Time to market for drugs approved in Canada between 2014 and 2018: an observational study

ObjectivesThis study examines the length of time between when a patent application is filed in Canada for a new drug and when it is available for patients (time to market) and various components of that time. It also looks at whether various factors explain the time between patent application to New Drug Submission (NDS) and compares Canadian and American times. Drugs approved between 1 January 2014 and 31 December 2018 are examined.DesignDescriptive study.Data sourcesWebsites from Health Canada, Food and Drug Administration, Merck Index, United States Patent and Trademark Office, WHO and previously published articles.InterventionsNone.Primary and secondary outcomesThe primary outcomes are time to market, time from patent application to NDS (pre-NDS time), review time, time from approval to availability (postapproval time) and factors that may influence the pre-NDS time. The secondary outcome is a comparison of Canadian and American review times and times between patent application and approval.ResultsThere were 113 drugs available for analysis. The median time to market was 11.80 years (IQR 9.40–14.05). The component median times were pre-NDS 10 years (IQR 8.05–12.80), review time 0.96 years (IQR 0.75–1.15) and postapproval time 0.15 years (IQR 0.08–0.28). Less than 8% of the pre-NDS time was explained by the factors that were analysed in a multiple linear regression equation. There was no statistically significant difference between Canadian and American pre-NDS times.ConclusionOnce a drug reaches the market, companies have a median of 8.2 years before the patent expires and generics can reach the market. Most of the time between the filing of a patent application and when a drug is marketed is determined by decisions that are largely under the control of the company.

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Clinical Evaluation of Microendoscopy-Assisted Oblique Lateral Interbody Fusion

Medicina ◽

10.3390/medicina57020135 ◽

2021 ◽

Vol 57 (2) ◽

pp. 135

Author(s):

Tomohide Segawa ◽

Hisashi Koga ◽

Masahito Oshina ◽

Katsuhiko Ishibashi ◽

Yuichi Takano ◽

...

Keyword(s):

Interbody Fusion ◽

Outcome Measure ◽

Operation Time ◽

Secondary Outcome ◽

Invasive Technique ◽

Lateral Interbody Fusion ◽

Surgical Methods ◽

Significant Difference ◽

Oblique Lateral Interbody Fusion ◽

Lateral Interbody

Background and objectives: Oblique Lateral Interbody Fusion (OLIF) is a widely performed, minimally invasive technique to achieve lumbar lateral interbody fusion. However, some complications can arise due to constraints posed by the limited surgical space and visual field. The purpose of this study was to assess the short-term postoperative clinical outcomes of microendoscopy-assisted OLIF (ME-OLIF) compared to conventional OLIF. Materials and Methods: We retrospectively investigated 75 consecutive patients who underwent OLIF or ME-OLIF. The age, sex, diagnosis, and number of fused levels were obtained from medical records. Operation time, estimated blood loss (EBL), and intraoperative complications were also collected. Operation time and EBL were only measured per level required for the lateral procedure, excluding the posterior fixation surgery. The primary outcome measure was assessed using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ). The secondary outcome measure was assessed using the Oswestry Disability Index (ODI) and the European Quality of Life–5 Dimensions (EQ-5D), measured preoperatively and 1-year postoperatively. Results: This case series consisted of 14 patients in the OLIF group and 61 patients in the ME-OLIF group. There was no significant difference between the two groups in terms of the mean operative time and EBL (p = 0.90 and p = 0.50, respectively). The perioperative complication rate was 21.4% in the OLIF group and 21.3% in the ME-OLIF group (p = 0.99). In both groups, the postoperative JOABPEQ, EQ-5D, and ODI scores improved significantly (p < 0.001). Conclusions: Although there was no significant difference in clinical results between the two surgical methods, the results suggest that both are safe surgical methods and that microendoscopy-assisted OLIF could serve as a potential alternative to the conventional OLIF procedure.

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Single Versus Dual Headless Compression Screw Fixation of Scaphoid Nonunions: A Biomechanical Comparison

Hand ◽

10.1177/1558944720974111 ◽

2021 ◽

pp. 155894472097411

Author(s):

Luke T. Nicholson ◽

Kristen M. Sochol ◽

Ali Azad ◽

Ram Kiran Alluri ◽

J. Ryan Hill ◽

...

Keyword(s):

Screw Fixation ◽

Qualitative Assessment ◽

Secondary Outcome ◽

Scaphoid Nonunion ◽

Compression Screw ◽

Single Screw ◽

Headless Compression Screw ◽

Significant Difference ◽

Load To Failure ◽

Headless Compression Screws

Background: Management of scaphoid nonunions with bone loss varies substantially. Commonly, internal fixation consists of a single headless compression screw. Recently, some authors have reported on the theoretical benefits of dual-screw fixation. We hypothesized that using 2 headless compression screws would impart improved stiffness over a single-screw construct. Methods: Using a cadaveric model, we compared biomechanical characteristics of a single tapered 3.5- to 3.6-mm headless compression screw with 2 tapered 2.5- to 2.8-mm headless compression screws in a scaphoid waist nonunion model. The primary outcome measurement was construct stiffness. Secondary outcome measurements included load at 1 and 2 mm of displacement, load to failure for each specimen, and qualitative assessment of mode of failure. Results: Stiffness during load to failure was not significantly different between single- and double-screw configurations ( P = .8). Load to failure demonstrated no statistically significant difference between single- and double-screw configurations. Using a qualitative assessment, the double-screw construct maintained rotational stability more than the single-screw construct ( P = .029). Conclusions: Single- and double-screw fixation constructs in a cadaveric scaphoid nonunion model demonstrate similar construct stiffness, load to failure, and load to 1- and 2-mm displacement. Modes of failure may differ between constructs and represent an area for further study. The theoretical benefit of dual-screw fixation should be weighed against the morphologic limitations to placing 2 screws in a scaphoid nonunion.

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Donepezil for mild cognitive impairment in Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-84243-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyoungwon Baik ◽

Seon Myeong Kim ◽

Jin Ho Jung ◽

Yang Hyun Lee ◽

Seok Jong Chung ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Treatment Group ◽

Outcome Measures ◽

Rating Scale ◽

Secondary Outcome ◽

Control Group ◽

Significant Difference

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.

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1692. Retrospective Review on the Safety and Efficacy of Nitrofurantoin for the Treatment of Cystitis in the Veteran Population With or Without Renal Insufficiency

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1870 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S829-S830

Author(s):

Elwyn W Welch ◽

Shaila Sheth ◽

Chester Ashong ◽

Caroline Pham

Keyword(s):

Renal Function ◽

Renal Dysfunction ◽

Clinical Cure ◽

Clinical Cure Rate ◽

Retrospective Chart Review ◽

Outpatient Setting ◽

Secondary Outcome ◽

Cure Rate ◽

Acute Cystitis ◽

Significant Difference

Abstract Background Nitrofurantoin has been used to treat cystitis in women; however, data supporting its use in men is lacking. In addition, recent retrospective studies have challenged the manufacturer’s recommendation to avoid nitrofurantoin with creatinine clearances (CrCl) less than 60 mL/min. The purpose of this study is to compare the efficacy and safety of nitrofurantoin for the treatment of acute cystitis in male and female veterans with variable degrees of renal dysfunction. Methods A retrospective chart review was conducted in adult patients who received nitrofurantoin for acute cystitis in the outpatient setting between May 1, 2018 and May 1, 2019. The primary outcomes were rates of clinical cure as compared between males and females, and across various renal function groups (CrCl greater than 60 mL/min, 30 to 60 mL/min, and less than 30 mL/min) following treatment with nitrofurantoin. The secondary outcome was adverse event rates. Results A total of 446 patients were included with 278 females and 168 males. Overall clinical cure rate was 86.5% (n=386). Clinical cure rate did not vary between genders (p=0.0851) or CrCl ranges (p=1.0) as shown in the tables. Benign prostatic hyperplasia (BPH) was associated with decreased odds of clinical cure (OR 0.50 [95% CI 0.26-0.97], p=0.0404) in addition to cirrhosis (OR 0.22 [95% CI 0.06-0.91], p=0.0357). Adverse events occurred in 2% of patients and did not vary based on gender or renal function. RATES OF CLINICAL CURE Conclusion There was no statistically significant difference in clinical cure with nitrofurantoin between genders and various renal impairments. However, history of BPH and cirrhosis were associated with decreased efficacy. Subgroup analysis also revealed lower efficacy in males with CrCl greater than 60 mL/min versus females with similar renal function. This study adds to the growing body of literature suggesting that renal dysfunction with CrCl of 30 to 60 mL/min may not carry the risk of treatment failure and adverse effects previously associated with nitrofurantoin, but large randomized trials are needed to confirm these results. Disclosures All Authors: No reported disclosures

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The high risk of malarial recurrence in patients with Plasmodium-mixed infection after treatment with antimalarial drugs: a systematic review and meta-analysis

Parasites & Vectors ◽

10.1186/s13071-021-04792-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Aongart Mahittikorn ◽

Frederick Ramirez Masangkay ◽

Kwuntida Uthaisar Kotepui ◽

Giovanni De Jesus Milanez ◽

Manas Kotepui

Keyword(s):

Systematic Review ◽

Mixed Infection ◽

Subgroup Analysis ◽

Initial Treatment ◽

Meta Analysis ◽

Antimalarial Drugs ◽

Secondary Outcome ◽

Significant Heterogeneity ◽

Pooled Prevalence ◽

Significant Difference

Abstract Background Malaria mixed infections are often unrecognized by microscopists in the hospitals, and a delay or failure to treat Plasmodium-mixed infection may lead to aggravated morbidity and increased mortality. The present study aimed to quantify the pooled proportion and risk of malarial recurrences after the treatment of Plasmodium-mixed infection. The results of the study may provide benefits in the management of Plasmodium-mixed infection in co-endemic regions. Methods This systematic review and meta-analysis searched the international Prospective Register of Systematic Reviews (PROSPERO; ID = CRD42020199709), MEDLINE, Web of Science, and Scopus for potentially relevant studies in any language published between January 1, 1936, and July 20, 2020, assessing drug efficacy in patients with Plasmodium-mixed infection. The primary outcome was the pooled prevalence of Plasmodium parasitemia after initiating antimalarial treatment for Plasmodium-mixed infection. The secondary outcome was the pooled risk ratio (RR) of malarial recurrence in Plasmodium-mixed infection compared with those in Plasmodium falciparum and Plasmodium vivax mono-infection. The pooled analyses were calculated by random-effects meta-analysis. After the initial treatment in different days of recurrences (≤ 28 days or > 28 days), the risk of Plasmodium parasitemia was compared in subgroup analysis. Results Out of 5217 screened studies, 11 were included in the meta-analysis, including 4390 patients from six countries. The pooled prevalence of all recurrences of Plasmodium-mixed parasitemia was 30% (95% confidence interval (CI) 16–43; I2: 99.2%; 11 studies). The RR of malarial recurrence within 28 days after the initial treatment (clinical treatment failure) of Plasmodium-mixed parasitemia compared with the treatment of P. falciparum was 1.22 (p: 0.029; 95% CI 1.02–1.47; Cochran Q: 0.93; I2: 0%; six studies), while there was no significant difference in the risk of recurrence 28 days after initial treatment compared with the treatment of P. falciparum (p: 0.696, RR: 1.14; 95% CI 0.59–2.18; Cochran Q < 0.05; I2: 98.2%; four studies). The subgroup analysis of antimalarial drugs showed that significant malarial recurrence within 28 days was observed in patients treated with artemisinin-based combination therapies (ACTs) with no significant heterogeneity (p: 0.028, RR: 1.31; 95% CI 1.03–1.66; Cochran Q: 0.834; I2: 0%). Conclusions The present findings showed a high prevalence of malarial recurrence after the initial treatment of Plasmodium-mixed infection. Moreover, significant malaria recurrence of mixed infection occurred within 28 days after treatment with ACTs. Graphic Abstract

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Prevalence of dysmenorrhoea, associated risk factors and its relationship with academic performance among graduating female university students in Ethiopia: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2020-043814 ◽

2021 ◽

Vol 11 (3) ◽

pp. e043814

Author(s):

Mesfin Tadese ◽

Andargachew Kassa ◽

Abebaw Abeje Muluneh ◽

Girma Altaye

Keyword(s):

Risk Factors ◽

Academic Performance ◽

University Students ◽

Cross Sectional Study ◽

Secondary Outcome ◽

Sectional Study ◽

Cross Sectional ◽

Grade Point ◽

Significant Difference ◽

Associated Risk Factors

ObjectivesThe study aimed to provide an association between dysmenorrhoea and academic performance among university students in Ethiopia. Further, the study attempts to determine the prevalence and associated risk factors of dysmenorrhoea.Design and methodInstitution-based cross-sectional study was conducted from 1 April to 28 April 2019. A semistructured and pretested self-administered questionnaire was used to collect data. Binary logistic regression analysis and one-way analysis of variance were performed to model dysmenorrhoea and academic performance, respectively.Setting and participantsEthiopia (2019: n=647 female university students).OutcomesThe primary outcome is dysmenorrhoea, which has been defined as painful menses that prevents normal activity and requires medication. The self-reported cumulative grade point average of students was used as a proxy measure of academic performance, which is the secondary outcome.ResultsThe prevalence of dysmenorrhoea was 317 (51.5%). The educational status of father (adjusted OR (AOR) (95% CI) 2.64 (1.04 to 6.66)), chocolate consumption (AOR (95% CI) 3.39 (95% 1.28 to 8.93)), daily breakfast intake (<5 days/week) (AOR (95% CI) 0.63 (0.42 to 0.95)), irregular menstrual cycle AOR (95% CI) 2.34 (1.55 to 3.54)) and positive family history of dysmenorrhoea AOR (95% CI) 3.29 (2.25 to 4.81)) had statistically significant association with dysmenorrhoea. There was no statistically significant difference in academic performance among students with and without dysmenorrhoea (F (3611)=1.276, p=0.28)).ConclusionsDysmenorrhoea was a common health problem among graduating University students. However, it has no statistically significant impact on academic performance. Reproductive health officers should educate and undermine the negative academic consequences of dysmenorrhoea to reduce the physical and psychological stress that happens to females and their families.

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Pharmacokinetic and safety study of co-administration of albendazole, diethylcarbamazine, Ivermectin and azithromycin for the integrated treatment of Neglected Tropical Diseases

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1202 ◽

2020 ◽

Author(s):

Lucy N John ◽

Catherine Bjerum ◽

Pere Millat Martinez ◽

Rhoda Likia ◽

Linda Silus ◽

...

Keyword(s):

Drug Interactions ◽

Large Scale ◽

Neglected Tropical Diseases ◽

Pharmacokinetic Interaction ◽

Integrated Treatment ◽

Secondary Outcome ◽

Pharmacokinetic Data ◽

Tropical Diseases ◽

Open Label ◽

Significant Difference

Abstract Background Pharmacokinetic data are a pre-requisite to integrated implementation of large-scale mass drug administration (MDA) for neglected tropical diseases (NTDs). We investigated the safety and drug interactions of a combination of azithromycin (AZI) targeting yaws and trachoma, with the newly approved ivermectin, albendazole, diethylcarbamazine (IDA) regime for Lymphatic Filariasis. Methodology An open-label, randomized, 3-arm pharmacokinetic interaction study in adult volunteers was carried out in Lihir Island, Papua New Guinea. Healthy adult participants were recruited and randomized to (I) IDA alone, (II) IDA combined with AZI, (III) AZI alone. The primary outcome was lack of a clinically relevant drug interaction. The secondary outcome was the overall difference in the proportion of AEs between treatment arms. Results Thirty-seven participants, eighteen men and nineteen women, were randomized and completed the study. There were no significant drug-drug interactions between the study arms. The GMR of Cmax, AUC0–t, and AUC0–∞ for IVM, DEC, ALB-SOX, and AZI were within the range of 80–125% (GMR for AUC0–∞ for IVM, 87.9; DEC, 92.9; ALB-SOX, 100.0; and AZI, 100.1). There was no significant difference in the frequency of AEs across study arms (AZI and IDA alone arms 9/12 (75%), co-administration arm 12/13 (92%); p = 0.44). All AEs were grade 1 and self-limiting. Conclusions Co-administration of AZI with IDA did not show evidence of significant drug-interactions. There were no serious AEs in any of the study arms. Our data support further evaluation of the safety of integrated MDA for NTDs. Clinical Trials Registration. NCT03664063

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A preliminary study of bowel rest strategy in the management of Clostridioides difficile infection

Scientific Reports ◽

10.1038/s41598-020-79211-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hiroshi Sugimoto ◽

Ayaka Yoshihara ◽

Takao Yamamoto ◽

Keisuke Sugimoto

Keyword(s):

Secondary Outcome ◽

Control Group ◽

Matched Cohort ◽

Full Cohort ◽

Clostridioides Difficile ◽

Significant Difference ◽

All Cause Mortality ◽

Clostridioides Difficile Infection ◽

Bowel Rest ◽

Preliminary Study

AbstractClostridioides difficile infection (CDI) is an important nosocomial infection and is the leading cause of infectious diarrhea in hospitalized patients. We aimed to assess the effect of bowel rest on the management of CDI. A single-center retrospective cohort study was conducted. The primary outcome was the composite of the all-cause mortality and CDI recurrence within 30 days. The main secondary outcome was switching from metronidazole to vancomycin. Of the 91 patients with CDI enrolled as the full cohort, 63 patients (69%) and 28 patients (31%) constituted the control group and the bowel rest group, respectively. After one-to-one propensity score matching, a total of 46 patients were included as the matched cohort. In the full cohort, the composite outcome occurred in 19.0% and 14.3% of the patients in the control and the bowel rest group, respectively (p = 0.768). In the matched cohort, it was 17.4% in each group. Although there was no statistically significant difference, the trend of switching was lower in the bowel rest group. The bowel rest may not affect the all-cause mortality and CDI recurrence within 30 days. However, in those prescribed bowel rest, switching from metronidazole to vancomycin may reduce.

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Abstract WP341: Difference in Acute Ischemic Post Thrombolytic Stroke Outcomes in Pre Comprehensive and Post Comprehensive Status: Single Center Experience

Stroke ◽

10.1161/str.47.suppl_1.wp341 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Vishal B Jani ◽

Achint Patel ◽

Jillian Schurr ◽

Erin Shell ◽

Julie Bey ◽

...

Keyword(s):

Hospital Stay ◽

Secondary Outcome ◽

Rank Test ◽

Stroke Severity ◽

Complication Rates ◽

Single Center ◽

Stroke Treatment ◽

Significant Difference ◽

Multivariable Regression ◽

Iv Tpa

Background: In last decade there is a significant change in stroke care especialy with newer data for ischemic stroke treatment there is a movement to obtain comprehensive stroke center certification (CSCC) to provide enhanced complex care for stroke. This study aims to assess the single center quality matrix assessment pre and post CSC status Methods: We reviewed single center cohort of IV tPA (tissue plasminogen activator) in-between year 2010 to 2014 at sparrow health system in mid Michigan region. This cohort was dichotomized in pre CSCC and post CSCC era. Stroke quality matrics data was collected for these patients. Severity of stroke was categorized in mild-moderate vs moderate-severe based on NIH stroke scale (NIHSS) scale. Primary out come for this study was any complication, which is composite end point of in-hospital mortality, and hemorrhage and secondary outcome was hospital stay. Chi square, student’s t test and wilcoxon sum rank test was used to compare both groups. Multivariable regression models were utilized to calculate odd ratios after adjusting with stroke severity. Results: Cohort of IV tPA was identified in-between year 2010 to 2014 (332 hospitalizations off which 241 were pre CSCC and 91 were Post CSCC ). In- hospital complication was lower after receiving CSCC (9.89% vs. 21.99%; p:0.011). In multivariable regression analysis the trend for in hospital complication persisted [Adjusted Odds ratio (OR):0.43–95%confidence-Interval(CI):0.20-0.93–p:0.032] but there was no significant difference in hospital stay (Median days 5 vs. 5; P:673) Conclusion: There is a clear and persistent trend of low in-hospital complication rates after acquiring CSCC quality matrics.

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Recurrent Instability after Arthroscopic Glenoid Labral Repair with a Minimum of Three Points of Fixation: Do the Number of Anchors or Fixation Points Correlate to Outcomes?

Surgical Technology Online ◽

10.52198/21.sti.38.os1411 ◽

2021 ◽

Author(s):

Sean Mc Millan ◽

Brian Fliegel ◽

Michael Stark ◽

Elizabeth Ford ◽

Manuel Pontes ◽

...

Keyword(s):

Shoulder Instability ◽

Statistical Significance ◽

Labral Repair ◽

Secondary Outcome ◽

Consecutive Series ◽

Recurrent Instability ◽

Significant Difference ◽

Fixation Points ◽

Definition Of ◽

Shoulder Score

Introduction: The goal of this study was to evaluate the recurrence rate of instability following arthroscopic Bankart repairs in regard to the number and types of fixation utilized. A Bankart lesion is a tear in the anteroinferior capsulolabral complex within the shoulder, occurring in association with an anterior shoulder dislocation. These injuries can result in glenoid bone loss, decreased range of motion, and recurrent shoulder instability. Successful repair of these lesions has been reported in the literature with repair constructs that have three points of fixation. However, the definition of “one point of fixation” is yet to be fully elucidated. Materials and Methods: A consecutive series of arthroscopically repaired Bankart lesions were evaluated pertaining to the points of fixation required to achieve shoulder stability. This included the number, position, and types of anchors used. Patients consented to complete a series of surveys at a minimum of two years postoperatively. The primary outcome was to determine recurrent instability via the UCLA Shoulder Score, the ROWE Shoulder Instability Score, and the Oxford Shoulder Score. A secondary outcome included pain on a Visual Analog Scale (VAS). Results: There were 116 patients reviewed, 46 patients achieved three points of fixation in their surgical repair via two anchors and 70 patients achieved a similar fixation with three or more anchors. There was no significant difference in the mean age, gender, or body mass index (BMI). Patients receiving two anchors demonstrated recurrent instability 8.7% of the time (4 of 46 patients). Patients who received three or more anchors demonstrated recurrent instability 8.6% of the time (6 of 70 patients). Overall, there was no statistical significance between the number/types of anchors used. Between the two cohorts, there was no statistically significant difference found between VAS, ROWE, UCLA, and Oxford Scores. There was a significant difference in pain reported on the VAS scale with an average VAS score of 0.43 versus 2.5 in those without and with recurrent instability respectively. Conclusion: Contention still exists surrounding the exact definition of “a point of fixation” in arthroscopic Bankart repairs. Three-point constructs can be created through a variety of combinations including anchors and sutures, ultimately achieving the goal of a stable shoulder.

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