Search

Carfilzomib is an active and commonly used treatment in patients with multiple myeloma (MM). Using the Canadian Myeloma Research Group Database, we performed a retrospective observational study of patients treated with carfilzomib for relapse of MM in a real-world setting in Canada between years 2007 and 2020. A total of 445 patients were included in this study: the doublet (Kd/p

Pontocerebellar hypoplasia (PCH) type 12 is a rare, perinatal lethal neurodegenerative genetic disorder caused by biallelic mutations in the COASY gene. Herein, we describe the clinical and neuroradiological profile of nine affected fetuses/neonates from five families identified with a common COASY: c.1486-3CG biallelic variant. Four of the five families were identified after data reanalysis of unresolved, severe PCH like phenotype and the fifth family through collaboration. The common antenatal phenotype was cerebellar hypoplasia. Microcephaly, arthrogryposis, and intrauterine growth restriction were the shared postnatal findings. The neurological manifestations included seizures, poor sucking, and spasticity. Novel findings of corpus callosum agenesis, simplified gyral pattern, normal sized pons, optic neuropathy, and a small thorax are reported in this series. The allele frequency of the COASY: c.1486-3CG variant was 0.62% in the available Asian Indian database. We describe this as a possible common Indian origin variant. To the best of our knowledge, this is the largest PCH12 series reported.

To determine nurses' perceived barriers to the delivery of person-centred care to complex patients with multiple chronic conditions in acute care settings.Complex patients have multiple physical and mental health problems, and their life is also greatly affected by sociocultural and economic determinants of health. These patients require person-centred care, but nurses often find it challenging to provide effective care to these patients due to their complex health needs.A descriptive qualitative design was used. The COREQ guidelines were followed for reporting.Semi-structured interviews were conducted with a purposive sample of 19 nurses in two hospitals. Data were analysed using deductive thematic analysis guided by the Theoretical Domains Framework, which entails 14 domains about factors affecting behaviours.The key barriers were identified under environmental context and resources, social influences, emotions, knowledge and skills domains. Deep-rooted social issues delay patients' health-seeking and nurses' abilities to understand patients' needs and discern appropriate care. Interpersonal hostility influenced nurse-patient-families interactions, and doctor-nurses conflicts affected collaborative efforts towards optimal care.Nurses' perceived barriers to care were intertwined with the deep-rooted social and cultural beliefs about nurses' image, patients' expectations and families' preference for home remedies over specialised nursing care. These barriers to person-centred care demonstrate an intricate interplay of personal, social and organisational issues and power struggles. Multifaceted implementation strategies targeting environmental context and resources, social influences, emotions, knowledge and skills domains may be beneficial to enable nurses to provide better person-centred care to complex patients.Designing implementation facilitation teams, organising person-centred care grand rounds, and allocation of stress management resources to address hostility, social-cultural influences, and organisational barriers is essential. Nurses could focus on their self-awareness and collaborative skills to address emotional and interprofessional conflicts.

Occurrences of chlorinated and brominated polycyclic aromatic hydrocarbons (ClPAHs and BrPAHs, respectively) in fine aerosol particulate matter

INTRODUCTION Hemophilia B is associated with molecular heterogeneity, with more than 1200 unique variants in the F9 gene. We hereby describe the mutational spectrum of severe hemophilia B patients presenting in a tertiary-care center in India. METHOD DNA was extracted from peripheral blood samples of 35 diagnosed severe hemophilia B patients belonging to 32 families, and were subjected to Sanger sequencing. Determination of the effect of novel variants on the protein structure and correlation between genotype and phenotype was attempted using in-silico tools. RESULTS Twenty-seven different mutations were detected in 30 probands, including 20 known and 7 novel variants. Also, we found one suspected case of whole gene deletion. The serine peptidase domain harbored most of the variants (48.1%). Inhibitory antibodies were found in two patients. CONCLUSIONS This study provides a comprehensive mutational spectrum and mutation screening strategy by Sanger sequencing of F9 gene in severe hemophilia B patients, in a resource-constraint setting.

AIM The aim of this study was to design, implement, and to evaluate the success of an oral health care programme specially designed for visually impaired children over a 12-month period. DESIGN A structured questionnaire collected information regarding oral health knowledge and practices of the study population. A specially designed oral health education programme was conducted for the children and their teachers and reinforced after 1, 3, 6, 9, and 12 months. The oral health status of the children was assessed and scored at baseline examination and after each follow-up visit. Independent t-test and paired t-test were used for comparison of scores. Spearman's correlation test was used to measure the correlation between knowledge and practices scores with oral hygiene status. RESULTS The study population (5-16 years) had good knowledge about oral health which, however, did not translate into everyday practices. The overall oral hygiene scores declined from 2.06 ± 1.20 at the preliminary examination to 1.24 ± 0.79 at the end of 12 months (p

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm mostly originates from pleura, but rarely from other parts of the body including pericardium. We report a case of a 44-year-old woman with dyspnea and intermittent edema in whom a large intrapericardial mass was discovered by echocardiography. Computed tomography (CT) revealed a focal pericardial calcification in right AV grove with pressure on right ventricle and right atrial, with no connection to cardiac chambers. Histopathological findings after complete resection of the mass revealed fibroconnective tissue with heavy calcification and no evidence of inflammation or malignancy. We reviewed the literature on pericardial solitary fibrous tumors up to 2020.

Objectives To understand the impact of therapy sequencing on progression-free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low-dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting. Methods We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second-line therapy, 575 patients were included. Results Patients treated with LM had statistically similar 2nd PFS when re-exposed to lenalidomide in second-line therapy compared to those receiving non-lenalidomide-containing regimens (10.2 vs 14.0 months, P =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P =.004). Patients treated with LM also demonstrated deeper responses to second-line therapy than their non-LM counterparts. Conclusion Our data suggest that patients progressing on LM who receive lenalidomide-containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non-lenalidomide-containing second-line regimens. Identification of patients mostly likely to benefit from further lenalidomide-containing therapy is paramount.

Peroxisome biogenesis disorders (PBDs) are a group of autosomal recessive disorders caused due to impaired peroxisome assembly affecting the formation of functional peroxisomes. PBDs are caused by a mutation in PEX gene family resulting in disease manifestation with extreme variability ranging from the onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults. Disease causing variations in PEX7 is known to cause severe rhizomelic chondrodysplasia punctata type 1 and PBD 9B, an allelic disorder resulting in a milder phenotype, often indistinguishable from that of classic Refsum disease. This case report highlights the variability of PEX7 related phenotypes and suggests that other than RCDP1 and late onset phenotype similar to Refsum disease, some cases present with cataract and neurodevelopmetal abnormalities during childhood without chondrodysplasia or rhizomelia. This report also underlines the importance of considering PBD 9B in children presenting with neurodevelopmental abnormalities especially if they have congenital cataract.

Bortezomib-containing regimens (BCRs) represented standard, first-line therapy for transplant-ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low-dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low-dose dexamethasone (Ld) using the Canadian Myeloma Research Group database. Of 1156 TIMM patients evaluated, 82% received bortezomib combinations while 18% received Ld. Median progression-free survival (PFS) was 21·0, 21·1, 13·2 and 28·5 months (P = 0·0002) and median overall survival (OS) was 52·0, 63·6, 30·8 and 65·7 months (P < 0·0001) in the CyBorD/P, VMP, VD/P and Ld groups respectively. There was no significant difference in PFS and OS between the two triplet bortezomib regimens (VMP and CyBorD/P). Ld was associated with a longer PFS but not a significantly superior OS to date. Outcomes with the bortezomib-steroid doublet were inferior (VD/P). However, multivariable analysis identified features related to disease biology as the most important prognostic factors for PFS and OS. Such factors, as well as those affecting the physician's choice of regimen, are likely to influence the results observed with different regimens. This study demonstrated real-world outcomes in TIMM similar to those reported in clinical trials.

Aims The aim of this study is to investigate the association between adherence to beta‐blocker treatment after a first acute myocardial infarction (AMI) and long‐term risk of heart failure (HF) and death. Methods and results All patients admitted for a first AMI included in the nationwide Swedish web‐system for enhancement and development of evidence‐based care in heart disease evaluated according to recommended therapies register between 2005 and 2010 were eligible (n = 71 638). After exclusion of patients who died in‐hospital, patients with previous HF, patients with unknown left ventricular ejection fraction (EF), and patients who died during the first year after the index event, 38 608 patients remained in the final analysis. Adherence to prescribed beta‐blockers was determined for 1 year after the index event using the national registry for prescribed drugs and was measured as proportion of days covered, the ratio between the numbers of days covered by the dispensed prescriptions and number of days in the period. As customary, a threshold level for proportion of days covered ≥80% was used to classify patients as adherent or non‐adherent. At discharge 90.6% (n = 36 869) of all patients were prescribed a beta‐blocker. Among 38 608 1 year survivors, 31.1% (n = 12 013) were non‐adherent to beta‐blockers. Patients with reduced EF with and without HF were more likely to remain adherent to beta‐blockers at 1‐year compared with patients with normal EF without HF (NEF). Being married/cohabiting and having higher income level, hypertension, ST‐elevation MI, and percutaneous coronary intervention were associated with better adherence. Adherence was independently associated with lower all‐cause mortality [hazard ratio (HR) 0.77, 95% confidence interval [CI] 0.71–0.84] and a lower risk for the composite of HF readmission/death, (HR 0.83, 95% CI 0.78–0.89, P value

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation of the dermis and subcutaneous tissue. Usually, RMH occurs in the midline of the face and neck region. We described a case of RMH presenting as telangiectasia in a 57-year-old man with a history of pityriasis lichenoides chronicus. Histopathological examination revealed a subepidermal haphazard proliferation of striated muscular tissue perpendicular to the epidermis. These bundles of striated muscular tissue were admixed with adnexal structures. The diagnosis was consistent with RMH. RMH is more common in the neonatal period or in young children, but we should consider it as part of a differential diagnosis in older adults as well.

Designing effective settings for performance measures (e.g., fill rate) of a service-level agreement (SLA) is challenging. This challenge is intensified when a firm adopts the pooling inventory model to allocate inventory/capacity to multiple buyers. Each buyer has its own service-level contract outlining the required service level, the penalty structures, and the performance review period (PRP) length, which might not be the same as other buyers. This means the supplier requires an effective resource allocation policy whereby the different requirements of multiple buyers are integrated into a pooling model and capacities/inventories are allocated in the most effective way. Given a base-stock replenishment policy and finite time horizon PRP, in this study we propose two new (anticipative) allocation policies—foresight linear programming (FLP) and two-stage stochastic (TS)—and compare them with existing allocation policies. These allocation policies are developed for different penalty structures of linear, lump-sum, hybrid, and no-penalty settings. Results show that suppliers benefit from longer PRPs if linear or hybrid penalty structures are employed. We also find that when the length of PRP of buyers is not identical, TS is the recommending policy. Further, results provide a guideline for selecting the best resource allocation policy under various SLA terms, in particular, where buyers' PRP lengths are not identical.

The compounds were tested against panel of three Gram-positive, viz. Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and three Gram-negative bacterial strains viz. Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris where they showed significant to moderate antibacterial activity. The compound also showed considerable antibiofilm activity against S. aureus and B. subtilis. The most potent compounds 7l and 7m found bacteriostatic in time-kill assay via inhibition of DNA gyrase enzyme and interacting with Glu58, Val130, Ile175 and Ile186 via numerous H-bonds as revealed by docking. In S. aureus-induced murine infection model, compound 7m showed dose-dependent reduction of viability of bacteria with maximum activity in 25 mg/kg treated group. The antifungal activity against human fungal pathogens was also estimated, where these compounds showed considerable inhibitory activity as compared to standard. The metabolic liability of compound 7m was determined using RS-Predictor and MetaPrint 2D React. The molecules were proved as effective antibacterial agent via inhibition of DNA gyrase as a mechanism together with significant antifungal activity.