Patient and Provider Experience with Artificial Intelligence Screening Technology for Diabetic Retinopathy in a Rural Primary Care Setting

Introduction: The development of autonomous artificial intelligence for interpreting diabetic retinopathy (DR) images has allowed for point-of-care testing in the primary care setting. This study describes patient and provider experiences and perceptions of the artificial intelligence DR screening technology called EyeArt by EyeNuk during implementation of the tool at Western Maine Primary Care in Norway, Maine. Methods: This non-randomized, single-center, prospective observational study surveyed 102 patients and 13 primary care providers on their experience of the new screening intervention. Results: All surveyed providers agreed that the new screening tool would improve access and annual screening rates. Some providers also identified initial challenges in incorporating the tool into the primary care visit (31%). Patients expressed a favorable view of the service, sharing an openness to being screened more regularly (75%) and a desire to have screenings performed at Western Maine Primary Care going forward (81%). Discussion: Patients were generally favorable about their experience with the new DR screening technology. Providers indicated challenges due to the limited availability of trained medical assistant photographers during the initial implementation of DR screening, as well as timing issues in coordinating screening with regular office appointments. Conclusions: This study supports further investigation of this technology in primary care, particularly in areas with challenges to care access. The potential benefits of this innovative tool in caring for people with diabetes includes improving access to retinopathy screenings and supporting wider detection of vision-threatening retinopathy

Improving Colorectal Cancer Screening Decision Making Processes

Introduction: Although shared decision making is recommended for cancer screening, it is not routinely completed in practice because of time constraints. We evaluated a process for improving decision making about colorectal cancer (CRC) screening using mailed decision aids (DA) with follow-up telephone support in primary care practices. Methods: We identified patients aged 50-75 who were not up to date with CRC screening in three primary care practices. DA were distributed via mail with telephone follow-up to eligible patients, and charts were reviewed six months later for CRC screening completion. Results: Among 1,064 eligible patients who received the mailed DA, 513 (48.2%) were reached by phone. During the six months after the intervention, 148/1064 (13.9%) patients were screened for CRC (4.8% underwent FIT, 9.1% underwent colonoscopy). Younger patients (aged 50-54) had higher rates of any screening (32.4%) compared with all other age groups (range 12.8%-19.6%), p=0.026, while Medicaid patients had the lowest rates of screening (4.0%), and insured patients had the highest rates (45.3%), p=0.003. Overall, 113/513 (22.0%) who were reached by phone went on to complete screening within 6 months, compared with 35/551 (6.4%) of patients who were not reached by phone (p Conclusion: A standard process for identifying patients unscreened for CRC and DA distribution via mail with telephone decision support modestly increased CRC screening and is consistent with the goal of providing preference-sensitive care and informed decision making. Improving care processes to include decision support outside of office visits is possible in primary care practices

Pain, depression and quality of life in adults with MOG-antibody associated disease

BACKGROUND AND PURPOSE: Myelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) is an inflammatory autoimmune condition of the CNS. However, data on pain and depression have remained scarce. The aim of this study was to assess features of chronic pain and depression as well as their impact on health-related quality of life (hr-QoL) in MOGAD. METHODS: Patients with MOGAD were identified in the Neuromyelitis Optica Study Group (NEMOS) registry. Data were acquired by a questionnaire, including clinical, demographic, pain (PainDetect, Brief Pain Inventory - short form, McGill Pain Questionnaire - short form), depression (Beck Depression Inventory-II), and hr-QoL (Short Form-36 Health Survey) items. RESULTS: Twenty-two of 43 patients suffered from MOGAD-related pain (11 nociceptive, 8 definite neuropathic, 3 possible neuropathic) and 18 from depression. Patients with neuropathic pain had highest pain intensity and most profound ADL impairment. Fifteen patients reported spasticity-associated pain, including four with short-lasting painful tonic spasms. Later disease onset, profound physical impairment and depression were associated with chronic pain. Physical QoL was more affected in pain-sufferers (p<0.001) than in pain-free patients, being most severely reduced by neuropathic pain (p=0.016). Pain severity, visual impairment, and gait impairment independently predicted lower physical QoL. Depression was the only factor reducing mental QoL. Twelve patients received pain medication, still suffering from moderate pain (pain severity 4.6±2.3). Only four out of ten patients with moderate to severe depression took antidepressants. CONCLUSIONS: Being highly prevalent, pain and depression strongly affect QoL and ADL in MOGAD. Both conditions remain insufficiently controlled in real-life clinical practice

Obstetric and neonatal outcomes after natural versus artificial cycle frozen embryo transfer and the role of luteal phase support: a systematic review and meta-analysis

BACKGROUND: The number of frozen embryo transfers (FET) has increased dramatically over the past decade. Based on current evidence, there is no difference in pregnancy rates when natural cycle FET (NC-FET) is compared to artificial cycle FET (AC-FET) in subfertile women. However, NC-FET seems to be associated with lower risk of adverse obstetric and neonatal outcomes compared with AC-FET cycles. Currently, there is no consensus about whether NC-FET needs to be combined with luteal phase support (LPS) or not. The question of how to prepare the endometrium for FET has now gained even more importance and taken the dimension of safety into account as it should not simply be reduced to the basic question of effectiveness. OBJECTIVE AND RATIONALE: The objective of this project was to determine whether NC-FET, with or without LPS, decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET. SEARCH METHODS: A systematic review and meta-analysis was carried out. A literature search was performed using the following databases: CINAHL, EMBASE, and MEDLINE from inception to 10 October 2022. Observational studies, including cohort studies, and registries comparing obstetric and neonatal outcomes between singleton pregnancies after NC-FET and those after AC-FET were sought. Risk of bias was assessed using the ROBINS-I tool. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. We calculated pooled odds ratios (ORs), pooled risk differences (RDs), pooled adjusted ORs, and prevalence estimates with 95% CI using a random effect model, while heterogeneity was assessed by the I2. OUTCOMES: The conducted search identified 2436 studies, 890 duplicates were removed and 1546 studies were screened. Thirty studies (NC-FET n = 56 445; AC-FET n = 57 231) were included, 19 of which used LPS in NC-FET. Birthweight was lower following NC-FET versus AC-FET (mean difference 26.35 g; 95% CI 11.61-41.08, I2 = 63%). Furthermore NC-FET compared to AC-FET resulted in a lower risk of large for gestational age (OR 0.88, 95% 0.83-0.94, I2 = 54%), macrosomia (OR 0.81; 95% CI 0.71-0.93, I2 = 68%), low birthweight (OR 0.81, 95% CI 0.77-0.85, I2 = 41%), early pregnancy loss (OR 0.73; 95% CI 0.61-0.86, I2 = 70%), preterm birth (OR 0.80; 95% CI 0.75-0.85, I2 = 20%), very preterm birth (OR 0.66, 95% CI 0.53-0.84, I2 = 0%), hypertensive disorders of pregnancy (OR 0.60, 95% CI 0.50-0.65, I2 = 61%), pre-eclampsia (OR 0.50; 95% CI 0.42-0.60, I2 = 44%), placenta previa (OR 0.84, 95% CI 0.73-0.97, I2 = 0%), and postpartum hemorrhage (OR 0.43; 95% CI 0.38-0.48, I2 = 53%). Stratified analyses on LPS use in NC-FET suggested that, compared to AC-FET, NC-FET with LPS decreased preterm birth risk, while NC-FET without LPS did not (OR 0.75, 95% CI 0.70-0.81). LPS use did not modify the other outcomes. Heterogeneity varied from low to high, while quality of the evidence was very low to moderate. WIDER IMPLICATIONS: This study confirms that NC-FET decreases the risk of adverse obstetric and neonatal outcomes compared with AC-FET. We estimate that for each adverse outcome, use of NC-FET may prevent 4 to 22 cases per 1000 women. Consequently, NC-FET should be the preferred treatment in women with ovulatory cycles undergoing FET. Based on very low quality of evidence, the risk of preterm birth be decreased when LPS is used in NC-FET compared to AC-FET. However, because of many uncertainties-the major being the debate about efficacy of the use of LPS-future research is needed on efficacy and safety of LPS and no recommendation can be made about the use of LPS

Cladribine Exposure Results in a Sustained Modulation of the Cytokine Response in Human Peripheral Blood Mononuclear Cells

<div><p>Background and Objectives</p><p>Cladribine is a cytotoxic drug which ameliorates the clinical course of relapsing-remitting multiple sclerosis. In addition to cytotoxicity, the mode of action may include immunomodulatory mechanisms. This <i>in vitro</i> study was designed to investigate cladribine’s effects on cell function after the removal of cladribine to distinguish cytotoxic versus immunomodulatory effects.</p><p>Methods</p><p>Cells were incubated in the absence or presence of cladribine (1×10^-8 M to 1×10^-5 M) for 72 h. Cladribine was removed from the cell culture and surviving peripheral blood mononuclear cells were cultured up to 58 days to determine the immunomodulatory effects of cladribine on cell function (e.g., proliferation and cytokine release).</p><p>Results</p><p>In the long-term, brief cladribine exposure did not impair the proliferation of surviving peripheral blood mononuclear cells. However, it induced an anti-inflammatory shift in the cytokine milieu with significantly enhanced release of IL-4 (Days 9 and 44, p<0.01; Day 58, p<0.05) and IL-5 (Day 9, p<0.01), resulting in an increased IL-4/INF-gamma ratio (Days 9 and 44, p<0.01; Day 58, p<0.05). Additionally, a trend towards an increased IL-10 production was observed. No changes were found in the production of IFN-gamma, TNF-alpha, IL-6, IL-8, IL-17A, IL-23 or NGF-beta.</p><p>Conclusions</p><p><i>In vitro</i> cladribine exposure induces a sustained anti-inflammatory shift in the cytokine profile of surviving peripheral blood mononuclear cells. This immunomodulatory action might contribute to cladribine’s beneficial effects in the treatment of multiple sclerosis.</p></div

<i>In vitro</i> effects of cladribine on cell survival of PBMCs and proliferation of PBMCs, CD4⁺ cells and CD8⁺ cells Human immune cells were stimulated with anti-CD3/anti-CD28 antibodies (a, n = 4; c, n = 6) or PHA (b, n = 4; d, n = 3) in the absence or presence of cladribine (1×10⁻⁸ M to 1×10⁻⁵ M) for 72 h.

<p>Determination of cell survival in PBMCs (a, b) was performed by standard trypan blue exclusion method. Proliferation was determined separately in PBMC, CD4⁺ cells and CD8⁺ cells (c, d) by the incorporation of tritiated thymidine. Stimulation indices were calculated as the ratios of the counts per minute of stimulated samples to unstimulated and untreated samples. Data are depicted as mean + standard deviation (SD).</p

<i>In vitro</i> effects of initial cladribine treatment on cytokine secretion of PBMCs restimulated at Days 9, 16, 23, 30, 44 and 58 after transfer into cladribine-free medium.

<p>PBMCs from healthy blood donors (n = 5) were incubated in the absence or presence of cladribine. (1×10⁻⁸ M to 5×10⁻⁷ M) for 72 h. Then cells were washed three times and transferred into cladribine-free medium. Cells were restimulated with anti-CD3/anti-CD28 antibodies for 48 h at days 9, 16, 23, 30, 44 and 58; supernatants were collected and cytokine concentrations were determined. Data are depicted as box plot diagrams. Whiskers represent maximum and minimum values. The IL-4/IFN-γ ratio was defined as the ratio of IL-4 (pg/ml) to IFN-γ (pg/ml). *: p<0.05; **: p<0.01.</p

<i>In vitro</i> effects of initial cladribine treatment on cytokine secretion of PBMCs restimulated at Days 9, 16, 23 and 30 after transfer into cladribine-free medium.

<p><b>PBMCs from healthy blood donors (n = 4) were incubated in the absence or presence of cladribine</b>. (1×10⁻⁸ M to 5×10⁻⁷ M) for 72 h. Then cells were washed three times and transferred into cladribine-free medium. Cells were restimulated with PHA for 48 h at days 9, 16, 23 and 30; supernatants were collected and cytokine were determined. Data are depicted as box plot diagrams. Whiskers represent maximum and minimum values. The IL-4/IFN-γ ratio was defined as the ratio of IL-4 (pg/ml) to IFN-γ (pg/ml). *: p<0.05; **: p<0.01.</p