Understanding the Role of Caseworker-Cultural Mediators in Addressing Healthcare Inequities for Patients with Limited-English Proficiency: a Qualitative Study.

BACKGROUND: Patients with limited-English proficiency (LEP) face multiple barriers to equitable healthcare. Interventions that go beyond interpretation, such as the use of bicultural-bilingual patient navigators, hold promise for addressing multi-level barriers. However, data about how to operationalize the tasks that are key to such interventions across diverse LEP communities are lacking. OBJECTIVE: Using our health system's bicultural-bilingual caseworker-cultural mediator (CCM) program serving Amharic-, Cambodian/Khmer-, Somali-, Spanish-, and Vietnamese-speaking patients, we sought to understand the key tasks that comprise the CCMs' role and how these tasks enable them to address barriers to healthcare for patients with LEP. DESIGN: Semi-structured interviews were conducted in 2019 with a purposive sample (n=23) of clinicians, CCMs, and patients with LEP or their family members from all language groups. PARTICIPANTS: Patients or family members receiving CCM services, CCMs, and clinicians who referred patients to the program. APPROACH: Content analysis consisting of a hybrid deductive-inductive qualitative approach. KEY RESULTS: Seven CCM tasks were identified: advocacy, care coordination, navigation, interpretation, education, mediation, and emotional support. Additionally, four key impacts emerged that described the ways in which these tasks enabled the CCMs to facilitate equitable care: bridging the patient, family, community, clinical team, and healthcare system; impacting knowledge of cultural issues and of the healthcare system; troubleshooting cultural barriers and problem solving; and enhancing relationship building. CONCLUSIONS: We identified several tasks and impacts that enabled CCMs to address multi-level barriers to care experienced by patients with LEP and their families across diverse cultural and linguistic groups. Findings suggest opportunities for the generalizability of programs such as ours for multiple LEP populations. Additionally, interventions having a greater scope than interpretation and including relationships with communities may be more successful in addressing barriers to equitable care at the individual, system, and community levels.

Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study.

BACKGROUND: Prevalence estimates for monoclonal gammopathy of undetermined significance (MGUS) are based on predominantly White study populations screened by serum protein electrophoresis supplemented with immunofixation electrophoresis. A prevalence of 3% is reported for MGUS in the general population of European ancestry aged 50 years or older. MGUS prevalence is two times higher in individuals of African descent or with a family history of conditions related to multiple myeloma. We aimed to evaluate the prevalence and clinical implications of monoclonal gammopathies in a high-risk US population screened by quantitative mass spectrometry. METHODS: We used quantitative matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry and EXENT-iQ software to screen for and quantify monoclonal gammopathies in serum from 7622 individuals who consented to the PROMISE screening study between Feb 26, 2019, and Nov 4, 2021, and the Mass General Brigham Biobank (MGBB) between July 28, 2010, and July 1, 2021. M-protein concentrations at the monoclonal gammopathy of indeterminate potential (MGIP) level were confirmed by liquid chromatography mass spectrometry testing. 6305 (83%; 2211 from PROMISE, 4094 from MGBB) of 7622 participants in the cohorts were at high risk for developing a monoclonal gammopathy on the basis of Black race or a family history of haematological malignancies and fell within the eligible high-risk age range (30 years or older for PROMISE cohort and 18 years or older for MGBB cohort); those over 18 years were also eligible if they had two or more family members with a blood cancer (PROMISE cohort). Participants with a plasma cell malignancy diagnosed before screening were excluded. Longitudinal clinical data were available for MGBB participants with a median follow-up time from serum sample screening of 4·5 years (IQR 2·4-6·7). The PROMISE study is registered with ClinicalTrials.gov, NCT03689595. FINDINGS: The median age at time of screening was 56·0 years (IQR 46·8-64·1). 5013 (66%) of 7622 participants were female, 2570 (34%) male, and 39 (<1%) unknown. 2439 (32%) self-identified as Black, 4986 (65%) as White, 119 (2%) as other, and 78 (1%) unknown. Using serum protein electrophoresis with immunofixation electrophoresis, the MGUS prevalence was 6% (101 of 1714) in high-risk individuals aged 50 years or older. Using mass spectrometry, we observed a total prevalence of monoclonal gammopathies of 43% (1788 of 4207) in this group. We termed monoclonal gammopathies below the clinical immunofixation electrophoresis detection level (<0·2 g/L) MGIPs, to differentiate them from those with higher concentrations, termed mass-spectrometry MGUS, which had a 13% (592 of 4207) prevalence by mass spectrometry in high-risk individuals aged 50 years or older. MGIP was predominantly of immunoglobulin M isotype, and its prevalence increased with age (19% [488 of 2564] for individuals aged <50 years, 29% [1464 of 5058] for those aged ≥50 years, and 37% [347 of 946] for those aged ≥70 years). Mass-spectrometry MGUS prevalence increased with age (5% [127 of 2564] for individuals aged <50 years, 13% [678 of 5058] for those aged ≥50 years, and 18% [173 of 946] for those aged ≥70 years) and was higher in men (314 [12%] of 2570) compared with women (485 [10%] 5013; p=0·0002), whereas MGIP prevalence did not differ significantly by gender. In those aged 50 years or older, the prevalence of mass spectrometry was significantly higher in Black participants (224 [17%] of 1356) compared with the controls (p=0·0012) but not in those with family history (368 [13%] of 2851) compared with the controls (p=0·1008). Screen-detected monoclonal gammopathies correlated with increased all-cause mortality in MGBB participants (hazard ratio 1·55, 95% CI 1·16-2·08; p=0·0035). All monoclonal gammopathies were associated with an increased likelihood of comorbidities, including myocardial infarction (odds ratio 1·60, 95% CI 1·26-2·02; p=0·00016 for MGIP-high and 1·39, 1·07-1·80; p=0·015 for mass-spectrometry MGUS). INTERPRETATION: We detected a high prevalence of monoclonal gammopathies, including age-associated MGIP, and made more precise estimates of mass-spectrometry MGUS compared with conventional gel-based methods. The use of mass spectrometry also highlighted the potential hidden clinical significance of MGIP. Our study suggests the association of monoclonal gammopathies with a variety of clinical phenotypes and decreased overall survival. FUNDING: Stand Up To Cancer Dream Team, the Multiple Myeloma Research Foundation, and National Institutes of Health.

Prevalence of type 2 diabetes mellitus complications among palestinians with T2DM.

AIMS: To assess the prevalence of microvascular and macrovascular complications of type 2 diabetes (T2DM) among Palestinians. METHODS: 1308 diagnosed T2DM attending four main Primary Health Care Clinics on the Southern West Bank of Palestine examined by a Mobile Diabetes Clinic team. All diabetes patients visiting the clinics during a one-month period for each clinic were included. Interviews, anthropometric measurements, physical examination, and laboratory tests: HbA1c, lipid profile, and kidney function tests analyzed in a central laboratory were obtained RESULTS: 1308 diabetes patients, including 839 females (64%), with a mean age of 57 years (SD=8.7), and mean diabetes duration 7.1 years(SD=6.25), participated. 95.3% presented as overweight (BMI >25kg/m2) or obese (BMI>30kg/m2) with mean BMI of 33.46 (SD=5.95). The mean HbA1c (tested in 1221 patients) was 9.21(SD=2). Only 16.1% had HbA1c <7.0%. Hypertension (blood pressure>140/90mmHg) were found in 23%, and dyslipidemia (total cholesterol>200mg/dl) was present in 37.3% of patients. 213(16.3%) had a history of the macrovascular disease (previous myocardial infarction or stroke), and 290 (25.9%) had microvascular complications. Moreover, 40 (4.9%) had advanced kidney disease with serum creatinine>1.4mg/dl. CONCLUSIONS: The present cross-sectional study shows poor glycemic control in Palestine, while blood pressure and lipids are less poorly controlled. The study emphasizes the need to optimize the glucose-lowering treatment and to implement diabetes care program that could face the challenge of high uncontrolled diabetes as well as complications of diabetes.

Quantifying impacts of short-term plasticity on neuronal information transfer.

Short-term changes in efficacy have been postulated to enhance the ability of synapses to transmit information between neurons, and within neuronal networks. Even at the level of connections between single neurons, direct confirmation of this simple conjecture has proven elusive. By combining paired-cell recordings, realistic synaptic modeling, and information theory, we provide evidence that short-term plasticity can not only improve, but also reduce information transfer between neurons. We focus on a concrete example in rat neocortex, but our results may generalize to other systems. When information is contained in the timings of individual spikes, we find that facilitation, depression, and recovery affect information transmission in proportion to their impacts upon the probability of neurotransmitter release. When information is instead conveyed by mean spike rate only, the influences of short-term plasticity critically depend on the range of spike frequencies that the target network can distinguish (its effective dynamic range). Our results suggest that to efficiently transmit information, the brain must match synaptic type, coding strategy, and network connectivity during development and behavior.

Chloroquine transport via the malaria parasite's chloroquine resistance transporter.

The emergence and spread of chloroquine-resistant Plasmodium falciparum malaria parasites has been a disaster for world health. Resistance is conferred by mutations in the Chloroquine Resistance Transporter (PfCRT), an integral membrane protein localized to the parasite's internal digestive vacuole. These mutations result in a marked reduction in the accumulation of chloroquine (CQ) by the parasite. However, the mechanism by which this occurs is unclear. We expressed both wild-type and resistant forms of PfCRT at the surface of Xenopus laevis oocytes. The resistant form of PfCRT transported CQ, whereas the wild-type protein did not. CQ transport via the mutant PfCRT was inhibited by CQ analogs and by the resistance-reverser verapamil. Thus, CQ resistance is due to direct transport of the drug via mutant PfCRT.

Functional connectivity in layer IV local excitatory circuits of rat somatosensory cortex.

There are two types of excitatory neurons within layer IV of rat somatosensory cortex: star pyramidal (SP) and spiny stellate cells (SS). We examined the intrinsic properties and connectivity between these neurons to determine differences in function. Eighty-four whole cell recordings of pairs of neurons were examined in slices of rat barrel cortex at 36 +/- 1 degrees C. Only minimal differences in intrinsic properties were found; however, differences in synaptic strength could clearly be shown. Connections between homonymous pairs (SS-SS or SP-SP) had a higher efficacy than heteronymous connections. This difference was mainly a result of quantal content. In 42 pairs, synaptic dynamics were examined. Sequences of action potentials (3-20 Hz) in the presynaptic neuron consistently caused synaptic depression (E2/E1=0.53+/-0.18). The dominant component of depression was release-independent; this depression occurred even when preceding action potentials had failed to cause a response. The release-dependence of depression was target specific; in addition, release-independence was greater for postsynaptic SPs. In a subset of connections formed only between SP and any other cell type (43%), synaptic efficacy was dependent on the presynaptic membrane potential (Vm); at -55 mV, the connections were almost silent, whereas at -85 mV, transmission was very reliable. We suggest that, within layer IV, there is stronger efficacy between homonymous than between heteronymous excitatory connections. Under dynamic conditions, the functional connectivity is shaped by synaptic efficacy at individual connections, by Vm, and by the specificity in the types of synaptic depression.

Multiple mechanisms govern the dynamics of depression at neocortical synapses of young rats.

Synaptic transmission between pairs of excitatory neurones in layers V (N= 38) or IV (N= 6) of somatosensory cortex was examined in a parasagittal slice preparation obtained from young Wistar rats (14-18 days old). A combined experimental and theoretical approach reveals two characteristics of short-term synaptic depression. Firstly, as well as a release-dependent depression, there is a release-independent component that is evident in smaller postsynaptic responses even following failure to release transmitter. Secondly, recovery from depression is activity dependent and is faster at higher input frequencies. Frequency-dependent recovery is a Ca(2+)-dependent process and does not reflect an underlying augmentation. Frequency-dependent recovery and release-independent depression are correlated, such that at those connections with a large amount of release-independent depression, recovery from depression is faster. In addition, both are more pronounced in experiments performed at physiological temperatures. Simulations demonstrate that these homeostatic properties allow the transfer of rate information at all frequencies, essentially linearizing synaptic responses at high input frequencies.