Selection strategy of second-line biologic therapies in adult patients with ulcerative colitis following prior biologic treatment failure: Systematic review and meta-analysis.

BACKGROUND: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. OBJECTIVE: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. METHODS: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. RESULTS: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6-14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52-54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. CONCLUSION: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.

Statement of the Rehabilitation Medicine Society of Australia and New Zealand for the therapeutic use of botulinum toxin A in spasticity management.

The Rehabilitation Medicine Society of Australia and New Zealand advocates the safe, effective and evidence-based use of botulinum toxin type A for spasticity management. The process requires appropriate training, alongside considerable knowledge and skills, to maximise efficacy. The processes before and after injection contribute to effectiveness. The gold standard of managing spasticity is for assessment by a multidisciplinary specialist team, deriving patient-centric goals, and designing an injection protocol to match these goals. The patient and/or carers are considered part of the decision-making team. Postinjection therapy and measurement of goal achievement are highly recommended as part of the wider holistic approach to management. The Society believes treatment failures can be minimised by following clear clinical guidelines.

Long-term efficacy and safety of nonablative monopolar radiofrequency in the treatment of moderate to severe acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is a prevalent skin condition known for its potential to cause scarring and psychological distress, often leading to diminished self-esteem. While topical and oral treatments are commonly prescribed, some patients experience treatment failure, adverse effects, or contraindications to conventional therapies. In response to these challenges, laser and energy-based device therapies have emerged as promising alternatives for individuals who fall into these categories, showing considerable potential in the treatment of AV. OBJECTIVE: This study aimed to evaluate the long-term efficacy and safety of a nonablative monopolar radiofrequency (NMRF) in treatment of moderate to severe AV. METHODS: Twenty-four patients with moderate to severe AV underwent a series of two NMRF treatment sessions, spaced 4 weeks apart. To evaluate treatment outcomes, live in-person lesion counts and measurements of pore size and volume, and sebum production were quantified using Antera® 3D imaging system, and Sebumeter®, respectively. Patients' self-assessment data regarding degree of improvement and facial oiliness were gathered. Dermatology life quality index (DLQI) questionnaire was utilized to assess the impact of AV on their quality of life. All objective and subjective evaluations were conducted at the baseline, 1 month after the first treatment, and during follow-up visits 1, 3, and 6 months after the last treatment sessions. Adverse effects were also recorded during each visit. RESULTS: Twenty out of the 24 subjects completed the study protocol. The mean inflammatory lesion counts significantly reduced by 42.86% and 45.71% from the baseline at 3 (p = 0.027) and 6 months (p = 0.032) after the second treatment. Sebum excretion likewise significantly decreased from baseline by 11.62% (p = 0.012), 13.37% (p < 0.001), and 21.51% (p = 0.004), 1 month after the first treatment, 1 and 6 months after the second treatment, respectively. The pore volume continued to decrease by 35% (p = 0.003) and 41.5% (p < 0.001) at 1 and 6 months following the final treatment, respectively. The DLQI significantly decreased from 10.00 (interquartile range [IQR]: 6.50-15.00) to 2.00 (IQR: 1.00-4.75), corresponding to 80% improvement of the index, 1 month after the last treatment and was sustained up to the last follow-up visit. Patients' self-assessments on degree of improvement and facial oiliness also significantly improved following NMRF treatments. The treatments were well-tolerated without significant adverse effects. CONCLUSION: NMRF appears to be an effective and safe treatment for inflammatory AV, with therapeutic outcomes persisting up to 6 months after two treatment sessions.

Pushing Backwards: Evaluating Effectiveness of Conservative Treatment of Intestinal Intussusception.

OBJECTIVE: Intestinal intussusception (II) is a common cause for acute abdomen in children, occurring in 0.33 to 0.71 per 1000 children per year. Early diagnosis and treatment are fundamental for prevention of irreversible intestinal damage. The first line of treatment is conservative, with saline reduction enema or air reduction enema. Our goal is to evaluate results with conservative treatment of II in children. METHODS: A retrospective single-center review of all patients with diagnosis of II from January 2014 to December 2019 was performed. Demographics, clinical data, treatment option, and results were assessed. RESULTS: Thirty-eight cases were identified. The mean age was 26 months, and 68% were males. Most presented with abdominal pain (95%) and vomiting (66%), after an average of 30 hours. Rectal bleeding was present in 32% of patients. Abdominal ultrasound was performed in all patients for diagnosis. Conservative treatment was first option in 95% of patients, with a global effectiveness of 83% after 1 attempt. Saline reduction enema was more effective than air reduction enema (88% vs 70%), and patients with successful reduction were younger (24 vs 33 months), but neither reached statistical significance. Two patients had a subsequent II episode within 1 week after hospital discharge. Neither age, sex, symptoms and respective duration, rotavirus inoculation, intussuscepted bowel length, nor technique used was predictive of treatment failure or II relapse. CONCLUSIONS: Conservative treatment in II is a safe and effective option, preventing invasive surgical procedures. Effectiveness of such treatments may be as high as 88% after 1 attempt, with rapid diet reintroduction. Same-day discharge after oral feeding toleration is safe.

Antibiotic treatment failure of uncomplicated urinary tract infections in primary care.

BACKGROUND: Higher resistance rates of > 20% have been noted in Enterobacteriaceae urinary isolates towards ciprofloxacin and co-trimoxazole (C + C) in Singapore, compared with amoxicillin-clavulanate and nitrofurantoin (AC + N). This study examined if treatment failure varied between different antibiotics, given different resistant rates, for uncomplicated urinary tract infections (UTIs) managed in primary care. We also aimed to identify gaps for improvement in diagnosis, investigations, and management. METHODS: A retrospective cohort study was conducted from 2019 to 2021 on female patients aged 18-50 with uncomplicated UTIs at 6 primary care clinics in Singapore. ORENUC classification was used to exclude complicated UTIs. Patients with uncomplicated UTIs empirically treated with amoxicillin-clavulanate, nitrofurantoin, ciprofloxacin or co-trimoxazole were followed-up for 28 days. Treatment failure was defined as re-attendance for symptoms and antibiotic re-prescription, or hospitalisation for UTI complications. After 2:1 propensity score matching in each group, modified Poisson regression and Cox proportional hazard regression accounting for matched data were used to determine risk and time to treatment failure. RESULTS: 3194 of 4253 (75.1%) UTIs seen were uncomplicated, of which only 26% were diagnosed clinically. Urine cultures were conducted for 1094 (34.3%) uncomplicated UTIs, of which only 410 (37.5%) had bacterial growth. The most common organism found to cause uncomplicated UTIs was Escherichia coli (64.6%), with 92.6% and 99.4% of isolates sensitive to amoxicillin-clavulanate and nitrofurantoin respectively. Treatment failure occurred in 146 patients (4.57%). Among 1894 patients treated with AC + N matched to 947 patients treated with C + C, patients treated with C + C were 50% more likely to fail treatment (RR 1.49, 95% CI 1.10-2.01), with significantly higher risk of experiencing shorter time to failure (HR 1.61, 95% CI 1.12-2.33), compared to patients treated with AC + N. CONCLUSION: Treatment failure rate was lower for antibiotics with lower reported resistance rates (AC + N). We recommend treating uncomplicated UTIs in Singapore with amoxicillin-clavulanate or nitrofurantoin, based on current local antibiograms. Diagnosis, investigations and management of UTIs remained sub-optimal. Future studies should be based on updating antibiograms, highlighting its importance in guideline development.

[Association of Geriatric Nutritional Risk Index with Adverse Events and Time to Treatment Failure in Malignant Lymphoma Patients Treated with(R-)EPOCH].

To date, there are no reports that examine the relationship between geriatric nutritional risk index(GNRI)at the start of chemotherapy for malignant lymphoma and adverse effects. In this study, we investigated the relationship between GNRI at the start of chemotherapy and the incidence of side effects and time to treatment failure(TTF)in(R-)EPOCH-treated patients with relapsed or refractory malignant lymphoma. A significant difference in the incidence of Grade 3 or higher thrombocytopenia was observed between high and low GNRI groups(p=0.043). The GNRI may be an indicator of hematologic toxicity in malignant lymphoma patients treated with(R-)EPOCH. There was a statistically significant difference in TTF between the high and low GNRI groups(p=0.025), suggesting that nutritional status at the start of(R-)EPOCH may affect treatment continuation.

Treatment Failure Due to Adaptive Resistance Mechanisms in a Severe and Complicated Bloodstream Infection Due to Elizabethkingia meningoseptica.

Elizabethkingia meningoseptica is an uncommonly encountered multidrug-resistant gram-negative bacterium that causes infections primarily among vulnerable hosts. A true opportunistic pathogen, its ability to cause severe sepsis and complicated infection in selected patients has been noted. Very limited preclinical and clinical data exist with regard to suitable therapeutic options. In this study, we present the case of prolonged bloodstream and central nervous system infection due to E. meningoseptica treated with dose-optimized combination antibiotic therapy, with evidence of microbiological (including development of adaptive resistance mechanisms) and clinical failure.

Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure.

The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant Enterobacterales (CRE) infections as an "urgent" health care threat requiring public attention and research. Certain patients with CRE infections may be at higher risk for poor clinical outcomes than others. Evidence on risk or protective factors for CRE infections are warranted in order to determine the most at-risk populations, especially with newer beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics available to treat CRE. We aimed to identify specific variables involved in CRE treatment that are associated with clinical failure (either 30-day mortality, 30-day microbiologic recurrence, or clinical worsening/failure to improve throughout antibiotic treatment). We conducted a retrospective, observational cohort study of hospitalized patients with CRE infection sampled from 2010 to 2020 at two medical systems in Detroit, Michigan. Patients were included if they were ≥18 years old and culture positive for an organism in the Enterobacterales order causing clinical infection with in vitro resistance by Clinical and Laboratory Standards Institute (CLSI) breakpoints to at least one carbapenem. Overall, there were 140 confirmed CRE infections of which 39% had clinical failure. The most common infection sources were respiratory (38%), urinary (20%), intra-abdominal (16%), and primary bacteremia (14%). A multivariable logistic regression model was developed to identify statistically significant associated predictors with clinical failure, and they included Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.06 to 1.32), chronic dialysis (aOR, 5.86; 95% CI, 1.51-22.7), and Klebsiella pneumoniae in index culture (aOR, 3.09; 95% CI, 1.28 to 7.47). Further research on CRE infections is needed to identify best practices to promote treatment success. IMPORTANCE This work compares carbapenem-resistant Enterobacterales (CRE) infections using patient, clinical, and treatment variables to understand which characteristics are associated with the highest risk of clinical failure. Knowing which risk factors are associated with CRE infection failure can provide clinicians better prognostic and targeted interventions. Research can also further investigate why certain risk factors cause more clinical failure and can help develop treatment strategies to mitigate associated risk factors.

OnabotulinumtoxinA discontinuation in patients with prior nerve stimulation.

PURPOSE: The objective of this study is to describe the characteristics of patients who discontinue onabotulinumtoxinA treatment for overactive bladder (OAB) and to determine the impact of prior sacroneuromodulation or peripheral nerve stimulation on the discontinuation rates of onabotulinumtoxinA. MATERIALS AND METHODS: This is a retrospective cohort study of women with at least two onabotulinumtoxinA (BTX-A) treatments for OAB with a Female Pelvic Medicine and Reconstructive surgeon at a referral center between January 2014 and July 2019. Patients were excluded if they underwent BTX-A treatment in the operating room or utilized clean intermittent catheterization at baseline. Women who continued injections throughout the study period were compared to those who did not. Discontinuation was defined as stopping BTX-A during the study period. Treatment failure was defined as a documented failure in the chart and/or moving to other OAB treatments. Loss to follow-up was defined as no follow-up greater than 12 months after the last injection. Discontinuation-free and failure-free survival were estimated by Kaplan-Meier analysis. RESULTS: A total of 214 women met the inclusion criteria with a mean age of 62.9 ± 14 years. Fifty percent were Black. Eighty-six (40.2%) discontinued onabotulinumtoxinA treatment during the study period. There were no demographic differences between patients who discontinued BTX-A and those who continued with the following exceptions: patients who discontinued had higher rates of prior pelvic reconstructive surgery (19.8% vs. 10.2%, p = 0.04) and were more likely to have the concurrent diagnosis of painful bladder syndrome (9.3% vs. 2.3%, p = 0.03). Patients diagnosed with a urinary tract infection (UTI) after ≥50% of treatments were more likely to discontinue (27.9% vs. 14.1%, p = 0.01). On multivariate logistic regression analysis, patients with recurrent UTIs after treatment were significantly more likely to discontinue than those who do not (odds ratio: 2.61, [1.17, 5.82]). Of the cohort, 54 (25%) patients had previously undergone nerve stimulation. A total of 27.8% of patients with prior nerve stimulation discontinued BTX-A compared to 44.4% of those without prior third line treatment (p = 0.03). Patients with prior nerve stimulation had a higher discontinuation-free survival rate (p = 0.013) but there was no difference in failure-free survival. CONCLUSIONS: Patients who have recurrent UTIs after onabotulinumtoxinA injections are 2.6 times more likely to discontinue treatment than those who do not have infections. Patients with prior exposure to nerve stimulation have a significantly lower onabotulinumtoxinA discontinuation rate, but there is no difference in failure rates.

Sorafenib versus nivolumab after lenvatinib treatment failure in patients with advanced hepatocellular carcinoma.

BACKGROUND AND AIM: An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC. METHODS: Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020. RESULTS: The median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively ( P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P < 0.05). CONCLUSIONS: Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.

Prospects of Probiotic Adjuvant Drugs in Clinical Treatment.

In modern society, where new diseases and viruses are constantly emerging, drugs are still the most important means of resistance. However, adverse effects and diminished efficacy remain the leading cause of treatment failure and a major determinant of impaired health-related quality of life for patients. Clinical studies have shown that the disturbance of the gut microbial structure plays a crucial role in the toxic and side effects of drugs. It is well known that probiotics have the ability to maintain the balance of intestinal microecology, which implies their potential as an adjunct to prevent and alleviate the adverse reactions of drugs and to make medicines play a better role. In addition, in the past decade, probiotics have been found to have excellent prevention and alleviation effects in drug toxicity side effects, such as liver injury. In this review, we summarize the development history of probiotics, discuss the impact on drug side effects of probiotics, and propose the underlying mechanisms. Probiotics will be a new star in the world of complementary medicine.

Moderate-to-Severe Malnutrition Identified by the Controlling Nutritional Status (CONUT) Score Is Significantly Associated with Treatment Failure of Periprosthetic Joint Infection.

The prevalence and role of malnutrition in periprosthetic joint infection (PJI) remain unclear. This study aimed to use measurable nutritional screening tools to assess the prevalence of malnutrition in PJI patients during two-stage exchange arthroplasty and to explore the association between malnutrition and treatment failure. Our study retrospectively included 183 PJI cases who underwent 1st stage exchange arthroplasty and had available nutritional parameters, of which 167 proceeded with 2nd stage reimplantation. The recently proposed Musculoskeletal Infection Society (MSIS) Outcome Reporting Tool was used to determine clinical outcomes. The Controlling Nutritional Status (CONUT), Nutritional Risk Index (NRI), and Naples Prognostic Score (NPS) were used to identify malnutrition at 1st and 2nd stage exchange, respectively. Multivariate logistic regression analyses were performed to determine the association between malnutrition and treatment failure. Restricted cubic spline models were further used to explore the dose−response association. Additionally, risk factors for moderate-to-severe malnutrition were evaluated. Malnourished patients identified by CONUT, NPS, and NRI accounted for 48.1% (88/183), 98.9% (181/183), and 55.7% (102/183) of patients at 1st stage, and 9.0% (15/167), 41.9% (70/167), and 43.1% (72/167) at 2nd stage, indicating a significant improvement in nutritional status. We found that poorer nutritional status was a predictor of treatment failure, with CONUT performing best as a predictive tool. Moderate-to-severe malnutrition at 1st stage identified by CONUT was significantly related to treatment failure directly caused by PJI (odds ratio [OR] = 5.86), while the OR was raised to 12.15 at 2nd stage (OR = 12.15). The linear dose−response associations between them were also confirmed (P for nonlinearity at both 1st and 2nd stage > 0.05). As for total treatment failure, moderate-to-severe malnutrition as determined by CONUT was associated with a 1.96-fold and 8.99-fold elevated risk at the 1st and 2nd stages, respectively. Age ≥ 68 years (OR = 5.35) and an increased number of previous surgeries (OR = 2.04) may be risk factors for moderate-to-severe malnutrition. Overall, the prevalence of malnutrition in PJI patients is very high. Given the strong association between moderate-to-severe malnutrition identified by CONUT and PJI treatment failure, COUNT could be a promising tool to evaluate the nutritional status of PJI patients to optimize treatment outcomes.

Intravenous to oral transition of antibiotics for gram-negative bloodstream infection at a University hospital in Thailand: Clinical outcomes and predictors of treatment failure.

BACKGROUND: Limited studies evaluate the outcome of intravenous antibiotics to oral transition in Gram-negative bloodstream infection (GN-BSI), particularly GN-BSI originating outside the urinary tract. This study aimed to evaluate treatment success in patients with GN-BSI treated with either intravenous therapy or intravenous to oral transition and to identify factors associated with treatment failure in those undergoing intravenous to oral transition. METHODS: A retrospective cohort study was conducted at King Chulalongkorn Memorial Hospital, Thailand. Patients were included if they were ≥18 years of age, hospitalized in general medical wards with GN-BSI between August 1, 2015, to July 31, 2020, received intravenous antibiotic agents and had a functioning gastrointestinal tract. RESULTS: Of 955 patients, 545 (57.1%) were in the intravenous to oral transition group. The urinary tract was the most common source of infection (38.8%). Ciprofloxacin was the most prescribed oral antibiotic (53%). Treatment success occurred in 94.3% in the intravenous antibiotic to oral transition group. There was no significant difference in treatment success between the two groups (P = 0.790) with a concordant result after using propensity score matching (P = 0.223). Independent predictors of treatment failure in the intravenous to oral transition group included metastatic solid cancer (aOR = 4.355), HIV infection with CD4 < 200 cells/mm3 (aOR = 8.452), qSOFA score ≥ 2 (aOR = 2.545), multidrug-resistant infection (aOR = 2.849), and respiratory tract infection (aOR = 8.447). Hospital length of stay in the intravenous to oral transition group was shorter than in the intravenous group (P < 0.001). CONCLUSIONS: Intravenous to oral transition may be a practical approach in GN-BSI. Patients with Gram-negative bacteremia who have HIV infection with CD4 < 200 cells/mm3, multidrug-resistant infections, and respiratory tract sources of infection may not be ideal candidates for this approach. Future research is needed from a randomized controlled trial.

Case report: A 9-year systematic treatment failure of a pulmonary tuberculosis patient.

Objective: To explore the reasons of failure in a case of pulmonary tuberculosis (PTB) after 9 years systematic treatment. Methods: We extracted the patients' treatment history, drug susceptibility testing (DST), Computed tomography (CT) images, and sequenced the isolated strains by whole gene sequencing (WGS). Results: Although most results of the phenotypical DSTs were consistent with the genotype DST, the occurrence of gene resistance to amikacin (AMK), capreomycin (CAP), moxifloxacin (MFX) was earlier than the phenotypical DST. Based on the continuously reversed results of phenotypical DSTs, CT images in different stages and WGS, it can be confirmed that the patient was infected with two different strains of Mycobacterium tuberculosis (M.TB). Moreover, severe cavities may be another factor leading to treatment failure. Conclusion: Given the suggestive effect of genotype DST is earlier than the phenotypical DST, so genotype DST can play a better guiding role in patients with MDR-TB. Additionally, for patients who have not been cured for a long time, medication should be more cautious and the role of WGS in drug resistance surveillance should be fully utilized.

Adherence challenges and opportunities for optimizing care through enhanced adherence counseling for adolescents with suspected HIV treatment failure in Kenya.

BACKGROUND: Adolescents living with HIV (ALHIV) experience higher mortality and are more likely to have poor antiretroviral therapy (ART) adherence and unsuppressed viral load (VL) compared to adults. Enhanced adherence counseling (EAC) is a client-centered counseling strategy that aims to identify and address barriers to optimal ART use and can be tailored to the unique needs of adolescents. This study aimed to better understand adherence barriers among ALHIV with suspected treatment failure and their experience with EAC to inform future programming. METHODS: A qualitative study was conducted in Homa Bay and Turkana counties, Kenya in 2019 with adolescents and caregivers of children and adolescents living with HIV with suspected treatment failure after ≥6 months on ART and who had received ≥1 EAC sessions. Sixteen focus group discussions (FGDs) were conducted; five FGDs each were held with adolescents 12-14 years (n = 48) and 15-19 years (n = 36). Caregivers (n = 52) participated in six FGDs. Additionally, 17 healthcare workers providing pediatric/adolescent HIV services participated in in-depth interviews. Audio recordings were transcribed and translated from Kiswahili or Dholuo into English and coded using MAXQDA software. Data were thematically analyzed by participant group. RESULTS: Participants identified adolescents' fear of being stigmatized due to their HIV status and their relationship with and level of support provided by caregivers. This underpinned and often undermined adolescents' ART-taking behavior and progress towards more independent medication management. Adolescents were generally satisfied with EAC and perceived it to be important in improving adherence and reducing VL. However, problems were noted with facility-based, individual EAC counseling, including judgmental attitudes of providers and difficulties traveling to and keeping EAC clinic appointments. Participant-suggested improvements to EAC included peer support groups in addition to individual counseling, allowing for greater flexibility in the timing and location of sessions and greater caregiver involvement. CONCLUSIONS: The findings provide opportunities to better tailor EAC interventions to promote improved ALHIV adherence and caregiver-supported disease management. Multi-prong EAC interventions that include peer-led and community approaches and target adolescent and caregiver treatment literacy may improve EAC delivery, address issues contributing to poor adherence, and position adolescents to achieve viral suppression. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04915469.

Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022.

We describe a gonorrhoea case with ceftriaxone plus high-level azithromycin resistance. In April 2022, an Austrian heterosexual male was diagnosed with gonorrhoea after sexual intercourse with a female sex worker in Cambodia. Recommended treatment with ceftriaxone (1 g) plus azithromycin (1.5 g) possibly failed. Worryingly, this is the second strain in an Asian Neisseria gonorrhoeae genomic sublineage including high-level azithromycin-resistant strains that developed ceftriaxone resistance by acquisition of mosaic penA-60.001. Enhanced resistance surveillance and actions are imperative to prevent spread.

atpE Mutation in Mycobacterium tuberculosis Not Always Predictive of Bedaquiline Treatment Failure.

We report the emergence of an atpE mutation in a clinical Mycobacterium tuberculosis strain. Genotypic and phenotypic bedaquiline susceptibility testing displayed variable results over time and ultimately were not predictive of treatment outcome. This observation highlights the limits of current genotypic and phenotypic methods for detection of bedaquiline resistance.

Ceftriaxone treatment failure in two cases of Enteric Fever caused by CTX-M15 positive Salmonella Typhi and its gastrointestinal carriage.

We report two cases of culture positive typhoid fever caused by ceftriaxone resistant Salmonella Typhi. Bacterial isolates from both the cases were positive for ESBL by phenotypic methods. Both patients didn't respond to ceftriaxone and were finally treated with meropenem. Screening of family members of one patient isolated a similar strain from a healthy carrier with the same antibiogram pattern. All isolates were subjected to PCR, which confirmed the presence of blaCTX-M15 ESBL gene. These two cases confirm emergence of ESBL-producing Salmonella Typhi causing Enteric Fever in India and also their presence in the gut flora of healthy carriers.

Treatment Patterns and Health Resource Utilization in Patients With Hepatocellular Carcinoma After Failure of Sorafenib in Real-World Setting in Taiwan.

OBJECTIVES: This study aimed to characterize current treatment patterns and healthcare resource utilization (HRU) observed among patients with hepatocellular carcinoma (HCC) after the failure of sorafenib in real-world setting in Taiwan. METHODS: A chart review was conducted in 130 patients; the inclusion criteria were patients with HCC who were aged 20 years or older and had received systemic therapy or best supportive care after failure of first-line systemic treatment with sorafenib between 2016 and 2018. Anonymized data on patient characteristics, treatment pathways, and survival were abstracted. RESULTS: The mean age of patients was 61.7 years (range 27-84); of these 130 patients, 103 (79%) were male, 81 (62%) had high alpha-fetoprotein (AFP) levels (≥400 ng/mL), and 96 (78.0%) were deceased at the time of data abstraction. After sorafenib therapy, 60 patients (46%) received systemic therapy, including nivolumab monotherapy (42%) and chemotherapy (25%). Oncologist visits at a semiannual per-patient rate of 3.7 (95% confidence interval [CI] 3.4-4.0) and hospitalizations at rate of 1.1 (95% CI 1.0-1.3) were the key contributors to HRU. Semiannual per-patient hospitalization rate was 1.3 (95% CI 1.1-1.5) in the high-AFP group. Median survival from discontinuation of sorafenib was 6.9 months (95% CI 5.9-9.0). CONCLUSIONS: This real-world evidence research on treatment patterns reflected substantial HRU consistent with the severity of HCC, particularly in the high-AFP group. Findings highlighted continuing high mortality in HCC, underlying a need for new treatments that can lengthen survival. Results can inform future evaluations of new HCC treatments that estimate the health economic impact of their adoption in Taiwan.