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Abstract Wound dressing development is an area of active research. Traditional dressings lack antibacterial activity, biocompatibility, and tissue regeneration. Alginate is a heavily investigated polymer employed as wound dressings and can be combined with a wide range of additives. Herein, we report the preparation of alginate gel using the crosslinking technique as potential wound dressing, with insight investigation of the influence of employing single, two, or three cross-linkers: Strontium (Sr), zinc oxide (ZnO), and gentamicin sulfate. Rheology was used to confirm the gel’s preparation, where the samples’ viscosity curves show decreased viscosity with increased shear rate, indicating pseudoplastic flow. The linear viscoelastic region shows constant G’ and G” within the sample structure. In this study, we used three gels with different mixtures of ingredients: Gels A, B, and C contain sodium alginate (1% w/v) and 0.5 mL of Sr nitrate (4% w/v). However, Gels B and C contain 0.25 mL of ZnO (0.5% w/v). Gel C also includes 0.1 mL of gentamicin (1% w/v). The study examined the effectiveness of Gel A, B, and C on wound healing, calculating the reduction of wound area after seven, 14, and 20 days of a single topical treatment. Gel A, B, and C significantly reduced wound area, while Gel B and C showed a significant reduction. The zone of inhibition was used to detect the gels’ efficacy against microorganisms. The study found zinc deposition in the liver and bone, with Gel B and C showing higher levels. The study also found significant overexpression of MIP α and MIP β in tissues and downregulation of CCL2, IL8, and TGF β, explaining wound healing with minimal scar formation. Graphical Abstract

In planar superconducting circuits, decoherence due to materials imperfections, especially two-level-system (TLS) defects at different interfaces, is a primary hurdle for advancing quantum computing and sensing applications. Traditional methods for mitigating TLS loss, such as etching oxide layers at metal and substrate interfaces, have proven to be inadequate due to the persistent challenge of oxide regrowth. In this work, we introduce a novel approach that employs molecular self-assembled monolayers (SAMs) to chemically bind at different interfaces of superconducting circuits. This technique is specifically tested here on coplanar waveguide (CPW) resonators, in which this method not only impedes oxide regrowth after surface etching but can also tailors the dielectric properties at different resonators interfaces. The deployment of SAMs results in a consistent improvement in the measured quality factors across multiple resonators, surpassing those with only oxide-etched resonators. The efficiency of our approach i3s supported by microwave measurements of multiple devices conducted at millikelvin temperatures and correlated with detailed X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) characterizations of SAM-passivated resonators. The compatibility of SAMs materials with the established fabrication techniques offers a promising route to improve the performance of superconducting quantum devices.

C19H30N2O2S, monoclinic, P21/n (no. 14), a = 6.4977(5) Å, b = 28.728(2) Å, c = 10.1806(8) Å, β = 101.549(3)°, V = 1861.9(2) Å3, Z = 4, Rgt(F) = 0.0460, wRref(F2) = 0.1213, T = 296 K.

Despite the routine use of high-fidelity patient simulation (HFPS) in health care disciplines, pharmacy residents' involvement in HFPS is limited. To evaluate pharmacy residents' self-reported confidence in their clinical skills dealing with acute medical scenarios. Three separate HFPS sessions (stroke, Advanced cardiovascular life support [ACLS], and acetaminophen poisoning) were conducted for pharmacy residents at a designated simulation center using a high-fidelity mannequin. The scenarios were facilitated by experienced physicians, nurses, and clinical pharmacists. A questionnaire that addressed 5 clinical skills was administered to the residents pre- and post-HFPS and 6 months afterward. The primary outcome was an assessment of residents' confidence in acute medical scenarios. Fourteen pharmacy residents participated (mean age of 27.7 years; 71.4% female; 57% have [greater than or equal to]3 years of work experience as a pharmacist). Around 85.6%, 78.6%, and 64.3% of the residents had encountered stroke, ACLS, and acetaminophen poisoning cases, respectively, before the HFPS. After the HFPS sessions, the residents felt significantly more confident in making decisions during an emergency in a timely manner (P = 0.006 for stroke; P = 0.02 for poisoning), providing recommendations to the health care team (P = 0.006 for stroke; P = 0.024 for ACLS), and providing optimal patient care during a stressful situation (P = 0.02 for stroke and poisoning). We found no significant difference between post-simulation and 6 months post-simulation scores in most of the domains in all scenarios, indicating residents' confidence was maintained at 6 months. HFPS is a valuable active learning tool for enhancing pharmacy residents' confidence in managing an emergency situation.

Introduction: Despite the availability of new cardio-protective oral hypoglycemic drugs, insulin is often recommended as an add-on therapy for type-2 diabetes with hemoglobin A1C (HbA1C) ≥ 9. Introducing insulin as a choice for patients with uncontrolled hyperglycemia (HbA1C≥9) has been questionably associated with cardiovascular sequelae. This study aims to examine the association between insulin use and cardiovascular effects in type-2 diabetic patients with uncontrolled hyperglycemia. Methodology: A retrospective observational cohort study was conducted to identify cardiovascular complications between the two groups (patients with HbA1C≥9% on insulin versus those with HbA1C≥9% without insulin) at King Saud University Medical City (KSUMC). Patients with type-2 diabetes whose HbA1C was ≥ 9 during the period from 2015 to 2018 and who were followed up within the hospital for at least 5 years until the end of 2022 were included in the study. Results: A total of 366 patients were included in the study; 286 patients were on insulin, while 80 patients were not. The median baseline HbA1C levels were comparable between the two groups (10.2 versus 9.8). After 5 years of follow-up, there was no significant difference between the groups (29.4 % of insulin users versus 18.8 % of non-insulin users; p = 0.065). However, the incidence of other diabetes complications, such as retinopathy, nephropathy, and neuropathy, was significantly higher among patients who were on insulin compared to those not on insulin (50.7 % versus 27.5 %; p = 0.005). Additionally, the average of the last three HbA1C readings and the overall average HbA1C readings were significantly higher among patients who were on insulin (9.67 % versus 9.07 %; p = 0.001) compared to those not on insulin (9.64 % versus 9.11 %; p = 0.005). Conclusion: Our study did not find a significant association between the use of insulin and cardiovascular complications. The association between insulin therapy and the development of other diabetes complications warrants further investigation.

Summary: Adult humans cannot regenerate the enamel-forming cell type, ameloblasts. Hence, human induced pluripotent stem cell (hiPSC)-derived ameloblasts are valuable for investigating tooth development and regeneration. Here, we present a protocol for generating three-dimensional induced early ameloblasts (ieAMs) utilizing serum-free media and growth factors. We describe steps for directing hiPSCs toward oral epithelium and then toward ameloblast fate. These cells can form suspended early ameloblast organoids. This approach is critical for understanding, treating, and promoting regeneration in diseases like amelogenesis imperfecta.For complete details on the use and execution of this protocol, please refer to Alghadeer et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Materials imperfections in planar superconducting quantum circuits - in particular, two-level-system (TLS) defects - contribute significantly to decoherence, ultimately limiting the performance of quantum computation and sensing. The identification of specific parasitic layers and their associated loss contributions has, however, proven elusive. Using a combination of x-ray photoemission spectroscopy (XPS) and analytical scanning transmission electron microscopy (STEM), we determine the thickness, chemical composition, and location of the oxides present in niobium-on-silicon coplanar-waveguide (CPW) resonators and quantify their respective contributions to the measured single-photon quality factor (Q). Using selective chemical etching, we reduce first the substrate-air oxide then the metal-air oxide thickness, dramatically reducing both TLS (δTLS) and non-TLS (δhi) losses, resulting in a median Q value over 5×106, with individual devices approaching 6×106. We find that silicon surface oxides host 70% of TLS losses, with a δTLS:δhi loss-density ratio near 11:1. In contrast, niobium surface oxides host 77% of non-TLS losses, uniformly distributed within the oxide layer, with a δTLS:δhi loss-density ratio of 3:4 for the superconducting circuits investigated in this work. Only 7% of losses come from other sources, including the niobium-silicon interface, which is sufficiently clean in our devices to allow epitaxial Nb nucleation on Si. As we mitigate surface losses through selective modification of the interface dielectrics, we arrive in a regime where TLS losses are no longer dominant, which will allow other types of losses in superconducting circuits to be investigated in more detail, including nonequilibrium quasiparticles.

Background Premature newborns are susceptible to retinopathy of prematurity (ROP), a vasoproliferative disease of the developing retinal vessels, which is a major cause of potentially avoidable blindness. Due to geographical variations in newborn care, geographic variations in the epidemiology of ROP have been observed internationally during the last several decades. There was a correlation between the severity of the condition and the number of prenatal, postnatal, and other risk factors. This study aimed to examine the incidence and risk factors associated with retinopathy of prematurity in preterm infants. Methods A retrospective review of preterm newborns evaluated for retinopathy of prematurity between January 2016 and December 2022 was carried out at King Fahd Hospital of the University (KFHU), Khobar, Saudi Arabia. Infants who fulfilled the screening criteria (GA < 34 or Birth Weight (WT) ≤ 1500 g) underwent the screening test, and the International Classification of Retinopathy of Prematurity was used to classify retinopathy of prematurity. Risk factors and demographic information regarding ROP were assessed. Statistical analysis was performed using SPSS (version 20) with a 95% confidence interval (CI). Statistical significance was set at p < 0.05. Results Among the 200 preterm neonates that were evaluated and admitted to neonatal critical care units, 37% exhibited premature retinopathy, with 46.7% of those cases being in stage 1. The development of ROP was linked to gestational age, length of mechanical ventilation, septicemia, intraventricular hemorrhage, bronchopulmonary dysplasia, respiratory distress syndrome, and septicemia, according to univariate and multivariate logistic regression analyses. Conclusion The incidence of total retinopathy in premature infants in this population was 37%. Evaluating these risk factors during the screening of high-risk premature infants will help determine the appropriate timing of examinations and treatment.

Background: The e-prescriptions service connects primary healthcare centers and hospitals to selected community pharmacies in various locations to allow easy access to the nearest pharmacy in the neighborhood, thus facilitating the process of drug dispensing. This study aims to assess patients' satisfaction towards Wasfaty services delivered by Ministry of Health healthcare centers. Materials and Methods: A cross-sectional study was conducted in Al Ahsa province in Saudi Arabia among adult patients who used Wasfaty services. An electronic Arabic questionnaire including demographic characteristics of patients and questions to assess their satisfaction level with the e-prescription “Wasfaty” service in terms of different aspects. Results: A total of 481 participants were included in the study. Females represented 53.4% of them, and 28.1% were aged 50 years or over. Overall, most of the patients (84.1%) were either satisfied or strongly satisfied with the service (4.28 ± 0.57). After controlling for confounding, patients with chronic diseases were more satisfied with the “wasfaty” service compared to those without chronic diseases. The history of chronic disease was responsible for approximately 2.4% variability of patient satisfaction (r-square = 0.024). Patients' geographic region, age, sex, and educational level were not significantly associated with their satisfaction with “wasfaty” service. Conclusion: The majority of patients, particularly those with chronic diseases, were satisfied with Wasfaty service. However, less satisfaction was observed regarding medication availability.

Over 90% of the U.S. adult population suffers from tooth structure loss due to caries. Most of the mineralized tooth structure is composed of dentin, a material produced and mineralized by ectomesenchyme derived cells known as odontoblasts. Clinicians, scientists, and the general public share the desire to regenerate this missing tooth structure. To bioengineer missing dentin, increased understanding of human tooth development is required. Here we interrogate at the single cell level the signaling interactions that guide human odontoblast and ameloblast development and which determine incisor or molar tooth germ type identity. During human odontoblast development, computational analysis predicts that early FGF and BMP activation followed by later HH signaling is crucial. Here we generate a differentiation protocol based on this sci-RNA-seq analysis to produce mature hiPSC derived odontoblasts in vitro (iOB). Further, we elucidate the critical role of FGF signaling in odontoblast maturation and its biomineralization capacity using the de novo designed FGFR1/2c isoform specific minibinder scaffolded as a C6 oligomer that acts as a pathway agonist. Using computational tools, we show on a molecular level how human molar development is delayed compared to incisors. We reveal that enamel knot development is guided by FGF and WNT in incisors and BMP and ROBO in the molars, and that incisor and molar ameloblast development is guided by FGF, EGF and BMP signaling, with tooth type specific intensity of signaling interactions. Dental ectomesenchyme derived cells are the primary source of signaling ligands responsible for both enamel knot and ameloblast development.

Background/Objectives: Owing to the growing use of immune checkpoint inhibitors (ICIs) in the treatment of cancer, a wide spectrum of toxicity has arisen among cancer patients. Yet, limited ICI toxicity-related research is currently conducted in our region. Methods: This is a retrospective observational study conducted on adult cancer patients who received at least one cycle of ICI single therapy. Toxicity profiles of different ICI monotherapies were described and compared, and their association with different risk factors was assessed. SPSS version 28 was used for statistical analyses, and p < 0.05 was considered statistically significant. Results: A total of 428 patients were treated with anti-PD1 (nivolumab [n = 221, 51.6%] and pembrolizumab [n = 126, 29.5%]) or anti-PD-L1 (atezolizumab [n = 78, 18.2%] and durvalumab [n = 3, 0.7%]). Pneumonia was the most common complication (10%), followed by acute kidney injury (AKI; 8.2%) and hepatitis (7.9%). The proportion of hepatitis cases was significantly higher among atezolizumab compared to nivolumab-, pembrolizumab-, and durvalumab-treated patients (17.95% vs. 7.7% vs. 2.4% vs. 0.0%, respectively; p < 0.001). Gastrointestinal complication (colitis) was detected in 3.3% of patients with a significant difference between treatment groups (4.5%, 1.6%, 1.3%, and 33.3% in nivolumab, pembrolizumab, atezolizumab, and durvalumab, respectively; p = 0.008). Cardiac complications occurred in 1.2% of patients with a significant difference between treatment groups (0.5% in the nivolumab, 3.8% in the atezolizumab, 33.3% in the durvalumab, and none in the pembrolizumab groups (p < 0.001)). Musculoskeletal side effects, including both arthralgia and fatigue, were the most-reported side effects by 39.5% of patients, with significantly higher arthralgia complainers only in nivolumab (7.7%) compared to other treatment groups (0%, 2.6%, and 0% in pembrolizumab, atezolizumab, and durvalumab, respectively, p = 0.007). Hepatic, cardiovascular, hematological, respiratory, renal, gastrointestinal complications, thyroid complications, and dermatological side effects were found to occur on weeks 6, 7.5, 8, 8, 10, 10, 10.5, and 12 after treatment initiation, respectively, with no significant difference between treatment groups. Despite that, hepatitis and AKI tended to occur earlier with atezolizumab (week 2, p = 0.084) and pembrolizumab (week 2, p = 0.062), respectively, compared to their comparators. The female gender and a history of hepatitis were found to increase the odds of hepatic complication with anti-PD1 or anti-PD-L1 use [OR = 2.71; 95% CI 1.07–6.85, OR = 11.14; 95% CI 3.46–35.88, respectively]. Previous exposure to cancer therapy only was found to increase the odds of developing pneumonia among the treated patients [OR = 3.08; 95% CI 1.12–8.85]. Having hematological malignancy influenced the odds of hematological complications positively (either neutropenia or thrombocytopenia) compared to solid malignancies when patients were treated with anti-PD1 or anti-PD-L1 [OR = 17.18; 95% CI 4.06–72.71]. Finally, the female gender was found to positively associate with the odds of nausea/vomiting and fatigue secondary to anti-PD1 or anti-PD-L1 administration [OR = 2.08; 95% CI 1.34–3.21, OR = 1.65; 95% CI 1.09–2.51, respectively]. On the other hand, previous exposure to cancer therapy was found to reduce the risk of having arthralgia with anti-PD1 or anti-PD-L1 administration [OR = 0.344; 95% CI 0.121–0.974]. Conclusions: Treatment with anti-PD1 or anti-PD-L1 was associated with a spectrum of complications and side effects. Several risk factors have been identified to impact their occurrence. ICI toxicities and risk factors influencing their odds should be recognized and considered in clinical practice, as this could help in individualizing therapeutics regimens and avoiding treatment interruption. [ABSTRACT FROM AUTHOR]

Background: The prevalence of gastroparesis in individuals with diabetes mellitus varies significantly across different studies. This study is aimed at estimating the prevalence of gastroparesis among diabetic patients in Riyadh, Saudi Arabia, and evaluating the association between metformin use and clinical manifestations of gastroparesis. Methods: This cross‐sectional study employed an online survey distributed via Google Forms, targeting patients at a diabetes clinic. The survey comprised three sections, including the Gastroparesis Cardinal Symptom Index (GCSI). Eligible participants were those diagnosed with either type 1 or type 2 diabetes mellitus and aged 18 or older. Results: The study included 385 participants, with the majority diagnosed with type 2 diabetes (55.6%) for over 10 years (59.5%). A significant proportion had poorly controlled blood glucose levels (56.6%) and were taking metformin (50.9%). Among gastrointestinal (GI) symptoms, "stomach fullness" was reported most frequently (53.2%), whereas "vomiting" was reported least often (17.9%). GCSI scores did not differ significantly between type 1 and type 2 diabetes patients (p = 0.88). However, patients with diabetes durations of less than 3 years, those with durations of 5–7 years controlled blood glucose levels, and those on metformin exhibited higher GCSI scores (p = 0.20, p = 0.02, and p = 0.10, respectively). Conclusion: This study identified some commonalities as well as differences in the prevalence and symptomatology of gastroparesis among diabetic patients. We observed no significant variation in GCSI scores between type 1 and type 2 diabetes. Nevertheless, higher GCSI scores were associated with shorter diabetes durations, controlled blood glucose levels, and metformin use. However, due to the small sample size and reliance on self‐reported data, one should interpret the study's findings with caution. [ABSTRACT FROM AUTHOR]

Methanol is a widely used industrial and household alcohol that poses significant health risks upon exposure. Despite its extensive use, methanol poisoning remains a critical public health concern globally, often resulting from accidental or intentional ingestion and outbreaks linked to contaminated beverages. Methanol toxicity stems from its metabolic conversion to formaldehyde and formic acid, leading to severe metabolic acidosis and multiorgan damage, including profound CNS effects and visual impairments. Epidemiological data underscore the widespread impact of methanol poisoning, with alarming case fatality rates reported in various countries. Comprehensive prevention and effective management strategies are urgently needed to address the significant morbidity and mortality associated with methanol poisoning. The clinical manifestations of methanol toxicity vary between adult and pediatric populations and between acute and chronic exposure. Adults typically present with gastrointestinal and neurological symptoms, whereas pediatric patients often exhibit more severe outcomes due to differences in metabolism and body weight. The diagnosis of methanol poisoning involves a combination of clinical evaluation, laboratory testing, and advanced diagnostic techniques. The identification of metabolic acidosis, elevated anion and osmolal gaps, and confirmation through methanol and formate levels are critical for accurate diagnosis. Timely intervention is crucial, and the management of methanol poisoning includes securing the airway, breathing, and circulation; addressing metabolic acidosis with sodium bicarbonate; administering antidotes such as fomepizole or ethanol; and administering hemodialysis, which plays a pivotal role in eliminating methanol and its toxic metabolites, especially in severe cases. The complexity of methanol poisoning necessitates a comprehensive approach encompassing early recognition, prompt intervention, and coordinated care among healthcare providers. Increased awareness, effective prevention strategies, and timely treatment protocols are essential to mitigate severe health consequences and improve patient survival and recovery. [ABSTRACT FROM AUTHOR]

Background: Burns are considered a serious health affection that leads to several consequences affecting a person both physically and emotionally. Herbal and traditional medicine have become popular remedies among patients worldwide. Aim: This study explores common practices followed in burns as first aid management. Methods: A cross-sectional study was conducted in the Eastern province of Saudi Arabia using a designed questionnaire distributed electronically through different social media. The questionnaire consisted of socio-demographic details, history of burns, causative material, and practices followed in response to burns. Results: 461 individuals have participated in this study. The commonest reason for burns was hot water or steam. The majority of the respondents (63%) had a satisfactory response to self-aid alone at home. The most common first aid options for managing burns at home were cold water alone 195 (42%), any sort of cream alone 177 (38%), or both 317 (69%). Overall, the result shows no statistically significant difference between the outcome of burn injury and the most commonly used burn aids. Conclusions: Most people use creams and water as the first-aid management of burns, while a good number of people use traditional medicine. Overall, people who receive hospital treatment after getting first aid at home give a better outcome.

Multiple pathologies and non-pathological factors can disrupt the function of the non-regenerative human salivary gland including cancer and cancer therapeutics, autoimmune diseases, infections, pharmaceutical side effects, and traumatic injury. Despite the wide range of pathologies, no therapeutic or regenerative approaches exist to address salivary gland loss, likely due to significant gaps in our understanding of salivary gland development. Moreover, identifying the tissue of origin when diagnosing salivary carcinomas requires an understanding of human fetal development. Using computational tools, we identify developmental branchpoints, a novel stem cell-like population, and key signaling pathways in the human developing salivary glands by analyzing our human fetal single-cell sequencing data. Trajectory and transcriptional analysis suggest that the earliest progenitors yield excretory duct and myoepithelial cells and a transitional population that will yield later ductal cell types. Importantly, this single-cell analysis revealed a previously undescribed population of stem cell-like cells that are derived from SD and expresses high levels of genes associated with stem cell-like function. We have observed these rare cells, not in a single niche location but dispersed within the developing duct at later developmental stages. Our studies introduce new human-specific developmental paradigms for the salivary gland and lay the groundwork for the development of translational human therapeutics.

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants’ emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2’s structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.

Anterior megalophthalmos is a rare, bilateral, nonprogressive, hereditary, congenital disorder characterized by the enlargement of all anterior segment structures of the eye, with megalocornea, iris atrophy, and zonular abnormalities. We report a case of an 8-year-old male who presented to the emergency department with a history of visual loss after a blunt ocular trauma to the left eye. The patient presented with markedly enlarged corneas and deepened anterior chambers bilaterally. Best-corrected visual acuity (BCVA) was hand motion in the left eye. An additional examination revealed multiple anterior segment abnormalities, leading to the diagnosis of megalophthalmos and lens dislocation in the anterior chamber. The patient underwent a lensectomy and anterior vitrectomy in the left eye. At six months postoperatively, the BCVA was 20/200 in the left eye. Lens dislocation in patients with megalocornea is rare. Cataract surgery in these patients requires attention to the zonular abnormalities and lens enlargement, resulting in increased rates of intraoperative and postoperative complications. Ophthalmologists should be able to diagnose this rare disorder and manage the associations and complications.

This review seeks to establish, through the recent available literature, the prevalence of therapeutic intensification delay and its sequences in poorly controlled Type 2 Diabetes Mellitus (T2DM) patients. The strategy identified studies exploring the clinical inertia and its associated factors in the treatment of patients with T2DM. A total of 25 studies meeting the pre-established quality criteria were included in this review. These studies were conducted between 2004 and 2021 and represented 575,067 patients diagnosed with T2DM. Trusted electronic bibliographic databases, including Medline, Embase, and the Cochrane Central Register of Controlled Trials, were used to collect studies by utilizing a comprehensive set of search terms to identify Medical Subject Headings (MeSH) terms. Most o the studies included in this review showed clinical inertia rates over 50% of T2DM patients. In the USA, clinical inertia ranged from 35.4% to 85.8%. In the UK, clinical inertia ranged from 22.1% to 69.1%. In Spain, clinical inertia ranged from 18.1% to 60%. In Canada, Brazil, and Thailand, clinical inertia was reported as 65.8%, 68%, and 68.4%, respectively. The highest clinical inertia was reported in the USA (85.8%). A significant number of patients with T2DM suffered from poor glycemic control for quite a long time before treatment intensification with oral antidiabetic drugs (OADs) or insulin. Barriers to treatment intensification exist at the provider, patient, and system levels. There are deficiencies pointed out by this review at specialized centers in terms of clinical inertia in the management of T2DM including in developed countries. This review shows that the earlier intensification in the T2DM treatment is appropriate to address issues around therapeutic inertia.

Background: Immune checkpoint inhibitors (ICIs) offer a new treatment approach for cancer, with an improvement in patient survival. However, it remains unclear whether their use impacts the quality of life of treated patients. This study aims to compare the health-related quality of life (HRQoL) of patients treated with different anti-PD-1 and anti-PD-L1 drugs, including several single or combination therapies. Methods: This is a prospective observational study conducted with adult cancer patients who received at least one dose of anti-PD-1 or anti-PD-L1. The HRQoL of all adult patients was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 module (QLQ-C30), version 3, Arabic version. Results: A total of 199 patients were found to be eligible for this study. Of these, 93 patients (82 on a single medication and 11 on multiple ICIs) completed the questionnaire, with a response rate of 46.7%. The majority of patients were treated with pembrolizumab (39.8%), followed by a smaller number treated with nivolumab (35.5%). Most of the patients were diagnosed with solid and advanced malignancies—88.2% (p = 0.023) and 87.1% (p = 0.021), respectively—with a significant difference between treatment groups. The median functioning score was 84.7%, with no significant difference between treatment groups (p = 0.752). Fatigue and pain were noted in >50% of patients, influencing the overall cohort's score related to these symptoms, with scores of 88.8% and 83.3%, respectively. Although a non-significant variation was found in the scores of all combined symptoms among all groups, ranging from 82.1% to 90.4% (p = 0.931), patients receiving anti-PD-1 + anti-PD-L1 tended to more frequently complain about fatigue, pain, dyspnea, and constipation and hence, exhibited the worst, yet non-significant, scores compared to those of the other groups, with p = 0.234, p = 0.79, p = 0.704, and p = 0.86, respectively. All combined groups scored 83.3% on the global health scale. Nevertheless, the nivolumab-treated patients scored 75%, which was the worst global health score compared with those of the other groups, but this score was not statistically significant (p = 0.809). Conclusions: Our findings revealed no significant difference in the impact of different ICIs on the HRQoL of cancer patients. However, a larger number of cases would be necessary to provide a robust analysis and to yield conclusive results. [ABSTRACT FROM AUTHOR]