scholarly journals Multidrug therapy with terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India: Results of a randomized pragmatic trial

2019 ◽  
Author(s):  
Sanjay Singh ◽  
Bandana Jha ◽  
Prakriti Shukla ◽  
Vinayak N Anchan

AbstractBackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine daily plus fluconazole weekly (TFw) and terbinafine daily plus fluconazole daily (TFd) versus oral terbinafine daily (T) in tinea corporis, tinea cruris and tinea faciei in a pragmatic randomized open trial.MethodsOne hundred and seventeen microscopy confirmed patients were allocated to T (6 mg/kg/day), TFw (terbinafine 6 mg/kg/day+fluconazole 12 mg/kg once weekly), or TFd (terbinafine 6 mg/kg/day+fluconazole 6 mg/kg/day) groups by concealed randomization and treated for 8 weeks or cure. Each group included 39 patients.ResultsAt 4 weeks, 9 (23.1%), 8 (20.5%) and 14 (35.9%) patients were cured in T, TFw and TFd groups, respectively (P=0.279). At 8 weeks, number of patients cured was as follows: T 13 (33.3%), TFw 18 (46.2%) and TFd 25 (64.1%). TFd was more effective than T (P=0.012), other comparisons were not significantly different. However, effect size as calculated by number needed to treat (NNT) (versus terbinafine) was 8 for TFw and 4 for TFd. Relapse rates one month after cure were similar in all groups (P=0.664).ConclusionsIn view of cure rates and NNT, terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India.One Sentence SummaryTerbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India.

2019 ◽  
Author(s):  
Sanjay Singh ◽  
Vinayak N Anchan ◽  
Usha Chandra ◽  
Radhika Raheja

AbstractBackgroundTreatment responsiveness of dermatophytosis has decreased considerably in recent past in India. We compared effectiveness of oral terbinafine daily (Terb) (active control) versus itraconazole daily (Itra) versus terbinafine plus itraconazole daily (TI) versus terbinafine daily plus itraconazole pulse (TIp) in tinea corporis, tinea cruris and tinea faciei in a pragmatic randomized open trial.MethodsNinety-two microscopically confirmed patients were allocated to Terb (6 mg/kg/day), Itra (5 mg/kg/day), TI (terbinafine 6 mg/kg/day, itraconazole 5 mg/kg/day), or TIp (terbinafine 6 mg/kg/day, itraconazole 10 mg/kg/day for 1 week in 4 weeks) group by concealed block randomization and treated for 8 weeks or cure.ResultsCure rates were similar at 4 weeks (P=0.768). At 8 weeks, 5 (21.7%), 18 (78.3%), 16 (69.6%), and 16 (69.6%) patients were cured in Terb, Itra, TI, and TIp groups, respectively. All experimental regimens (Itra, TI, TIp) were more effective than Terb (P≤0.0027). All experimental regimens had similar effectiveness (P≥0.738). Relapse rates 4 and 8 weeks after cure were similar (P=0.869 and 0.314, respectively). Number-needed-to-treat (NNT) was 2 for Itra, 3 for TI, and 3 for TIp.ConclusionsOral itraconazole given daily (NNT=2) is the most effective treatment and combining it with terbinafine does not increase effectiveness.One Sentence SummaryCombination of oral terbinafine and itraconazole is not more effective than itraconazole alone in current epidemic of altered dermatophytosis in India.


2019 ◽  
Author(s):  
Sanjay Singh ◽  
Vinayak N Anchan ◽  
Radhika Raheja

AbstractBackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine plus griseofulvin versus terbinafine alone in tinea corporis, tinea cruris and tinea faciei in a randomized pragmatic open trial.MethodsOne hundred and thirty two microscopy confirmed patients were randomly allocated (ratio 1:1) to two groups, terbinafine (T) and terbinafine plus griseofulvin (T+G). Doses given were as follows: T, oral terbinafine (6 mg/kg/day, maximum 500 mg/day, once daily); T+G, terbinafine (as above) plus oral griseofulvin (children [<18 years] 10 mg/kg/day, adults [18 years or more] 10 mg/kg/day, but not <500 mg and not >1000 mg per day, in two divided doses). Patients were treated for 8 weeks or cure, whichever occurred earlier.ResultsAt 4 weeks, none of the patients were cured in both groups. At 6 weeks, 1(1.5%) and 4 (6.1%) patients were cured in T and T+G groups, respectively (P=0.417). At 8 weeks, 17 (25.8%) and 19 (28.8%) patients were cured in T and T+G groups, respectively (P=0.845). For cure rate at 8 weeks, number needed to treat (NNT) for T+G (versus T), was 33.ConclusionsAddition of griseofulvin to terbinafine does not increase effectiveness of terbinafine in current epidemic of altered dermatophytosis in India.


2019 ◽  
Author(s):  
Sanjay Singh ◽  
Usha Chandra ◽  
Priyanka Verma ◽  
Vinayak N Anchan ◽  
Ragini Tilak

AbstractBackgroundDermatophyte infections have undergone unprecedented changes in India in recent past. Clinical trials comparing effectiveness of 4 main oral antifungal drugs are not available. We tested effectiveness of oral fluconazole, griseofulvin, itraconazole and terbinafine in chronic and chronic-relapsing tinea corporis, tinea cruris and tinea faciei.MethodsTwo hundred microscopy confirmed patients were allocated to 4 groups, fluconazole (5mg/kg/day), griseofulvin (10 mg/kg/day), itraconazole (5mg/kg/day), and terbinafine (7.5mg/kg/day), by concealed block randomization and treated for 8 weeks or cure. Effectiveness was calculated based on intention to treat analysis.ResultsAt 4 weeks, 4, 1, 2, and 4 patients were cured with fluconazole, griseofulvin, itraconazole and terbinafine, respectively (P=0.417). At 8 weeks, 21 (42%), 7 (14%), 33 (66%) and 14 (28%) patients were cured, respectively (P=0.000); itraconazole was superior to fluconazole, griseofulvin and terbinafine (P≤0.016). Relapse rates after 4 and 8 weeks of cure in different groups were similar. Numbers-needed-to-treat (NNT) (versus griseofulvin), calculated based on cure rates at 8 weeks, for itraconazole, fluconazole, and terbinafine were 2, 4 and 8, respectively.ConclusionIn view of cure rates and NNT, itraconazole is the most effective drug, followed by fluconazole (daily), terbinafine and then griseofulvin, in chronic and chronic-relapsing dermatophytosis in India.One Sentence SummaryEffectiveness of all four antifungals has declined, with itraconazole being the most effective currently in dermatophytosis in India.


CJEM ◽  
2016 ◽  
Vol 18 (S1) ◽  
pp. S53-S53
Author(s):  
T. Kawano ◽  
B.E. Grunau ◽  
K. Gibo ◽  
F.X. Scheuermeyer ◽  
R. Stenstrom

Introduction: H1-antihistamines are often used to treat allergic reactions, however, the influence of H1-antihistamines on progression to anaphylaxis remains unclear. Among patients initially presenting with allergic reactions, we investigated whether H1-antihistamines were associated with a lower proportion of patients progressing to anaphylaxis during observation. Methods: This was a retrospective cohort study conducted at two urban EDs from 2007 to 2012. We included adult patients with allergy and excluded those who met criteria of anaphylaxis at first evaluation by medical professionals and/or received antihistamines before the evaluation. Primary outcomes of interest were the number of patients who developed anaphylaxis during observation at ED and/or transportation by EMS. Secondary outcomes were the number of biphasic reactions and severe anaphylaxis (defined as sBP<90; SpO2<92%; and/or confusion, collapse, loss of conscious, or incontinence). Logistic regression was performed comparing primary and secondary outcomes between H1-antihistamine treated and non-treated groups with propensity score adjustment of the baseline covariates. Number needed to treat (NNT) was calculated by adjusted absolute risk reduction of H1-antihistamine compared to non H1-antihistamine use on primary outcome. Results: This study included 1717 patients with allergic reactions, of whom 1228 were treated with H1-antihistamines. In the H1-antihistamine group 1.0% and 0.2% developed anaphylaxis and severe anaphylaxis, respectively; in the non-H1-antihistamine group 2.6% and 0.6% developed anaphylaxis and severe anaphylaxis, respectively. There were no biphasic reactions (0%, 95% confidence interval [CI] 0 to 0.17%). Administration of H1-antihistamines was associated with a lower incidence of subsequent anaphylaxis (adjusted odds ratio [OR] 0.23, 95% CI 0.10 to 0.53; NNT to benefit 49.1, 95% CI 41.6 to 83.3). There were no significant associations between H1-histamines administration and secondary outcomes. Conclusion: Among ED patient with allergic reactions, H1-antihistamine administration was associated with a lower likelihood of progression to anaphylaxis. These findings suggest that H1-antihistamines should be administered early in the care of patients with allergic reactions.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anna Sureda ◽  
Marc André ◽  
Peter Borchmann ◽  
Maria G. da Silva ◽  
Christian Gisselbrecht ◽  
...  

Abstract Autologous stem cell transplantation (ASCT) is a well-established approach to treatment of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) recommended by both the European Society for Medical Oncology and the National Comprehensive Cancer Network based on the results from randomized controlled studies. However, a considerable number of patients who receive ASCT will progress/relapse and display suboptimal post-transplant outcomes. Over recent years, a number of different strategies have been assessed to improve post-ASCT outcomes and augment HL cure rates. These include use of pre- and post-ASCT salvage therapies and post-ASCT consolidative therapy, with the greatest benefits demonstrated by targeted therapies, such as brentuximab vedotin. However, adoption of these new approaches has been inconsistent across different centers and regions. In this article, we provide a European perspective on the available treatment options and likely future developments in the salvage and consolidation settings, with the aim to improve management of patients with HL who have a high risk of post-ASCT failure. Conclusions We conclude that early intervention with post-ASCT consolidation improves outcomes in patients with R/R HL who require ASCT. Future approvals of targeted agents are expected to further improve outcomes and provide additional treatment options in the coming age of personalized medicine.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 840-840
Author(s):  
Rachael E. Hough ◽  
Clare Rowntree ◽  
Rachel Wade ◽  
Nicholas Goulden ◽  
Chris Mitchell ◽  
...  

Abstract Despite the substantial improvements made in the outcomes of paediatric ALL, with ‘cure' rates now in excess of 90%, survival in teenage and young adult (TYA) patients has remained inferior. The reasons for this are likely multifactorial, including tumour biology, toxicity, compliance, access to clinical trials and protocol (adult or paediatric) used. We report the toxicity profiles observed in children, teenagers and young adults treated on the UK intensive, minimal residual disease (MRD) directed ALL protocol, UKALL2003. Of a total of 3126 patients treated, 1520 patients were under 5 years old, 767 were aged 5-9 years, 610 aged 10-15 years and 229 aged 16-24 years, with a median overall follow-up of 4 year and 10 months. The risk of serious adverse events (SAEs) was higher in patients older than 10 years (56% in 10-15 year olds, 53% in 16-24 year olds) compared to those aged 9 or younger (30% in under 5 years and 31% in 5-9 years)(p<0.0001), with no difference in the those aged 16-24 compared to younger teenagers (p=0.5). The incidence (per number of patients in each group) and distribution of toxicities according to age group is summarised in the table.Table 1Age in years<55-910-1516-24AllTotal number of patients1520767610229 NB: 56 pts≥20 years3126Infection n (%)328 (21.6%)130 (17.0%)145 (23.8%)72 (31.4%)675 (21.6%)Asaparaginase n (%)57 (3.8%)57 (7.4%)64 (10.5%)31 (13.5%)209 (6.7%)Methotrexate n (%)100 (6.6%)74 (9.6%)123 (20.2%)33 (14.4%)330 (10.6%)Steroid n (%)54 (3.6%)37 (4.8%)141 (23.1%)52 (22.7%)284 (9.0%)Vincristine n (%)34 (2.2%)11 (1.4%)22 (3.6%)7 (3.0%)74 (2.4%)Other SAEs94 (6.2%)42 (5.5%)90 (14.8%)25 (10.9%)251 (8.0%) The incidence of certain toxicities including viral infection (5.3%), asparaginase hypersensitivity (1.9%) and vincristine neurotoxicity (2.1%) appeared equivalent across all age groups. Avacular necrosis was seen predominantly in adolescents (83% of 147 events in 10-19 year olds) and was rare in those younger than 10 years (n=18) or older than 20 years (n=7). Asparaginase thrombotic events increased in frequency with increasing age (1.5% in under 5 years, 3.3% in 5-9 years, 4.4% in 10-15 years and 8.3% in 16-24 year olds)(p<0.0001). All other toxicities were more frequently observed in over 10 year olds compared to patients aged 9 or younger, with no difference between 16-24 year olds and 10-15 year olds. The impact of age on SAEs associated with intensive ALL chemotherapy varies according to specific toxicities. In general, toxicity is higher in those over 10 years compared to younger patients, with no excess toxicity in those aged 16-24 compared to 10-15 years. However, specific toxicities may increase with increasing age (thrombosis), be restricted to adolescence (AVN) or be unrelated to age (vincristine neurotoxicity, asparaginase hypersensitivity). Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 30-30
Author(s):  
Firas Abdollah ◽  
Giorgio Gandaglia ◽  
Alberto Briganti ◽  
Quoc-Dien Trinh ◽  
Paul Linh Nguyen ◽  
...  

30 Background: Although adjuvant radiotherapy (aRT) after radical prostatectomy (RP) improves biochemical recurrence (BCR)-free survival rates, its effect on cancer-specific mortality (CSM) in patients with prostate cancer (PCa) is still controversial. The aim of our study was to test the effect of aRT on CSM according to a risk score based on the number and nature of adverse pathological characteristics (Gleason score 8-10; pT3b/4, lymph node invasion [LNI]). Methods: Overall, 7,616 patients with pT3/4 N0/1 PCa treated with RP between 1995 and 2009 within the Surveillance Epidemiology and End Results Medicare-linked database were included in the study. Patients were stratified according to the risk score (less than 2 vs. 2 or more adverse characteristics), and the impact of aRT on CSM was examined in each sub-group. Additionally, to evaluate the effectiveness of aRT, we calculated the number needed to treat (NNT), defined as the average number of patients who must be treated to prevent one detrimental outcome. Subsequently, competing-risks regression models were used to test the effect of aRT on CSM rates in the overall population and after stratifying patients according to their risk score (less than 2 vs. 2 or more). Results: The risk score was associated with increasing 10-year CSM rates (P<0.001). When focusing on patients with a risk score 2 or more, 10-year CSM rates were significantly lower for individuals undergoing aRT compared to their counterpart not receiving aRT (6.9 vs. 16.2%, respectively; P=0.002). The corresponding NNT to prevent one death from PCa was 10. Adjuvant RT was not associated with lower CSM rates overall and in patients with a risk score less than 2. This was confirmed in multivariable analyses, where aRT decreased the risk of CSM only in patients with a risk score 2 or more (P≤0.02). Conclusions: Our findings confirm the validity of the previously reported risk score in selecting the most optimal candidates for aRT after surgery in a large contemporary population-based cohort of patients with pT3/4 N0/1 PCa. Patients with two or more adverse pathological characteristics at RP might benefit the most from aRT in terms of reduced CSM.


1996 ◽  
Vol 7 (2) ◽  
pp. 110-114 ◽  
Author(s):  
Canadian Itraconazole Study Group ◽  
Thomas W Austin ◽  
Marc Steben ◽  
Marion Powell ◽  
Barbara Romanowski ◽  
...  

OBJECTIVE: To determine the clinical and mycological effectiveness of oral itraconazole in the treatment of acute candida vulvovaginitis.DESIGN: A prospective, randomized and single-blinded, multicentre trial of 221 women, comparing a one-day course of oral itraconazole 200 mg bid with vaginal clotrimazole 500 mg single-dose therapy.MAIN OUTCOME MEASURES: Symptoms, signs and mycological results were assessed up to two months following treatment. Adverse events were recorded and evidence of hepatotoxicity sought.RESULTS: At 10 and 30 days post-treatment, clinical and mycological cure rates were similar (61.3% clinical and 88.6% mycological 10 days after, and 67.7% clinical and 79.5 mycological 30 days after itraconazole; 64.0 clinical and 85.9% mycological 10 days after, and 62.1% clinical and 78.6 mycological 30 days after clotrimazole) with the majority of both treatment groups free from infection. A total of 69 patients reported adverse events, which were generally transient and mild. Itraconazole was more often associated with gastrointestinal or central nervous system complaints, while clotrimazole recipients more often had genitourinary symptoms. No evidence of hepatotoxicity was found. A higher incidence of relapse was noted among women on the birth control pill and among those who were symptomatic for longer than 10 days before treatment.CONCLUSIONS: A one-day course of oral itraconazole is as effective as intravaginal clotrimazole in the treatment of acute yeast vulvovaginitis. The number of patients reporting adverse events was similar for the treatment groups, although the side effect profile differed. No hepatotoxicity was observed.


2019 ◽  
Vol 25 (6) ◽  
pp. 613-618 ◽  
Author(s):  
Juan Carlos Martinez-Gutierrez ◽  
Thabele Leslie-Mazwi ◽  
Ronil V Chandra ◽  
Kevin L Ong ◽  
Raul G Nogueira ◽  
...  

Background The number needed to treat is a commonly used statistical term in modern neurointerventional practice. It represents the number of patients that need to be treated for one patient to benefit from an intervention. Given its growing popularity in reflecting study results, understanding the basics behind this statistic is of practical value to the neurointerventionalist. Methods Here, we review the basic theory and calculation of the number needed to treat, its application to stroke interventions, and its limitations. In addition, we demonstrate several simple methods of calculating the number needed to treat utilizing recent thrombectomy trial results. By presenting the number needed to treat as a universal metric, we provide a comprehensive comparative of the number needed to treat for key stroke therapies, including mechanical thrombectomy, tissue plasminogen activator, carotid endarterectomy, and prevention with antiplatelet and statin drugs. Conclusions In comparison with available stroke therapies, mechanical thrombectomy stands out as the most effective acute intervention in patients with emergent large-vessel occlusions. Understanding how the number needed to treat is derived and its implications helps provide perspective to clinical trial data, identify health-care resource priorities, and improve communication with patients, health-care providers, and additional key stakeholders.


2015 ◽  
Vol 38 (1) ◽  
pp. 11 ◽  
Author(s):  
Graeme M Rocker ◽  
Jennifer Y Verma ◽  
Jillian Demmons ◽  
Nicole Mittmann

The ‘Number Needed to Treat’ (NNT) is a useful measure for estimating the number of patients that would need to receive a therapeutic intervention to avoid one of the adverse events that the treatment is designed to prevent. We explored the possibility of an adaption of NNT to estimate the ‘Number Needed to $ave’ (NN$) as a new, conceptual systems metric to estimate potential cost-savings to the health system from implementation of a treatment, or in this case, a program. We used the outcomes of the INSPIRED COPD Outreach ProgramTM to calculate that 26 patients would need to complete the program to avoid healthcare expenditures of $100,000, based on hospital bed days avoided. The NN$ does not translate into 'cost savings' per se, but redirection of resource expenditures for other purposes. We propose that the NN$ metric, if further developed, could help to inform system-level resource allocation decisions in a manner similar to the way that the NNT metric helps to inform individual-level treatment decisions.


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