Initiation Of Pharmacotherapy Research Articles

ADHD Pharmacotherapy and Mortality in Individuals With ADHD

Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first. ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings). Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05). Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

2023 position statement on improving management for patients with heart failure in Aotearoa New Zealand.

Heart failure affects 1-3% of the population and remains a major public health problem, with high rates of hospitalisation and mortality. Health inequities in the incidence of heart failure have widened over the last 13 years in Aotearoa New Zealand. Urgent action is required to address the inequitable burden of heart failure among Māori and Pasifika. Regional and international heart failure guidelines now provide clear and consistent guidance on the contemporary approach to management for patients with heart failure. The purpose of this position statement is to ensure that all people in Aotearoa New Zealand have access to optimal healthcare delivery and pharmacotherapy for contemporary management of heart failure. Three main areas are addressed, including: 1) access to evidence-based pharmacotherapy for patients with heart failure, 2) the importance of early initiation and titration of pharmacotherapy, and 3) the workforce required to ensure timely delivery of heart failure therapies. Implementation of evidence-based healthcare will ensure all patients with heart failure in Aotearoa New Zealand have opportunity for substantial improvement in health.

Effectiveness of antipsychotics for managing agitated delirium in patients with advanced cancer: a secondary analysis of a multicenter prospective observational study in Japan (Phase-R)

PurposeDelirium is a common and serious comorbidity in patients with advanced cancer, necessitating effective management. Nonetheless, effective drugs for managing agitated delirium in patients with advanced cancer remain unclear in real-world settings. Thus, the present study aimed to explore an effective pharmacotherapy for this condition.MethodsWe conducted a secondary analysis of a multicenter prospective observational study in Japan. The analysis included patients with advanced cancer who presented with agitated delirium and received pharmacotherapy. Agitation was defined as a score of the Richmond Agitation-Sedation Scale for palliative care (RASS-PAL) of ≥ 1. The outcome was defined as -2 ≤ RASS-PAL ≤ 0 at 72 h after the initiation of pharmacotherapy. Multiple propensity scores were quantified using a multinomial logistic regression model, and adjusted odds ratios (ORs) were calculated for haloperidol, chlorpromazine, olanzapine, quetiapine, and risperidone.ResultsThe analysis included 271 patients with agitated delirium, and 87 (32%) showed -2 ≤ RASS-PAL ≤ 0 on day 3. The propensity score-adjusted OR of olanzapine was statistically significant (OR, 2.91; 95% confidence interval, 1.12 to 7.80; P = 0.030).ConclusionsThe findings suggest that olanzapine may effectively improve delirium agitation in patients with advanced cancer.

Patterns of metformin use and glycated haemoglobin trends among patients with newly diagnosed type 2 diabetes in Alberta, Canada.

Canadian guidelines recommend metformin as first-line therapy for incident uncomplicated type 2 diabetes and the vast majority of patients are treated accordingly. However, only 54% 65% remain on treatment after 1 year, with the highest discontinuation rates within the first 3 months. The purpose of this study was: (a) to identify individual and clinical factors associated with metformin discontinuation among patients with newly diagnosed uncomplicated type 2 diabetes in Alberta, Canada, and (b) describe glycated haemoglobin (HbA1c) trajectories in the first 12 months after initiation of pharmacotherapy, stratified by metformin usage pattern. We conducted a retrospective cohort study using linked administrative datasets from 2012 to 2017 to define a cohort of individuals with uncomplicated incident type 2 diabetes. Using logistic regression, we determined individual and clinical characteristics associated with metformin discontinuation. We categorized individuals based on patterns of metformin use and then used mean HbA1c measurements over a 12-month follow-up period to determine glycaemic trajectories for each pattern. Characteristics associated with metformin discontinuation were younger age, lower baseline HbA1c and having fewer comorbidities. Sex, income and location (urban/rural) were not significantly associated with metformin discontinuation. Individuals who continued metformin with higher adherence and individuals who discontinued metformin entirely had lowest HbA1c values at 12 months from treatment initiation. Those who changed therapy or had additional therapies added had higher HbA1c values at 12 months. Identifying characteristics associated with discontinuation of metformin and individuals' medication usage patterns provide an opportunity for targeted interventions to support patients' glycaemic management.

Factors associated with pharmacological treatment in children with attention-deficit/hyperactivity disorders: a retrospective study of a series of 77 cases in a single third-level reference Centre in Apulia region

BackgroundThe present study analysed data on children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who were referred to the ADHD reference centre of Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences in pharmacological treatment status (i.e., treatment continuation vs discontinuation) between patients.MethodsSeventy-seven children and adolescents (mean age at pharmacotherapy initiation = 9.5, standard deviation = 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used.ResultsPharmacological treatment status was examined for patients (n = 63) with at least 12 months of follow-up after the first pharmacological treatment for ADHD. After starting pharmacotherapy treatment, 77.8% (n = 49) patients were still on treatment whereas 22.2% (n = 14) discontinued it. No between group difference were observed in demographic and clinical data except for the intelligence quotient/intellectual disability and rule-breaking behavior (n = 40).ConclusionsThis study stressed the need of periodical assessments, monitoring difficulties with treatment and/or reasons for poor treatment compliance to provide individualized care.

Emergency department initiation of pharmacotherapy for alcohol use disorder: A retrospective cohort study.

Emergency department initiation of pharmacotherapy for alcohol use disorder: A retrospective cohort study.

Independent Impact of Eat, Sleep, Console Assessment on Neonatal Opioid Withdrawal Syndrome.

Compared with the Finnegan Neonatal Abstinence Scoring System (FNASS), the Eat, Sleep, Console (ESC) approach reduces pharmacotherapy and length of stay (LOS) for neonatal opioid withdrawal syndrome (NOWS) infants. The independent outcome contribution of ESC is unknown as the approach combines ESC assessment with additional management changes. Our objective was to evaluate ESC assessment's independent impact on outcomes compared with FNASS. We conducted a retrospective cohort study of in utero opioid-exposed infants ≥35 weeks gestation managed with FNASS versus ESC. Outcomes included pharmacotherapy initiation, LOS, length of pharmacotherapy, and emergency department visit/readmissions. Among 151 FNASS and 100 ESC managed infants, pharmacotherapy initiation (P = .47), LOS for all infants (P = .49), and LOS for pharmacologically treated infants (P = .68) were similar. Length of pharmacotherapy did not differ (P = .84). Emergency department evaluation/NOWS readmission was equally rare (P = .65). Using equivalent models of care, comparison of ESC and FNASS assessment tools showed no difference in NOWS outcomes.

Predicting Heterogeneity in Patient Response to Morphine Treatment for Neonatal Opioid Withdrawal Syndrome.

Infants with neonatal opioid withdrawal syndrome (NOWS) commonly receive morphine treatment to manage their withdrawal signs. However, the effectiveness of this pharmacotherapy in managing the infants' withdrawal signs varies widely. We sought to understand how information available early in infant monitoring can anticipate this treatment response, focusing on early modified Finnegan Neonatal Abstinence Scoring System (FNASS) scores, polygenic risk for opioid dependence (polygenic risk score, PRS), and drug exposure. Using k-means clustering, we divided the 213 infants in our cohort into 3 groups based on their FNASS scores in the 12 hours before and after the initiation of pharmacotherapy. We found that these groups were pairwise significantly different for risk factors, including methadone exposure, and for in-hospital outcomes, including total morphine received, length of stay, and highest FNASS score. While PRS was not predictive of receipt of treatment, PRS was pairwise significantly different between a subset of the groups. Using tree-based machine learning methods, we then constructed network graphs of the relationships between these groups, FNASS scores, PRS, drug exposures, and in-hospital outcomes. The resulting networks also showed meaningful connection between early FNASS scores and PRS, as well as between both of those and later in-hospital outcomes. These analyses present clinicians with the opportunity to better anticipate infant withdrawal progression and prepare accordingly, whether with expedited morphine treatment or non-pharmacotherapeutic alternative treatments.

Factors associated with non-initiation of osteoporosis pharmacotherapy after hip fracture: analysis of claims data in Japan

SummaryIn an analysis of claims data from a city in Japan, male patients and patients with dementia were less likely to receive osteoporosis pharmacotherapy after hip fracture. Treatment initiation rate has improved between 2014 and 2017.PurposeOlder adults with recent hip fractures are at a high risk of recurrent fractures. However, the post-fracture care gap has been reported globally. This study examines factors associated with pharmacotherapy non-initiation within 1 year after hip surgery.MethodsUsing medical and long-term care (LTC) claims, and LTC needs certification data in Tsukuba City, Japan, we identified individuals aged 65 years or older who had hip fractures with subsequent surgical procedures between October 1, 2014, and December 31, 2017. Patient (age, sex, dementia, and comorbidities) and health service–related characteristics (fiscal year, type of hospital, number of hospital beds, and admission to recovery phase rehabilitation wards) were examined. The association of these factors with non-pharmacotherapy for osteoporosis within 1 year after hip fracture using multivariable logistic models was analyzed.ResultsWe identified 275 patients with hip fractures who did not receive pharmacotherapy pre-fracture. Forty percent of them received pharmacotherapy within 1 year of post-fracture. Male sex (odds ratio (OR) = 4.49 [2.14–9.44]) and dementia (OR = 1.90 [1.03–3.52]) were associated with no pharmacotherapy, whereas later fiscal year (OR = 0.64 [0.48–0.87]) and admission to rehabilitation wards (OR = 0.25 [0.14–0.46]) were associated with pharmacotherapy initiation within 1 year of post-fracture. Comorbidities were not associated with the initiation of pharmacotherapy.ConclusionPharmacotherapy for osteoporosis was less likely to be initiated after a hip fracture in male patients and patients with dementia. These patients should be considered for pharmacotherapy because they are at high risk of recurrent fractures.

#4381 INCIDENCE AND FREQUENCIES OF HYPERKALEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RETROSPECTIVE DATABASE STUDY FROM US CLINICAL CARE

Abstract Background and Aims Hyperkalemia (HK) is associated with significant risks for premature mortality, adverse clinical outcomes, and with a potentially more rapid decline of renal function. Reported numbers on the epidemiology of HK in patients diagnosed with chronic kidney disease (CKD) vary significantly and are unclear in real-world patients across different CKD stages, eGFR and UACR strata. We aimed to evaluate the occurrence of moderate to severe hyperkalemia episodes among a large, representative sample of patients with CKD from the US between 2009 and 2020. Method Using Optum Electronic Health Records data, we included patients with CKD between January 2009 and December 2020, who had at least two qualifying estimated glomerular filtration rate (eGFR) (15-60 ml/min/1.73 m2) and/or UACR values (≥30 mg/g) between 90 and 365 days apart. The second qualifying value was considered confirmatory and set as the index date. Patients had to have 365 days of baseline activity prior to index, be ≥18 years of age, and not show any diagnoses, procedures, or lab values of kidney failure or hemodialysis or kidney transplant during baseline. A HK episode was defined in two ways, (1.) as either a combination of two elevated inpatient or outpatient serum potassium values (sK+) ≥5.5 mmol/l, not longer than 7 days apart, or (2.) a combination of one elevated sK+ and the initiation of pharmacotherapy (e.g., i.v. calcium or insulin-glucose, nebulized albuterol, potassium binders) or a diagnostic code for HK, not longer than 3 days apart. We calculated relative frequencies and incidences of HK in the overall CKD study population and specific subgroups of interest. Results 1,771,900 patients met our selection criteria for CKD, with advanced stages 3 and 4 predominantly represented (85.7% and 10.2%, respectively). The cohort consisted of 57.7% females, 83.8% Caucasian and 9.8% African American. Most common baseline comorbidities were hypertension (68.5%), hyperlipidemia (55.1%) and T2D (34.2%). 69.3% of patients were prescribed antihypertensives, 45.7% statins and 45.6% antiarrhythmics. 99.1% of patients had at least one baseline potassium measurement with values averaging 4.3 mmol/L (median, 4.3; IQR, 4.0-4.55). During an average follow up 3.9 years, 220,339 (12.4%) patients experienced at least one episode of hyperkalemia. Of those, 69.3%, 17.5%, and 13.2% showed one, two, and three or more HK episodes, respectively. Across all patients with CKD, the mean incidence rate was 3.37 (95% CI, 3.36-3.38) cases per 100 patient years (PYs). HK incidence correlated with lower eGFR and increased UACR values, with rates of 1.32 (1.25-1.39), 2.48 (2.40-2.55), 3.00 (2.99-3.01) and 8.80 (8.71-8.88) cases/100 PYs for patients with CKD stage 1, stage 2, stage 3 and stage 4, respectively. Highest incidence rates (13.81; 12.96-14.70) were found in patients with UACR values ≥3500, irrespective of their eGFR value. In addition, across disease-related subgroups, significantly higher incidence rates were found in patients co-diagnosed with T2D (5.43; 95% CI, 5.40-5.47) and HF (8.70; 8.62-8.77), and sMRA users (7.66; 7.57-7.76) at baseline. Conclusion Our contemporary findings demonstrate that HK is common in patients with CKD undergoing routine clinical care in the US, and it is notable in patients with reduced eGFR and elevated UACR. In addition, HK was more predominant in patients with T2D, heart failure or sMRA use, emphasizing a need for more routine sK+ monitoring in patients with these risk factors. Further research is needed to assess additional intrinsic risks, clinical consequences and management approaches of HK in patients with CKD to further inform clinical practice.

A152 Weight Regain Following Bariatric Surgery: Initiation of Pharmacotherapy

A152 Weight Regain Following Bariatric Surgery: Initiation of Pharmacotherapy

(121) Validation of a Digital Rigidometer for the Evaluation of Erection Hardness During In-office Rigidity Assessment in Patients with Erectile Dysfunction

Abstract Introduction The evaluation of erectile function should include the measurement of axial rigidity, since it is one of the key factors in the pathophysiology, diagnosis and treatment of ED. This assessment is usually performed following in-office intracavernosal injections of vasoactive agents during Doppler ultrasound studies, curvature assessments or simply prior to initiation of intracavernosal pharmacotherapy. In this scenario, the Erectile Hardness Score (EHS) is the most common validated tool to evaluate penile rigidity. Although highly reproducible, EHS is still based on the examiner’s subjective perspective and might eventually lead to conflicting results. Objective The aim of the present study was to assess the diagnostic accuracy of a digital rigidometer in comparison to the EHS scale to allow for a more detailed rigidity assessment using an objective measure of penile axial load. Methods First we performed a controlled experiment using a digital dynamometer coupled to a 3D-printed tip to assess the maximal load applied to the Pfizer’s Erection Hardness Meter (Figure 1). Three urologists with expertise on the management of ED performed 2 different measures of axial rigidity on each shaft corresponding to the EHS scale in order to suggest a 4-grade classification range. Then, a sample of patients was analyzed during in-office erectile tests performed by 2 different urologists using redosing protocols of vasoactive agents from February to June 2022. Coefficients of variation were calculated using analysis of variance (ANOVA) and t-test was performed to compare the interval data. ROC curves were used to estimate the diagnostic accuracy of the digital rigidometer in comparison to the EHS. P values below 0.05 were considered significant. Results Mean axial load supported by each shaft of the Pfizer’s Erection Hardness Meter was: EHS 1: 0.51 ± 0.05 Kg; EHS 2: 0.75 ± 0.05 Kg; EHS 3: 1.2 ± 0.13 Kg; and EHS 4: 2.5 ± 0.51 Kg. The following coefficients of variations were found: EHS 1: 10.1%, EHS 2: 6.85%, EHS 3: 11.2%, and EHS 4: 20.4%. Distribution of different measures is shown in Figure 2. A total of 30 men with mean age of 54.5 ± 15.5 years were included in the analysis. The mean IIEF-EFD was 16.3 ± 5.1. During erection assessment 3 (10%) presented erection EHS 2, 7 (23.3%) EHS 3, and 20 (66.6%) EHS 4. The mean dose of trimix was 0,35 ml and 50% required sympathomimetic medication for erection reversion after the procedure. The digital rigidometer had an AUC of 0.91 (95% CI 0.78-1.00, p=0.0005) to discriminate EHS>3 (Figure 3). The best cuff value for that purpose is 1.2 Kg, yielding a sensitivity of 85.7% and specificity of 88.9%. Conclusions The digital rigidometer tested in the present study appears to provide reproducible measures of axial penile rigidity that might be useful in clinical practice. It has demonstrated interesting diagnostic properties for the in-office assessment of erectile rigidity in comparison to the EHS, in which the cutoff of 1.2 Kg is the one with the best diagnostic properties. An objective measurement of penile axial rigidity can contribute to both clinical and research environment. Disclosure No

Social Vulnerability and Initiation of Pharmacotherapy for Gestational Diabetes Mellitus in a Medicaid Population.

Our study examines the association between social vulnerability index (SVI) and pharmacotherapy initiation for gestational diabetes mellitus (GDM). We studied a retrospective cohort of pregnant patients with GDM, enrolled in Tennessee Medicaid, who gave birth between 2007 and 2019. Enrollment files were linked to birth and death certificates, state hospitalization registries, and pharmacy claims. SVI, measured at the community level and determined by residential census tract, ranged from 0 to 100 (low to high vulnerability). Multivariable logistic regression assessed the association between SVI and the odds of initiating the most common pharmacotherapies for GDM-insulin, glyburide, or metformin-and adjusted for relevant covariates. SVI was modeled with restricted cubic splines to account for nonlinear associations, using the median Tennessee SVI as a reference. Secondary analysis assessed associations with the SVI subthemes. Among 33,291 patients with GDM, 21.7% (7,209) initiated pharmacotherapy during pregnancy. Patients from areas with higher SVI were more likely to be non-Hispanic Black with higher body mass index, whereas those with lower SVI were more likely to be nulliparous. Multivariable modeling demonstrated a complex nonlinear association between SVI and GDM pharmacotherapy initiation, relative to the reference. Higher SVI was associated with elevated odds of GDM pharmacotherapy initiation (e.g., odds ratio 1.11 [95% confidence interval 1.02-1.22] for SVI 80) and low to medium SVI had variable nonsignificant associations with GDM pharmacotherapy initiation, relative to the reference (lower odds of initiation for values 25-50, higher odds of initiation for values<25). Secondary analysis demonstrated a nonlinear association between subtheme 3 and the odds of GDM pharmacotherapy initiation. Social vulnerability is associated with initiation of pharmacotherapy for GDM, highlighting the possible role of social determinants of health in achieving glycemic control.

A nationwide study of initiation of antidepressant pharmacotherapy and the risk of seizures

ObjectiveThe present study aimed to examine whether antidepressant initiation increases the risk of hospitalizations and unplanned outpatient visits for seizures. Research has provided conflicting evidence as to whether antidepressant initiation causes seizures. Because epilepsy and depression are comorbid, this remains an important question, particularly in the care of those already at-risk for seizures. MethodsWe used Swedish-register data, including 658,766 antidepressant initiators and 1:1 age-, region-, and sex-matched non-initiators, ages 12–65. We used filled prescriptions to identify any antidepressant and serotonergic antidepressant and inpatient hospitalizations and unplanned outpatient (to avoid coding routine epilepsy maintenance as a seizure) visits to identify seizures, respectively. We first compared seizure visit incidence between antidepressant-initiators and matched non-users in the year following initiation from 2006 to 2013. To examine seizure risk over months pre- and post-initiation, within-individual analyses compared risk during the month one year prior to initiation with all subsequent months. We examined associations for any antidepressant and serotonergic antidepressants, as well as for any initiator and initiators with a history of seizures. ResultsOur matched-cohort results showed higher incidence of seizure visits among antidepressant users compared with non-users (e.g., adjusted incidence rate ratio [IRR]=3.14, 95% confidence interval [CI]=2.83–3.49). In within-individual analyses, the months after initiation were associated with higher incidence of seizure visits when compared with the month one year prior to initiation (e.g., one month after initiation IRR=1.96, 95%CI=1.64–2.34), but in individuals with a seizure history we observed weaker or no associations in the months after initiation (e.g., two months after initiation IRR=1.12, 95%CI=0.87–1.45). Notably, irrespective of potential seizure history, the months preceding initiation were associated with the greatest risk (e.g., one month before initiation IRR=2.86, 95% CI=2.42–3.38). ConclusionsOur findings suggest that there may be an elevated risk of seizures during antidepressant treatment, though the period of highest risk was before the initiation of antidepressants. Risk for seizure visits was lower among individuals with a history of prior seizures, which may be reassuring for the clinical care of these patients or indicate lack of treatment seeking following seizures. This study highlights the need to consider seizure risk across time; the failure to account for these dynamics may help account for discrepant findings in previous studies.

Parental Attitudes and Ideas Regarding Newborn Screening for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an inherited disease which causes premature atherosclerotic cardiovascular disease. However, less than 10% of individuals with FH have been identified. To assess parental perspectives for inclusion of FH on routine newborn screening (NBS) and to highlight potential benefits, harms, and ethical concerns. Telephone interviews of two groups were conducted: 1) parents of children diagnosed with FH, and 2) parents of children diagnosed with a genetic condition through NBS. Stratified purposive sampling was used to ensure adequate representation. The 11 telephone interviews were conducted in 30-min sessions guided by a semi-structured interview script. At the beginning of the interview, participants were educated on the NBS process and FH. The interviews were transcribed verbatim, and a thematic analysis was performed in multiple steps. All interviewees indicated that they would be interested in having their child be screened for FH on the newborn screen. Reasons supporting screening during the newborn period included knowing their child's diagnosis, the ability to screen family members for FH, incorporation of lifestyle changes, and access to preventive care. Negatives surrounding screening during the newborn period included increased stress or anxiety, knowledge, stigma, and the delay from diagnosis to initiation of pharmacotherapy for FH. While these interviewees were in favor of NBS for FH, further education of parents and clinicians is needed to ensure proper implementation. The results of this study may be useful to formulate family notification and care protocols for newborns diagnosed with FH and other diseases.

Pharmacotherapy for Depression and Anxiety in the Primary Care Setting

The prevalence of mental health disorders is rising with the coronavirus of 2019 pandemic, and millions of Americans reside in areas with mental health professional shortages. Primary care providers have an opportunity to provide care for commonly occurring mental health disorders. Using a holistic conceptualization of recovery in mental illness, this report provides evidence-based guidance for initiation, titration, and discontinuation of pharmacotherapy for mild to moderate depression and anxiety in the primary care setting. The use of measurement-based care, selection of appropriate class and agent for individual candidates, and patient education are addressed. Best practices for troubleshooting, titration, and referral are discussed.

Cronkhite-Canada syndrome: treatment responses and improved overall survival.

Cronkhite-Canada syndrome (CCS) is considered a relentlessly progressive disease with high mortality rates. Although disease understanding and treatment options have greatly improved, the prognosis from these advancements has not been well documented. This study aimed to evaluate treatment outcomes and overall survival of CCS. Seventeen patients who were diagnosed and treated over a 20-year period at Mayo Clinic (Rochester, Minnesota) were included. Data were abstracted, which included clinical and endoscopic manifestations, treatment course, and survival outcomes. The median (interquartile range) duration of follow-up was 8.3 (3.7-15.8) years. All patients received an initial prednisone dose equivalence of 30-80mg daily, and five patients required steroids at the time of the last follow-up. Twelve patients trialed thiopurine therapy, and ten patients continued with a thiopurine until the last follow-up. Fifteen patients achieved clinical complete remission, and eleven patients achieved endoscopic complete remission after pharmacotherapy initiation. Seven patients required gastrointestinal surgeries during their disease course. The 5-year overall survival was 93.3% (95% confidence interval (CI): 81.5-100%), and the 3-year relapse-free survival was 82.4% (95% CI: 66.1-100%). The prognosis and overall survival of patients with CCS have markedly improved with advancement in disease understanding and therapies. Pharmacotherapy, including corticosteroids and immunomodulators, is effective in inducing and maintaining remission, and gastrointestinal surgery is commonly needed as an adjunct for managing CCS disease complications.

Bifidobacterium pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut–Joint Axis

Early intervention in rheumatoid arthritis (RA) is critical for optimal treatment, but initiation of pharmacotherapy to prevent damage remains unsatisfactory currently. Manipulation of the gut microbiome and microbial metabolites can be effective in protecting against RA. Thus, probiotics can be utilized to explore new strategies for preventing joint damage. The aim of this study was to explore the metabolites and mechanisms by which Bifidobacterium pseudocatenulatum affects RA. Based on 16S rRNA sequencing and UPLC-MS/MS assays, we focused on bile acid (BA) metabolism. In a collagen-induced arthritis (CIA) mouse model, B. pseudocatenulatum prevented joint damage by protecting the intestinal barrier and reshaped gut microbial composition, thereby elevating bile salt hydrolase (BSH) enzyme activity and increasing the levels of unconjugated secondary BAs to suppress aberrant T-helper 1/17-type immune responses; however, these benefits were eliminated by the Takeda G protein-coupled receptor 5 (TGR5) antagonist SBI-115. The results suggested that a single bacterium, B. pseudocatenulatum, can prevent RA, indicating that prophylactic administration of probiotics may be an effective therapy.

A case of cold agglutinin disease in a bottlenose dolphin (Tursiops truncatus).

Cold agglutinin disease, one of the serological classifications of immune-mediated hemolytic anemia, is caused by the production of autoantibodies that react with erythrocytes at low temperatures. A captive bottlenose dolphin presented with regenerative and hemolytic anemia. Anticoagulated whole blood was agglutinated at room temperature (approximately 18°C), with reversal of agglutination on warming to 37°C, indicating the presence of cold agglutinin. Based on these findings, this animal was diagnosed with cold agglutinin disease. Clindamycin, doxycycline, and prednisolone were administered orally to treat the infection and immune-mediated hemolytic anemia. Anemia gradually improved after initiation of pharmacotherapy, and erythrogenesis slowed as erythroblasts disappeared and reticulocyte count decreased in peripheral blood. This represents the first report of cold agglutinin disease in a cetacean.

Transient left bundle branch block associated with very high coronary artery calcium: a case report.

Coronary artery calcium (CAC) is the measure of subclinical coronary artery atherosclerosis most strongly associated with atherosclerotic cardiovascular disease (ASCVD) risk. However, CAC is rarely reported in the inpatient setting to guide chest pain management. We present a case of very high CAC in a 64-year-old woman with hypertension, type 2 diabetes, and hyperlipidemia presenting with dyspnea. Initial electrocardiogram (ECG) demonstrated normal conduction with a heart rate of 76 beats/min, but new T-wave inversions in V1-V4 and a high-sensitivity troponin-I (hsTnI) value of 6 ng/L (normal < 6 ng/L). Repeat ECG in the emergency department showed normal sinus rhythm (heart rate of 80 beats/min); however, it subsequently demonstrated a left bundle branch block (LBBB) with a repeat hsTnI of 7 ng/L. Stress testing with pharmacologic single-photon emission computerized tomography did not show scintigraphic evidence of ischemia but noted extensive CAC and a concern for balanced ischemia. Subsequent coronary computed tomography angiography (CCTA) showed nonobstructive disease and a total Agatston CAC score of 1262. Invasive evaluation with left heart catheterization was deferred given the patient's unchanged symptoms and CCTA findings. Statin therapy was intensified and aspirin, metoprolol succinate, and antihypertension therapies were continued. Initiation of glucose-lowering therapy and lipoprotein(a) testing was strongly recommended on follow-up. Our case suggests that CAC ⩾ 1000 may be incidentally associated with transient LBBB during the workup of coronary artery disease. Here, we specifically show that functional testing that incorporates measurement of CAC burden can help to improve ASCVD-preventive pharmacotherapy initiation and intensification beyond the identification of obstructive disease alone.