PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial

Abstract Background Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment. Methods This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection. Results Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups. Conclusions PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871

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Delayed PCI 12 Hours after the Onset of Symptoms Is Associated with Improved Outcomes for Patients with ST-Segment Elevation Myocardial Infarction: A Real-World Study

Journal of Interventional Cardiology ◽

10.1155/2019/2387929 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Wen-Juan Xiu ◽

Hai-Tao Yang ◽

Ying-Ying Zheng ◽

Yi-Tong Ma ◽

Xiang Xie

Keyword(s):

Myocardial Infarction ◽

Real World ◽

Time Window ◽

Therapy Group ◽

Trial Registration ◽

St Segment Elevation ◽

Medication Therapy ◽

Segment Elevation Myocardial Infarction ◽

St Segment ◽

Significant Difference

Background. Primary percutaneous coronary intervention (PPCI) plays a pivotal role in the treatment of ST-segment elevation myocardial infarction (STEMI). However, it remains controversial whether PCI delayed beyond the recommended time window of 12 h after the onset of symptoms is applicable to STEMI. Objective. The acute myocardial infarction (AMI) registration study in Xinjiang, China, is a real-world clinical trial (retrospective cohort study) that includes hospitalized patients. The purpose of this study was to compare delayed PCI and medication therapy beyond the recommended time window of 12 h after the onset of symptoms on the outcomes of STEMI patients. Methods and Results. From May 2012 to December 2015, a total of 1072 STEMI patients received delayed PCI (n=594) or standard medication therapy (MT) (n=478) more than 12 h after the onset of symptoms. The number of all-cause deaths in the delayed PCI group and that in the MT group were 55 (9.3%) and 138 (28.9%), respectively, and a significant difference between the groups was indicated for this variable (P<0.001). The number of cardiac deaths in the delayed PCI group and that in the medication therapy group were 47 (7.9%) and 120 (25.1%), respectively, and a significant difference between the groups was indicated for this variable (P<0.001). We also found that the MACE incidence in the delayed PCI group was significantly higher than it was in the MT group (32.2% versus 43.5%, P<0.001). Propensity score matching (PSM) analyses remained significant differences between the delayed PCI group and the MT group, respectively, in all-cause deaths (9.3% versus 25.8%, P<0.001) and cardiac death (8.7% versus 21.6%, P<0.001). Conclusion. Compared to medication therapy, PCI for STEMI delayed beyond 12 h after the onset of symptoms can better reduce mortality and the incidence of MACEs. Trial Registration. This study is registered with the following: Trial Registration: clinicaltrials.gov; Identifier: NCT02737956.

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The Fertility Outcome of Royal Jelly versus Intra Uterine Insemination: A Pilot Randomized Controlled Trial Study

Jundishapur Journal of Natural Pharmaceutical Products ◽

10.5812/jjnpp.107420 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Tahereh Fathi Najafi ◽

Nayereh Khadem ◽

Narjes Bahri ◽

Mojtaba Meshkat ◽

Shirin Sadri ◽

...

Keyword(s):

Royal Jelly ◽

Intrauterine Insemination ◽

Controlled Trial ◽

Treatment Success ◽

Sperm Concentration ◽

Success Rates ◽

Similar Treatment ◽

Significant Difference ◽

Study Power ◽

Sterile Plastic

Background: The popularity of complementary and alternative medicine is on the rise. Objectives: The current study aimed to compare the effect of vaginal royal jelly with intrauterine insemination (IUI) on sub-fertility in men. Methods: The sample size was estimated as 27 subjects, based on a study power and confidence interval of 80% and 95%, respectively. The study was conducted in Mashhad, in the Northeast of Iran, from 2015 to 2017. Men with sub-fertility (asthenozoospermia, defined as total sperm motility below 40% and sperm concentration below 20 million/mL), with healthy wives, based on salpingography, participated in this study. Patients were assigned to the royal jelly group, which received 5 grams of royal jelly, and the IUI group, which received 75 units of Follicle Stimulating Hormone (FSH) from the second day of the menstrual cycle. Semen samples were collected in sterile plastic caps after 72 hours of sexual abstinence by normal sexual intercourse. Samples were prepared using the standard swim-up technique. Results: This study showed no significant difference between groups concerning spousal age, occupation, education (husband and wife), and social class (P = 0.745). Also, no significant difference was found between groups concerning fertility success rate (P = 0.573). Conclusions: Based on similar treatment success rates of royal jelly and IUI, it seems that royal jelly can be considered as an alternative to IUI.

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1116. Comparison of Short-Course vs. Prolonged-Course Antimicrobial Therapy in the Management of Intra-Abdominal Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.949 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S334-S334

Author(s):

Mina Phlamon ◽

Sarah Petite ◽

Kelli Cole

Keyword(s):

Logistic Regression ◽

Antimicrobial Therapy ◽

Clinical Cure ◽

Antimicrobial Treatment ◽

Multivariable Logistic Regression ◽

Short Course ◽

Significant Difference ◽

All Cause Mortality ◽

Secondary Outcomes ◽

Abdominal Infections

Abstract Background When managing complicated intra-abdominal infections (IAIs), the current Infectious Diseases Society of America (IDSA) guidelines recommend an antimicrobial treatment duration of 4–7 days. Although recent evidence supports this shorter course of therapy, antimicrobials are still often administered for 10–14 days due to concern for subsequent complications. The purpose of this study was to compare clinical outcomes of short-course (SC) vs. prolonged-course (PC) antimicrobial therapy in the management of IAI at our institution. Methods IRB-approved, single-center, retrospective cohort including all patients at the University of Toledo Medical Center who were admitted between January 1, 2012–June 30, 2017 with an IAI, received antimicrobials for ≥48 hours, and had at least one sign of IAI. Patients with concomitant infections at sites other than the abdomen, primary peritonitis or pancreatitis, immunocompromising conditions, or bacteremia were excluded. Primary outcome of clinical cure was compared between SC (≤7 days of antimicrobial treatment) and PC (>7 days) groups. Secondary outcomes included hospital length of stay (LOS), ICU LOS, 28-day all-cause mortality, and 30-day readmission. Multivariable logistic regression was performed to assess for factors associated with clinical cure. Results One hundred seventy-five patients were included, 73 SC and 102 PC. Baseline characteristics were similar between groups. Rate of clinical cure for SC vs. PC was 74.0% vs. 67.6% (P = 0.367). Secondary outcomes including hospital LOS (5.5 days vs. 5.8 days, P = 0.372), ICU LOS (3.0 days vs. 5.0 days, P = 0.117), 28-day all-cause mortality (4.1% vs. 2.0%, P = 0.651), and 30-day readmission (19.2% vs. 20.6%, P = 0.818) were also not significantly different. After multivariable logistic regression, the only variable independently associated with clinical cure was diverticulitis (adjusted odds ratio 0.337, 95% CI 0.133 – 0.853). Conclusion In patients with IAI, there was no significant difference observed in rates of clinical cure between SC and PC antimicrobial therapy. These results further support the IDSA recommendations for a shorter duration of therapy for patients with IAI. Disclosures All authors: No reported disclosures.

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Subcutaneous Marzeptacog Alfa (Activated) Versus Intravenous rFVIIa for Treatment of Episodic Bleeding in FVIII Deficient Hemophilia a Rats

Blood ◽

10.1182/blood-2021-151284 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3181-3181

Author(s):

Tom Knudsen ◽

Peter Johansen ◽

Jill Reckless ◽

Shraddha Desai ◽

Grant E. Blouse

Keyword(s):

Allometric Scaling ◽

Hemophilia A ◽

Treatment Success ◽

Coagulation Factor ◽

Factor Vii ◽

Success Rates ◽

Knock Out ◽

Exact Test ◽

Coagulation Factor Vii ◽

Significant Difference

Abstract Background: FVIII deficient knock-out (F8 -/-) rats mimic the bleeding incidents seen in severe human hemophilia A (HA). Subcutaneous (SQ) marzeptacog alfa activated (MarzAA), a novel, engineered recombinant activated coagulation Factor VII (rFVIIa) has been shown to effectively treat episodic bleeding in a pilot experiment in HA rats. This study evaluated the effect of single SQ doses of MarzAA and a single intravenous (IV) dose of rFVIIa on episodic bleeding in F8 -/- rats. Moreover, it compared the effect of SQ MarzAA and IV rFVIIa directly. Methods: Animals were allocated to treatment with either SQ vehicle, SQ MarzAA (60, 180 or 385 µg/kg) or IV rFVIIa (NovoSeven ®) (580 µg/kg) immediately after the bleeding was diagnosed. Doses were based on allometric scaling from humans (Nair AB and Jacob S. J Basic Clin Pharm 2016; 7: 27-31). The primary endpoint of the study was clinical efficacy as rated by a well-defined 4-point scale (Excellent, Good, Fair or Poor), and the efficacy assessment was either treatment success (Excellent or Good) or treatment failure (Fair or Poor) at the 24-hour timepoint. All personnel handling or assessing animals were blinded to the treatment status of each animal except those dosing animals who knew the route of administration. Results: A total of 86 F8 -/- rats was enrolled in the study. Of these, 61 rats presented treatment eligible bleeds between 3 and 10 weeks of age. No statistically significant difference in bleeding severity score were found across groups on diagnosis. As assessed by the clinical outcome at 24 hours, all three SQ MarzAA dose groups exhibited a statistically significant effect on treatment response when compared to SQ vehicle treatment (Figure 1). Conversely, no statistically significant effect could be identified when the single IV rFVIIa 580 µg/kg dose group was compared to vehicle. The overall treatment success rates at 24 hours were: SQ vehicle: 8%, SQ MarzAA 60 µg/kg: 58%, SQ MarzAA 180 µg/kg: 67%, SQ MarzAA 385 µg/kg: 85%, and IV rFVIIa 580 µg/kg: 33%. When compared directly using allometric scaling of clinical doses, SQ MarzAA at 385 µg/kg exhibited a statistically superior effect compared to IV rFVIIa at 580 µg/kg (p=0.0154, Fischer's exact test). Conclusion: Single doses of SQ MarzAA were effective in treating episodic bleeding in HA rats and statistically distinguishable from vehicle at all dose levels tested. When clinically relevant doses were compared directly to rFVIIa, SQ MarzAA compared favorably to IV rFVIIa. Taken together, these data provide robust nonclinical evidence that a single dose of SQ MarzAA may be successful in treating episodic bleeding when administered after bleeding has started. Figure 1 Figure 1. Disclosures Knudsen: Catalyst Biosciences: Current Employment, Current holder of individual stocks in a privately-held company. Blouse: Catalyst Biosciences: Current Employment.

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Clinical audit of current Helicobacter pylori treatment outcomes in Singapore

Singapore Medical Journal ◽

10.11622/smedj.2021105 ◽

2021 ◽

Author(s):

TL Ang ◽

KW Lim ◽

D Ang ◽

YJ Wong ◽

M Tan ◽

...

Keyword(s):

Treatment Outcomes ◽

Clinical Audit ◽

Day Treatment ◽

Treatment Success ◽

Similar Efficacy ◽

Second Line ◽

Success Rates ◽

First Line ◽

Ulcer Disease ◽

H Pylori

Introduction: H. pylori eradication reduces the risk of gastric malignancies and peptic ulcer disease. First-line therapies include 14-day PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) and PBMT (PPI, bismuth, metronidazole, tetracycline). Second-line therapies include 14-day PBMT and PAL (PPI, amoxicillin, levofloxacin). This clinical audit examined current treatment outcomes in Singapore. Methods: Clinical data of H. pylori-positive patients who underwent empirical first- and second-line eradication therapies from 1 January 2017 to 31 December 2018 were reviewed. Treatment success was determined by 13C urea breath test performed at least 4 weeks after treatment and 2 weeks off PPI. Results: A total of 963 patients (862 PAC, 36 PMC [PPI, metronidazole, clarithromycin], 18 PBMT, 13 PBAC [PAC with bismuth], 34 others) and 98 patients (62 PMBT, 15 PAL, 21 others) received first- and second-line therapies respectively. A 14-day treatment duration was appropriately prescribed for first- and second-line therapies in 65.2% and 82.7% of patients, respectively. First-line treatment success rates were noted for PAC (seven-day: 76.9%, ten-day: 88.3%, 14-day: 92.0%), PMC (seven-day: 0, ten-day: 75.0%, 14-day: 69.8%), PBMT (ten-day: 100%, 14-day: 87.5%) and PBAC (14-day: 100%). 14-day treatment was superior to seven-day treatment (90.8% vs. 71.4%; p = 0.028). PAC was superior to PMC (p < 0.001) but similar to PBMT (p = 0.518) and PBAC (p = 0.288) in 14-day therapies. 14-day second-line PAL and PBMT had similar efficacy (90.9% vs. 82.4%; p = 0.674). Conclusion: First-line empirical treatment using PAC, PBMT and PBAC for 14 days had similar efficacy. Success rates for second-line PBMT and PAL were similar.

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Drivers and Trajectories of Resistance to New First-Line Drug Regimens for Tuberculosis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu073 ◽

2014 ◽

Vol 1 (2) ◽

Cited By ~ 11

Author(s):

Sourya Shrestha ◽

Gwenan M. Knight ◽

Mariam Fofana ◽

Ted Cohen ◽

Richard G. White ◽

...

Keyword(s):

Drug Resistance ◽

Treatment Success ◽

Drug Regimen ◽

Transmission Model ◽

Drug Resistant ◽

Success Rates ◽

First Line ◽

New Drug ◽

Drug Regimens ◽

Line Drug

Abstract Background. New first-line drug regimens for treatment of tuberculosis (TB) are in clinical trials: emergence of resistance is a key concern. Because population-level data on resistance cannot be collected in advance, epidemiological models are important tools for understanding the drivers and dynamics of resistance before novel drug regimens are launched. Methods. We developed a transmission model of TB after launch of a new drug regimen, defining drug-resistant TB (DR-TB) as resistance to the new regimen. The model is characterized by (1) the probability of acquiring resistance during treatment, (2) the transmission fitness of DR-TB relative to drug-susceptible TB (DS-TB), and (3) the probability of treatment success for DR-TB versus DS-TB. We evaluate the effect of each factor on future DR-TB prevalence, defined as the proportion of incident TB that is drug-resistant. Results. Probability of acquired resistance was the strongest predictor of the DR-TB proportion in the first 5 years after the launch of a new drug regimen. Over a longer term, however, the DR-TB proportion was driven by the resistant population's transmission fitness and treatment success rates. Regardless of uncertainty in acquisition probability and transmission fitness, high levels (>10%) of drug resistance were unlikely to emerge within 50 years if, among all cases of TB that were detected, 85% of those with DR-TB could be appropriately diagnosed as such and then successfully treated. Conclusions. Short-term surveillance cannot predict long-term drug resistance trends after launch of novel first-line TB regimens. Ensuring high treatment success of drug-resistant TB through early diagnosis and appropriate second-line therapy can mitigate many epidemiological uncertainties and may substantially slow the emergence of drug-resistant TB.

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Randomised clinical trial comparing concomitant and hybrid therapy for eradication of Helicobacter pylori infection

PLoS ONE ◽

10.1371/journal.pone.0244500 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244500

Author(s):

Antonio Mestrovic ◽

Nikola Perkovic ◽

Josko Bozic ◽

Mirela Pavicic Ivelja ◽

Jonatan Vukovic ◽

...

Keyword(s):

Clinical Trial ◽

Helicobacter Pylori ◽

Adverse Events ◽

Therapy Group ◽

Compliance Rate ◽

Randomised Clinical Trial ◽

First Line ◽

Open Label ◽

Hybrid Therapy ◽

Significant Difference

Background The primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols. Materials and methods In an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group. Results Eradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate. Conclusion Hybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic’s usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.

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Surgical Therapy of Peri-Implantitis with Local Minocycline: A 6-Month Randomized Controlled Clinical Trial

Journal of Dental Research ◽

10.1177/0022034518818479 ◽

2019 ◽

Vol 98 (3) ◽

pp. 288-295 ◽

Cited By ~ 19

Author(s):

J.K. Cha ◽

J.S. Lee ◽

C.S. Kim

Keyword(s):

Surgical Treatment ◽

Treatment Success ◽

Test Group ◽

Controlled Clinical Trial ◽

Success Rates ◽

Control Groups ◽

Pocket Depth ◽

Radiographic Measurements ◽

Significant Difference ◽

And Control

The purpose of this study was to determine the clinical, microbial, and radiographic effects of local minocycline combined with surgical treatment of peri-implantitis. Fifty patients with peri-implantitis were recruited, and surgical treatment with the local application of either minocycline or placebo ointment was performed. The application of minocycline was repeated with supragingival debridement at 1, 3, and 6 mo postoperatively. Plaque index, gingival index (GI), probing pocket depth (PPD), and bleeding/suppuration on probing were measured at baseline and 1-, 3-, and 6-mo evaluations. The change in supporting bone level (SBL) measured with cone beam computed tomography was analyzed between baseline and 6 mo. Microbial analysis was performed with real-time polymerase chain reaction. Both groups exhibited improvements in clinical and radiographic measurements after surgical treatment. There was a significant difference in the changes of mean PPD between the test and control groups (2.68 ± 1.73 and 1.55 ± 1.86 mm, respectively, P = 0.039). The changes of mean GI and SBL differed significantly between the groups (ΔGI: 0.83 ± 0.60 and 0.40 ± 0.68; ΔSBL: 0.72 ± 0.56 and 0.31 ± 0.49 mm, respectively, P = 0.026 and 0.014). Treatment success rates (defined as PPD <5 mm, absence of bleeding/suppuration on probing, and no further bone loss) were 66.7% and 36.3% in the test and control groups, respectively. The count of red complex bacteria tended to decrease in both groups until 6 mo; however, no significant intergroup difference was found. None of the patients in the test group carried Porphyromonas gingivalis or Tannerella forsythia at 6 mo. These findings indicate that the repeated local delivery of minocycline combined with surgical treatment provides significant benefits in terms of clinical parameters and radiographic bone fill, with a higher treatment success rate in the short healing period (cris.nih.go.kr KCT0002844).

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