This approach can be achieved by the application of nanotechnology associated with conventional therapy. Nanotechnology has attributed the promising effects associated with optimized treatment against chronic diseases. This novel technology has the ability to reduce the dose frequency and even resolves the poor patient compliance.

Structure and Properties of Highly Porous Alumina-Based Ceramic Materials after Heating by Concentrated Solar Radiation

Three ceramic fibrous materials of the Al2O3-SiO2 system with different densities have been treated using concentrated solar radiation. The experiment was performed using technological capabilities of the Big Solar Furnace in the 2 modes: the first mode includes heating up to 1400–1600 °C, holding for 1.5–2 h; the second mode (the fusion mode) includes heating up to 1750–1900 °C until the sample destruction, which is accompanied by fusion. Upon completion of the experiment, the phase composition, microstructure, and compressive strength of the materials were studied. It was shown that the investigated materials retained their fibrous structure under prolonged treatment in the first mode up to temperatures of 1600 °C. The phase composition of the ceramic materials changes during the experiment, and with a decrease in the density, the modification is more pronounced. Treatment of all three materials under study in the fusion mode resulted in the formation of the eutectic component in the form of spherulites. The compressive strength of the materials was found to be slightly reduced after exposure to concentrated solar radiation.

Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum

Long-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management.

Treatment of Polarized Cystic Fibrosis Airway Cells With HGF Prevents VX-661-Rescued F508del-CFTR Destabilization Caused by Prolonged Co-exposure to VX-770

Cystic fibrosis (CF), the most common inherited disease in Caucasians, is caused by mutations in CFTR, the most frequent of which is F508del. F508del causes ER retention and degradation of the mutant CFTR protein, but also defective channel gating and decreased half-life at the plasma membrane. Despite the recent successes with small-molecule CFTR modulator drugs, the folding-corrector/gating-potentiator drug combinations approved for CF individuals carrying F508del-CFTR have sometimes produced severe side effects. Previously, we showed that a prolonged, 15-days treatment of polarized bronchial epithelial monolayers with the VX-809+VX-770 combination resulted in epithelial dedifferentiation effects that we found were caused specifically by VX-809. Moreover, prolonged VX-770 exposure also led to the destabilization of VX-809-rescued F508del-CFTR. Notably, co-treatment with the physiological factor HGF prevented VX-809-mediated epithelial differentiation and reverted the destabilizing effect of VX-770 on VX-809-rescued CFTR. Here, we show that prolonged treatment with VX-661, a second-generation corrector developed based on VX-809 structure, does not perturb epithelial integrity of polarized bronchial epithelial monolayers. Yet, its efficacy is still affected by co-exposure to VX-770, the potentiator present in all VX-661-containing combination therapies approved in the United States and Europe for treatment of F508del-CFTR carriers. Importantly, we found that co-treatment with HGF still ameliorated the impact of VX-770 in F508del-CFTR functional rescue by VX-661, without increasing cell proliferation (Ki-67) or altering the overall expression of epithelial markers (ZO-1, E-cadherin, CK8, CK18). Our findings highlight the importance of evaluating the cellular effects of prolonged exposure to CFTR modulators and suggest that the benefits of adding HGF to current combination therapies should be further investigated.

Prosthodontic Rehabilitation of Bilateral Maxillary Lateral Incisors Agenesis: A Case Report with One-Year Follow-Up

Globally, non-syndromic tooth agenesis is commonly seen in clinical practice. However, its management is often complex and requires a multidisciplinary team approach for the maximal outcome. While various treatment options are possible, considerations for the treatment are not only based on the dentofacial conditions but also cultural and social background and personal preference of the patient. Thus, patientcentred care approach should always be practised for an optimal outcome. In the present case, a patient with established craniofacial growth presenting with bilateral agenesis of maxillary lateral incisors and over-retained deciduous maxillary left canine sought for aesthetic improvements. The patient did not prefer any orthodontic treatment citing a prolonged treatment duration and sub-optimal motivation as a hindrance. Thus, a prosthodontic only approach was taken by providing a conventional cantilever bridge and ceramic veneers to achieve the aims of treatment. This article discusses the possible limitation of such prosthodontic only solution in managing tooth agenesis.

Individualizing the use of [18F]FDG-PET/CT in patients with complicated Staphylococcus aureus bacteremia: experiences from a tertiary care center

Purpose [18F]FDG-PET/CT scanning can help detect metastatic infectious foci and reduce mortality in patients with Staphylococcus aureus bacteremia (SAB), but it is unknown if patients with SAB and an indication for prolonged treatment because of possible endovascular, orthopaedic implant, or other metastatic infection still need [18F]FDG-PET/CT. Methods In a retrospective single-center cohort study, we included all consecutive adult patients with SAB between 2013 and 2020 if an [18F]FDG-PET/CT scan was performed and antibiotic treatment was planned for ≥ 6 weeks prior to [18F]FDG-PET/CT. We aimed to identify patients for whom treatment was adjusted due to the results of [18F]FDG-PET/CT, and assessed concordance of [18F]FDG-PET/CT and clinical diagnosis for infected prosthetic material. Results Among 132 patients included, the original treatment plan was changed after [18F]FDG-PET/CT in 22 patients (16.7%), in the majority (n = 20) due to diagnosing or rejecting endovascular (graft) infection. Antibiotic treatment modifications were shortening in 2, iv-oral switch in 3, extension in 13, and addition of rifampicin in 4 patients. Ninety additional metastatic foci based on [18F]FDG-PET/CT results were found in 69/132 patients (52.3%). [18F]FDG-PET/CT suggested vascular graft infection in 7/14 patients who lacked clinical signs of infection, but showed no infection of prosthetic joints or osteosynthesis material in eight patients who lacked clinical signs of such an infection. Conclusion [18F]FDG-PET/CT can help refine treatment for SAB in patients with clinically suspected endovascular infection or vascular grafts, even if 6 weeks treatment is already indicated, but can be safely omitted in other patients who are clinically stable.