Lower Rate Of Treatment Failure Research Articles

Microbiology, Treatment, and Postoperative Outcomes of Gram-Negative Prosthetic Joint Infections-A Systematic Review of the Literature.

Gram-negative prosthetic joint infections (PJIs) represent 10% to 25% of all PJIs and are associated with worse outcomes than gram-positive infections. We sought to assess the microbiology, surgical treatment, and outcomes of patients with gram-negative PJIs. A systematic review using the PubMed and Embase databases was conducted. Our study was conducted following the PRISMA guidelines. Included studies were assessed for quality using the STROBE checklist. The primary outcome of analysis was treatment failure. A total of 593 patients with gram-negative PJIs were included. Two-year survival free of treatment failure for hip and knee PJIs was 66% and 68% for acute infections, 39% and 78% for acute hematogenous infections, and 75% and 63% for chronic infections, respectively. Two-year survival free of treatment failure for acute infections treated with débridement, antibiotics, and implant retention was 65% and 67% for hip and knee PJIs, respectively. Exchange of the polyethylene during débridement, antibiotics, and implant retention was associated with higher treatment success (P = 0.045). Chronic PJIs treated with two-stage revision had a two-year treatment success rate of 87% and 65% for the hip and knee, respectively. Risk factors of treatment failure were chronic obstructive pulmonary disease and C-reactive protein ≥30 mg/L in acute PJIs and female sex, knee infection, and previously revised implant in chronic PJIs. Acute PJIs caused by Pseudomonas spp. were associated with lower treatment failure rates. Gram-negative PJIs are associated with a high treatment failure rate. Patient comorbidities, preoperative biochemical tests, microorganism etiology, and PJI characteristics affected the treatment success rate.

High Flow Nasal Cannula Versus Conventional Oxygen Therapy and Incidence of Post-Extubation Airway Obstruction in PICU: An Open-Label Randomized Controlled Trial (HiFloCOT-PICU Trial).

To study the impact of high flow nasal cannula (HFNC) vs. conventional oxygen therapy (COT) (by simple nasal cannula) as respiratory support after extubation on the rates of post-extubation airway obstruction (PEAO) among mechanically ventilated critically ill children. This open-label randomized controlled trial was conducted in pediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India over a period of 7 mo (11 August 2021 to 10 March 2022). Children aged 3 mo to 12 y who required invasive mechanical ventilation for > 72h and had passed spontaneous breathing trial (ready for extubation) were enrolled and randomized by computer generated block randomization to receive HFNC or COT after extubation. Primary outcome was rate of PEAO (assessed by modified Westley croup score, mWCS) within 48h of extubation; and secondary outcomes were rate and number of adrenaline nebulization, treatment failure (requiring escalation of respiratory support), extubation failure, adverse events, and length of PICU stay in two groups. During the study period, 116 children were enrolled (58 each in HFNC and COT groups). There was no difference in rate of PEAO (55% vs. 51.7%, respectively), need of adrenaline nebulization, extubation failure, adverse events, and duration of PICU stay in two groups. However, the HFNC group had significantly lower rates of treatment failure (27.6% vs. 48.3%, p = 0.02). The rate of PEAO was similar in HFNC and COT groups. However, HFNC group had significantly lower rate of treatment failure requiring escalation of respiratory support.

Antibiotic treatment for patients with exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundAlthough respiratory tract infection is a significant factor that triggers exacerbation of chronic obstructive pulmonary disease (COPD), the benefit of antibiotics for patients with COPD exacerbation remains controversial. It is necessary to evaluate the efficacy and safety of antibiotics versus placebo in such patients. MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials of antibiotics versus placebo for the treatment of COPD exacerbation, and compared the frequencies of treatment failure, mortality, and adverse events between patients treated with antibiotics and those treated with placebo. ResultsA total of six studies were included in this meta-analysis. The frequency of treatment failure was significantly lower in the antibiotic-treated patients compared to the placebo-treated patients (odds ratios [OR] 0.50, 95% confidence intervals [CI] 0.35–0.71, p = 0.0001). There was no significant difference between the two groups in mortality (OR 0.44, 95% CI 0.05–3.76, p = 0.45) or frequency of adverse events (OR 1.05, 95% CI 0.75–1.48, p = 0.78). ConclusionIn the current systematic review and meta-analysis, we found that antibiotics were superior to placebo in patients with exacerbated COPD, as shown by the lower treatment failure rate.

Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis.

Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5days) with long-course (≥ 7days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15-2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47-1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8-2.71; p = 0.270). Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15months. PROSPERO identifier: CRD42023456745. What is Known: • Urinary tract infections (UTIs) are common in children, affecting around 7.5% of those under 18. • The optimal duration of antibiotic treatment for pediatric UTIs has been a subject of debate. What is New: • Short-course therapy (5 or fewer days) was associated with a significantly higher failure rate when compared to long-course therapy. • There was no significant difference in reinfection and relapse rates within 15months between short and long-course therapy.

Core decompression combined with platelet-rich plasma-augmented bone grafting for femur head necrosis: a systematic review and meta-analysis.

The clinical potential of biologic augmentation in core decompression and bone grafting for femoral head necrosis is widely acknowledged, with platelet-rich plasma (PRP) being a frequently employed biologic adjunct. However, its clinical application is not standardized, and high-level evidence is lacking. This study aimed to evaluate the efficacy and safety of core decompression and bone grafting combined with PRP for femur head necrosis. Several databases were systematically retrieved for randomized controlled trials comparing core decompression and bone grafting combined with or without PRP. A systematic review and meta-analysis were conducted following the PRISMA 2020 and AMSTAR 2 guidelines. The study is registered with PROSPERO under the code CRD42022361007, and it is also listed in the research registry under the identification number reviewregistry1537. Eleven studies with 642 participants (742 hips) were included. The pooled estimates revealed that when core decompression and bone grafting were combined with PRP, the Harris hip score (mean difference: 7.98; 95% CI: 5.77-10.20; P <0.001), visual analog scale (SMD: -0.68; 95% CI: -0.96 - -0.40; P <0.001) and the pain component of Harris hip score (SMD: 8.4; 95% CI: 4.12-12.68; P <0.001), and reduction of radiographic progression [risk ratio (RR): 0.40; 95% CI: 0.27-0.59; P <0.001] were superior to core decompression and bone grafting alone. Fewer patients with treatment failure (RR: 0.27; 95% CI: 0.14-0.52; P <0.001) and higher good-to-excellent results (RR: 1.48; 95% CI: 1.17-1.86; P <0.001) were observed in treatment groups than control groups. Meanwhile, the pooled analysis substantiated the superior safety profile of PRP (RR: 0.29; 95% CI: 0.11-0.77; P =0.01). The combination of core decompression and bone grafting with PRP is superior to the approach without PRP, demonstrating enhanced effectiveness in terms of function, pain relief, and radiographic progression. Additionally, it results in lower rates of treatment failure and adverse events. However, further high-quality RCTs are needed to evaluate their effectiveness due to methodological and implementation limitations observed in the existing evidence.

Influence of Surgeon Experience and Clinic Volume on Subjective Knee Function and Revision Rates in Primary ACL Reconstruction: A Study from the Swedish National Knee Ligament Registry.

Anterior cruciate ligament reconstruction (ACLR) performed by high-volume surgeons/clinics has been associated with increased graft individualization and decreased operating times, complication rates, and total costs. To investigate the influence of surgeon/clinic volume on subjective knee function and revision surgery rates at 2 years after primary ACLR. Cohort study; Level of evidence, 3. Data from the Swedish National Knee Ligament Registry were used to study patients who underwent primary ACLR between 2008 and 2019. Surgeons/clinics were categorized based on a combination of total caseload volume (cutoff: 50 ACLRs/surgeon, 500 ACLRs/clinic) and annual volume (cutoff: 29 ACLRs/year/surgeon, 56 ACLRs/year/clinic). The thresholds of minimal important change (MIC), Patient Acceptable Symptom State (PASS), and treatment failure (TF) relative to the Knee injury and Osteoarthritis Outcome Score (KOOS) and KOOS4 (mean score of the KOOS Pain, Symptoms, Sports/Rec, and QoL subscales) were applied. Adjusted multivariable logistic regression was performed to assess variables influencing the MIC, PASS, or TF of the KOOS and KOOS4. Adjusted Cox regression analysis was conducted to determine the hazard ratio of subsequent ACLR. Of 35,371 patients, 16,317 had 2-year follow-up outcome data and were included. Patients who underwent primary ACLR by high-volume surgeons had significantly higher MIC and PASS rates and lower TF rates when compared with patients who underwent the procedure by low-volume surgeons: MICKOOS4: 70.6% vs 66.3%; PASSKOOS4: 46.0% versus 38.3%; and TFKOOS4: 8.7% versus 11.8% (all P < .02). Significantly decreased odds of achieving MICKOOS4 (OR, 0.74; 95% CI, 0.62-0.88) and PASSKOOS4 (OR, 0.71; 95% CI, 0.60-0.84) were found for ACLRs performed by low-volume surgeons. Clinic volume did not influence the odds of reaching MIC, PASS, or TF. Overall, 804 patients (2.3%) underwent subsequent ACLR at <2 years, with significantly higher revision rates among patients operated on at high-volume clinics (2.5% vs 1.7%; P < .001). However, in the adjusted Cox regression, surgeon/clinic volume had no influence on subsequent ACLR rates. High-volume surgeons/clinics had decreased time to surgery, operating time, perioperative complication rates, and use of thromboprophylaxis and nonroutine antibiotics (P < .001). Patients who underwent primary ACLR by high-volume surgeons experienced increased improvement and satisfaction regarding subjective knee function. Factors other than surgical volume influenced subsequent surgery rates. Patients might benefit from undergoing primary ACLR by high-volume providers.

Surgery for Vertebral Osteomyelitis Lowers 1-Year Mortality and Failure Rates Compared with Nonsurgical Treatment: A Propensity-Matched Analysis.

The aim of this study was to determine differences between patients who underwent surgical treatment and those who underwent nonsurgical treatment of vertebral osteomyelitis (VO) and to identify potential factors influencing treatment failure (death and/or recurrence within 1 year). We performed a retrospective analysis of clinical data prospectively collected from patients treated for VO between 2008 and 2020. The decision between surgical and nonsurgical treatment was made for each patient based on defined criteria. A 1:1 propensity score matching was performed to exclude confounders between the 2 treatments. Univariate and multivariable analyses were performed to identify potential risk factors for death and/or recurrence within the first year after VO diagnosis. Forty-two patients (11.8%) were treated nonsurgically and 313 patients (88.2%) underwent surgery. A higher percentage of the surgically treated patients than the nonsurgically treated patients had an American Society of Anesthesiologists score of >2 (69.0% versus 47.5%; p = 0.007), and the thoracic spine was affected more often in the surgical group (30.4% versus 11.9%; p = 0.013). Endocarditis was detected significantly more often in the nonsurgically treated patients (14.3% versus 4.2%; p = 0.018). The recurrence rate was 3 times higher in the nonsurgically treated patients (16.7% versus 5.4%; p = 0.017), but this difference was no longer detectable after propensity matching. After matching, the nonsurgically treated patients showed an almost 7-fold higher 1-year mortality rate (25.0% versus 3.7%; p = 0.018) and an almost 3-fold higher rate of treatment failure (42.9% versus 14.8%; p = 0.022). Multivariable analysis revealed nonsurgical treatment and bacteremia to be independent risk factors for treatment failure. In our matched cohort of patients with VO, surgical intervention resulted in a significantly lower rate of treatment failure (death and/or recurrence within 1 year) compared with nonsurgical intervention. Furthermore, nonsurgical treatment was an independent risk factor for treatment failure. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

1306. Lower Treatment Failure Rates in Patients with Non-Staphylococcal Prosthetic Joint Infections (PJI) Treated with Debridement and Implant Retention (DAIR) Receiving Chronic Antibiotic Suppression (CAS)

Abstract Background PJI occurs in 0.5-2% of Joint Arthroplasty. Patients with acute non-Staphylococcal PJI who undergo DAIR are treated with 6 weeks of antimicrobials after which CAS may be considered. We aimed to compare the incidence of treatment failure between people who received CAS and those who did not. Methods This is a retrospective cohort study of patients admitted to Veterans Affairs (VA) hospitals from 2003-2017 with a non-Staphylococcal PJI, underwent DAIR and received 6 weeks of antimicrobial treatment (Table 1). CAS was defined as at least 30 days of oral antibiotics after 6 weeks of antimicrobial treatment. Duration of CAS was categorized as short (1-3 months), moderate (3-6 months) and long ( &amp;gt;6 months) (Fig 1). Patients were followed for 5 years. Treatment failure was defined as microbiologically confirmed recurrent PJI, additional debridement or re-operation at the same site. Cause-specific Kaplan-Meier curves were used to compare treatment failure rates between those who did and did not receive CAS, censoring on death. Results Among 468 patients with non-staphylococcal PJI who underwent DAIR, 208 (44.4%) received CAS. Patients with Enterococcus PJI were statistically more likely to receive CAS. K-M curves showed patients on CAS had a higher estimated failure free survival probability at 5 years when compared to those who did not get CAS (66% vs. 55%, p&amp;lt; 0.01) (Fig 2). When antibiotic use was considered as a time-dependent covariate, CAS was associated with a decreased hazard of treatment failure (hazard ratio (HR): .47 (95% confidence interval [CI]: 0.29, 0.76). After statistically adjusting for surgical site, severity of illness, and alcohol abuse, a short duration of CAS was significantly associated with decreased treatment failure (HR=0.24; 95% CI: 0.11, 0.52). There was no significant association between moderate or long duration of CAS and treatment failure (Table 2) Table 2 Conclusion A short duration of CAS may be beneficial among patients with non-Staphylococcal PJI who underwent DAIR. However, there was not a statistically significant association between longer duration of CAS use and treatment failure. Thus, the risks and benefits of long-term antibiotics should be weighed when aiming to prevent recurrence of PJI. Disclosures Mireia Puig-Asensio, MD, GILEAD: Honoraria Andrew Pugely, MD, MBA, Globus Medical: Advisor/Consultant|Globus Medical: Grant/Research Support|Globus Medical: IP royalties|Medtronic: Advisor/Consultant|Medtronic: Grant/Research Support|RDB Bioinformatics: Grant/Research Support|United Healthcare: Advisor/Consultant

A PROSPECTIVE STUDY OF LOOP DRAINAGE OF SUBCUTANEOUS ABSCESS- A NEW GOLD STANDARD?

Abscess is a common ailment presenting to the Surgical OPD and Emergency on a daily basis. Conventionally, incision and drainage(ID) by making an incision in the most fluctuant part and later packing the cavity with a wick has been practised(1). We postulate a newer method of loop drainage(LD) of the cavity should be the new Gold Standard. This study aims to compare clinical outcome on conventional incision and drainage versus loop drainage of subcutaneous abscess. Study design was a prospective, observational study. Study was conducted in Silchar Medical College, from 23/12/2022 - 23/06/2023 , with a total of 120 patients. Of the 120 patients followed up, 48 underwent ID and 72 underwent LD. LD patients had a better pain profile post operatively on FLACC and Likert scales (-7.62 D1, 5.46 D3, 4.05 D5), lower treatment failure rate(-10.8%), more favourable scar formation(POSAS patient and observer -17.52, - 10.30). Latex loops had better scores than PVC loops(POSAS - 15.30, - 9.45 vs -18.34, - 12.45). Loop drainage of abscess, especially with Latex Loops have lower failure rates, better compliance and better clinical outcomes. Especially in paediatric patients where ID is more difficult and cumbersome and loss to follow up more common, LD should no doubt be considered the new Gold Standard in surgical practice.

Short-Course Therapy for Urinary Tract Infections in Children

There is a paucity of pediatric-specific comparative data to guide duration of therapy recommendations in children with urinary tract infection (UTI). To compare the efficacy of standard-course and short-course therapy for children with UTI. The Short Course Therapy for Urinary Tract Infections (SCOUT) randomized clinical noninferiority trial took place at outpatient clinics and emergency departments at 2 children's hospitals from May 2012, through, August 2019. Data were analyzed from January 2020, through, February 2023. Participants included children aged 2 months to 10 years with UTI exhibiting clinical improvement after 5 days of antimicrobials. Another 5 days of antimicrobials (standard-course therapy) or 5 days of placebo (short-course therapy). The primary outcome, treatment failure, was defined as symptomatic UTI at or before the first follow-up visit (day 11 to 14). Secondary outcomes included UTI after the first follow-up visit, asymptomatic bacteriuria, positive urine culture, and gastrointestinal colonization with resistant organisms. Analysis for the primary outcome included 664 randomized children (639 female [96%]; median age, 4 years). Among children evaluable for the primary outcome, 2 of 328 assigned to standard-course (0.6%) and 14 of 336 assigned to short-course (4.2%) had a treatment failure (absolute difference of 3.6% with upper bound 95% CI of 5.5.%). Children receiving short-course therapy were more likely to have asymptomatic bacteriuria or a positive urine culture at or by the first follow-up visit. There were no differences between groups in rates of UTI after the first follow-up visit, incidence of adverse events, or incidence of gastrointestinal colonization with resistant organisms. In this randomized clinical trial, children assigned to standard-course therapy had lower rates of treatment failure than children assigned to short-course therapy. However, the low failure rate of short-course therapy suggests that it could be considered as a reasonable option for children exhibiting clinical improvement after 5 days of antimicrobial treatment. ClinicalTrials.gov Identifier: NCT01595529.

An examination of loss to follow-up and potential bias in outcome ascertainment in a study of direct-to-patient telemedicine abortion in the United States

ObjectivesTo examine associations between factors associated with loss to follow-up and effectiveness in the TelAbortion project, which provided medication abortion by direct-to-patient telemedicine and mail in the United States. Study designThe study population for this descriptive analysis included abortions among participants enrolled in the TelAbortion study with data present in a web-based database tool from November 2018 to September 2021 who were mailed a medication package. The analysis included information on abortions across nine sites. In this analysis, we used generalized estimating equations to examine factors associated with loss to follow-up and effectiveness. ResultsOf the 1831 abortions included in this analysis, 1553 (84.8%) were classified as having complete follow-up and 278 (15.2%) were classified as lost to follow-up. In a multivariable analysis, factors significantly associated with loss to follow-up included history of medical abortion, education, gestational age, study site, and whether the TelAbortion was performed pre- or post-COVID-19 onset (p < 0.05). The rate of treatment failure (i.e., abortions resulting in continuing pregnancy or uterine evacuation) reported in this study was 5.1%. The only covariate associated with both loss to follow-up and treatment failure was higher gestational age. However, using gestational age to impute missing abortion outcomes did not substantially change the estimated failure rate. ConclusionsAbortions that were lost to follow-up differed substantially from those with complete follow-up, which could bias the effectiveness estimate. However, imputing outcomes based on available and appropriate pretreatment data did not substantially affect the estimate. This finding is encouraging, although it does not exclude the possibility of bias due to unmeasured factors. ImplicationsSignificant differences between abortion cases with complete follow-up and those lost to follow-up provide insights into abortion cases that may be at a higher risk for being lost. The low treatment failure rate indicates that the telemedicine provision of medication abortion is effective.

Clinical outcomes and toxicities of 100 patients treated with proton therapy for chordoma on the proton collaborative group prospective registry

BackgroundWe present efficacy and toxicity outcomes among patients with chordoma treated on the Proton Collaborative Group prospective registry. MethodsConsecutive chordoma patients treated between 2010–2018 were evaluated. One hundred fifty patients were identified, 100 had adequate follow-up information. Locations included base of skull (61%), spine (23%), and sacrum (16%). Patients had a performance status of ECOG 0–1 (82%) and median age of 58 years. Eighty-five percent of patients underwent surgical resection. The median proton RT dose was 74 Gy (RBE) (range 21–86 Gy (RBE)) using passive scatter proton RT (PS-PBT) (13%), uniform scanning proton RT (US-PBT) (54%) and pencil beam scanning proton RT (PBS-PBT) (33%). Rates of local control (LC), progression-free survival (PFS), overall survival (OS) and acute and late toxicities were assessed. Results2/3-year LC, PFS, and OS rates are 97%/94%, 89%/74%, and 89%/83%, respectively. LC did not differ based on surgical resection (p = 0.61), though this is likely limited by most patients having undergone a prior resection. Eight patients experienced acute grade 3 toxicities, most commonly pain (n = 3), radiation dermatitis (n = 2), fatigue (n = 1), insomnia (n = 1) and dizziness (n = 1). No grade ≥ 4 acute toxicities were reported. No grade ≥ 3 late toxicities were reported, and most common grade 2 toxicities were fatigue (n = 5), headache (n = 2), CNS necrosis (n = 1), and pain (n = 1). ConclusionsIn our series, PBT achieved excellent safety and efficacy outcomes with very low rates of treatment failure. CNS necrosis is exceedingly low (<1%) despite the high doses of PBT delivered. Further maturation of data and larger patient numbers are necessary to optimize therapy in chordoma.

Intranasal Dexmedetomidine Use in Pediatric Patients for Anxiolysis in the Emergency Department.

In recent years, dexmedetomidine has gained traction as a treatment for anxiolysis in the emergency department (ED). When used with an atomizer, it may also be given intranasally for anxiolysis. The primary objective was to determine the level of ED provider satisfaction and comfort with intranasal (IN) dexmedetomidine for anxiolysis in pediatric patients with behavioral agitation and/or acute psychosis. The secondary objectives included determining safety, rates of therapy failure, and ED length of stay compared with oral midazolam. The efficacy of IN dexmedetomidine versus oral midazolam in patients with autism spectrum disorder (ASD) was also evaluated. This was a single-center, prospective study in a pediatric ED from March 1 to December 31, 2021. Patients were included in the study if the ED provider requested IN dexmedetomidine anxiolysis and completed a postadministration survey. Safety and efficacy outcomes were assessed by chart review and compared with patients who received oral midazolam during the same study period. Efficacy was defined as the rate of treatment failure, as the need for procedural termination, progression to procedural sedation, or the requirement of additional medications for anxiolysis. Sixty-two patients received IN dexmedetomidine {median dose [interquartile range (IQR)] of 3.05 [2.04-4.00] μg/kg/dose} compared with 58 who received oral midazolam [median (IQR) dose of 0.29 (0.25-0.48) mg/kg/dose). Providers reported high comfort and satisfaction scores, with median (IQR) scores of 90 (75-100) and 88 (60-100) of 100. Twenty-nine percent of patients experienced treatment failure, most commonly because of the need for additional medications. Those who received IN dexmedetomidine had a longer ED length of stay (6.0 vs 4.4 hours, P = 0.010). Among the patients with ASD, those who received IN dexmedetomidine had a lower rate of treatment failure compared with oral midazolam (21.2% vs 66.7%, P = 0.039). This study demonstrates that IN dexmedetomidine has high levels of provider comfort and satisfaction, moderately high success rate, and a promising safety profile. In addition, IN dexmedetomidine may be superior to oral midazolam in patients with ASD for anxiolysis, but additional studies are needed.

Cost-Effectiveness Analysis of Frontline Treatment with Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma

Introduction: The POLARIX trial (NCT03274492) recently demonstrated that substituting polatuzumab vedotin (pola), a CD79b-targeted antibody-drug conjugate, for vincristine in standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemoimmunotherapy for first-line therapy can prolong progression-free survival in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, the medication cost of pola-R-CHP (pola, rituximab, cyclophosphamide, doxorubicin, and prednisolone) regimen is substantially higher than that of R-CHOP treatment. It remains unknown whether the lower rate of treatment failure with pola-R-CHP can be translated into reduced subsequent healthcare costs, increased life years (LYs), and improved quality of life, which may offset the higher medication cost. This study aimed to investigate the cost-effectiveness of substituting pola for vincristine in first-line therapy for patients with newly diagnosed DLBCL from a US payer perspective. Methods: We developed a decision analytic model to project lifetime quality-adjusted life years (QALYs) gained, LYs gained, and direct healthcare costs in newly diagnosed DLBCL patients. The model utilized a hypothetical cohort of patients at 65 years (the median age of disease onset). Direct healthcare costs were adjusted to 2021 US dollars, and an annual rate of 3% was used to discount future costs and benefits. Incremental cost-effectiveness ratios (ICERs) were calculated, and a willingness-to-pay (WTP) threshold of USD 150,000 per QALY gained was used as the acceptable level for determining cost-effectiveness. Sensitivity analyses and scenario analyses were conducted to assess the uncertainty of the base-case scenario and input parameters. Results: Pola-R-CHP, compared to standard R-CHOP, was associated with an incremental cost of USD 90,439, an improvement of 0.89 QALYs and 1.14 LYs, leading to an ICER of USD 101,510/QALY. The model was most sensitive to the survival benefit provided by pola-R-CHP, the age of the patients at initial treatment, and the price of pola. The ICER would increase significantly if pola-R-CHP is ineffective in providing long-term remissions. Furthermore, the ICER value increased as patients were older at the beginning of the treatment. When patients were older than 76.5 years at initial treatment, the ICER would exceed the WTP threshold of USD 150,000/QALY. To make the pola-R-CHP regimen cost-effective in all age groups (up to 80 years old), the current price of pola, which was estimated to be USD 19,307 for 170 mg per treatment cycle, needed to be reduced by 20%. In the probabilistic sensitivity analysis, 48% and 73% of the iterations produced ICERs below WTP thresholds of USD 100,000/ QALY and USD 150,000/ QALY, respectively. Conclusion: Our study findings suggest that pola-R-CHP, compared to the standard R-CHOP regimen, could be a cost-effective strategy in treatment-naïve DLBCL patients aged 65 years from a US payer perspective. However, several noticeable factors that could affect the cost-effectiveness profile of pola-R-CHP therapy should be considered in decision-making. The follow-up period of the POLARIX trial was relatively short, and mature survival data would be required to fully evaluate the value of pola in the treatment of newly diagnosed DLBCL.

Retreatment with anti-tumor necrosis factor therapy in combination with an immunomodulator for recurrence of Crohn's disease after ileocecal resection results in prolonged continuation as compared to anti-tumor necrosis factor monotherapy.

A considerable proportion of Crohn's disease patients that undergo ileocecal resection (ICR) have failed anti-tumor necrosis factor (TNF) therapy preoperatively. This study aimed to assess the effectiveness of retreatment of anti-TNF therapy in patients with postoperative recurrence. A real-world cohort study was performed on Crohn's disease patients who underwent primary ICR after anti-TNF therapy failure, and who were retreated with anti-TNF therapy for postoperative symptomatic Crohn's disease. The primary outcome was treatment failure (the need for (re)introduction of corticosteroids, immunosuppressants, or biologicals or the need for re-resection). Sub-analyses were performed on the nature of preoperative anti-TNF failure (primary non-response, secondary loss of response, intolerance), indication for ICR (refractory, stricturing, penetrating disease), combination therapy with immunomodulators, retreatment with the same anti-TNF agent and preoperative exposure to 1 vs. >1 anti-TNF agents. In total, 66 of 364 patients retreated with anti-TNF therapy following ICR. Cumulative rates of treatment failure at 1 and 2 years were 28% and 47%. Treatment failure rate at 2 years was significantly lower in patients receiving combination therapy as compared to anti-TNF monotherapy (30% vs. 49%, P = 0.02). No difference in treatment failure was found with regards to the nature of preoperative anti-TNF failure (P = 0.76), indication for ICR (P = 0.88) switch of anti-TNF agent (P = 0.55) agent, and preoperative exposure to 1 vs. >1 anti-TNF agents (P = 0.88). Retreatment with anti-TNF therapy for postoperative Crohn's disease recurrence is a valid strategy after preoperative failure. Combination therapy is associated with a lower rate of treatment failure.

Second-Generation Antipsychotics' Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders.

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics’ (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms.

Light-Emitting Diode (LED) Phototherapy versus Non-LED Phototherapy Devices for Hyperbilirubinemia in Neonates: A Systematic Review and Meta-analysis.

This review was conducted to evaluate the efficacy of light-emitting diode (LED) phototherapy as compared with the conventional phototherapy in neonates with unconjugated hyperbilirubinemia and their adverse effects. We searched the following databases right from their inception till April, 2021: MEDLINE, EMBASE, Cochrane Library, and LILACS. Randomized clinical trials (RCTs) comparing the LED phototherapy with other light sources, which enrolled newborns (term and preterm) with unconjugated hyperbilirubinemia were included. We included 21 articles in this review. The treatment with the LED light therapy had a lower failure rate as compared with the non-LED one (RR = 0.60, 95% CI: 0.39-0.94). The mean duration of phototherapy was significantly shorter in the group with the LED light source as compared with the one with the non-LED light source (mean difference [hours]: -8.07, 95% CI: -8.45 to -7.68), regardless of the type of non-LED units. However, the rate of bilirubin showed a comparable decline (mean difference [mg/dL/h]: 0.01, 95% CI: -0.00, 0.03) in both the light sources, irrespective of irradiance or distance. No studies reported primary outcomes related to the neurotoxicity effects of hyperbilirubinemia in neonates. The LED light devices caused a significantly higher risk of hypothermia. Neonates were at a lower risk of developing hyperthermia and skin rash with the LED light therapy. Our findings provide support for the use of LED light source phototherapy due to its better clinical efficacy, which is evidenced by its shorter duration and lower rate of treatment failure, as compared with the non-LED light sources. KEY POINTS: · The efficacy of phototherapy is dependent on specific characteristics of light sources of phototherapy devices.. · LED phototherapy demonstrated better efficacy with shorter duration and lower rate of treatment failure.. · Adverse effects of phototherapy devices such as hypothermia, hyperthermia, and skin rash should be monitored..

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Optimal Dose of Cefoperazone-Sulbactam for Acute Bacterial Infection in Patients with Chronic Kidney Disease.

The optimal dosage of cefoperazone-sulbactam for patients with chronic kidney disease (CKD) remains unclear. This study aimed to investigate two treatment strategies of cefoperazone-sulbactam–2 g/2 g twice daily and adjusted dose according to renal function for patients with CKD. A total of 155 patients with CKD received cefoperazone-sulbactam either at a dose of 2 g/2 g twice daily (study group) or adjusted according to renal function (control group) for the treatment of acute bacterial infection. The primary outcome was the clinical response rate at day 14 and the secondary outcomes included treatment failure and all-cause death. The study group had a higher clinical response rate (80.0% vs. 65.0%) and a lower treatment failure rate (4.0% vs. 23.8%) as compared with the control group. Further multivariable analysis showed that compared with the control group, the study group had a higher clinical response rate (adjusted OR = 4.02; 95% CI, 1.49–10.81) and lower treatment failure rate (adjusted OR = 0.06; 95% CI, 0.01–0.28). In addition, no significant difference in all-cause mortality was observed between the study and the control group (adjusted OR = 1.95; 95% CI, 0.57–6.66). Finally, no significant difference was observed between the study and the control group in the risk of the adverse events (AEs)–diarrhea (p = 0.326), eosinophilia (p = 1.000), prolonged PT (p = 0.674), alteration in renal function (p = 0.938) and leukopenia (n = 0.938). In conclusion, cefoperazone-sulbactam at a dose of 2 g/2 g twice daily could achieve better clinical efficacy than the reduced dosage regimen. Additionally, this dosage did not increase the risk of AE compared to the reduced dose. Therefore, cefoperazone-sulbactam at a dose of 2 g/2 g twice daily is an effective and safe regimen for acute bacterial infection in patients with CKD.

Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections in Patients With Liver Cirrhosis

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients with cirrhosis represent a significant therapeutic challengeas they are associated with poor outcomes due to high rates of treatment failure, and frequently induce liver decompensation. To evaluate treatment failure and in-hospital mortality in two cohorts of patients with cirrhosis and with CRKP infectionstreated with antibiotic regimens including or excluding Ceftazidime-avibactam. Data from hospitalized patients with liver cirrhosis and CRKP infections were extracted and retrospectively analyzed. During the study period, 39 cirrhotic patients with confirmed invasive CRKP infections were enrolled. Overall, the median age was 60 years with a median MELD score of 16 points. Urinary tract infections were diagnosed in 46%, followed by pneumonia in 23%, and primary bacteremia in 18% of patients. Treatment failure was reported in 10 patients (26%), while in-hospital mortality in 15 patients (38%). A monotherapy was used in 8 patients (20.5%), while a combination therapy was required in 31 patients (79.5%). Ceftazidime-avibactam therapy was associated with lower rates of treatment failure (7% vs. 38%, P= 0.032) independent of severity of liver disease (Child Class) and mono or combination antibiotic therapy. Acute kidney injury, hepatorenal syndrome, and acute-on-chronic liver failure were the consequences more frequently observed in patients with treatment failure. In-hospital mortality was associated with treatment failure, and Ceftazidime-avibactam therapy improved in-hospital survival (log rank test: P= 0.035) adjusted for Child class and mono or combination therapy. Treatment including ceftazidime-avibactam was associated with a lower rate of treatment failure in cirrhotic patients with CRKP infections. Considering the favorable efficacy and outcomes of ceftazidime-avibactam, this drug should be considered for the treatment of these severe infections in patients with liver cirrhosis, though further investigation is required.