Longer Duration Of Therapy Research Articles

Pattern of physical growth and pubertal changes in adolescent girls with Systemic Lupus Erythematosus

ABSTRACT Aims: To study the pattern of physical growth and pubertal changes in adolescent girls with Systemic Lupus Erythematosus (SLE). Methods and Material: Weight, height, BMI, waist and hip circumference among 50 adolescent SLE girls (aged 8–17 years) were cross-sectionally studied using standardized techniques and instruments. Breast development stage, presence or absence of pubic and axillary hair and age of attainment of menarche were also noted. Results: With the advancement of age, weight and height of SLE girls increased but they were lighter and shorter compared to normal Indian peers. 18.4% of study girls were short-statured while only one participant was underweight. As per mid-parental height, 34.3% were predicted to have shorter final heights. BMI demonstrated an inconsistent trend with 12.3% and 9.2% being obese and overweight, respectively. Interestingly, 10.7% of SLE girls were at risk of metabolic syndrome (waist circumference >70th centile). About 50% of study girls had attained menarche (mean age: 13.04 ± 1.38 years). Appearance of pubic and axillary hair occurred around 1 year later than attainment of menarche. 33.80% of study subjects were in prepubertal stage of breast development and rest 66.20% were in advanced stages of breast development. SLE girls who had younger age at diagnosis and longer duration of therapy had significant delay in breast development and attainment of menarche. Conclusions: SLE girls show delayed growth and pubertal attainments compared to their normal Indian and Western counterparts. The data presented will provide an understanding of the auxological dynamics and pattern of pubertal changes among adolescent girls with SLE living in north-western India.

Depletion of essential mycobacterial gene glmM reduces pathogen survival and induces host-protective immune responses against tuberculosis

The limitations of TB treatment are the long duration and immune-dampening effects of anti-tuberculosis therapy. The Cell wall plays a crucial role in survival and virulence; hence, enzymes involved in its biosynthesis are good therapeutic targets. Here, we identify Mycobacterium tuberculosis (Mtb) GlmM, (GlmMMtb) engaged in the UDP-GlcNAc synthesis pathway as an essential enzyme. We generated a conditional knockdown strain, Rv-glmMkD using the CRISPR interference-mediated gene silencing approach. Depletion of GlmMMtb affects the morphology and thickness of the cell wall. The Rv-glmMkD strain attenuated Mtb survival in vitro, in the host macrophages (ex vivo), and in a murine mice infection model (in vivo). Results suggest that the depletion of GlmMMtb induces M1 macrophage polarization, prompting a pro-inflammatory cytokine response, apparent from the upregulation of activation markers, including IFNɣ and IL-17 that resists the growth of Mtb. These observations provide a rationale for exploring GlmMMtb as a potential therapeutic target.

Hand-foot syndrome in sorafenib and lenvatinib treatment for advanced thyroid cancer.

The aim of this study was to assess the clinical impact of hand-foot syndrome (HFS) during treatment with two multikinase inhibitors, sorafenib and lenvatinib, in a large group of patients with advanced thyroid cancer. Moreover, we looked for possible associations between HFS occurrence and clinical and pathological features. We retrospectively evaluated 239 patients with advanced thyroid cancer: 165 treated with lenvatinib and 74 with sorafenib. Statistical analyses were performed to verify which features could be correlated with HFS development. HFS was observed in 35/74 (47.4%) and in 43/165 (26.7%) patients treated with sorafenib or lenvatinib, respectively. The median latency from the drug beginning and HFS appearance was 27 days for sorafenib and 2.9 months for lenvatinib. G3/G4 toxicity was observed in 16/35 (45.7%) patients treated with sorafenib and only in 3/43 (7%) treated with lenvatinib. Drug dose reduction due to HFS was required in 19/74 (25.7%) and 3/165 (1.8%) patients treated with sorafenib and lenvatinib, respectively. HFS occurrence was significantly associated with a longer duration of therapy in both groups. HFS was a frequent adverse event during both lenvatinib and sorafenib therapy, with a higher frequency and toxicity grade during sorafenib treatment. HFS was the most frequent reason for drug reduction or discontinuation in patient treated with sorafenib. Early diagnosis of HFS is important to allow early intervention, possibly in a multidisciplinary setting, and to avoid treatment discontinuation, which is highly relevant to obtain the maximum effectiveness of systemic therapy.

Antibiotic Prescribing Practices on Hospital Discharge for Management of Urinary Tract Infections: A Single Center Study

Background: Appropriate antibiotic use has been described as one of the key strategies in tackling antibiotic resistance. Although the majority of antimicrobial therapy is completed following discharge, there lacks clear guidance in addressing antibiotic stewardship in the outpatient setting. Particularly, broader coverage as well as longer durations of therapy are often encountered following hospitalization. In our study we examine the various antibiotic prescribing practices on hospital discharge for management of urinary tract infections (UTI). Methods: We conducted a single-center, retrospective observational chart review of patients discharged from St. Francis Hospital and Medical Center in Hartford between May and July 2022. Medical records were reviewed for patients who were prescribed antibiotic therapy for management of UTI and met inclusion criteria. Variables of interest included type of UTI treated, antibiotic used, duration of antibiotics during and following hospitalization, fluoroquinolone use, as well reported adverse events. Total duration of therapy was defined as days on susceptible antimicrobials with appropriate source control. Results: A total of 84 patients met inclusion criteria. 44 received treatment for simple UTI (sUTI) and 40 for complicated UTI (cUTI). Figure 1 shows the various organisms identified on culture. The most common antimicrobials prescribed on discharge were cefpodoxime and ciprofloxacin [figure 2]. Quinolones were prescribed in 11.4% of sUTIs and 39.1% of cUTIs on hospital discharge. Of those, only one patient had no alternative to quinolone use due to drug allergies. The mean duration of therapy for treatment of sUTI was 6.4 days total (SD 2.40) with 3.9 days outpatient (SD 1.78). The mean duration of therapy for treatment of cUTI was 10.9 days total (SD 3.62) with 6.7 days outpatient (SD 2.99). Comparison of mean durations is shown in figure 3. In 49% of all cases (including both sUTI and cUTI) patients received greater than 7 days of antimicrobial therapy. Conclusion: There is increased evidence favoring shorter courses of antimicrobial therapy for management of both simple and complicated UTIs. A 7-day course has been shown as effective duration of therapy for cUTI with appropriate source control, regardless of presence of bacteremia. Results from our single center-study show both sUTI and cUTI are subject to unnecessarily prolonged durations of therapy on hospital discharge. In addition we noted a significant use of fluoroquinolones in cUTI treatment. We believe stewardship interventions at time of discharge may particularly benefit shorter courses of therapy for cUTI as well as reduced quinolone use.

Assessing the feasibility and cost-effectiveness of all oral adjuvant chemotherapy (cyclophosphamide, methotrexate, capecitabine) in high-risk hormone receptor positive breast cancer.

TPS616 Background: Women with high-risk HR+/HER2- breast cancer (BCA) receive additional chemotherapy to reduce disease recurrence. Preferred Taxane and Anthracycline based chemotherapy regimens have debilitating side effects such as cardiotoxicity, leukemia, peripheral neuropathy, severe fatigue, alopecia, downtime which are more common in black women thereby necessitating dose reductions. Metronomic cyclophosphamide, methotrexate, 5-fluourouracil (CMF) is an option but less preferred due to frequent dosing and longer therapy duration. Head-to-head comparison of CMF to anthracycline-based chemotherapy conducted 3 decades ago in early-stage BCA showed anthracycline benefit was driven by HER2+ disease with no benefit for HR+/HER2- BCA. Head-to-head comparison trials of CMF and Taxane-based regimen have not been conducted but single institution data suggest similar disease-free and similar overall survival but different toxicity profiles favoring CMF. In our ongoing trial, we converted all three chemotherapy drugs in CMF regimen to an all-oral regimen namely oral Cyclophosphamide, oral Methotrexate, oral Capecitabine (CMC) with the potential benefit of increased patient convenience, decreased costs (oral agents are generic; no chair time; no growth factors), and improved toxicity profile (low rates of grade III neutropenia, no port complications, no alopecia). This trial in progress aims to evaluate the feasibility of oral CMC by measuring the relative dose intensity in addition to the safety and tolerability of oral CMC. We hypothesize that 80% of patients will receive >85% of the intended dose of oral CMC. Methods: This is a Phase II, single arm, non-randomized study enrolling 25 patients with high-risk early-stage HR+ HER2- breast cancer to receive oral CMC regimen based on dose conversion equivalent bioavailability with conventional metronomic CMF chemotherapy. Enrolled patients will receive adjuvant therapy of oral cyclophosphamide 60 mg/m2 PO days 1-21 continuously, Methotrexate 15 mg/m2 PO Day 1, 8, and 15 and Capecitabine 650 mg/m2 PO BID Day 1- 14 to be given every 21 days for 8 cycles. The primary objective is to assess feasibility which is defined as 80% of patients (greater than 20 patients) maintaining a relative dose intensity (RDI) > 85%. The RDI is calculated as the ratio of the actual dose intensity/standard dose intensity; the average RDI for oral CMC regimen is the sum of RDI for each drug divided by 3. This study will be stopped if >25% of patients report Grade 4+ toxicity on oral CMC. The secondary objectives will assess quality of life as reported by the patients and report adverse effects. Clinical trial information: NCT06085742 . [Table: see text]

Short versus long duration of ceftaroline combination therapy and outcomes in persistent or high-grade MRSA bacteremia: A retrospective single-center study.

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with high mortality rates. Despite antibiotic therapy, persistent bacteremia is challenging to treat. Combination therapy with ceftaroline has emerged as a potential treatment option; however, the optimal duration and clinical implications after bacteremia clearance are unknown. This retrospective cohort study examined patients with high-grade or persistent MRSA bacteremia who were treated with ceftaroline combination therapy at the University of New Mexico Hospital between January 2014 and June 2021. Patients were categorized into short- (<7 days) or long-duration (≥7 days) groups based on the duration of combination therapy after bacteremia clearance. Outcomes included 30-day all-cause mortality, bacteremia recurrence, post-bacteremia clearance length of stay, and adverse events. A total of 32 patients were included in this study. The most common sources of bacteremia were bone/joint and endovascular (28.1%, 9/32 each). The median duration of combination therapy after clearance was seven days (IQR 2.8, 11). Patients in the long-duration group had a lower Charlson comorbidity index (1.0 vs 5.5, p = 0.017) than those in the short-duration group. After adjusting for confounders, there was no significant difference in the 30-day all-cause mortality between the groups (AOR 0.17, 95% CI 0.007-1.85, p = 0.18). No association was found between combination therapy duration and recurrence (OR 2.53, 95% CI 0.19-inf, p = 0.24) or adverse drug events (OR 3.46, 95% CI 0.39-74.86, p = 0.31). After controlling for total hospital length of stay, there was no significant difference in the post-bacteremia clearance length of stay between the two groups (p = 0.37). Prolonging ceftaroline combination therapy after bacteremia clearance did not significantly improve outcomes in patients with persistent or high-grade MRSA bacteremia. The limitations of this study warrant cautious interpretation of its results. Larger studies are needed to determine the optimal duration and role of combination therapy for this difficult-to-treat infection.

Home nursing and self-administered outpatient parenteral antimicrobial treatment: a comparison of demographics and outcomes from a large regional hospital in Queensland, Australia.

Outpatient parenteral antimicrobial treatment (OPAT) is a safe and effective therapy used in several settings across Australia. As OPAT services expand their inclusion criteria to include complex patient populations, there is an increased need for selecting appropriate patients to receive either healthcare-administered OPAT (H-OPAT) or self-administered OPAT (S-OPAT). To describe patient demographics, diagnosis, microbiology and outcomes of patients treated by H-OPAT and S-OPAT within the Sunshine Coast Hospital and Health Service, Australia. Data on demographics, diagnoses, treatment and outcomes on all patients treated by H-OPAT and S-OPAT from March 2017 to December 2019 were collected retrospectively. One hundred and sixty-five patients (62.26%) were enrolled in H-OPAT and 100 patients (37.74%) in S-OPAT. S-OPAT patients were significantly younger. H-OPAT patients were more comorbid. Bone and joint infections were the most treated infections and were more likely to be treated by S-OPAT. There was no difference in treatment duration, cure and complication rates between S-OPAT and H-OPAT. Longer duration of therapy was associated with more complications. Treatment failure was associated with infections due to multiple organisms, number of comorbidities and treatment of surgical site, skin and soft tissue infections. There were significant differences in demographics between H-OPAT and S-OPAT without any difference in outcomes. Overall failure and complication rates were low. Higher rates of treatment failure were predicted by the diagnosis, number of comorbidities and number of organisms treated.

Evaluation of Osteoporosis Among Epileptic Patients on Monotherapy

Epilepsy is a common chronic neurological disorder that affects almost 50 million people worldwide. Most patients require long-term, and sometimes lifelong therapy with antiseizure medications (ASMs), our case control study evaluates the long-term effect of carbamazepine (CBZ) and valproate (VPA) on bone mineral density and bone health biochemical markers. 50 patients with newly diagnosed epilepsy who had no history of antiseizure medications (ASMs) intake prior were divided into 2 groups. In the first group, 25 patients started carbamazepine (CBZ) monotherapy, while the second group included 25 patients who started receiving valproate (VPA) monotherapy. Another 25 healthy individuals were considered as a control group. The primary outcome of our study is to evaluate the percentage of osteoporosis compared to the duration of ASM therapy measured by the T score at two different sites in the body at baseline, after 3 and 6 months of therapy, while measurements of bone biomarker variables are considered secondary outcomes. We found that CBZ and VPA significantly decreased the level of vitamin D3, Ca, P, the L3-L5, and right femoral neck T score with prolonged treatment duration, while the level of ALP increased with increasing duration of treatment in patients treated with CBZ but not in the VPA group. Furthermore, CBZ significantly decreased bone health biomarkers and T score before VPA and the control group, as well as there were no significant differences between the two sexes who received CBZ or VPA therapy on bone biomarkers. In conclusion, valproate will not affect bone biomarkers earlier, but with a longer duration of therapy, they may have the same effect as carbamazepine which requires the prescription of supportive vitamin D and Ca along with ASMs.

Outcome of complicated osteoarticular brucellosis in a tertiary care center in Saudi Arabia.

To evaluate the outcome of complicated osteoarticular brucellosis. A retrospective chart review was conducted at King Abdulaziz Medical City (KAMC), in Riyadh, Saudi Arabia. All patients aged more than 14 who have been diagnosed with complicated brucellosis with osteoarticular disease between July 2016 and December 2022 were included. A total of 82 (10.7%) patients met the criteria, with a male predominance of 66 (80.4%), and their mean age was 56.4 ± 19.3 years. A positive blood culture was found in 33 (40.2%). The most common clinical presentation was fever (57.3%). All patients received a doxycycline-based regimen except one. 62 (75.60%) patients were treated with three or more medication regimens, while 20 (24.40%) patients received two drug regimens. The mean duration of therapy was 94.2 days for two-drug therapy and 116.4 days for three-drug therapy. A total of 78 out of 82 (95.1%) cases were cured at the end of treatment. Unfavorable outcomes were documented in four cases (two relapses and two treatment failures). Neither using three drugs regimen nor longer duration of therapy was associated with better outcome. Unfavorable outcomes have been noticed to be minimal in our cohort of patients with osteoarticular brucellosis, treated mainly with a three-drug regimen and a longer duration of therapy.

Effectiveness of antibiotic therapy for early recurrence of peritonsillar cellulitis and abscesses: A retrospective cohort study

ObjectiveShort-term recurrence is common in patients with peritonsillar cellulitis and abscesses, leading to socioeconomic problems. Early switching from intravenous to oral antibiotics is feasible for treating certain diseases. However, reports on early switching and total antibiotic administration duration in peritonsillar cellulitis and abscesses are limited. This study aimed to determine the appropriate antibiotic therapy duration and examine the impact of early oral switch therapy on peritonsillar cellulitis and abscesses. MethodsWe retrospectively identified 98,394 patients who received antibiotic therapy during hospitalization for peritonsillar cellulitis and abscesses between July 1, 2010, and December 31, 2019, using the Japanese Diagnosis Procedure Combination database. ResultsPropensity score matching analysis revealed no significant between-group difference in the rehospitalization rate (early oral switch therapy and long intravenous therapy: 1.7 % [198 of 11,621] vs. 2.0 % [234 of 11,621], odds ratio [OR] 0.84, 95 % confidence interval [CI] 0.70–1.02). A long total duration of antibiotic therapy (reference: 1–9 days) was associated with a low risk of rehospitalization (10–14 days: OR 0.86, 95 % CI 0.78–0.95; 15+ days: OR 0.51, 95 % CI 0.38–0.66). ConclusionEarly oral switch therapy may be a viable option for treating patients with peritonsillar cellulitis and abscesses in good condition who can tolerate oral intake. No less than 10 days of antibiotic therapy is desirable.

Long-term consequences of osteoporosis therapy with bisphosphonates

Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis (OP) and reduce fragility fractures. The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. Аtypical femoral fracture (AFF) and medication-related osteonecrosis of the jaw (MRONJ) are more common in patients with high cumulative doses and longer duration of therapy. The risk of AFF depends on the duration of treatment and is significantly increased among patients receiving BPs for more than 8 years. The risk may decrease and return to the initial level with discontinuation of BPs, it decreases by more than 50% during one year after the discontinuation. The risk of MRONJ is less dependent on the duration of therapy, it occurs more often in patients with cancer who are receiving higher cumulative doses of BPs. The combination of local trauma, microbial contamination and concomitant diseases induces this condition in patients with OP who are receiving BPs. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, and these benefits overweight the risks of rare adverse events.

Linezolid-Induced Thrombocytopenia in Patients with Renal Impairment: A Case Series, Review and Dose Advice.

Oral linezolid is often used as alternative therapy for intravenous vancomycin. According to the current guidelines, no dose adjustment has to be made in case of renal impairment. Nevertheless, in our hospital we have seen several patients with renal impairment who developed linezolid-induced thrombocytopenia when linezolid was taken in the standard dose. In this case series and review we want to emphasize the necessity of reviewing the Dutch and international guidelines. We describe five cases with renal impairment that developed linezolid-induced thrombocytopenia in our hospital. A PubMed literature review was conducted to identify other cases and find the optimal dosing regimen for these patients. Our cases join a long list of cases and available literature about linezolid-induced thrombocytopenia in patients with renal impairment. Less linezolid-induced thrombocytopenia was found, both in our cases and in the literature, after dose reduction of 50%. High linezolid trough concentrations were associated with a higher risk of linezolid-induced thrombocytopenia. Besides renal impairment, other risk factors for developing linezolid-induced thrombocytopenia were also identified, such as low body weight, high daily dose/kg, higher age, longer duration of therapy, low baseline count, malignity, low-dose aspirin and interacting co-medication. Re-evaluation of the current dose advice is necessary. We advocate for a standard dose reduction to 50% after 2days of standard dosing for all patients with an estimated glomerular filtration of <60mL/min/1.73m2. Besides this, therapeutic drug monitoring and thrombocytes monitoring may be executed weekly when patients have renal impairment or other risk factors for developing linezolid-induced thrombocytopenia.

P880 The real-world use of five-aminosalicylate (5ASA) treatment for Ulcerative Colitis in Australia and New Zealand: Crohn’s Colitis Cure (CCC) data insight’s program

Abstract Background Five-aminosalicylates (5ASAs) promote &amp; maintain remission in people with ulcerative colitis (UC) and are administered orally or rectally, with combination therapy (oral + rectal) more effective than oral monotherapy, especially when treating flares1. 5ASAs may be perceived as out-dated and thus neglected. With increasing UC incidence &amp; prevalence in emerging nations, understanding real-world 5ASA use and value is vital. Methods Crohn’s Colitis Care is a cloud-based electronic medical record used in Australasia. Data feed into a de-identified clinical quality registry (CQR), which was interrogated in September 2023. People with UC under active care (encounter within 14 months) were included. Results Of the 2,522 eligible people, 78.4% resided in Australia &amp; 21.6% in New Zealand (NZ). The median age was 41 years (IQR 31-56), with an even gender distribution (50.3% female). Median disease duration was 9 years (IQR 4.4-16.7). Median duration of follow up was 25.9 months (IQR 13.0-41.4). Overall, 39.2% (n=989) had no documentation of 5ASA therapy (42.0% in Australia, 28.9% in NZ; Table 1). In those with documented 5ASA therapy (60.8%, n=1,534), the average 5ASA treatment duration was 9 years (IQR 4.4-16.7) and women were more likely to receive rectal administration than men (p&amp;lt;0.05). In those who ceased 5-ASA therapy, 782 (44.8%) had a reason documented, with the most common being medication rationalisation and/or deep remission (40.0%) (Figure 1), usually due to up-titration to a more advanced therapy. A total of 608 (39.6%) were recorded as already receiving additional IBD therapy at CQR entry (immunomodulators [IMs]/biologics/small molecules). Of those receiving 5ASAs alone at CQR entry (n=926), 5ASAs were subsequently judged to have failed in 37.8% (n=350). 5ASA failure was defined as the need for additional IBD therapies (99.1%, n=230 for IMs/biologics/small molecules and n=117 for steroids, total n=347); hospitalisation (n=3, 0.9%) or IBD surgery (n=0). Conclusion Despite not working for everyone, the long duration of 5ASA therapy indicates they are well tolerated &amp; perceived as beneficial by consumers. There was greater 5ASA utilisation in NZ, possibly due to restricted advanced therapy access. Gender-specific trends in 5ASA administration were identified, raising the question as to why this should be so, given this is not obviously explained by disease phenotype. Further analysis is needed to tease out how such trends interact with other therapeutic access, choices and outcomes. 1 - Probert C et a. Combined oral and rectal mesalazine for the treatment of mild-to-moderately active ulcerative colitis: rapid symptom resolution and improvements in quality of life. J Crohns Colitis. doi:10.1016/j.crohns.2013.08.007

Dermal lesions associated with anti-tumor necrosis factor α therapy in patients with inflammatory bowel disease (IBD): findings from a tertiary IBD center in Poland.

There are scarce data on the occurrence of dermal lesions in patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor α (anti-TNF‑α) antibodies. Characteristics of the skin lesions, their clinical course, and impact on treatment are of high importance. The aim of this study was to assess the prevalence, risk factors, and clinical sequelae of dermal lesions in IBD patients treated with anti-TNF‑α antibodies. This retrospective, single‑center study evaluated 541 IBD patients treated with anti-TNF‑α drugs and 688 IBD individuals with no history of anti-TNF‑α treatment. Higher prevalence of dermal lesions was noted in the patients on anti-TNF‑α therapy than in the individuals not receiving such treatment (30.9% vs 16.4%; P <0.001). Risk factors for dermal lesions included higher body mass index (BMI), Crohn disease located in the small intestine, and longer duration of therapy. Some types of dermal lesions were associated with anti-TNF‑α therapy; these included infusion reactions and injection site reactions, cutaneous infection, psorasiform reactions, and lupus‑like symptoms. Overall, 5.9% of the patients on anti-TNF‑α therapy required treatment change or discontinuation due to dermal lesions (alopecia, lupus‑like symptoms, melanoma, and psoriasis). We observed a higher prevalence of dermal lesions in patients with IBD undergoing anti-TNF‑α therapy than in the treatment-naive group, although development of such lesions rarely necessitated a change in or discontinuation of treatment. Patients with IBD should regularly undergo follow-up dermatologic evaluation, which may improve detection of dermal lesions. Moreover, biologic therapy in IBD patients requires close collaboration with an experienced dermatologist.

Peritoneal Dialysis of Three-Cuff Catheter Experience in Qassim Province, Saudi Arabia.

Background: The global rise in noncommunicable diseases, including chronic kidney diseases (CKDs), has led to a significant increase in the use of dialysis units to enhance patient longevity and quality of life. Over time, two-cuff catheters have been replaced by three-cuff catheters, with their usage expanding in nephrology centers across Saudi Arabia. This study aimed to evaluate the benefits, complications, and duration of therapy associated with three-cuff catheters in peritoneal dialysis (PD) patients. Methodology: To ensure the reliability of our results, we conducted a comprehensive cross-sectional study involving 257 patients who underwent three-cuff PD catheter (PDC) insertion and omentopexy. Data were retrospectively collected from 2016 to 2023 at King Fahad Specialist Hospital, Buraidah. The questionnaire was designed based on available variables in the records section and validated by subject experts and experienced research faculty. Data were then entered and analyzed using SPSS version 21.0. Descriptive statistics were employed for inferential statistics, while the chi-square test and logistic regression analysis were used to identify predictors of PD outcomes. Results: The average duration of therapy was 27.84 months, with a standard deviation of 27.23 months. Early complications were minimal, with just 5.1% (n = 13) experiencing peritonitis, 0.8% (n = 2) facing catheter migration, and 0.4% (n = 1 each) encountering omental wrap and exit site infection (ESI) within 30 days of catheter insertion. Remarkably, only 7.8% (n = 20) required catheter reinsertion. In addition, catheter removal due to catheter-related issues was low, affecting only 3.8% of patients. Conclusions: According to the study findings, three-cuff catheters exhibited fewer complications, superior performance, and longer therapy duration. These outcomes may be attributed to the thorough design of the three-cuff catheters, the dedication of the staff, and the implementation of strict policies. To maintain these positive results, it is crucial for the Ministry of Health and the Health Cluster to adopt long-term supportive measures.

Tolerability and Outcomes of Bruton Tyrosine Kinase Inhibitors for Chronic Lymphocytic Leukemia in Patients with Severe Renal Dysfunction

Introduction: There is limited data on the outcomes and tolerability of Bruton Tyrosine Kinase (BTK) inhibitors for chronic lymphocytic leukemia (CLL) in patients with severe renal dysfunction, particularly older adults. The most commonly prescribed BTK inhibitor, ibrutinib, is believed to be safe for mild to moderate renal dysfunction. However, severe renal failure has been excluded from prospective studies, and there is no guidance on dosing under the FDA label. Furthermore, ibrutinib itself can cause kidney injury and worsen existing renal dysfunction. This national Veterans Affairs (VA) analysis aims to review the safety and tolerability of BTK inhibitors in severe renal impairment. Methods: An electronic query of the VA Corporate Data Warehouse and retrospective chart review were performed to identify patients with CLL treated with a BTK inhibitor between 2013-2022 and who had severe chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) &amp;lt; 30 ml/min/1.73 m 2 overlapping with their treatment period. Isolated acute kidney injuries lasting &amp;lt; 1 month were excluded. Fisher's exact test was utilized to evaluate categorical variables, logistic regression for binary outcomes, and log-rank and Cox regression for time-to-event analyses. Results: A total of 115 patients across 68 VA medical centers received 124 lines of BTK inhibitors with an eGFR &amp;lt; 30 (Table 1). The median duration of follow-up from the start of therapy was 26 months (range, 0.5 - 94). The median age was 74, and 98% were male, reflecting the U.S. veteran population. 64% had an eGFR &amp;lt; 30 at the start of therapy, with 18% requiring dialysis, while the remaining 36% experienced progressive renal dysfunction during treatment. The oral BTK agents prescribed were ibrutinib ( n = 103), acalabrutinib ( n = 18), and zanubrutinib ( n = 3). Most BTK inhibitors (n = 94 of 124 lines, 76%) were initiated at the FDA-label dose. 46 (37%) later required dose reduction, primarily due to drug toxicity ( n = 37). The most common reasons for dose reduction were cytopenia ( n = 10), failure to thrive ( n = 6), bleeding ( n = 5), and worsening renal function ( n = 5). Discontinuation of therapy for toxicity occurred in 50% (ibrutinib), 39% (acalabrutinib), and 33% (zanubrutinib). The most common reasons for discontinuation were infection ( n = 15), bleeding ( n = 10), arrhythmia ( n = 9), and disease progression ( n = 9). Among patients who received ibrutinib ( n = 103), the median progression-free survival (PFS) and overall survival (OS) were 45 and 49 months, respectively. In multivariate Cox regression, covariates associated with shorter PFS included the baseline severity of renal failure (HR 1.85, 95% CI 1.21 - 2.88), cirrhosis (HR 6.36, 95% CI 1.45 - 19.76), and heart failure (HR 4.20, 95% CI 1.82 - 9.47). Younger age, dialysis, and absence of atrial fibrillation at the start of therapy were protective in univariate but not multivariate models. Heart failure and cirrhosis retained their prognostic impact on OS in multivariate modeling. Factors including race, rural residence, obesity, IGHV status, and TP53 deletion were not significantly associated with survival in this cohort. The median duration of therapy of ibrutinib was 33 months. Ibrutinib dose reductions at initiation or during treatment were associated with a longer duration of therapy (Figure 1). Of note, dose reductions did not significantly reduce the response rate to ibrutinib or worsen survival. Interestingly, 11 patients had CLL-related kidney dysfunction. However, kidney function did not improve after treatment with a BTK inhibitor in any of the 115 patients. Progression of renal impairment was observed in 51 patients (50%) on ibrutinib, 8 (44%) on acalabrutinib, and none on zanubrutinib. The etiology of worsening renal function was uncertain for the majority of patients. Conclusion: The clinical outcomes of BTK inhibitors in patients with CLL and severe renal dysfunction have not been well-described. In our real-world data analysis, these agents appear to be a reasonable therapeutic option in severe renal impairment, including in older adults and those on dialysis. Lab monitoring is needed, given the risk of worsening renal function. Dose modifications may help improve tolerability without reducing efficacy. Unfortunately, severe renal dysfunction is unlikely to improve with CLL treatment, even in CLL-related kidney failure.

Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders.

The standard treatment for Langerhans cell histiocytosis (LCH) is chemotherapy, although the failure rates are high. Since MAP-kinase activating mutations are found in most cases, BRAF- and MEK-inhibitors have been used successfully to treat patients with refractory or relapsed disease. However, data on long-term responses in children are limited and there are no data on the use of these inhibitors as first-line therapy. We treated 34 patients (26 with LCH, 2 with juvenile xanthogranuloma, 2 with Rosai-Dorfman disease, and 4 with presumed single site-central nervous system histiocytosis) with dabrafenib and/or trametinib, either as first line or after relapse or failure of chemotherapy. Sixteen patients, aged 1.3-21 years, had disease that was recurrent or refractory to chemotherapy, nine of whom had multisystem LCH with risk-organ involvement. With a median treatment duration of 4.3 years, 15 (94%) patients have sustained favorable responses. Eighteen patients, aged 0.2-45 years, received an inhibitor as first-line treatment. All of these have had sustained favorable responses, with a median treatment duration of 2.5 years. Three patients with presumed isolated central nervous system/pituitary stalk histiocytosis had stabilization or improvement of their disease. Overall, inhibitors were well tolerated. Five patients with single-system LCH discontinued therapy and remain off therapy without recurrence. In contrast, all four patients with multisystem disease who discontinued therapy had to restart treatment. Our data suggest that children suffering from histiocytoses can be treated safely and effectively with dabrafenib or trametinib. Additional studies are, however, needed to determine the long-term safety and optimal duration of therapy.

Short Versus Long Duration of Dual Antiplatelet Therapy After Second-Generation Drug-Eluting Stents Implantation in Patients with Diabetes.

Duration of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) remains uncertain, with increasing data suggestive of acceptable short-term duration. Metabolically accelerated atherosclerosis associated with diabetes makes it essential to study short-term DAPT in this subgroup. With limited studies determining optimal DAPT strategies after second-generation stents in this subset, we aimed to establish the optimal duration of DAPT in the diabetic population using second-generation stents. To determine optimal DAPT duration in diabetic population undergoing PCI in 2nd generation stents. We conducted an electronic database search of randomized controlled trials from PubMed/Medline, Embase, Cochrane, and Web of Science databases. A meta-analysis was conducted comparing outcomes of short-term (3-6 months) DAPT therapy versus long-term (12 months) DAPT therapy in the diabetic population undergoing PCI with second-generation stents. A total of 5 randomized controlled trials were included with a total of 3117 diabetic patients. Short-term DAPT did not show any statistical difference from long-term DAPT in achieving primary outcomes (relative ratio: 0.96, 95% confidence interval (CI) 0.68-1.35, P = 0.84). Overall mortality (OR 0.92; 95% CI, 0.52-1.63, P = 0.98), myocardial infarction [odds ratio (OR)OR 1.02; 95% CI, 0.53-1.94, P = 0.85], stent thrombosis (OR 1.20; 95% CI, 0.55-2.60, P = 0.55), target vessel revascularization (OR 1.10; 95% CI, 0.45-2.73, P = 0.74), and stroke (OR 0.50; 95% CI, 0.082-2.43, P = 0.81) did not show any statistical difference between the 2 groups. Similarly, a subgroup analysis of study population comparing 6 versus 12 months of DAPT in diabetic population did not show any difference in net primary outcomes (relative ratio: 0.86, 95% CI 0.45-1.45, P = 0.60). There was no significant heterogeneity noted between the 2 groups. This meta-analysis showed no statistically significant benefit of longer DAPT over shorter DAPT therapy in patients undergoing PCI with drug-eluting stent in patients with diabetes.

Role of splenic and bone marrow uptake at 18 F-FDG PET/CT for the assessment of large vessels vasculitis and the influence of glucocorticoids therapy on their values.

To assess the relationship between splenic and bone marrow (BM) uptake with the presence of large vessel vasculitis (LVV) at 18 F-FDG PET/CT and to evaluate the influence of glucocorticoid (GC) therapy on these uptakes. One hundred and one subjects with LVV and 18 F-FDG PET/CT were included in the study. Clinical features, including blood samples and duration of GC therapy, were collected. Standardized uptake value body weight max (SUVmax) of the spleen, BM, liver and arterial walls were extracted; spleen/liver (SL) and BM/liver (BML) ratios were calculated. Chi-square and T-test were used to assess the relationship between PET/CT parameters and clinical features with the presence of LVV. Rank correlation was used to evaluate the correlation between PET/CT parameters and clinical parameters. Receiver operating curve (ROC) analysis was used to find the best parameter able to discriminate between positive and negative PET/CT. All analyses were performed considering the duration of GC therapy. Significant correlation for PET/CT results with spleen uptake (P-value = 0.001), SL (P-value < 0.001) and BML (P-value = 0.005) were reported in patients with no more than 3 days of therapy; the correlation with SL was confirmed in the total cohort of patients. A value of 0.92 for SL had an AUC of 0.959, a sensitivity of 92.6% and a specificity of 96.6% (P-value < 0.001) in predicting PET/CT results. Higher splenic and BM uptake in patients with positive PET/CT for LVV were reported. A long duration of GC therapy is able to reduce such uptakes.

Influence of Anxiety on Non Adherence to Tuberculosis Treatment among Tb Patients in Selected Chest Clinics in Mombasa County, Kenya

Purpose. The aim of this study was to determine the influence of anxiety on Non adherence to tuberculosis treatment among Tb patients in selected chest clinics in Mombasa County, Kenya. Methodology. The study adopted correlation research design as guided by the hypothesis that anxiety had an effect on Nonadherence to tuberculosis treatment. It was conducted in Mombasa County, Kenya in 3 selected Chest clinics. All tuberculosis patients were the target population. Convenience sampling was used to identify those registered and on active treatment while simple random sampling was used for those who accepted to participate in the study. Data collection was done using questionnaires that had both open and close ended questions. Descriptive statistics helped in data analysis which were then presented using frequencies, percentages and tables. Results. 312 respondents were interviewed, 91% reported that anxiety affected their Tb treatment. 75% of them reported that side effects of the Tb medicines were the reason they had anxiety, 16.3% said the long duration of therapy while 8.7% stated that misinformation was the cause. 17.3% of respondents with severe anxiety had moderate Nonadherence to their Tb treatment. Summary, Conclusion and Recommendation. From the result the study noted that the two most common triggers of anxiety in tuberculosis patients were Side effects and the long duration of treatment. It was noted there exists a relationship between anxiety and Non adherence but the association was not significant as indicated by chi-square (X2(4, 312) = [2.532], p = [p=.639]). Screening and assement of patients on long term treatment would be needful in helping manage comorbidities.