Comparative efficacy and optimal duration of first-line antibiotic regimens for acute otitis media in children and adolescents:a systematic review and network meta-analysis of 89 randomized clinicaltrials

Introduction Antibiotic use for acute otitis media(AOM)is one of the major sources of antimicrobial resistance.However,the effective minimal antibiotic duration for AOM remains unclear.Moreover,guidelines often recommend broad ranges(5-10 days)of antibiotic use,yet the clinical impact of such a wide window has not been assessed.Methods We systematically searched PubMed/MEDLINE,Embase,Scopus,Web of Science,and Cochrane Library from database inception to 6 October 2021.Network meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children(PROSPERO CRD42020196107).Results For amoxicillin and amoxicillin-clavulanate,7-day regimens were noninferior to 10-day regimens in clinical responses[amoxicillin:risk ratio(RR)0.919(95%CI 0.820-1.031),amoxicillin-clavulanate:RR 1.108(0.957-1.282)],except for≤2 years.For the third-generation cephalosporins,7-day and 10-day regimens had similar clinical responses compared to placebo[7-day:RR 1.420(1.190-1.694),10-day:RR 1.238(1.125-1.362)compared to placebo].However,5-day regimens of amoxicillin-clavulanate and third-generation cephalosporins were inferior to 10-day regimens.Compared to amoxicillin,a shorter treatment duration was tolerable with amoxicillin-clavulanate.Conclusions Our findings indicated that 1O days of antibiotic use may be unnecessarily long,while the treatment duration should be longer than 5 days.Otherwise,5-day regimens would be sufficient for a modest treatment goal.Our findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM,and a narrower antibiotic duration window should be re-established.

Predictive indicators of successful tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia

Clinical trials have demonstrated that some patients with chronic myeloid leukemia(CML)treated for several years with tyrosine kinase inhibitors(TKIs)who have maintained a molecular response can successfully discontinue treatment without relapsing.Treatment free remission(TFR)can be reached by approximately 50%of patients who discontinue.Despite having similar levels of deep molecular response and an identical duration of treatment,the factors that influence the successful discontinuation of CML patients remain to be determined.In this review we will explore the factors identified to date that can help predict whether a patient will successfully achieve TFR.We will also discuss the need for the identification of predictive biomarkers associated with a high probability of achieving TFR for the future personalized identification of patients who are suitable for the discontinuation of TKI treatment.

Prolonged survival in patients with hand-foot skin reaction secondary to cooperative sorafenib treatment

BACKGROUND Sorafenib is an oral drug that prolongs overall survival(OS)in patients with hepatocellular carcinoma.Adverse events,including hand-foot skin reaction(HFSR),lead to permanent sorafenib discontinuation.AIM To clarify the association between interventions for adverse events and patient prognosis.METHODS We performed a retrospective,multicenter study of patients treated with sorafenib monotherapy between May 2009 and March 2018.We developed a mutual cooperation system that was initiated at the start of sorafenib treatment to effectively manage adverse events.The mutual cooperation system entailed patients receiving consultations during which pharmacists provided accurate information about sorafenib to alleviate the fear and anxiety related to adverse events.We stratified the patients into three groups:Group A,patients without HFSR but with pharmacist intervention;Group B,patients with HFSR and pharmacist interventions unreported to oncologists(nonmutual cooperation system);and Group C,patients with HFSR and pharmacist interventions known to oncologists(mutual cooperation system).OS and time to treatment failure(TTF)were evaluated using the Kaplan-Meier method.RESULTS We enrolled 134 patients(Group A,n=41;Group B,n=30;Group C,n=63).The median OS was significantly different between Groups A and C(6.2 vs 13.9 mo,p<0.01)but not between Groups A and B(6.2 vs 7.7 mo,P=0.62).Group A vs Group C was an independent OS predictor(HR,0.41;95%CI:0.25-0.66;P<0.01).In Group B alone,TTF was significantly lower and the nonadherence rate was higher(P<0.01).In addition,the Spearman’s rank correlation coefficients between OS and TTF in each group were 0.41(Group A;P<0.01),0.13(Group B;P=0.51),and 0.58(Group C;P<0.01).There was a highly significant correlation between OS and TTF in Group C.However,there was no correlation between OS and TTF in Group B.CONCLUSION The mutual cooperation system increased treatment duration and improved prognosis in patients with HFSR.Future prospective studies(e.g.,randomized controlled trials)and improved adherence could help prevent OS underestimation.

The conflict on posttreatment Lyme disease syndrome: a clinical mini review

Is Borrelia burgdorferi responsible for the persistence of symptoms after the standard successful course of antibiotics in Lyme disease patients?This highly controversial issue,concerning the underlying mechanism of posttreatment Lyme disease syndrome(PTLDS),still seems to be a matter of intense conflict of opinion.PTLDS is the manifestation of nonspecific symptoms including fatigue,musculoskeletal pain,dysesthesias,and neurocognitive deterioration after the standard antimicrobial therapy administered to patients suffering from Lyme disease.In this article,we review the conflicting views and published highlights of recent human studies regarding PTLDS.