Discontinuation Of Therapy Research Articles

Hyperkalemia and maintenance of renin-angiotensin system inhibitor therapy after initiating SGLT-2 or DPP-4 inhibitors.

Post-hoc analyses of clinical trials suggest that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) lower the risk of hyperkalemia and facilitate the use of renin-angiotensin system inhibitors (RASi) in people with type 2 diabetes. Whether this is also observed in routine care is unclear. We investigated whether SGLT-2i lowered the risk of hyperkalemia and RASi discontinuation as compared to dipeptidyl peptidase 4 inhibitors (DPP-4i). Using the target trial emulation framework, we studied adults with type 2 diabetes (T2D) who started SGLT-2i or DPP-4i in Stockholm, Sweden (2014-2021). The outcomes were incident hyperkalaemia (potassium>5.0 mmol/L), mild hyperkalemia (potassium>5-≤5.5mmol/L) and moderate to severe hyperkalemia (potassium>5.5mmol/L). Among RASi users, we studied time to RASi discontinuation through evaluation of pharmacy fills. Cox regression with inverse probability of treatment weighting was used to estimate per-protocol hazard ratios (HRs). 29 849 individuals (15 326 SGLT-2i and 14 523 DPP-4i initiators) were included (mean age 66 years, 37% women). About one third of participants in each arm discontinued treatment within a year. Compared with DPP-4i, SGLT-2i use was associated with a lower rate of hyperkalemia (HR 0.77; 95% CI: 0.64-0.93), including both mild (0.76; 0.62-0.93) and moderate/severe (0.53; 0.40-0.69) hyperkalemia events. Of 19.116 participants that used RASi at baseline, 7% discontinued therapy. Initiation of SGLT-2i vs. DPP-4i was not associated with the rate of RASi discontinuation (0.97; 0.83-1.14). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. In patients with diabetes managed in routine clinical care, the use of SGLT-2i was associated with lower rates of hyperkalemia compared with DPP-4i. Possibly because of a relatively high rate of treatment discontinuations, this was not accompanied by higher persistence on RASi therapy.

Expected Eight-Week Prenatal Versus Twelve-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-To-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-label, Randomized Controlled Trial.

The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)

MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10−5, received ≥1 year of maintenance, and were prospectively confirmed to have undetectable disease by positron emission tomography, bone marrow (BM) flow cytometry (limit of detection [LoD] 10−5), and BM clonoSEQ (LoD 10−6). BM aspirates enriched for CD138+ cells were analyzed by clonoSEQ to achieve MRD 10−7 sensitivity. We evaluated the incidence of disease resurgence and progression-free survival (PFS), stratified by 10−7 status. Forty-seven patients discontinued maintenance after a median of 36 months. Baseline MRD ≥ 10−7 was observed in 19% (9/47). The median follow-up post-discontinuation was 30 months. Disease resurgence (MRD 10 ≥ −6) occurred in 11 patients, including 5 disease progressions. One patient died from a second cancer. The estimated 3-year cumulative incidence of disease resurgence was 20% for patients with baseline MRD < 10−7 compared to 75% for MRD ≥ 10−7 (HR 7.8, 95% CI 2.2-27.6, p = 0.001). Baseline MRD ≥ 10−7 was associated with inferior PFS compared to MRD < 10−7 (HR 10.1, 95% CI 1.6–62.3; 3-year PFS 49% vs 92%). Maintenance discontinuation in patients with MM and MRD < 10−6 led to low rates of disease resurgence. MRD < 10−7 may be a superior cessation threshold, requiring further validation.

6590 Androgen Derived Hepatocellular Adenoma And Reinitiation Of Gender Affirming Hormone Therapy

Abstract Disclosure: A.L. McKenna: None. Y. Huang: None. L. Yang: None. N. Loo: None. C. Ritchie: None. A. Metcalfe: None. R. Nakhleh: None. M. Krishna: None. S. Thota-Kammili: None. J. Eleazer: None. A.Y. Chang: None. Hepatocellular adenomas (HCA) are uncommon, benign epithelial tumors of the liver. Risk factors include exogenous estrogen or androgen use, and genetic and metabolic syndromes. Management of HCA is delineated by sex assigned at birth; Observation is recommended in an HCA less than 5 cm in an individual assigned female at birth, while resection of an HCA in an individual assigned male at birth is recommended no matter the size due to risk of malignant transformation. What is not known is whether risk is different for individuals with gender incongruence on gender affirming hormone therapy (GAHT). There is limited data on the risk of HCA in this population. One case report of a transgender man who continued GAHT after diagnosis of an HCA though no follow-up information was available. We present follow-up on a transgender man assigned female at birth with multiple hemorrhagic HCA that was re-initiated on GAHT after stabilization of adenomas off GAHT. Unlike prior cases, the molecular profile showed ß-catenin negative, estrogen and androgen receptors positive. This is the first case report to our knowledge reporting detailed follow-up after restarting masculinizing GAHT after diagnosis of HCA. A 24-year-old transgender man presented to the emergency department with right upper quadrant pain. Initial labs were notable for ALT of 239 units per liter (U/L) and AST 165 U/L. Magnetic resonance imaging (MRI) of the abdomen and liver elastogram revealed multiple bilobar hepatic masses, the largest measuring 9.9 cm concerning for hemorrhagic HCA which was subsequently confirmed on liver biopsy. Immunostains were positive for estrogen and androgen receptors. The patient had no history of alcohol or illicit drug use, tattoos, or family history of liver disease. The patient had been treated with 100 mg of intramuscular testosterone cypionate weekly for the past six years for gender incongruence locally. No testosterone concentrations were available from prior to or during acute presentation. Discontinuation of hormone therapy was recommended along with conservative management with frequent MRI. Over the next 19 months, monitoring revealed improvement/resolution of the auto infarcting adenomas with the last MRI noting two stable HCA measuring 2.1 cm and 0.8 cm without new or enlarging liver lesions. Due to gender dysphoria off GAHT, reinitiation of hormone therapy with low dose AndroGel 1.62% topically was prescribed at 18 months after presentation. The patient has been monitored with labs monthly and plans to obtain MRI abdomen every three months. To date, the patient has tolerated reinitiation of therapy. This case demonstrates that patients on masculinizing GAHT who develop HCA can be conservatively managed and monitored based on pathology and that testosterone does not necessarily explain sex differences in the presentation/malignant transformation of HCA cisgender men as opposed to cisgender women. Presentation: 6/3/2024

Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.

Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC. We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. A total of 417 patients were enrolled-EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.

Squamous cell carcinoma of the cervix associated with choriocarcinomatous differentiation: a case report and review of the literature.

The morphology of the choriocarcinomatous variant of cervical squamous cell carcinoma (SCC) suggests an undifferentiated aggressive biological behaviour and a poor outcome, for which standard treatment has not been established. In addition, cases are rarely reported, with only five cases of patients with cervical carcinoma with choriocarcinoma reported previously in the literature. This current case report describes in detail a patient who was diagnosed with cervical SCC mixed with choriocarcinomatous differentiation. The case report includes details of the diagnosis, pathology, short tandem repeat genotyping, treatment and follow-up of this patient. As there is no standard treatment for this variant, the patient underwent surgery followed by radiotherapy. Unfortunately, 4 months after therapy discontinuation, radiological evaluation and laboratory tests documented a recurrence of the disease and the patient died. This report also systematically reviews the literature on cervical cancer associated with choriocarcinomatous differentiation and the five previous cases. It provides the most up-to-date summary of this disease, including its clinical manifestations, histopathology, diagnosis, treatment and prognosis.

Mevalonate in blood and muscle: Response to atorvastatin treatment and the relationship to statin intolerance in patients with coronary heart disease.

Statin-associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. Invitro studies suggest that statin-mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL-cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self-perceived muscle side effects. Furthermore, we assessed the correlation between mevalonate in blood and muscle and the relationship to statin intolerance due to muscle symptoms. We used blood plasma from a randomized crossover trial (n = 70) and muscle biopsies and plasma from a subgroup in a subsequent open intervention study (n = 26). Both studies tested atorvastatin 40 mg/day. Seven patients did not tolerate ≥3 statins throughout the follow-up and were classified as statin-intolerant. Mevalonate in blood plasma decreased during atorvastatin treatment (median difference -38%, range -77% to 43%, p < 0.001), whereas mevalonate in muscle tissue was not lowered (0.05%, range -47% to 145%). Mevalonate correlated poorly with LDL-cholesterol and atorvastatin metabolites (Spearman's rho -0.28 to 0.10). The statin-intolerant patients had a smaller reduction in circulating mevalonate compared with the tolerant patients; median difference -8.1 (-22 to 3.5) nmol/L versus -25 (-93 to 12) nmol/L, p = 0.028. A similar observation was made for LDL-cholesterol. Cutoffs based on these biomarkers classified >50% correctly as tolerant. Inhibition of the mevalonate pathway does not appear to be the mechanism underlying statin intolerance in the present study. Further studies of mevalonate as a biomarker for statin tolerance are needed to clarify the potential.

Late Relapse of Atypical Hemolytic Uremic Syndrome 36 Months after Discontinuation of Complement Blockade Therapy

Late Relapse of Atypical Hemolytic Uremic Syndrome 36 Months after Discontinuation of Complement Blockade Therapy

Development of a Novel Protocol for Successful Discontinuation of Continuous Kidney Replacement Therapy: A Pilot Study

Development of a Novel Protocol for Successful Discontinuation of Continuous Kidney Replacement Therapy: A Pilot Study

Urine Output at Continuous Kidney Replacement Therapy Discontinuation Predicts 1-Year Mortality and Kidney Outcome in Critically Ill Patients with AKI

Urine Output at Continuous Kidney Replacement Therapy Discontinuation Predicts 1-Year Mortality and Kidney Outcome in Critically Ill Patients with AKI

Gemcitabine: Association with Thrombocytosis

Gemcitabine is a pyrimidine antimetabolite that affects DNA synthesis in the S-phase of the cell cycle. It is effective against cancers such as ovarian carcinoma, non-small cell lung cancer, and pancreatic cancer. However it causes significant side effects like myelosuppression, which leads to thrombocytopenia in about 71% of patients, prompting discontinuation of therapy. Even though thrombocytopenia is common, some patients experience thrombocytosis during Gemcitabine therapy, especially in the second and third cycles, possibly due to a rebound effect. Thrombocytosis is usually asymptomatic and occasionally leads to venous thrombosis, but its clinical significance is uncertain because of conflicting studies. Further research is required to understand the physiology behind thrombocytosis in Gemcitabine-treated patients. Fluctuations between thrombocytosis and thrombocytopenia need to be closely monitored. Management for Gemcitabine-induced thrombocytosis can be improved if more comprehensive studies are undertaken to explore the role of thrombocytosis in cardiovascular events.

Back on track - digital health applications to treat back pain of rheumatic patients? Results of a qualitative interview study.

Non-specific low back pain (NLBP) is prevalent among patients with rheumatic conditions. Digital health applications (DiGAs) provide reimbursed, personalized home treatment for patients, promising to overcome limitations of traditional healthcare systems. However, the adoption and effectiveness of back pain-specific DiGAs in rheumatology are not well understood. This study aims to explore the experiences and perspectives of a diverse group of rheumatology stakeholders regarding the use of DiGAs for back pain management. Qualitative interviews and a focus group discussion were conducted with a wide range of stakeholders including rheumatic patients, rheumatologists, nurses and DiGA producers. The data were analysed using qualitative content analysis. The study included 15 interviews (10 rheumatic patients, 4 rheumatologists, 1 DiGA producer) and 1 focus group with mixed participants (n = 12). Most stakeholders valued the instant access to personalized and effective back pain treatment provided by DiGAs. Patients appreciated the flexibility and ease of use of DiGAs which can be used anywhere and anytime. Concerns were raised about insufficient guidance regarding correct execution of exercises, which was seen as potentially dangerous and unsettling for patients. Healthcare professionals (HCPs) highlighted barriers, such as the lack of reimbursement, time constraints, and inadequate DiGA-specific education as barriers to prescribing DiGAs. Additionally, poor patient onboarding often led to delays, increased skepticism, and premature discontinuation of therapy. Stakeholders emphasized the challenges of current care driven by a shortage of HCPs and generally supported usage of back pain DiGAs. Various barriers and solution approaches were identified to enhance the performance, usability, and implementation of DiGAs in rheumatology.

Exceeding the guideline-recommended maximum daily dose of opioids for long-term treatment of non-cancer pain in Germany – a large retrospective observational study

BackgroundHigh-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data.MethodsThe retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time.ResultsThe sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p < .001), receiving predominantly strong opioids (OR = 6.79, p < .001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p < .001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time.ConclusionsThe results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal.Trial registrationGerman Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021.

Propensity score matching-based analysis of the effect of corticosteroids in treating severe drug-induced liver injury

Background and aimThere is no conventional treatment for patients with severe drug-induced liver injury (DILI) except for discontinuation of liver injury drugs and symptomatic supportive therapy. Opinions on whether corticosteroids can be used to treat severe DILI are conflicting, and most of the relevant clinical studies are case reports or retrospective studies, which still need to be supported by high-level evidence-based medical studies. This study aimed to evaluate the effect and tolerance of corticosteroids in patients with severe DILI. Risk factors associated with patient failure to cure were also explored. MethodsPropensity score matching based on nearest-neighbor 1:1 matching was used to screen severe DILI patients in the corticosteroids and control groups. Severe DILI was defined as elevated serum ALT and/or ALP with TBIL≥5 ULN (5 mg/dL or 85.5 μmol/L) with or without INR ≥1.5. Patients were treated with conventional therapy combined with corticosteroids in the corticosteroids group and only conventional therapy in the control group. ResultsA total of 146 patients, 73 each in the corticosteroids and control groups, were included in this study. By analyzing the entire cohort, we found no significant difference in cure rates between patients in the corticosteroid group and control group (34.2% vs. 20.5 %, p = 0.095), and there was no significant difference in the incidence of adverse effects between the two groups (20.5% vs. 20.5 %, p = 1.000). However, TBIL decreased more in the corticosteroids group on day 7 (89.2 ± 107.6 μmol/L vs. 58.8 ± 70.7 μmol/L, p = 0.046). In subgroup analyses, patients whose TBIL remained elevated despite conventional treatment had a higher TBIL decline on day 7,14 after use of corticosteroid (99.2 ± 98.5μmol/L vs. -23.3 ± 50.4μmol/L, p < 0.001; 120 ± 119.1μmol/L vs. 61.2 ± 98.5μmol/L, p = 0.047). The cure rate of patients in the corticosteroid group was significantly higher than that of the control group (36.1 % versus 4.5 %, p = 0.016). The proportion of patients with TBIL <85.5 μmol/L was also significantly higher in the corticosteroid group than in the control group at day 7 (p = 0.016) and day 14 (p = 0.004) after treatment. In the subgroup analysis of patients with different clinical phenotypes, the causative agent was herbal, autoimmune antibody-positive and 40 % < PTA ≤ 50 % of patients, corticosteroid use did not increase the cure rate of the patients. Univariate and multifactorial analyses found corticosteroid use to be a protective factor for failure to cure in patients with severe DILI (p < 0.001, OR:0.191,95 % CI:0.072–0.470), and peak TBIL to be a risk factor (p = 0.003, OR:1.016,95 % CI:1.007–1.028). ConclusionsThe addition of corticosteroids could not increase the cure rate in patients with severe DILI, but it could rapidly reduce the patient's TBIL at an earlier stage. Corticosteroids could also promote curing in patients with elevated TBIL after conventional treatment. Corticosteroid use was a protective factor for failure to cure in patients with severe DILI and peak TBIL was a risk factor.

Systemic lupus erythematosus induced by anti-tumor necrosis factor α therapy in inflammatory rheumatic diseases: a case series.

This case series aims to characterize the development of systemic lupus erythematosus (SLE) induced by anti-tumor necrosis factor α (anti-TNFα) therapy in patients with inflammatory rheumatic diseases, namely rheumatoid arthritis (RA), spondylarthritis (SpA), and psoriatic arthritis (PsA). Patients with a diagnosis of SLE induced by anti-TNFα therapy and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2001 and 2020 were included. Demographic, clinical, and laboratory data were obtained by consulting Reuma.pt. The diagnosis of SLE induced by anti-TNFα was considered if there was a temporal relationship between the onset of anti-TNFα therapy and manifestations (clinical and immunological) in accordance with the American College of Rheumatology/European League Against Rheumatism criteria (2019). A total of 607 patients with inflammatory rheumatic diseases and six cases of SLE induced by anti-TNF-α therapy were reviewed: two patients were affected by RA, three patients by SpA, and one by PsA. All these patients had articular and constitutional symptoms that improved after discontinuation of the anti-TNFα agent. After switching to a second anti-TNFα agent, there was no recurrence of SLE over time. The development of SLE secondary to anti-TNFα agents in inflammatory rheumatic patients is rare. In this case series, all patients had a mild disease that improved after therapy discontinuation without recurrence of the disease. SLE induced by anti-TNFα should be considered in the follow-up of RA, SpA, and PsA patients.

Unveiling the psychiatric dimensions of hypopituitarism: investigating associations, challenges, and treatment strategies.

Dear Editor, Hypopituitarism is a disorder characterized by insufficient hormone production from the pituitary gland,1,2 manifesting as either pan or partial dysfunction.2 Hypopituitarism is considered a rare disorder by National Institute of Health and there is limited information on its occurrence. A study in Spain demonstrated prevalence of 45.5 cases per 100,000 people.2 Hypopituitarism can be caused by pituitary tumours, head injury, infections, radiation therapy, autoimmune conditions, and genetic abnormalities.2 Hypopituitarism occurs when about 75% of the pituitary gland is affected, causing a spectrum of clinical features from mild to severe.2 Sheehan syndrome, resulting from anterior pituitary ischaemia typically after postpartum haemorrhage, occurs in approximately 5/10,000 births in developing countries.3 Hypopituitarism diagnosis may take a decade or longer due to its diverse clinical presentations.3 As of now, the link between psychotic disorders and hypopituitarism is not completely understood.1 While a few case reports have documented a link between pituitary insufficiency and mental health issues, larger-scale studies are limited in number. Hypopituitarism raises depression and anxiety risk, especially in females and those over 18, with females having tenfold higher risk of depression than males.1 Growth hormone deficiency (GHD) is linked to cognitive impairments, and atypical depression.4 In their 1949 report, Sheehan and Summer noted that one-third of total 143 hypopituitarism patients displayed loss of drive and initiative, and disinterest in social connections.5 Acute psychosis as an initial presentation of hypopituitarism has been reported in cases involving Sheehan's syndrome, traumatic brain injury, and glucocorticoid therapy.5 A 37-year-old pregnant woman diagnosed with Sheehan syndrome exhibited neuropsychiatric symptoms, prompting early diagnosis.3 The 2010 study found that growth hormone therapy improved cognitive function and reduced depression severity in traumatic brain injury patients with GHD. However, discontinuation of therapy led to worsened cognitive function and increased psychiatric symptoms, highlighting the potential benefits of growth hormone therapy and the need for more experimental studies to confirm its effects on neurophysiological and psychiatric wellbeing.4 Adults with Childhood Onset Multiple Pituitary Hormone Deficiency have a notably lower quality of life, underscoring the importance of addressing psychosocial and psychosexual challenges in this population.6 A 60-year-old man with macroprolactinoma and hypopituitarism developed acute psychosis due to non-adherence to cabergoline, treatment with hydrocortisone, and thyroxine lead to full recovery within 48 hours.5 A 41-year-old man with osmophobia improved with sertraline transiently. Later, he was diagnosed with partial hypopituitarism with adrenocorticotropic hormone deficiency. Prednisolone supplementation significantly improved his condition.7 ---Continue

Clinical course and radiographic resolution of pneumonia in dogs treated with a shorter versus longer course of antimicrobials: a randomized, double-masked, placebo-controlled study.

To describe clinical and radiographic outcomes in dogs with uncomplicated pneumonia receiving a shorter (2-week) versus longer (4-week) duration of antimicrobial therapy. 30 client-owned dogs with radiographic evidence of pneumonia. Dogs were randomly assigned to either a 2-week course of antimicrobials followed by a 2-week course of placebo medication (2-week group) or a 4-week course of antimicrobials (4-week group). All study investigators and owners were masked to the treatment group. Dogs were reevaluated at 12 ± 2 days and again at 28 ± 2 days for a physical examination and thoracic radiography. Standard documentation at visits included owner-reported clinical signs, nurse-acquired history, the clinician's physical examination, the number of affected lung lobe segments, and the global radiographic severity scores assigned. Outcomes investigated included the persistence of clinical and radiographic signs of pneumonia. 28 dogs (93.3%) experienced complete resolution of clinical signs by the first visit, and no dogs in either group experienced relapse of clinical signs during the study period. Eighteen of 30 dogs (60%) and 25 of 30 dogs (83%) experienced complete resolution of radiographic lesions at the first and second study visits, respectively. The remaining 5 dogs (17%) had either stable (4 dogs) or continued (1 dog) improvement in radiographic lesions. Resolution of clinical and radiographic signs followed similar courses in dogs with uncomplicated pneumonia receiving a 2-week course of antimicrobials compared to a 4-week course. Clinical signs may be more useful for guiding discontinuation of antimicrobial therapy for pneumonia than radiographic signs.

Pubertal development and bone growth following discontinuation of testosterone therapy for management of delayed puberty in glucocorticoid treated young adults with duchenne muscular dystrophy

Pubertal development and bone growth following discontinuation of testosterone therapy for management of delayed puberty in glucocorticoid treated young adults with duchenne muscular dystrophy

Prognosis After Withdrawal of Cardioprotective Therapy in Patients With Improved Cancer Therapeutics–Related Cardiac Dysfunction

BackgroundThe long-term prognosis after the discontinuation of cardioprotective therapy (CPT) in patients with cancer therapeutics–related cardiac dysfunction (CTRCD) that has shown improvement remains unclear. ObjectivesThis study aims to assess the prognosis after CPT withdrawal in patients exhibiting improved CTRCD. MethodsIn this retrospective analysis of a single-center prospective cohort study, patients with improved CTRCD, defined as an increase in left ventricular ejection fraction (LVEF) ≥10 percentage points from the time of CTRCD diagnosis, were included. We analyzed their clinical outcomes, which included hospitalization for heart failure or a decrease in LVEF ≥10 percentage points within 2 years after CTRCD improvement, alongside echocardiographic changes. ResultsThe cohort comprised 134 patients with improved CTRCD. The median follow-up duration after CTRCD diagnosis was 368.3 days (Q1-Q3: 160-536 days). After improvement, 90 patients continued CPT (continued group [CG]) and 44 withdrew CPT (withdrawn group [WG]). Among patients whose baseline LVEF at CTRCD diagnosis ranged from 45% to 55%, the final mean LVEF was comparable between both groups (CG: 64.9% ± 4.4% vs WG: 62.9% ± 4.2%; P = 0.059). However, for patients with a baseline LVEF <45%, the final mean LVEF was significantly lower in the WG (CG: 53.3% ± 6.4% vs WG: 48.2% ± 6.9%; P < 0.001). The occurrence of composite major clinical events was notably higher in the WG (HR: 3.06; 95% CI: 1.51-7.73; P = 0.002). ConclusionsPatients who withdrew CPT after demonstrating improvement in CTRCD experienced worse clinical outcomes. Notably, a significant decrease in LVEF was observed after CPT withdrawal in patients with a baseline LVEF <45%.

Extent and causes of unused medications among patients in rural Ethiopia: a prospective multicenter cohort study

BackgroundMedication waste poses health, economic, and environmental challenges. However, the extent among patients living in rural areas is underexplored. This study assessed the proportion of prescribed medications remaining unused by patients living in rural areas of Ethiopia, and identify the causes thereof and disposal practices.MethodsA prospective multicenter cohort study was conducted in 5 rural health centers in Ethiopia. Patients (≥ 18 years), who received a prescription for acute or chronic medication for pick up from the outpatient pharmacy were included. After 3 months, participants received a house visit by a health employee during which a questionnaire was verbally administered to assess the quantity of unused medication, reason thereof, and disposal practices used. Data were analyzed using descriptive statistics and multivariate logistic regression to identify factors associated with presence of unused medications.ResultsIn total, 178 patients participated. Up to 136 out of 601 (22.6%) dispensed medications ended up unused, mainly antibiotics and analgesics, with an average economic value of $0.37. Of 178 patients, 72 (40.4%) ended up with unused medication, and 15 (8.4%) did not use 80% or more of the prescribed quantity. Early discontinuation of therapy was the main reason (61.8%) for patients’ ending with unused medication. Patients reported to primarily dispose of unused medication either through the toilet (43.6%), household garbage (22.7%), burning (13.6%), or returning it to the pharmacy (2.7%). Medications dispensed to be administered with two or more-unit doses at a time were more likely to remain unused (adjusted OR 1.6 [1.0–3.4]) compared to medications dispensed to be administered one-unit dose.ConclusionA substantial amount of prescribed medications remains unused by patients in rural areas, frequently not properly disposed. Interventions are needed to ensure medications are not wasted and reduce the unwanted consequences.