Is Adherence to Imatinib Mesylate Treatment Among Patients with Chronic Myeloid Leukemia Associated with Better Clinical Outcomes in Qatar?

Background: Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients' treatments fail. Aim: This study investigates the correlation between patient adherence and failure of TKIs' treatment in a follow-up study. Methods: This is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd). The 9-item Morisky Medication Adherence Scale, medication possession ratio (MPR) calculation, and the electronic medical records are used for identifying potential factors that influence adherence. Clinical outcomes are assessed according to the European LeukemiaNet 2013 guidelines via reverse transcriptase quantitative polymerase chain reaction measurement of the level of BCR-ABL1 transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure. Results: A total of 36 CML patients (5 citizens and 31 noncitizen residents) consented to participate in the study. The overall mean MEMS score was 89. Of the 36 patients, 22 (61%) were classified as adherent (mean: 95) and 14 (39%) were classified as nonadherent (mean: 80.2). Adherent patients were significantly more likely to obtain optimal response (95%) compared to the nonadherent group (14.3%; P < 0.0001). The rate of poor adherence was as high as 39% using MEMS, which correlates with 37% treatment failure rate. The survey results show that 97% of patients increased the IM dose by themselves when they felt unwell and 31% of them took the missing IM dose when they remembered. Other factors known to influence adherence show that half of patients developed one or more side effects, 65% of patients experienced lack of funds, 13% of patients declared unavailability of the drug in the NCCCR pharmacy, and 72% of patients believed that IM would cure the disease. The MPR results reveal that 16% of patients had poor access to treatment through the hospital pharmacy. Discussion and conclusion: This is the first prospective study to evaluate CML patients' adherence and response to IM in Qatar. The high rate of treatment failure observed in Qatar is explained by poor adherence. An economic factor (unaffordable drug prices) is one of the main causes of nonadherence and efforts should be made locally to improve access to medication for cancer diseases. Other risk factors associated with poor adherence could be improved by close monitoring and dose adjustment. Monitoring risk factors for poor adherence and patient education that include direct communication between the health-care teams, doctors, nurses, pharmacists, and patients are essential components for maximizing the benefits of TKI therapy and could rectify this problem. The preliminary results show that patients' response to treatment may be directly linked to patients' adherence to treatment. However, further in-depth and specific analysis may be necessary in a larger cohort

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

Expanding the genetic heterogeneity of intellectual disability

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms

Modelling of redox flow battery electrode processes at a range of length scales : a review

In this article, the different approaches reported in the literature for modelling electrode processes in redox flow batteries (RFBs) are reviewed. RFB models vary widely in terms of computational complexity, research scalability and accuracy of predictions. Development of RFB models have been quite slow in the past, but in recent years researchers have reported on a range of modelling approaches for RFB system optimisation. Flow and transport processes, and their influence on electron transfer kinetics, play an important role in the performance of RFBs. Macro-scale modelling, typically based on a continuum approach for porous electrode modelling, have been used to investigate current distribution, to optimise cell design and to support techno-economic analyses. Microscale models have also been developed to investigate the transport properties within porous electrode materials. These microscale models exploit experimental tomographic techniques to characterise three-dimensional structures of different electrode materials. New insights into the effect of the electrode structure on transport processes are being provided from these new approaches. Modelling flow, transport, electrical and electrochemical processes within the electrode structure is a developing area of research, and there are significant variations in the model requirements for different redox systems, in particular for multiphase chemistries (gas–liquid, solid–liquid, etc.) and for aqueous and non-aqueous solvents. Further development is essential to better understand the kinetic and mass transport phenomena in the porous electrodes, and multiscale approaches are also needed to enable optimisation across the relevent length scales

Nutritional therapy and infectious diseases: a two-edged sword

The benefits and risks of nutritional therapies in the prevention and management of infectious diseases in the developed world are reviewed. There is strong evidence that early enteral feeding of patients prevents infections in a variety of traumatic and surgical illnesses. There is, however, little support for similar early feeding in medical illnesses. Parenteral nutrition increases the risk of infection when compared to enteral feeding or delayed nutrition. The use of gastric feedings appears to be as safe and effective as small bowel feedings. Dietary supplementation with glutamine appears to lower the risk of post-surgical infections and the ingestion of cranberry products has value in preventing urinary tract infections in women

Non-medical prescribing versus medical prescribing for acute and chronic disease management in primary and secondary care.

The aim of this Cochrane review was to find out if prescribing by health professionals other than doctors delivers comparable outcomes to prescribing by doctors. Cochrane researchers collected and analysed all relevant studies to answer this question and found 46 studies. Key messages With appropriate training and support, nurses and pharmacists are able to prescribe medicines as part of managing a range of conditions to achieve comparable health management outcomes to doctors. The majority of studies focus on chronic disease management in higher-income counties where there is generally a moderate-certainty of evidence supporting similar outcomes for the markers of disease in high blood pressure, diabetes, and high cholesterol. Further high-quality studies are needed in poorer countries and to better quantify differences in prescribing outcomes for adverse events, and to determine health economic outcomes. Further studies could also focus more specifically on the prescribing component of care. What was studied in the review? A number of countries allow health professionals other than doctors to prescribe medicines. This shift in roles is thought to provide improved and timely access to medicines for consumers where there are shortages of doctors or the health system is facing pressures in coping with the burden of disease. In addition, this task shift has been supported by a number of governments as a way to more appropriately use the skills of health professionals, such as nurses and pharmacists, in the care of patients. We compared the outcomes of any healthcare workers who were prescribing with a high degree of autonomy with medical prescribers in the hospital or community setting in low-, middle- and high-income countries. What are the main results of the review? This review found 45 studies where nurses and pharmacists with high levels of prescribing autonomy were compared with usual care medical prescribers. A further study compared nurse prescribing with guideline support with usual nurse prescribing care. No studies were found with other health professionals or lay prescribers. Four nurse prescribing studies were undertaken in the low- and middle-income settings of Colombia, South Africa, Uganda, and Thailand. The remainder of studies were undertaken in high-income Western countries. Forty-two studies were based in a community setting, two studies were located in hospitals, one study in the workplace, and one study in an aged care facility. Prescribing was but one part of many health-related interventions, particularly in the management of chronic disease. The review found that the outcomes for non-medical prescribers were comparable to medical prescribers for: high blood pressure (moderate-certainty of evidence); diabetes control (high-certainty of evidence); high cholesterol (moderate-certainty of evidence); adverse events (low-certainty of evidence); patients adhering to their medication regimeans (moderate-certainty of evidence); patient satisfaction with care (moderate-certainty of evidence); and health-related quality of life (moderate-certainty of evidence). Pharmacists and nurses with varying levels of undergraduate, postgraduate, and specific on-the-job training related to the disease or condition were able to deliver comparable prescribing outcomes to doctors. Non-medical prescribers frequently had medical support available to facilitate a collaborative practice model

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children &lt;18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p&lt;0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p&lt;0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p&lt;0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: a global survey, current guidelines, and expert recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial