Proline derived guanidine catalysts forge extensive H-bonded architectures: a solution and solid state study

The preparation of a range of amino acid derived guanidine organocatalysts is reported together with their application to the Michael addition of 2-hydroxy-1,4-napthoquinone to β-nitrostyrene, achieving a maximum ee of 56%. Some insight into the mechanism was sought by using X-ray crystallography and a detailed study of the intra- and intermolecular hydrogen bonding is reported.

Catalysts assemble! We present the design and synthesis of a large family of amino acid derived guanidine organic moieties as catalysts in the solution state and building blocks towards extended H-bonded architectures upon crystallisation.     

Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity

Objective

To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them.

Methods

A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0–10‐cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within ±2 cm), higher patient rating group (PTGL exceeding MDGL by >2 cm), and lower patient rating group (PTGL less than MDGL by >2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance.

Results

The mean ± SD VAS scores for PTGL and MDGL were 4.01 ± 2.70 and 2.91 ± 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels.

Conclusion

Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the “disease experience” of patients, particularly pain and fatigue, is warranted for effective care of RA.     

Primary aldosteronism: making sense of partial data sets from failed adrenal venous sampling-suppression of adrenal aldosterone production can be used in clinical decision making

Background

It has been suggested that accurate clinical decisions may be made in patients with primary aldosteronism (PA) in the setting of failed cannulation of an adrenal vein, thereby utilizing only data from either right or left adrenal venous sampling (AVS) alone.

Selective drug delivery approaches to lesioned brain through blood brain barrier disruption

Introduction: The development of therapeutics for central nervous system (CNS) disorders is still considered a challenging area in drug development due to insufficient translocation through the blood-brain barrier (BBB). Under normal conditions, BBB restrict the penetration of more than 98% of blood-borne molecules including drugs to the CNS. However, recent research findings have proven that the nature of the BBB is altered in several neurological conditions. This complexity encourages revisiting drug delivery strategies to the CNS as this can give a wide range of opportunities for CNS drug development.

Areas covered: This review focuses on nanotechnology-based drug delivery platforms designed for selective recruitment into the lesioned brain by taking advantages of BBB disruption that is associated with certain neurological conditions.

Expert opinion: Current CNS therapeutic strategies do not fully address the pathophysiological adaptation of BBB in their design. The lack of selective delivery to the brain lesions has been the culprit behind the failure of many CNS therapeutics. This highlighted the need for smart designs of advanced drug delivery systems that take advantage of BBB structural changes in CNS diseases. Recently, promising examples have been reported in this area, however, more work is still required beyond the preclinical testing.     

Views,experiences and contributory factors related to medication errors associated with direct oral anticoagulants: a qualitative study with physicians and nurses

Background

Direct oral anticoagulants (DOACs) have become preferable for the management of thromboembolic events. Recent publications have however identified high volume of medication errors related to DOACs. There is limited literature on why and how such errors occur or happen in clinical practice.

Aim

This study aimed to explore views, experiences, contributory factors related to DOACs medication errors from the perspectives of healthcare professionals.

Method

Semi-structured interviews using online videoconferencing were conducted with physicians and nurses from tertiary care hospitals in three different regions in Saudi Arabia. Questions included views, experiences and perceived factors contributing to errors. Interviews were transcribed verbatim and were thematically analyzed using MAXQDA Analytics Pro 2020 (VERBI Software).

Results

The semi-structured interviews (n?=?34) included physicians (n?=?20) and nurses (n?=?14) until data saturation was achieved. The analysis identified five themes: Factors related to healthcare professionals (e.g. knowledge, confidence and access to guidelines); Factors related to patients (e.g. comorbidity, polypharmacy, medication review, and communication barriers); Factors related to organization (e.g. guidelines, safety culture and incidents reporting system); Factors related to the DOACs medications (e.g. lack of availability of antidotes and dosing issues); and Strategies for error prevention/mitigation (e.g. the need for professional training and routine medication review).

Conclusion

Healthcare professionals identified errors in relation to DOACs as multifactorial including their own and patient lack of knowledge, lack of clinical guidelines and organizational factors including safety culture. Medication review and reconciliation on discharge were key strategies suggested to reduce DOACs related errors. These strategies support the role of pharmacists as direct patients care providers to minimize DOACs errors.

     

COVID-19 vaccine candidates and vaccine development platforms available worldwide

The pandemic caused by the worldwide spread of the coronavirus, which first appeared in 2019, has been named coronavirus disease 19 (COVID-19). More than 4.5 million deaths have been recorded due to the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), according to the World Health Organization. COVID-19 Dashboard in September 2021. Apart from the wildtype, other variations have been successfully transmitted early in the outbreak although they were not discovered until March 2020. Modifications in the SARS-CoV-2 genetic material, such as mutation and recombination, have the ability to modify the viral life span, along with transitivity, cellular tropism, and symptom severity. Several processes are involved in introducing novel vaccines to the population, including vaccine manufacturing, preclinical studies, Food and Drug Administration permission or certification, processing, and marketing. COVID-19 vaccine candidates have been developed by a number of public and private groups employing a variety of strategies, such as RNA, DNA, protein, and viral vectored vaccines. This comprehensive review, which included the most subsequent evidence on unique features of SARS-CoV-2 and the associated morbidity and mortality, was carried out using a systematic search of recent online databases in order to generate useful knowledge about the COVID-19 updated versions and their consequences on the disease symptoms and vaccine development.     

Presurgical language mapping using event-related high-gamma activity: The Detroit procedure

A number of investigators have reported that event-related augmentation of high-gamma activity at 70–110?Hz on electrocorticography (ECoG) can localize functionally-important brain regions in children and adults who undergo epilepsy surgery. The advantages of ECoG-based language mapping over the gold-standard stimulation include: (i) lack of stimulation-induced seizures, (ii) better sensitivity of localization of language areas in young children, and (iii) shorter patient participant time. Despite its potential utility, ECoG-based language mapping is far less commonly practiced than stimulation mapping. Here, we have provided video presentations to explain, point-by-point, our own hardware setting and time–frequency analysis procedures. We also have provided standardized auditory stimuli, in multiple languages, ready to be used for ECoG-based language mapping. Finally, we discussed the technical aspects of ECoG-based mapping, including its pitfalls, to facilitate appropriate interpretation of the data.     

Perioperative Management of Women Undergoing Risk-reducing Surgery for Hereditary Breast and Ovarian Cancer

Carriers of genetic mutations that predispose to cancer syndromes are often faced with complex decisions. For women with hereditary breast and ovarian cancer in particular, the decision to undergo risk-reducing mastectomy or bilateral salpingo-oophorectomy is burdensome from a physical and psychological perspective. Although risk-reducing surgery is the most effective preventative measure in reducing a genetic mutation carrier's risk of breast or ovarian cancer, the success of these procedures requires a multidisciplinary approach that centers on careful counseling regarding the risks and benefits of risk-reducing surgery. The physical and psychological distress associated with risk-reducing surgery often makes a combined surgical approach attractive to some patients. In this review, we present the evidence surrounding the comprehensive surgical care of women with hereditary breast and ovarian cancer syndromes and evaluate the perioperative factors that influence surgical management.