Treatment Failure Group Research Articles

Idiopathic Retroperitoneal Fibrosis-Related Hydronephrosis: Evaluation of Comprehensive Management and Prediction of Inflammatory Markers for Stent-Free Outcomes.

This study investigated the efficacy of comprehensive management and predictable inflammatory markers for idiopathic retroperitoneal fibrosis (iRPF)-related hydronephrosis outcomes. Patients with iRPF-related hydronephrosis underwent surgical (ureteral stent and/or nephrostomy tube placement) and medical (corticosteroid-based multiple immunosuppressants) management were classified according to stent-indwelling outcomes. Univariate analysis of clinical profiles was conducted to screen possible predictors of hydronephrosis remission. In a series of 38 patients, 52.6% achieved hydronephrosis remission and stent/tube removal (stent-free group). The median indwelling time in the stent-free group (12 months) was significantly lower than that in the treatment-failure group (37 months, p<0.05). Mean retroperitoneal mass diameters was significantly reduced (anteroposterior by 11.66 mm (95% CI 2.31-21.01), transverse by 15.41 mm (95% CI 3.37-27.46), suprainferior by 30.53 mm (95% CI 4.87-56.19); p<0.05) during the treatment course, in line with mean renal pelvis width (by 36.2%) and renal function parameters (serum creatinine by 16.9%, blood urea nitrogen by 12.9%). Renal function improved (36.9%) or remained stable (44.7%) in most patients, the mean estimated glomerular filtration rate increasing by 8.7% (from 55.4 mL/min/1.73 m2 to 60.2 mL/min/1.73 m2). At the initial diagnosis, median serum immunoglobulin IgG and CRP levels were significantly higher in the stent-free group than in the treatment-failure group (IgG 17.55 g/L vs. 13.50 g/L, CRP 19.60 mg/L vs. 3.15 mg/L; p<0.05). Decline in serum IgG (-5.80 g/L vs. -2.30 g/L), CRP (-18.93 mg/L vs. -1.72 mg/L) and erythrocyte sedimentation rate (-22.00 mm/h vs. -1.50 mm/h) levels in the stent-free group surpassed those in the treatment-failure group (p<0.05). Comprehensive management benefits iRPF patients with hydronephrosis by preserving renal function. The 24-month scale might guide stent/tube removal. Elevated inflammatory markers (IgG and CRP) at the initial iRPF diagnosis and IgG, CRP, and erythrocyte sedimentationrate (ESR) variations associated with hydronephrosis outcomes.

Assessment of Molecular Response to Treatment of Chronic Myeloid Leukemia at Kigali University Teaching Hospital of Kigali

Abstract Introduction/Objective Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm that gives proliferation advantage to the granulocytes, it is one of the commonest chronic hematological malignancies and it is a burden to the world especially Rwanda. Since the introduction of Tyrosine Kinase Inhibitors (TKIs) especially the first line Imatinib in 2001, the outcomes of CML have been much improved and currently, in developed world, the life expectancy of patients with CML is almost the same as general population. However, it is not the case in developing world especially Rwanda due to limitation on access of all TKIs. The aim of this study is to assess molecular response on Imatinib of patients with CML. Methods/Case Report This was a one arm open label prospective cohort study that recruited 31 patients with CML and on Imatinib for at least three months and followed for 11 months. The clinical features at diagnosis and recruitment were captured from the hospitals filing systems and investigator’s own assessment at the time of recruitment respectively. Information was filled to a well-structured questionnaire. Lab results at the time of diagnosis was obtained from laboratories reporting systems. Samples for full blood count and BCR-ABL1/ABL1 were withdrawn from the patients at the time of diagnosis and they were run at University Teaching Hospital of Kigali (CHUK). Data analysis was performed using Statistical Package for the Social Sciences (SPSS 28) and South Texas Art Therapy Association (STATA 15.0). Results (if a Case Study enter NA) Better response according to European LeukemiaNet (ELN) defined as optimal response was found among only 38.7% and resistance to imatinib defined by ELN as Failure and warning was found in 45.2% and 16.1% respectively. The eleven months survival rate was 93.5% in which it is 85.7% among those in treatment failure group. Late presentation showed by presence of very high White Blood Cells above 100x109/L and massive splenomegaly at diagnosis, and poor adherence to Imatinib according to Morsiky Medication Adherence Scale (MMAS-8) are associated with poor molecular response to Imatinib. Conclusion CML is a serious disease especially to those who suffer from it; on time diagnosis, access to all available lines of TKIs and better follow up are crucial for patients with CML to access the same life expectancy as general population as it is in developed world.

Effect of Fresnel prism in small-angle esotropia (≤ 20 prism diopters) with fixation preference.

We aimed to investigate the effects of Fresnel prism treatment for small-angle esotropia (≤ 20 prism diopters [PD]) with fixation preference. We included 32 patients with remaining esotropia ≤ 20 PD measured using the simultaneous prism and cover test (SPCT) after full refractive error correction. Fresnel prism was applied to make patients orthotropic with glasses. Treatment was discontinued if remaining esotropia ≤ 4 PD was sustained during two consecutive follow-ups (2-month intervals) or if the angle continued to increase with prism adaptation. Patients were divided into treatment success and failure groups. Treatment success was defined by motor and visual acuity (VA) aspects. Criteria for motor success was residual esotropia ≤ 8 PD in patients with initial esotropia > 8 PD and a 30% decrease of esotropia in those with initial esotropia ≤ 8 PD. VA success was improvement of > 0.2 logMAR in the non-dominant eye. The initial esodeviation angle was 6.92 ± 4.66 PD at distance and 10.53 ± 5.58 at near. The logMAR VA was 0.10 ± 0.13 and 0.26 ± 0.20 in the dominant and non-dominant eye, respectively. Among the 32 patients, 14 showed motor success. Among 26 patients whose VA could be measured, 15 showed VA success. Factors influencing motor success were a small amount of maximum prescribed Fresnel prism, less frequent need for Fresnel prism adaptation, and high percentage of achieving orthotropia with Fresnel prism treatment. VA success was influenced by low frequency of anisometropia and the small amount of maximum prescribed Fresnel prism. Fresnel prism could be a non-invasive treatment option for some patients with small-angle esotropia with fixation preference. What is known The optimal approach for addressing small-angle esotropia is a topic of debate. Not much research has been conducted on Fresnel prism treatment in patients with small-angle esotropia. What is new Motor success and visual acuity improvement were observed in some patients undergoing Fresnel prism treatment. Factors contributing to motor success were the small maximum angle of esodeviation, the less frequent necessity for Fresnel prism adaptation, and the achievement of orthotropia during Fresnel prism treatment. Visual acuity improvement was hindered by the presence of anisometropia and thelarge maximum prescribed amount of Fresnel prism. Fresnel prism treatment can be used as a treatment option for some patients with small-angle esotropia with fixation preference.

Pediatric Epilepsy Genetic Testing Results and Long-term Seizure Freedom.

Objective: To determine whether there is a correlation of genetic diagnosis/result with long-term seizure freedom in pediatric epilepsy patients. Methods: This was a prospective and retrospective cohort study of children with epilepsy referred for genetic testing at a single center. The primary outcomes were presence and type of genetic diagnosis (pathogenic, benign, or variant of uncertain significance) and patient epilepsy status (seizure free, treatment failure, uncertain). Epilepsy gene panels were the primary method of genetic testing. Results: The prospective cohort had 22 patients followed for >11 years and for whom genetic testing was then performed; the retrospective cohort had 78 patients with previous genetic testing followed for >8 years. In the prospective cohort, one patient each of the seizure free or treatment failure groups had a pathogenic genetic variant; mean Combined Annotation Dependent Depletion (CADD) scores 22 and 24, respectively (P = .62). In the retrospective cohort, there was no difference in the number of variants (P = .97), the variant interpretations (P = .29 ClinVar, P = .39 lab interpretation) or mean CADD scores (P = .29) between the seizure-free, treatment failure, and uncertain epilepsy patients. Whole exome and genome sequencing identified pathogenic variants in 70% of patients with treatment failure but were not performed in seizure-free patients. Significance: Our findings show no correlation of the presence or type of epilepsy gene panel result with long-term seizure freedom in pediatric patients. The yield and specificity of pathogenic variants may be higher using whole exome and whole genome sequencing in patients with treatment-resistant epilepsy. Whole exome and whole genome sequencing, or more targeted understanding of specific variants, may be needed to improve the utility of pediatric epilepsy genetic testing.

Drug-Related Problems in HIV Treatment Failure.

Background Antiretroviral therapy (ART) is used in human immunodeficiency virus (HIV) treatment to reduce morbidity and mortality rates among people living with the virus. The types of drug-related problems (DRPs) and their causes that contributed to HIV treatment failure were unknown. Thus, this study aimed to determine the types and causes of DRPs associated with HIV treatment failure. Methods A multicentre, retrospective cohort study was conducted at the Infectious Disease Centre of Sungai Buloh Hospital, Selangor, and Tuanku Ja'afar Hospital, Negeri Sembilan. Data were collected from patients' medical records by reviewing the medical progress notes, laboratory parameters, and treatment regimen. Pharmaceutical Care Network of Europe's (PCNE) classification system V9.1 was used to identify and classify the types and causes of DRPs. Patients were classified as having treatment failure if the HIV RNA viral load was more than 1000 copies/ml for two consecutive readings. Patients were categorized as treatment successful if there was a decrease in HIV RNA viral load suppression after six months of ART initiation and had no history of persistent HIV RNA viral load greater than 1000 copies/ml for two consecutive measurements. Data were analyzed using the chi-square test. Results The number of patients recruited for this study was 355 (treatment success group = 263, treatment failure group = 92). Almost all patients (n = 354, 99.7%) had experienced at least one DRP. A total of 811 problems and 1605 causes of DRPs were encountered. The occurrence of DRPs in the HIV treatment failure group was 5.77 DRPs per patient compared to the success group (4.08 DRPs per patient). In the treatment failure group, treatment effectiveness was identified as the most frequent domain of problems (P) (P1: n = 169, 59.93%), followed by treatment safety (P2: n = 111, 39.36%). The common domains of causes (C) include patient-related (C7: n = 367, 69.11%), other (C9: n = 105, 19.77%), and drug selection (C1: n = 49, 9.23%). Significant differences were found in several causes (C7.1, C7.10, and C9.1) between the two groups. Conclusion The occurrence of DRPs in HIV treatment failure was high, contributing to treatment effectiveness and treatment safety issues.

Risk factors for vancomycin treatment failure in heterogeneous vancomycin-intermediate Staphylococcus aureus bacteremia.

The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.

A novel multivariate logistic model for predicting risk factors of failed treatment with carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia.

This study aimed to explore the risk factors for failed treatment of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia (CRAB-VAP) with tigecycline and to establish a predictive model to predict the incidence of failed treatment and the prognosis of CRAB-VAP. A total of 189 CRAB-VAP patients were included in the safety analysis set from two Grade 3 A national-level hospitals between 1 January 2022 and 31 December 2022. The risk factors for failed treatment with CRAB-VAP were identified using univariate analysis, multivariate logistic analysis, and an independent nomogram to show the results. Of the 189 patients, 106 (56.1%) patients were in the successful treatment group, and 83 (43.9%) patients were in the failed treatment group. The multivariate logistic model analysis showed that age (OR = 1.04, 95% CI: 1.02, 1.07, p = 0.001), yes. of hypoproteinemia (OR = 2.43, 95% CI: 1.20, 4.90, p = 0.013), the daily dose of 200 mg (OR = 2.31, 95% CI: 1.07, 5.00, p = 0.034), yes. of medication within 14 days prior to surgical intervention (OR = 2.98, 95% CI: 1.19, 7.44, p = 0.019), and no. of microbial clearance (OR = 0.31, 95% CI: 0.14, 0.70, p = 0.005) were risk factors for the failure of tigecycline treatment. Receiver operating characteristic (ROC) analysis showed that the AUC area of the prediction model was 0.745 (0.675-0.815), and the decision curve analysis (DCA) showed that the model was effective in clinical practice. Age, hypoproteinemia, daily dose, medication within 14 days prior to surgical intervention, and microbial clearance are all significant risk factors for failed treatment with CRAB-VAP, with the nomogram model indicating that high age was the most important factor. Because the failure rate of CRAB-VAP treatment with tigecycline was high, this prediction model can help doctors correct or avoid risk factors during clinical treatment.

CT findings as predictive factors for treatment failure in Mycobacterium abscessus complex lung disease: a retrospective cohort study

PurposeMycobacterium abscessus complex (MABC) commonly causes lung disease (LD) and has a high treatment failure rate of around 50%. In this study, our objective is to investigate specific CT patterns for predicting treatment prognosis and monitoring treatment response, thus providing valuable insights for clinical physicians in the management of MABC-LD treatment.MethodsWe retrospectively assessed 34 patients with MABC-LD treated between January 2015 and December 2020. CT scores for bronchiectasis, cellular bronchiolitis, consolidation, cavities, and nodules were measured at initiation and after treatment. The ability of the CT scores to predict treatment outcomes was analyzed in logistic regression analyses.ResultsThe CT scoring system had excellent inter-reader agreement (all intraclass correlation coefficients, > 0.82). The treatment failure (TF) group (17/34; 50%) had higher cavitation diameter (p = 0.049) and extension (p = 0.041) at initial CT and higher cavitation diameter (p = 0.049) and extension (p =0 .045), consolidation (p = 0.022), and total (p = 0.013) scores at follow-up CT than the treatment success (TS) group. The changes of total score and consolidation score (p = 0.049 and 0.024, respectively) increased in the TF group more than the TS group between the initial and follow-up CT. Multivariable logistic regression analysis showed initial cavitation extension, follow-up consolidation extension, and change in consolidation extension (adjusted odds ratio: 2.512, 2.495, and 9.094, respectively, per 1-point increase; all p < 0.05) were significant predictors of treatment failure.ConclusionsA high pre-treatment cavitation extension score and an increase in the consolidation extension score during treatment on CT could be alarm signs of treatment failure requiring tailor the treatment of MABC-LD carefully.

Evaluation of photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) in feline infectious keratitis-patient demographics, treatment protocols, risk factors, and treatment outcome: a retrospective study.

To describe patient demographics and treatment protocols in a population of feline patients undergoing photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) as an adjunctive treatment for infectious keratitis. Furthermore, to determine the proportion of PACK-CXL treatment success in the population studied, explore risk factors for treatment failure, and provide recommendations for future PACK-CXL clinical studies. Records from four veterinary ophthalmology practices were reviewed to identify eligible patients and extract data. Recorded variables included patient-related factors, ocular examination findings, PACK-CXL protocol parameters, and treatment outcome. Records for 153 cats (154 eyes) were included. Median age in the treatment success group was 8 years (interquartile range (IQR) 4-12), with a median ulcer depth of 30% (IQR 30-40). Median age in the treatment failure group was 10.5 years (IQR 4.75-12) with a median ulcer depth of 45.9% (IQR 30-75). Persian cats were the most represented brachycephalic breed (52 out of 64 cats). Modified PACK-CXL protocols were used, including fast energy delivery (134 eyes), and increased fluence (52 eyes). The overall proportion of success was 88% (95% CI 84-93), which was variable between clinics. Eighty-two of 89 mesocephalic cat eyes (92%), and 54 of 65 brachycephalic cat eyes (83%) were classified as treatment successes. PACK-CXL appeared to be a useful, adjunctive therapeutic modality for the treatment of infectious keratitis in the feline patient population presented here. Brachycephalic cats, older cats, and those with deeper ulcers may be at increased risk for treatment failure.

Improvement in axial rotation with bracing reduces the risk of curve progression in patients with adolescent idiopathic scoliosis.

New evidence highlights the significance of 3D in-brace correction for Adolescent Idiopathic Scoliosis (AIS) patients. This study explores how axial parameters relate to treatment failure in braced AIS patients. AIS patients (Sanders 1-5) undergoing Rigo-Chêneau bracing at a single institution were included. Axial vertebral rotation (AVR) was determined by utilizing pre-brace and in-brace 3D reconstructions from EOS® radiographs. The primary outcome was treatment failure: surgery or coronal curve progression > 5°. Minimum follow-up was two years. 75 patients (81% female) were included. Mean age at bracing initiation was 12.8 ± 1.3years and patients had a pre-brace major curve of 31.0° ± 6.5°. 25 patients (76% female) experienced curve progression > 5°, and 18/25 required surgical intervention. The treatment failure group had larger in-brace AVR than the success group (5.8° ± 4.1° vs. 9.9° ± 7.6°, p = 0.003), but also larger initial coronal curve measures. In-brace AVR did not appear to be associated with treatment failure after adjusting for the pre-brace major curve (Hazard Ratio (HR):0.99, 95% Confidence Interval (CI):0.94-1.05, p = 0.833). Adjusting for pre-brace major curve, patients with AVR improvement with bracing had an 85% risk reduction in treatment failure versus those without (HR:0.15, 95% CI:0.02-1.13, p = 0.066). At the final follow-up, 42/50 (84%) patients without progression had Sanders ≥ 7. While in-brace rotation was not an independent predictor of curve progression (due to its correlation with curve magnitude), improved AVR with bracing was a significant predictor of curve progression. This study is the first step toward investigating the interplay between 3D parameters, skeletal maturity, compliance, and brace efficacy, allowing a future prospective multicenter study. Retrospective study; Level III.

Ultrasound-based predictive indicators for treatment outcomes in pediatric vesicoureteral reflux

PurposeTo evaluate the effectiveness of preoperative ultrasound (US) measurements in predicting pediatric vesicoureteral reflux (VUR) treatment outcomes.MethodsThis prospective study enrolled 35 patients (53 renal units) aged 1–16 years who underwent subureteric injection therapy for primary VUR between July 2020 and June 2022. Preoperative ultrasound examinations measured the bladder wall thickness at the ureteral orifice, ureteral submucosal tunnel length, distal ureteral diameter, patient demographics, VUR grade, presenting complaints, bladder–bowel dysfunction, and renal scarring, and the impact of these variables on treatment success was analyzed.ResultsAmong the patients, 91.4% were female, with a mean age of 6.83 ± 3.84 years. A comparison between the treatment success and failure groups revealed no significant differences in the age, sex, VUR grade, laterality, bilaterality, presenting complaints, bladder–bowel dysfunction, bladder wall thickness, or distal ureteral diameter (p > 0.05). However, renal scarring occurred in 16 (38.1%) patients in the treatment success group and 10 (90.9%) in the treatment failure group (p = 0.002). The treatment failure group had shorter detrusor-to-ureteral orifice distances and smaller detrusor-ureteral orifice distance-to-distal ureteral diameter (D/U) ratios than that of the success group (p = 0.004 and p = 0.006, respectively). Patients with a detrusor-to-ureteral orifice distance < 7.4 mm had an 81.82% likelihood of treatment failure.ConclusionUltrasound measurements of the detrusor-to-ureteral orifice distance and D/U ratio proved reliable in predicting the success of endoscopic subureteric injection therapy for VUR.

Factors influencing the therapeutic failure of high-flow nasal cannula oxygen humidification in patients with interstitial pneumonia complicated by respiratory failure.

The aim of this study was to explore the factors influencing the treatment failure of high-flow nasal cannula (HFNC) therapy in patients with interstitial pneumonia (IP) complicated by respiratory failure. A total of 158 patients with IP and respiratory failure treated with HFNC in our hospital from January 2020 to August 2023 were selected as the study population. Based on treatment efficacy, they were categorized into the HFNC treatment failure group and the HFNC treatment success group. Clinical data were compared between the two groups. Multiple logistic regression analysis was employed to identify independent factors influencing treatment failure, and the predictive value of these factors for HFNC treatment failure was assessed using receiver operating characteristic (ROC) curve analysis. After 7 days of HFNC treatment, among the 158 patients with IP and respiratory failure, 25 (15.8%) declared treatment failure, while the remaining 133 (84.2%) showed treatment success. Patients in the HFNC treatment failure group had significantly higher age, duration of IP, pre-treatment respiratory rate, C-reactive protein (CRP), and controlling nutritional status (CONUT) scores compared to the HFNC treatment success group. The PaO2/FiO2 ratio, left ventricular ejection fraction, and Glasgow Coma Scale (GCS) were significantly lower in the HFNC treatment failure group (p<0.05). Multiple logistic regression analysis revealed that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores were independent factors influencing HFNC treatment failure in patients with IP and respiratory failure (p<0.05). Lower PaO2/FiO2 ratio and GCS scores, and higher CRP and CONUT scores were associated with an increased risk of HFNC treatment failure. ROC curve analysis indicated that pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores in patients with IP and respiratory failure had a high predictive value for HFNC treatment failure (p<0.05). The HFNC failure rate in patients with IP and respiratory failure is 15.8%. Pre-treatment PaO2/FiO2 ratio, CRP, CONUT, and GCS scores are independent factors associated with HFNC treatment failure and warrant clinical attention.

Impact of headache frequency and preventive treatment failure on quality of life, disability, and direct and indirect costs among individuals with episodic migraine in the United States.

To evaluate unmet needs among individuals with episodic migraine (EM) in the United States (US). Data are limited on the impact of headache frequency (HF) and preventive treatment failure (TF) on the burden of migraine in the US. A retrospective, cross-sectional analysis of 2019 National Health and Wellness Survey (NHWS) data was conducted from an opt-in online survey that identified respondents (aged ≥18 years) in the US with self-reported physician-diagnosed migraine. Participants were stratified by HF (low: 0-3 days/month; moderate-to-high: 4-14 days/month) and prior preventive TF (preventive naive; 0-1 TF; ≥2 TFs). Comparisons were conducted between preventive TF groups using multivariable regression models controlling for patient demographic and health characteristics. Among individuals with moderate-to-high frequency EM, the NHWS identified 397 with ≥2 TFs, 334 with 0-1 TF, and 356 as preventive naive. The 36-item Short-Form Health Survey (version 2) Physical Component Summary scores were significantly lower among those with ≥2 TFs, at a mean (standard error [SE]) of 41.4 [0.8] versus the preventive-naive 46.8 [0.9] and 0-1 TF 44.5 [0.9] groups; p < 0.001 for both). Migraine Disability Assessment Scale scores were significantly higher in the ≥2 TFs, at a mean (SE) of 37.7 (3.9) versus preventive-naive 26.8 (2.9) (p < 0.001) and 0-1 TF 30.1 (3.3) (p = 0.011) groups. The percentages of time that respondents experienced absenteeism (mean [SE] 21.6% [5.5%] vs. 13.4% [3.6%]; p = 0.022), presenteeism (mean [SE] 55.0% [8.3%] vs. 40.8% [6.5%]; p = 0.015), overall work impairment (mean [SE] 59.4% [5.6%] vs. 45.0% [4.4%]; p < 0.001), and activity impairment (mean [SE] 56.8% [1.0%] vs. 44.4% [0.9%]; p < 0.001) were significantly higher in the ≥2 TFs versus preventive-naive group. Emergency department visits (preventive-naive, p = 0.006; 0-1 TF, p = 0.008) and hospitalizations (p < 0.001 both) in the past 6 months were significantly higher in the ≥2 TFs group. Direct and indirect costs were significantly higher in the ≥2 TFs (mean [SE] $24,026 [3460]; $22,074 [20]) versus 0-1 TF ($10,897 [1636]; $17,965 [17]) and preventive-naive ($11,497 [1715]; $17,167 [17]) groups (p < 0.001 for all). Results were similar in the low-frequency EM group. In this NHWS analysis, individuals with more prior preventive TFs experienced significantly higher humanistic and economic burden regardless of HF.

Effectiveness and Tolerability of Dual Therapy with Dolutegravir Plus Darunavir/cobicistat in Treatment-Experienced Patients with HIV: A 144-Week Follow-Up.

A dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG+DRV/c) is a promising alternative for patients with human immunodeficiency virus (HIV) with resistance or intolerance to nucleoside reverse transcriptase inhibitors, especially those with a history of treatment failure. We included all treatment-experienced patients with HIV who switched to the DTG+DRV/c regimen at a tertiary university hospital. We assessed the regimen's effectiveness, safety, and tolerability through serial laboratory data and clinical findings. The primary endpoint was the proportion of patients with plasma HIV-RNA levels <50 copies/mL at week 144 post-switch. The secondary endpoints were safety and tolerability assessments. Our retrospective analysis involved 40 patients. The leading reasons for switching to DTG+DRV/c were treatment failure in 17 patients (42.5%), simplification after multiple previous regimens in 15 (37.5%), and adverse drug reactions in 8 (20.0%). Among the 17 patients in the treatment failure group, we observed enhanced viral suppression and improved CD4+ T-cell counts after initiating the dual regimen. In the non-treatment failure group (23 patients), viral suppression and CD4+ T-cell levels were consistently maintained. No significant alterations in renal function, liver function, glucose levels, or lipid profiles were observed post-switch. High tolerability was observed, with 34/40 patients (85.0%) responding well to the regimen. However, six patients discontinued treatment before reaching the 144-week mark. Our findings confirm that DTG+DRV/c is an effective and well-tolerated switch therapy regimen for treatment-experienced patients with HIV, with sustained benefits observed for up to 144 weeks of follow-up. This regimen showed adaptability across different patient groups and demonstrated virological and immunological improvements, particularly in patients with a history of treatment failure.

Predictors of Phosphodiesterase Type 5 Inhibitor Treatment Failure in Patients Diagnosed With Erectile Dysfunction.

Erectile dysfunction (ED) is a prevalent condition, especially in aging populations, with significant implications for quality of life. While phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line treatment, a substantial percentage of patients do not respond satisfactorily. This study aimed to identify predictors of PDE5I treatment failure in ED patients. Data from January 2016 to January 2022 was reviewed for patients with ED who either failed PDE5I treatment or had a successful outcome. Demographic, medical, and laboratory data were collected and analyzed. Patients with contraindications or who did not complete the treatment were excluded. The treatment failure group comprised 288 patients, while 225 age-matched patients formed the control responder group. There were no significant differences in marriage duration, comorbidities, smoking, or BMI. However, HbA1c levels, free testosterone, and SHBG were significantly different between the two groups. This study found that high HbA1c levels, low free testosterone, and high sex hormone-binding globulin (SHBG) were associated with PDE5I treatment failure. Managing high HbA1c levels and addressing hormonal imbalances may enhance PDE5I treatment effectiveness in ED patients. However, further research is needed to explore other factors contributing to treatment outcomes.

Predicting the effectiveness of drugs used for treating cardiovascular conditions in newborn infants.

Cardiovascular support (CVS) treatment failure (TF) is associated with a poor prognosis in preterm infants. Medical charts of infants with a birth weight <1500 g who received either dopamine (Dp) or dobutamine (Db), were reviewed. Treatment response (TR) occurred if blood pressure increased >3rd centile for gestational age or superior vena cava flow was maintained >55 ml/kg/min, with decreased lactate or less negative base excess, without additional CVS. A predictive model of Dp and Db on TR was designed and the impact of TR on survival was analyzed. Sixty-six infants (median gestational age 27.3 weeks, median birth weight 864 g) received Dp (n = 44) or Db (n = 22). TR occurred in 59% of the cases treated with Dp and 31% with Db, p = 0.04. Machine learning identified a model that correctly labeled Db response in 90% of the cases and Dp response in 61.4%. Sixteen infants died (9% of the TR group, 39% of the TF group; p = 0.004). Brain or gut morbidity-free survival was observed in 52% vs 30% in the TR and TF groups, respectively (p = 0.08). New predictive models can anticipate Db but not Dp effectiveness in preterm infants. These algorithms may help the clinicians in the decision-making process. Failure of cardiovascular support treatment increases the risk of mortality in very low birth weight infants. A predictive model built with machine learning techniques can help anticipate treatment response to dobutamine with high accuracy. Predictive models based on artificial intelligence may guide the clinicians in the decision-making process.

Factors Affecting Topical Treatment Success in Pediatric Scabies Cases: a Cross-Sectional Study.

Scabies is a common disease that affects the pediatric population. Treatment failure and relapse occur frequently in children. We aimed to identify the factors that affect topical treatment success in pediatric scabies patients. A multicenter cross-sectional study was conducted from April 2022 to December 2022. Pediatric scabies cases were classified as belonging to either the treatment failure (TF) group or the treatment success (TS) group. We enrolled 170 patients for the study. In the TF group, the presence of symptomatic household members and referrals from physicians other than dermatologists were more common (both P < 0.001), and relapse rates and total symptom duration were higher (P = 0.007, P < 0.001, respectively). Regarding treatment agents, 5% permethrin was more commonly used in the TF group (71.1% versus 25%; P < 0.001). The proportion of patients treated with sulfur preparations was significantly higher in the TS group (60.7% versus 16.9%; P < 0.001). Misapplication of topical therapy was significantly more common in the TF group (P < 0.001), with statistically significant errors being (i) lack of treatment of close contacts (p<0,001), (ii) single application (P < 0.001), and (iii) local application (P = 0.027). A multivariate analysis revealed that TS was mainly associated with (i) the presence of atopy (odds ratio [OR] 6.12, 95% CI: 1.39-27.04), (ii) the absence of symptomatic household members (OR 6.31, 95% CI: 2.14-18.63), and (iii) presentation to a dermatologist rather than another specialist (OR 6.51, 95% CI: 2.11-20.13). The use of permethrin negatively affected treatment success (OR 0.22, 95% CI: 0.07-0.71). Pediatric scabies patients should be treated before other family members become infested and with topicals other than permethrin. In addition, awareness of scabies needs to be increased among non-dermatologists.

Antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure.

Tuberculosis stands as a prominent cause of mortality in developing countries. The treatment of tuberculosis involves a complex procedure requiring the administration of a panel of at least four antimicrobial drugs for the duration of six months. The occurrence of treatment failure after the completion of a standard treatment course presents a serious medical problem. The purpose of this study was to evaluate antimicrobial drug resistant features of Mycobacterium tuberculosis associated with treatment failure. Additionally, it aimed to evaluate the effectiveness of second line drugs such as amikacin, linezolid, moxifloxacin, and the efflux pump inhibitor verapamil against M. tuberculosis isolates associated with treatment failure. We monitored 1200 tuberculosis patients who visited TB centres in Lahore and found that 64 of them were not cured after six months of treatment. Among the M. tuberculosis isolates recovered from the sputum of these 64 patients, 46 (71.9%) isolates were simultaneously resistant to rifampicin and isoniazid (MDR), and 30 (46.9%) isolates were resistant to pyrazinamide, Resistance to amikacin was detected in 17 (26,5%) isolates whereas resistance to moxifloxacin and linezolid was detected in 1 (1.5%) and 2 (3.1%) isolates respectively. Among MDR isolates, the additional resistance to pyrazinamide, amikacin, and linezolid was detected in 15(23.4%), 4(2.6%) and 1(1.56%) isolates respectively. One isolate simultaneously resistant to rifampicin, isoniazid, amikacin, pyrazinamide, and linezolid was also identified. In our investigations, the most frequently mutated amino acid in the treatment failure group was Serine 315 in katG. Three novel mutations were detected at codons 99, 149 and 154 in pncA which were associated with pyrazinamide resistance. The effect of verapamil on the minimum inhibitory concentration of isoniazid and rifampicin was observed in drug susceptible isolates but not in drug resistant isolates. Rifampicin and isoniazid enhanced the transcription of the efflux pump gene rv1258 in drug susceptible isolates collected from the treatment failure patients. Our findings emphasize a high prevalence of MDR isolates linked primarily to drug exposure. Moreover, the use of amikacin as a second line drug may not be the most suitable choice in such cases.

Predictive factors for treatment success of epidural steroid injections in patients with lumbar spinal surgery.

The efficacy of epidural steroid injections (ESIs) in the treatment of radicular pain in patients undergoing lumbar spinal surgery is still unclear. The aim of this study was to investigate the factors affecting the success of ESIs in the treatment of ongoing radicular pain in patients undergoing lumbar spinal surgery. This study was designed as a single-center, retrospective study, and was conducted at a Pain Management Center of a tertiary care center. A total of 260 patients with failed back surgery syndrome who received fluoroscopy-guided lumbar ESI were included. Treatment success was defined as ≥50% reduction in the numeric rating scale score at the one-month follow-up. The patients were divided into the treatment success and the treatment failure groups. The presence of spinal instrumentation was significantly lower in the treatment success group (p=0.045). Symptom duration and the numeric rating scale score at 1 hour were significantly lower in the treatment success group (p<0.05). The use of triamcinolone acetonide in the treatment success group was found to be significantly higher than in the treatment failure group (p=0.027). The short duration of symptoms and the absence of instrumentation seem to be prognostic factors that positively affect the success of ESI treatment in operated patients. A ≥50% pain reduction in the first hour after the procedure is a valuable indicator that treatment success can be achieved in the short term. Finally, the steroid type can also affect the treatment results.

Safety and survival analysis of haplo-identical hematopoietic stem cell transplantation in patients with severe aplastic anemia who had previous failure to antithymoglobulin treatment

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.