Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study.

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.

Shorter versus longer duration of antibiotic treatment in children with bacterial meningitis: a systematic review and meta-analysis.

The optimal duration of antibiotic treatment for the most common bacterial meningitis etiologies in the pediatric population, namely Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, is not well-established in the literature. Therefore, we aimed to perform an updated meta-analysis comparing shorter versus longer antibiotic treatment in children with meningitis. PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) that compared shorter (up to 7 days) versus longer (10 days or double the days of the equivalent short course) duration of antibiotic treatment in children with meningitis and reported the outcomes of treatment failure, death, neurologic sequelae, non-neurologic complications, hearing impairment, nosocomial infection, and relapse. Heterogeneity was examined with I2 statistics. RevMan 5.4.1 was used for statistical analysis and RoB-2 (Cochrane) for risk of bias assessment. Of 684 search results, 6 RCTs were included, with a cohort of 1333 children ages 3 weeks to 15.5 years, of whom 49.51% underwent a short antibiotic course. All RCTs included monotherapy with ceftriaxone, except one, which added vancomycin as well. No differences were found comparing the short and long duration of therapy concerning treatment failure, relapse, mortality, and neurologic complications at discharge and at follow-up.  Conclusion: Because no statistically significant differences were found between groups for the analyzed outcomes, the results of this meta-analysis support shorter therapy. However, generalizing these results to complicated meningitis and infections caused by other pathogens should be made with caution. (PROSPERO identifier: CRD42022369843). What is Known: • Current recommendations on the duration of antibiotic therapy for bacterial meningitis are mostly based on clinical practice. • Defining an optimal duration of antibiotic therapy is essential for antimicrobial stewardship achievement, improving patient outcomes, and minimizing adverse effects. What is New: • There are no differences between shorter versus longer antibiotic treatment duration in regard to treatment failure, relapse, mortality, neurologic complications, and hearing impairment at discharge and at follow-up.

Neurobrucellosis Presenting with Motor Damage or Hearing Loss, and Use of Steroids are Associated with a Higher Risk of Sequelae or Relapse: A Systematic Review of Individual Participant Data.

BACKGROUND: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications. OBJECTIVE: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature. METHODS: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool. RESULTS: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 - 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 - 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 - 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 - 0.11, p < 0.001). CONCLUSIONS: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up.

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.

Clinical profile of Spanish hepatitisC virus-infected treatment-naïve patients with compensated cirrhosis in the CREST study. / Perfil clínico de los pacientes españoles con hepatitisC naïve con cirrosis compensada tratados en el estudio CREST.

BACKGROUND AND AIM OF THE STUDY: There are still patients with hepatitisC in Spain who have yet to be diagnosed, but their clinical profile is unclear. In 2021, 21.93% of patients diagnosed had cirrhosis and were mostly treatment-naïve. METHODS: This sub-analysis describes the clinical profile of the 60Spanish treatment-naïve patients with compensated cirrhosis who were included in the CREST study. MAJOR RESULTS: Sixty percent of patients were male, median age 56years, and 33% had a history of drug use. Almost three-quarters (71.3%) had more than one comorbidity and 78.3% took concomitant medication. At treatment initiation, median platelet count was 139×103/µL and FibroScan® 17kPa. No virological failure was observed and no patient discontinued treatment due to adverse events. No clinically significant changes were noted during or after treatment in the median platelet, albumin, bilirubin, and transaminase levels. CONCLUSIONS: Treatment with glecaprevir/pibrentasvir for 8weeks in this cohort of treatment-naïve patients with compensated cirrhosis in Spain was safe and effective. This information reinforces the use of this short antiviral regimen even when there is compensated cirrhosis, simplifying the approach to hepatitisC among those patients still to be diagnosed and treated in Spain.

Diabetic foot wound ulcers management by vacuum sealing drainage: A meta-analysis.

The meta-analysis aimed to assess and compare diabetic foot wound ulcer management by vacuum sealing drainage. Using dichotomous or contentious random- or fixed-effects models, the outcomes of this meta-analysis were examined, and the odds ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. Twenty-three examinations from 2000 to 2023 were enrolled for the present meta-analysis, including 1928 individuals with diabetic foot ulcers. Vacuum sealing drainage had significantly lower wound healing (OR, 2.35; 95% CI, 1.79-3.08, p < 0.001), lower duration of therapy (MD, -6.19; 95% CI, -10.06 to -2.32, p = 0.002), higher wound size reduction (MD, 4.22; 95% CI, 0.87-7.56, p = 0.01) and lower complication (OR, 0.32; 95% CI, 0.13-0.80, p = 0.01) compared with standard therapy in patients with diabetic foot ulcers. The examined data revealed that vacuum sealing drainage had significantly lower wound healing, duration of therapy and complication rates, as well as higher wound size reduction, compared with standard therapy in patients with diabetic foot ulcers. Yet, attention should be paid to its values since most of the selected examinations had a low sample size.

Controversies in the management of community-acquired pneumonia in adults.

Community-acquired pneumonia (CAP) is a common infectious syndrome in Australia and a leading global cause of morbidity and mortality. It drives a significant amount of antimicrobial prescribing in Australia. Accurate assessment and stratification of CAP severity is important. However, adequate evaluation is challenging and controversy remains about the optimal method. Streptococcus pneumoniae is the most commonly identified bacterial pathogen causing CAP. As such, oral amoxicillin monotherapy is the mainstay of empirical therapy for low-severity CAP. The need to start empirical therapy for pathogens such as Mycoplasma pneumoniae and Legionella species in low-severity CAP remains controversial; evaluating the causative pathogen on clinical grounds alone is difficult. Oral antibiotics recommended for CAP (e.g. amoxicillin, doxycycline) have excellent bioavailability and may be used instead of intravenous therapy in some hospitalised patients. A duration of 5 days of antibiotic therapy is recommended in clinical practice guidelines for patients with uncomplicated CAP who meet stability criteria at follow-up.

Use of C-reactive protein to guide the antibiotic therapy in hospitalized patients: a systematic review and meta-analysis.

BACKGROUND: C-reactive protein (CRP) is an inflammatory protein used in clinical practice to identify and monitor inflammatory and infectious processes. Recent data suggest CRP might be useful in guiding antibiotic therapy discontinuation among critical care patients. This meta-analysis analyzed the benefits and risks of CRP-guided protocols to guide antibiotic therapy in hospitalized patients in comparison with standard treatment. METHODS: Studies were searched in four databases: CENTRAL, Medline, Embase and LILACS. The search was performed until Jan 25th, 2023. The reference lists of the articles retrieved and related review studies were hand-screened to find eligible trials that might have been missed. Primary endpoints included the duration of antibiotic therapy for the index episode of infection. The secondary endpoint was the all-cause hospital mortality and infection relapses. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Random effects were used to pool the mean differences and odds ratio of individual studies. The protocol was registered in PROSPERO (CRD42021259977). RESULTS: The search strategy retrieved 5209 titles, out of which three studies met the eligibility criteria and were included in this meta-analysis. 727 adult patients were analyzed, of whom 278 were included in the intervention group and 449 were included in the control group. 55,7% of all patients were women. Meta-analysis indicated that experimental groups (CRP-guided) had a lower duration of antibiotic therapy (days) [MMD = -1.82, 95%IC -3.23; -0.40]; with no difference in mortality [OR = 1.19 95%IC 0.67-2.12] or in the occurrence of infection relapse [OR = 3.21 95%IC 0.85-12.05]. CONCLUSION: The use of CRP-guided protocol reduces the total amount of time required for antibiotic therapy when compared to standard protocols of treatment in hospitalized patients with acute bacterial infection. We did not observe statistical differences regarding mortality and infection relapse rates.

Venetoclax and Hypomethylating Agents as First-line Treatment in Newly Diagnosed Patients with AML in a Predominately Community Setting in the US.

BACKGROUND: Treatment with venetoclax + hypomethylating agents (HMAs) is standard-of-care for newly diagnosed (ND) patients with acute myeloid leukemia (AML) aged ≥75 years, or with comorbidities precluding intensive chemotherapy. We describe real-world venetoclax + HMA treatment practices and outcomes in patients with ND AML in the US. PATIENTS AND METHODS: This retrospective cohort study used an electronic health record-derived, US nationwide, de-identified database, and included adults with ND AML, initiating venetoclax + HMA treatment ≤30 days from diagnosis (June 1, 2018-January 31, 2020). Venetoclax treatment variables included dosing information, schedule modifications, and drug-drug interactions. The median venetoclax + HMA treatment duration and overall survival (OS) from venetoclax initiation to discontinuation, death, or end of follow-up (August 31, 2020) were examined by Kaplan-Meier analyses. RESULTS: Overall, 169 patients were included. The median age at diagnosis was 77 years; 85.2% of patients were treated in community practice. Ninety-five of 169 patients (56.2%) had evaluable bone marrow response data following the start of treatment; 53.7% were assessed approximately at the end of cycle 1. Following the first treatment cycle, treatment schedule modifications were recorded in 101 patients and dose changes in 56, primarily due to toxicity. The median treatment duration was 5.2 months; the median OS was 8.6 months (median follow-up was 7.2 months). Venetoclax dose changes did not modify efficacy outcomes, but longer median OS was associated with venetoclax treatment schedule modifications (P = .02). CONCLUSIONS: This study reflects early real-world experience with venetoclax + HMAs in a predominantly community setting and emphasizes the importance of appropriate venetoclax management in optimizing patient outcomes.

Definitive results of a phase III adjuvant trial comparing six cycles of FEC-100 to four cycles of AC in women with operable node-negative breast cancer: the NSABP B-36 trial (NRG Oncology).

PURPOSE: Results from adjuvant trials evaluating 6 cycles of epirubicin-based chemotherapy regimens suggested these programs may be more effective than 4 cycles of doxorubicin-based chemotherapy. METHOD: NSABP B-36 was a phase III clinical trial originally designed as a 2 × 2 factorial study comparing 6 cycles of 5-FU, epirubicin, and cyclophosphamide (FEC-100) to 4 cycles of conventional doxorubicin and cyclophosphamide (AC) with celecoxib or placebo. Shortly after activation, concerns regarding increased cardiovascular risks among selective COX-2 inhibitors resulted in a decision to remove the celecoxib/placebo from the trial. Women with histologically node-negative invasive breast cancer who had undergone primary surgery with a lumpectomy or total mastectomy were eligible. Primary endpoint was disease-free survival (DFS). RESULTS: Between May 2004 and July 2008, 2722 patients were enrolled. Administration of FEC-100 did not result in improvement in DFS compared to AC (HR 1.09; 95% CI 0.92-1.29, p value = 0.31). The effect of FEC-100 compared to AC on DFS was significantly different for receptor-positive (HR 1.32, 95% CI 1.05-1.66) compared to receptor-negative patients (HR 0.86, 95% CI 0.66-1.11) (treatment-by-receptor status interaction p value = 0.02). There was no statistically significant difference in the effect of treatment on overall survival (OS) with FEC-100 compared to AC (HR 1.06; 95% CI 0.84-1.35, p value = 0.61). Overall, Grade 3 and 4 adverse events were more frequent in the FEC-100 group. CONCLUSION: The results of B-36 do not support use of six-cycle anthracycline-based regimens in node-negative breast cancer. Prolongation of anthracycline-based therapy with FEC-100 does not improve DFS or OS, relative to AC for 4 cycles, and was associated with expected increases in toxicity. A statistically significant interaction between treatment and hormone receptor status favoring AC in hormone-receptor-positive breast cancers is consistent with the hypothesis that optimal duration of chemotherapy may be four cycles in these patients. Late cardiac events and deaths prior to recurrence or second cancer were infrequent on both arms, but slightly higher with FEC-100. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00087178.

Shorter versus longer duration of Amoxicillin-based treatment for pediatric patients with community-acquired pneumonia: a systematic review and meta-analysis.

Streptococcus pneumoniae is the most common typical bacterial cause of pneumonia among children. The World Health Organization (WHO) recommends a 5-day Amoxicillin-based empiric treatment. However, longer treatments are frequently used. This study aimed to compare shorter and longer Amoxicillin regimens for children with uncomplicated community-acquired pneumonia (CAP). A search of PubMed, EMBASE, and Cochrane Central was conducted to identify randomized controlled trials (RCTs) comparing 5-day and 10-day courses of Amoxicillin for the treatment of CAP in children older than 6 months in an outpatient setting. Studies involving overlapping populations, lower-than-standard antibiotic doses, and hospitalized patients were excluded. The outcome of interest was clinical cure. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed using the Cochran Q test and I2 statistics. Two independent authors conducted the critical appraisal of the included studies according to the RoB-2 tool for assessing the risk of bias in randomized trials, and disagreements were resolved by consensus. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool to evaluate the certainty of evidence of our results. Three RCTs and 789 children aged from 6 months to 10 years were included, of whom 385 (48.8%) underwent a 5-day regimen. Amoxicillin-based therapy was used in 774 (98%) patients. No differences were found between 5-day and 10-day therapy regarding clinical cure (RR 1.01; 95% CI 0.98-1.05; p = 0.49; I2 = 0%). Subgroup analysis of children aged 6-71 months showed no difference in the rates of the same outcome (RR 1.01; 95% CI 0.98-1.05; p = 0.38; I2 = 0%). The GRADE tool suggested moderate certainty of evidence. CONCLUSION: These findings suggest that a short course of Amoxicillin (5 days) is just as effective as a longer course (10 days) for uncomplicated CAP in children under 10 years old. Nevertheless, generalizations should be made with caution considering the socioeconomic settings of the studies included.PROSPERO Identifier: CRD42022328519. WHAT IS KNOWN: • In the outpatient setting, a few international guidelines recommend a 10-day Amoxicillin course as first-line treatment for community-acquired pneumonia (CAP). • Recent trials have shown that shorter courses of Amoxicillin may be as effective as 10-day regimens in uncomplicated pneumonia. WHAT IS NEW: • When comparing 5-day to 10-day Amoxicillin regimens, evidence suggests no significant difference in clinical cure rates for uncomplicated CAP in outpatient settings. • Generalizations should be made with caution considering the socioeconomic context of the population within the included studies.

Antimicrobial treatment duration for uncomplicated bloodstream infections in critically ill children: a multicentre observational study.

BACKGROUND: Bloodstream infections (BSIs) cause significant morbidity and mortality in critically ill children but treatment duration is understudied. We describe the durations of antimicrobial treatment that critically ill children receive and explore factors associated with treatment duration. METHODS: We conducted a retrospective observational cohort study in six pediatric intensive care units (PICUs) across Canada. Associations between treatment duration and patient-, infection- and pathogen-related characteristics were explored using multivariable regression analyses. RESULTS: Among 187 critically ill children with BSIs, the median duration of antimicrobial treatment was 15 (IQR 11-25) days. Median treatment durations were longer than two weeks for all subjects with known sources of infection: catheter-related 16 (IQR 11-24), respiratory 15 (IQR 11-26), intra-abdominal 20 (IQR 14-26), skin/soft tissue 17 (IQR 15-33), urinary 17 (IQR 15-35), central nervous system 33 (IQR 15-46) and other sources 29.5 (IQR 15-55) days. When sources of infection were unclear, the median duration was 13 (IQR 10-16) days. Treatment durations varied widely within and across PICUs. In multivariable linear regression, longer treatment durations were associated with severity of illness (+ 0.4 days longer [95% confidence interval (CI), 0.1 to 0.7, p = 0.007] per unit increase in PRISM-IV) and central nervous system infection (+ 17 days [95% CI, 6.7 to 27.4], p = 0.001). Age and pathogen type were not associated with treatment duration. CONCLUSIONS: Most critically ill children with BSIs received at least two weeks of antimicrobial treatment. Further study is needed to determine whether shorter duration therapy would be effective for selected critically ill children.

Retrospective analysis of the efficacy and duration of botulinum toxin A injections in 30 patients with palmar hyperhidrosis.

Palmar hyperhidrosis is a common disorder characterised by excessive sweating due to hyperfunction of the sweat glands. It can be classified as primary disease, or secondary to other causes. It has a high morbidity, and a range of treatment options. Botulinum toxin injections inhibit the release of acetylcholine from the presynaptic receptors. It is an effective treatment; however, it is infrequently selected as only axillary hyperhidrosis currently attracts a Medicare subsidy. We conducted a retrospective review of 30 patients at a Sydney dermatology clinic who received botulinum toxin injections for palmar hyperhidrosis within the past 5 years. This study has the largest patient cohort with this condition in Australia. There was evidence for a median reduction in the Hyperhidrosis Disease Severity Scale, a qualitative self-reported score, as well as an increasing duration of efficacy with repeated injections. There were minimal side-effects of weakness and numbness. There is also an association between treatment of palmar disease and improvement in plantar disease, which suggests that treatment of palmar hyperhidrosis should be considered earlier and more frequently.

Real-World Outcomes and Value of First-Line Therapy for Metastatic Non-Small Cell Lung Cancer†.

Although physicians rely on clinical trial data to guide cancer treatment decisions, patient characteristics and outcomes often differ between real-world and clinical trial populations. We analyzed retrospective clinical data collected from a prior authorization (PA) tool linked with payer claims data to describe outcomes of first-line treatment for metastatic non-small cell lung cancer among 2,108 patients. Duration of therapy was shorter than observed in clinical trials. Healthcare costs and hospitalizations varied substantially by regimen. PA clinical data linked with administrative claims enable head-to-head comparisons of contemporary cancer treatments used in routine clinical practice, which are not available from clinical trials.

Craniofacial growth in infants with deformational plagiocephaly: does prematurity affect the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment?

OBJECTIVE: Although prematurity is a risk factor for developing deformational plagiocephaly (DP), to our knowledge, there are no studies that have analyzed the impact of a premature birth on the duration of head orthosis therapy and the extent of the reduction in asymmetry during treatment. MATERIALS AND METHODS: We examined 239 patients with DP who were undergoing head orthosis therapy. Depending on the gestational age, they were assigned to either a premature (gestational age of < 37 weeks) or a full-term (gestational age of ≥ 37 weeks) group. Head shape was analyzed using 3D-stereophotogrammetry at the start and end of treatment. We performed multiple linear regression analyses to evaluate the impact of prematurity on the duration of therapy and the extent of the reduction in asymmetry, taking age and the initial asymmetry of an infant's head into account. RESULTS: Head orthosis therapy led to a significant reduction in asymmetry in both groups. Using multiple linear regression analyses, we demonstrated that age at the start of treatment, the initial asymmetry and prematurity, significantly influenced the duration of therapy. Patients who were born at an earlier gestational age experienced a shorter treatment length. However, prematurity did not affect the extent of the reduction in cranial asymmetry that was achieved. CONCLUSIONS: Along with age at the start of treatment and the initial asymmetry, prematurity is significantly correlated with the duration of head orthosis therapy, but not with the extent of the reduction in asymmetry achieved. CLINICAL RELEVANCE: Knowledge of these findings is important for clinicians when planning treatment and discussing the effectiveness of head orthosis therapy with the parents of premature infants with DP.

Impact of Pharmacist-Led Procalcitonin-Guided Antibiotic Therapy in Critically Ill Patients With Pneumonia.

Purpose: Procalcitonin (PCT) is a peptide that is released in response to bacterial infections. The 2016 Infectious Diseases Society of America pneumonia guidelines recommend PCT monitoring to help guide antibiotic discontinuation. Utilization of PCT is well described in the literature; however, there is a paucity of literature regarding pharmacists' involvement for using PCT in antibiotic interventions. The objective of this study was to investigate the effect of pharmacist-led intervention with PCT-guided antibiotic therapy in critically ill patients with pneumonia. Methods: This was a pre-post study conducted at a 1368-bed community teaching hospital in the United States. A prospective cohort with pharmacist intervention utilizing PCT-algorithm guidance was compared with a retrospective historical cohort with standard therapy. Adult patients admitted to the intensive care unit (ICU) with pneumonia were included. The primary endpoint was duration of antibiotic therapy. Secondary endpoints included 28-day mortality, ICU and hospital length of stay, reinitiation of antibiotic therapy, and the incidence of Clostridium difficile infection. Results: From August 2016 to July 2017, 113 patients were screened in the PCT group and 123 patients in the standard therapy group. Of these, 37 patients were included in the PCT group and 37 patients in the standard therapy group. Baseline characteristics were similar between the 2 groups. The antibiotic duration of therapy was 6.3 days in the PCT group versus 9.7 days in the standard therapy group (P < .001). There were no differences in secondary endpoints between the 2 groups. Conclusion: Clinical pharmacists' intervention with PCT-guided antibiotic therapy led to a reduction in the duration of antibiotic therapy in critically ill patients with pneumonia without increasing complications.

Optimising trial designs to identify appropriate antibiotic treatment durations.

BACKGROUND: For many infectious conditions, the optimal antibiotic course length remains unclear. The estimation of course length must consider the important trade-off between maximising short- and long-term efficacy and minimising antibiotic resistance and toxicity. MAIN BODY: Evidence on optimal treatment durations should come from randomised controlled trials. However, most antibiotic randomised controlled trials compare two arbitrarily chosen durations. We argue that alternative trial designs, which allow allocation of patients to multiple different treatment durations, are needed to better identify optimal antibiotic durations. There are important considerations when deciding which design is most useful in identifying optimal treatment durations, including the ability to model the duration-response relationship (or duration-response 'curve'), the risk of allocation concealment bias, statistical efficiency, the possibility to rapidly drop arms that are clearly inferior, and the possibility of modelling the trade-off between multiple competing outcomes. CONCLUSION: Multi-arm designs modelling duration-response curves with the possibility to drop inferior arms during the trial could provide more information about the optimal duration of antibiotic therapies than traditional head-to-head comparisons of limited numbers of durations, while minimising the probability of assigning trial participants to an ineffective treatment regimen.

Duration of anticoagulant therapy and VTE recurrence in patients with cancer.

PURPOSE: Anticoagulant therapy for at least 3-6 months is currently recommended for treatment of venous thromboembolism (VTE) in patients with cancer, but the optimal duration of treatment is unknown. This study examines the association between the duration of anticoagulation treatment and VTE recurrence in cancer patients. METHODS: The Humana claims database was used to identify newly diagnosed cancer patients who had their first VTE diagnosis between January 1, 2013, and May 31, 2015, and initiated injectable or oral anticoagulant therapy. Follow-up was calculated from the index treatment initiation to the end of eligibility or end of data (June 2015). VTE recurrence was defined as a hospitalization with a primary diagnosis of VTE. Cox proportional hazards models were used to evaluate the risk of VTE recurrence by duration of therapy in patients who discontinued therapy. RESULTS: The study included 1158 patients. Compared to patients treated for 0 to 3 months, VTE recurrences were significantly lower among patients treated for 3 to 6, or over 6 months. After adjustment for baseline characteristics, patients treated for 3 to 6 months (HR [95%CI], 0.53; 0.37-0.76) and more than 6 months (HR [95%CI], 0.48; 0.34-0.68) were still significantly less likely to have VTE recurrences compared to patients treated for 0 to 3 months (both p < 0.01). Findings were similar using a VTE event definition that included outpatient visits. CONCLUSIONS: Among newly diagnosed cancer patients with VTE, anticoagulant therapy lasting more than 3 months was associated with a lower risk of VTE recurrence.

Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score-Matched Cohort.

Background: The recommended duration of antibiotic treatment for Enterobacteriaceae bloodstream infections is 7-14 days. We compared the outcomes of patients receiving short-course (6-10 days) vs prolonged-course (11-16 days) antibiotic therapy for Enterobacteriaceae bacteremia. Methods: A retrospective cohort study was conducted at 3 medical centers and included patients with monomicrobial Enterobacteriaceae bacteremia treated with in vitro active therapy in the range of 6-16 days between 2008 and 2014. 1:1 nearest neighbor propensity score matching without replacement was performed prior to regression analysis to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment comparing patients in the 2 treatment groups. Secondary outcomes included recurrent bloodstream infections, Clostridium difficile infections (CDI), and the emergence of multidrug-resistant gram-negative (MDRGN) bacteria, all within 30 days after the end of antibiotic therapy. Results: There were 385 well-balanced matched pairs. The median duration of therapy in the short-course group and prolonged-course group was 8 days (interquartile range [IQR], 7-9 days) and 15 days (IQR, 13-15 days), respectively. No difference in mortality between the treatment groups was observed (adjusted hazard ratio [aHR], 1.00; 95% confidence interval [CI], .62-1.63). The odds of recurrent bloodstream infections and CDI were also similar. There was a trend toward a protective effect of short-course antibiotic therapy on the emergence of MDRGN bacteria (odds ratio, 0.59; 95% CI, .32-1.09; P = .09). Conclusions: Short courses of antibiotic therapy yield similar clinical outcomes as prolonged courses of antibiotic therapy for Enterobacteriaceae bacteremia, and may protect against subsequent MDRGN bacteria.

Rethinking non-inferiority: a practical trial design for optimising treatment duration.

Background Trials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, tuberculosis and hepatitis C. However, standard non-inferiority designs have several limitations, including arbitrariness of non-inferiority margins, choice of research arms and very large sample sizes. Methods We recast the problem of finding an appropriate non-inferior treatment duration in terms of modelling the entire duration-response curve within a pre-specified range. We propose a multi-arm randomised trial design, allocating patients to different treatment durations. We use fractional polynomials and spline-based methods to flexibly model the duration-response curve. We call this a 'Durations design'. We compare different methods in terms of a scaled version of the area between true and estimated prediction curves. We evaluate sensitivity to key design parameters, including sample size, number and position of arms. Results A total sample size of ~ 500 patients divided into a moderate number of equidistant arms (5-7) is sufficient to estimate the duration-response curve within a 5% error margin in 95% of the simulations. Fractional polynomials provide similar or better results than spline-based methods in most scenarios. Conclusion Our proposed practical randomised trial 'Durations design' shows promising performance in the estimation of the duration-response curve; subject to a pending careful investigation of its inferential properties, it provides a potential alternative to standard non-inferiority designs, avoiding many of their limitations, and yet being fairly robust to different possible duration-response curves. The trial outcome is the whole duration-response curve, which may be used by clinicians and policymakers to make informed decisions, facilitating a move away from a forced binary hypothesis testing paradigm.