Identifying excessive length of antibiotic treatment duration for hospital-acquired infections: a semi-automated approach to support antimicrobial stewardship.

BACKGROUND: Avoiding excessive antibiotic treatment duration is a fundamental goal in antimicrobial stewardship. Manual collection of data is a time-consuming process, but a semi-automated approach for data extraction has been shown feasible for community-acquired infections (CAI). Extraction of data however may be more challenging in hospital-acquired infections (HAI). The aim of this study is to explore whether semi-automated data extraction of treatment duration is also feasible and accurate for HAI. METHODS: Data from a university-affiliated hospital over the period 1-6-2020 until 1-6-2022 was used for this study. From the Electronic Health Record, raw data on prescriptions, registered indications and admissions was extracted and processed to define treatment courses. In addition, clinical notes including prescription instructions were obtained for the purpose of validation. The derived treatment course was compared to the registered indication and the actual length of treatment (LOT) in the clinical notes in a random sample of 5.7% of treatment courses, to assess the accuracy of the data for both CAI and HAI. RESULTS: Included were 10.564 treatment courses of which 73.1% were CAI and 26.8% HAI. The registered indication matched the diagnosis as recorded in the clinical notes in 79% of treatment courses (79.2% CAI, 78.5% HAI). Higher error rates were seen in urinary tract infections (UTIs) (29.0%) and respiratory tract infections (RTIs) (20.5%) compared to intra-abdominal infections (7.4%), or skin or soft tissue infections (11.1%), mainly due to incorrect specification of the type of UTI or RTI. The LOT was accurately extracted in 98.5% of courses (CAI 98.2%, HAI 99.3%) when compared to prescriptions in the EHR. In 21% of cases however the LOT did not match with the clinical notes, mainly if patients received treatment from other health care providers preceding or following the present course. CONCLUSION: Semi-automatic data extraction can yield reliable information about the indication and LOT in treatment courses of hospitalized patients, for both HAI and CAI. This can provide stewardship programs with a surveillance tool for all in-hospital treated infections, which can be used to achieve stewardship goals.

Use of Fever Duration to Guide Management of Urinary Tract Infection.

BACKGROUND: The appropriate duration of antimicrobial therapy for febrile urinary tract infection (fUTI) in children has not been established. This study examined the optimal duration of treatment for fUTI in children. METHODS: We created a protocol that used fever duration to determine the duration of antibiotic administration. Transvenous antibiotics were administered until 3 days after resolution of fever, followed by oral antibiotics for 1 week. Diagnosis of fUTI was based on a fever of 37.5°C or higher and a quantitative culture of catheterized urine yielded a bacteria count of ≥5 × 104. Acute focal bacterial nephritis (AFBN) and pyelonephritis (PN) were diagnosed on the basis of contrast-enhanced computed tomography (eCT) findings. We retrospectively reviewed treatment outcomes. RESULTS: Of the 78 patients treated according to our protocol, data from 58 were analyzed-49 children (30 boys) had PN and nine (three boys) had AFBN. Blood test results showed that patients with AFBN had significantly higher white blood cell counts and C-reactive protein levels than did those with PN; however, urinary findings and causative bacteria did not differ between groups. Time to resolution of fever and duration of intravenous antibiotic administration were significantly longer in patients with AFBN than in those with PN. However, average duration of AFBN treatment was 14.2 days, which was shorter than the previously reported administration period of 3 weeks. No recurrence was observed in AFBN patients. CONCLUSIONS: A protocol that used fever duration to determine the duration of antimicrobial treatment was useful. Invasive examinations, such as eCT, were not required.

Association between duration of antidepressant treatment for major depressive disorder and relapse rate after discontinuation: A meta-analysis.

The optimal duration of antidepressant treatment for patients with major depressive disorder to reduce the risk of relapse after discontinuation remains uncertain. Medline, Cochrane Central Register of Controlled Trials, and Embase were systematically searched for randomized controlled trials (RCTs) with a discontinuation design. A single-group summary meta-analysis was performed to calculate 6-month relapse rates after discontinuation. Meta-regression with restricted cubic splines was performed to model the non-linear relationship between treatment duration and relapse rate after discontinuation. Thirty-five RCTs were included. The relapse rate after discontinuation was approximately 34.81 % at 6 months and 45.12 % at 12 months. After controlling for covariates, the meta-analysis shows that the duration of treatment is associated with the risk of relapse after discontinuation in a non-linear curve, with a relatively higher risk of relapse observed for a duration of less than three months. There appears to be no further reduction in the risk of relapse when treatment is continued for over six months. Our results indicate the importance of at least three months of treatment to avoid the relatively high risk of relapse after discontinuation. The additional benefit of longer treatment remains to be proven.

Duration of orthodontic treatment with clear aligners versus fixed appliances in crowding cases: a systematic review.

OBJECTIVE: To critically appraise and assess the currently observed evidence about the difference in orthodontic treatment duration between clear aligners and fixed appliances in crowding cases. MATERIALS AND METHODS: An electronic search without limitations was conducted from inception to June 2023 covering nine databases: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, Web of Science, Google Scholar, Trip, CINAHL via EBSCO, EMBASE via OVID and ProQuest. Randomized controlled trials (RCTs) and matched non-randomized studies were included in this systematic review. Risk of Bias was assessed via Cochrane's tool (RoB 2) for RCTs and ROBINS-I tool for non-randomized studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was employed to evaluate the overall quality of evidence. RESULTS: Out of the 3537 articles initially identified, ten eligible studies were included in this systematic review; six were RCTs. Only one study offered extraction-based treatment, while the other nine adopted non-extraction treatments. According to the GRADE, there is low evidence that treatment duration in mild to moderate crowding cases with clear aligners is similar to that in fixed orthodontic appliances. Meta-analysis was not administered due to high inconsistency. CONCLUSIONS: Based on currently available information, there was no significant difference in the treatment duration between the CA and FA groups in mild to moderate crowding cases. Further well-performed RCTs, especially in severe cases, are required. CLINICAL RELEVANCE: Time efficiency is an essential outcome measure for clinical orthodontic practice. While the type of appliance used is a critical determinant of treatment duration, orthodontists should be aware of other factors that can significantly impact treatment time, such as patient and treatment-related factors.

Short versus prolonged duration of therapy for Pseudomonas aeruginosa bacteraemia: a systematic review and meta-analysis.

The optimal duration of therapy for Pseudomonas aeruginosa bloodstream infection (PSA-BSI) is unknown, with prolonged therapy frequently favored due to severity of infection, patient complexity, risk of multi-drug resistance, and high mortality. We therefore conducted a systematic review and meta-analysis of studies with head-to-head comparison of short versus prolonged therapy for PSA-BSI. A comprehensive search including Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was performed. We pooled risk ratios using DerSimonian-Laird random effects model and performed subgroup analysis of outcomes including all-cause mortality, recurrent infection, and composite of these outcomes among patients receiving short versus prolonged therapy for PSA-BSI. Heterogeneity was assessed by the I2-index. Risk of bias for cohort studies was assessed using ROBINS-I tool. Of the 908 identified studies, six were included in the systematic review and five studies with head-to-head comparison of treatment duration were assessed in the meta-analysis, totalling 1746 patients. No significant difference in propensity score-weighted composite outcome (30-day all-cause mortality or recurrent infection) was noted between patients receiving short or prolonged therapy, with a pooled RR risk ratio of 0.80 (95% CI confidence interval 0.51-1.25, P=0.32; I2 = 0%). Additionally, duration of therapy did not impact individual outcomes of 30-day all-cause mortality or recurrent/persistent infection. Our meta-analysis demonstrated that short duration of antimicrobial therapy may have similar efficacy to prolonged treatment for PSA-BSI. Future randomized trials will be necessary to definitively determine optimal management of PSA bacteraemia.

Shorter versus longer duration of antimicrobial therapy for early Lyme disease: A systematic review and meta-analysis.

BACKGROUND: Antibiotic therapy for patients with early Lyme disease is necessary to prevent later-stage Lyme disease complications. This systematic review and meta-analysis compares shorter versus longer antibiotic regimens in treating early Lyme disease. METHODS: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted up to November 2023. We examined treatment failure, complete response, and photosensitivity. Short vs. long therapy was defined as ≤10 days vs. >10 days. Subgroup analyses included antibiotic type and varying treatment durations. Analysis utilized RStudio 4.1.2. PROSPERO registration: CRD42023423876. RESULTS: Seven studies, encompassing 1,462 patients, were analyzed. No significant differences in treatment failure, 12-month complete response, final visit complete response were found between short and long durations of antibiotic therapy. Subgroup and sensitivity analyses corroborated these findings. CONCLUSION: Shorter and longer antibiotic regimens for early Lyme disease show similar efficacy, highlighting the potential of ≤10-day courses, as effective treatment options.

Clinical outcomes of narrow- and regular-diameter implants with bone augmentation in the anterior maxilla: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the clinical outcomes of narrow-diameter implants (NDIs) and regular-diameter implants (RDIs) with bone augmentation in the anterior maxilla, with implant survival rate (ISR) as the primary outcome. Additionally, secondary outcomes such as peri-implant marginal bone loss (MBL), pocket probing depth (PPD), mechanical complications, and biological complications were also considered. MATERIALS AND METHODS: A thorough literature search was performed to identify randomized controlled trials and cohort studies comparing outcomes of NDIs and RDIs with bone augmentation in the anterior maxilla published up to February 2024. Only studies with a minimum follow-up period of 12 months were selected for analysis. Meta-analysis was performed if at least two articles with similar characteristics were available. RESULTS: Of the 288 articles initially considered, 5 were included in the analysis, involving 282 NDIs and 100 RDIs. At the 36-month follow-up, no statistically significant differences in ISR, which ranged 93.8-100% for NDIs and were 100% for RDIs, were observed between the two groups (relative risk, 0.989; 95% confidence interval, 0.839-1.165; p = 0.896). Similarly, MBL and PPD did not differ significantly between the two groups. Soft tissue dehiscence was the most common complication found in RDIs. CONCLUSION: The results indicate that NDIs yield clinical outcomes similar to those of RDIs with bone augmentation in the anterior maxilla over a 36-month follow-up period. CLINICAL RELEVANCE: Considering the similar clinical outcomes, the shortened treatment duration and more rapid esthetic improvement associated with NDIs may render them preferrable to RDIs with bone augmentation, particularly in this esthetic zone.

Associations of Valproate Doses With Weight Gain in Adult Psychiatric Patients: A 1-Year Prospective Cohort Study.

Objective: The aim of this study was to evaluate valproate dose association with weight change, blood glucose, lipid levels, and blood pressure in a psychiatric population.Methods: Data from 215 patients taking valproate for up to 1 year were collected from 2 longitudinal studies that monitored metabolic variables between 2007 and 2022. Linear mixed-effect models and logistic regressions were used to analyze the associations between valproate doses and metabolic outcomes.Results: An increase in valproate dose of 500 mg was associated with a weight change of +0.52% per month over a year (P < .001). The association between valproate dose and weight change was evident both before and after 3 months of treatment. Weight increase was greater for treatment durations of < 3 months compared to ≥ 3 months (+0.56%, P < .001 and +0.12%, P = .02 per month, respectively). Using piecewise regression, a significant association between dose and weight gain was observed in patients receiving doses equal to or above the median dose (1,300 mg/d), with a +0.50% increase in weight for each dose increment of 500 mg (P = .004). Among men, each 500 mg dose increment was associated with weight increases of +0.59% per month (P = .004), whereas a trend was observed for women (+0.40%, P = .09). No associations were found between valproate doses and blood glucose, lipid levels, or blood pressure over a 6-month treatment period.Conclusions: This study provides evidence that valproate dose, mainly for doses at or above 1,300 mg/d, is associated with weight gain in psychiatric patients, suggesting that the lowest effective doses should be prescribed to minimize weight gain.

Comparison of positional distraction with stabilisation exercises versus stabilisation exercises alone in the management of lumbar radiculopathy: A randomized controlled-trial.

OBJECTIVE: To compare the effects of positional distraction with stabilisation exercises versus stabilisation exercises alone in the management of lumbar radiculopathy. METHODS: The randomised controlled trial was conducted from July to December 2020 at the Institute of Physical Medicine and Rehabilitation, Dow University of Health Sciences, and the Neurosurgery ward of Civil Hospital, Karachi, and comprised individuals of either gender with lumbar radiculopathy pain who were randomised into positional distraction with stabilisation exercises group A and stabilisation exercise group B. The treatment duration was 3 sessions per week for 8 weeks. Intensity of pain and disability were assessed using the Visual Analogue Scale and the Roland Morris Disability Questionnaire, respectively. Data was analysed using SPSS 21. RESULTS: Of the 100 patients, 63(63%) were males and 37(37%) were females. Overall, 89(89%) were married. There were 50(50%) subjects in group A with mean age 39.42±6.36 years and 50(%) in group B with mean age 38.80±6.69 years. There was no significant difference in terms of age, gender and marital status between the groups (p>0.05). The study was completed by 96(96%) patients; 48(50%) in each of the 2 groups. Intragroup improvement post-intervention compared to baseline was significant (p<0.001) in both groups. Outcomes in group A were significantly better than in group B (p<0.05). CONCLUSIONS: Addition of positional distraction to stabilisation exercises was found to have superior effects compared to stabilisation exercise alone on pain and functional disability among patients with lumbar radiculopathy. Clinical Trial Number: NCT04427423 dated 27th April 2020.

Impact of Opioid Use on Duration of Therapy and Overall Survival for Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). We evaluated the effect of opioid use on outcomes in patients receiving ICI either alone or with chemotherapy. We conducted a retrospective review of 209 patients with advanced NSCLC who received an ICI at the University of Virginia between 1 February 2015 and 1 January 2020. We performed univariate and multivariate analyses to evaluate the impact of opioid use on duration of therapy (DOT) and overall survival (OS). Patients with no or low opioid use (n = 172) had a median DOT of 12.2 months (95% CI: 6.9-17.4) compared to 1.9 months (95% CI: 1.8-2.0) for those with high opioid use (n = 37, HR 0.26 95% CI: 0.17-0.40, p < 0.001). Patients with no or low opioid use had a median OS of 22.6 months (95% CI: 14.8-30.4) compared to 3.8 months (95% CI: 2.7-4.9) for those with high opioid use (HR 0.26 95% CI: 0.17-0.40 p < 0.001). High opioid use was associated with a shorter DOT and worse OS. This difference remained significant when accounting for possible confounding variables. These data warrant investigation of possible mechanistic interactions between opioids, tumor progression, and ICIs, as well as prospective evaluation of opioid-sparing pain management strategies, where possible.

Impact of a Best Practices Program in Patients with Relapsed/Refractory Multiple Myeloma Receiving Selinexor.

Best practice (BP) in cancer care consists of a multifaceted approach comprising individualized treatment plans, evidence-based medicine, the optimal use of supportive care and patient education. We investigated the impact of a BP program in patients with relapsed/refractory multiple myeloma (RRMM) receiving selinexor. Features of the BP program that were specific to selinexor were initiating selinexor at doses ≤80 mg once weekly and the upfront use of standardized antiemetics. Study endpoints included time to treatment failure (TTF), duration of therapy, dose limiting toxicities and overall survival. Comparative analysis on TTF and duration of therapy was conducted using a log-rank test and multivariate Cox proportional hazard regression. Over the ensuing 12-month post-BP period, 41 patients received selinexor-based therapy compared to 68 patients who received selinexor-based therapy pre-BP implementation. Patients treated in the post-BP period had reductions in TTF (hazard ratio [HR] = 0.50; 95% CI: 0.27 to 0.92). Patients in the pre-BP period were four times more likely to stop therapy than those in the post-period (odds ratio [OR] = 4.0, 95% CI: 1.75 to 9.3). The findings suggest a BP program tailored to selinexor could increase the time to treatment failure, increase treatment duration and lower the incidence of drug limiting toxicities.

Is there a prospective association between psychological distress as measured by the CORE-OM and treatment attendance and treatment duration? A follow-up study at a Norwegian Community Mental Health Centre.

BACKGROUND: Feasible and reliable methods for identifying factors associated with treatment duration and treatment attendance in mental health services are needed. This study examined to what degree the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) at the start of treatment is associated with treatment attendance and treatment duration. METHODS: Outpatients (N = 124) at a community mental health centre in Norway completed the 34-item CORE-OM questionnaire addressing the domains of subjective well-being, problems and symptoms, functioning and risk at the start of treatment. The CORE-OM subscales and the 'all' items total scale were used as predictor variables in regression models, with treatment duration, number of consultations attended, treatment attendance (number of therapy sessions attended divided by number of sessions offered) and termination of treatment (planned versus unplanned) as outcome variables. RESULTS: Higher CORE-OM subscale scores and the 'all' scale were associated with longer treatment duration. No association was found between CORE-OM scales and number of therapy sessions, treatment attendance (sessions attended/offered) or whether the patients unexpectedly ended treatment. CONCLUSION: Higher patient-reported psychological distress as measured by the CORE-OM at the start of treatment was prospectively associated with treatment duration but not with treatment attendance or drop-out of treatment. The findings imply that patients with higher initial psychological distress need longer treatment but that treatment attendance may be related to factors other than the severity of distress.

Efficacy and safety of alcohol reduction pharmacotherapy according to treatment duration in patients with alcohol dependence or alcohol use disorder: A systematic review and network meta-analysis.

BACKGROUND AND AIMS: Relapse is common in alcohol dependence (AD) and alcohol use disorder (AUD), so alcohol reduction therapy should be measured over as long a period as possible; however, existing reviews do not consider the duration of treatment and therefore alcohol reduction therapy may not have been appropriately evaluated. This review evaluated the efficacy and safety of alcohol reduction pharmacotherapy in patients with AD or AUD according to the duration of treatment. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that assessed 15 pharmacological agents. MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov and the International Clinical Trials Registry Platform were searched for eligible trials through to May 2021. Outcomes were heavy drinking days (HDD), total alcohol consumption (TAC), any adverse event and days without drinking. RESULTS: Fifty-five RCTs (n = 8891) were included. Nalmefene was superior to placebo for reducing HDD (standard mean difference [SMD] -0.28, 95% confidence interval [CI] -0.37, -0.18) and TAC (SMD -0.25, 95% CI -0.35, -0.16) in the long-term, but not in the short-term. Topiramate was superior to placebo for reducing HDD (SMD -0.35, 95% CI -0.59, -0.12) and days without drinking (SMD 0.46, 95% CI 0.11, 0.82), and baclofen was superior for reducing TAC (SMD -0.70, 95% CI -1.29, -0.11), in the short-term. The frequency of adverse events was higher with nalmefene and topiramate than with placebo. CONCLUSION: Nalmefene, topiramate and baclofen may be effective as alcohol reduction pharmacotherapy; however, only nalmefene has demonstrated long-term efficacy, and nalmefene and topiramate have a significantly higher frequency of adverse events compared with placebo.