scholarly journals Oral Cholera Vaccine Efficacy and Effectiveness

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1482
Author(s):  
Katerina Rok Song ◽  
Jacqueline Kyungah Lim ◽  
Se Eun Park ◽  
Tarun Saluja ◽  
Sung-Il Cho ◽  
...  
Keyword(s):  
Public Health ◽  
Real World ◽  
Vaccine Efficacy ◽  
Controlled Trial ◽  
Population Level ◽  
Phase Iii ◽  
Populations At Risk ◽  
Double Blinded ◽  
Effectiveness Studies ◽  
The Impact

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the “gold standard”, effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV. Although the results of OCV effectiveness studies sometimes showed outliers, the tendency seen is for effectiveness of the vaccine used in public health settings to be somewhat higher than estimated in randomized controlled trials due to the influence of indirect herd protection. Efficacy and Effectiveness studies both generate important information about the vaccine performance characteristics and its impact when used in real world populations at risk for the disease.

Validation of the decipher genomic classifier (GC) in SAKK 09/10: A phase III randomized trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy (RP).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5010-5010
Author(s):  
Alan Dal Pra ◽  
Pirus Ghadjar ◽  
Stefanie Hayoz ◽  
Daniel Eidelberg Spratt ◽  
Vinnie YT Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Controlled Trial ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Phase Iii ◽  
Clinical Progression ◽  
Clinical Value ◽  
Prognostic Utility ◽  
The Impact

5010 Background: GC has been shown to independently prognosticate outcomes in prostate cancer. Herein, we validate the GC in a European randomized phase III trial of dose escalated SRT after RP. Methods: SAKK 09/10 (NCT01272050) randomized 350 patients with biochemical recurrence after RP to 64Gy vs 70Gy. No patients received androgen deprivation therapy (ADT) or pelvic nodal radiotherapy. A pre-specified statistical plan was developed to assess the impact of the GC on clinical outcomes. RP samples were centrally reviewed for the highest-grade tumor and those passing quality control (QC) were run on a clinical-grade whole-transcriptome assay to obtain the GC score (0 to 1; < 0.45, 0.45-0.6, > 0.6 for low-, intermediate-, and high, respectively). The primary aim of this study was to validate the GC for the prediction of freedom from biochemical progression (FFBP) using Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, PSA at randomization, and randomization arm. The secondary aims were to evaluate the association of GC with clinical progression-free survival (CPFS) and use of salvage ADT. Results: Of 233 patients with tissue available, 226 passed QC and were included for analysis. The final GC cohort was a representative sample of the overall cohort, with a median follow-up of 6.3 years (IQR 6.0-7.2). GC score (continuous per 0.1 unit, score 0-1) was independently associated with FFBP (HR 1.14 [95% CI 1.03-1.25], p = 0.009). Higher GC scores were independently associated with CPFS, use of salvage ADT, and rapid biochemical failure ( < 18 months after SRT). High- vs. low/intermediate-GC showed a HR of 2.22 ([95% CI 1.37-3.58], p = 0.001) for FFBP, 2.29 ([95% CI 1.32-3.98], p = 0.003) for CPFS, and 2.99 ([95% CI 1.50-5.95], p = 0.002) for use of salvage ADT. Patients with high-GC had 5-year FFBP of 45% [95% CI 32-59] vs 71% [95% CI 64-78] in low-intermediate GC. Similar estimates for GC risk groups were observed in the 64Gy vs 70Gy in GC high (5-year FFBP of 51% [95% CI 32-70] vs 39% [95% CI 20-59]) and in low-intermediate GC (75% [95% CI 65-84] vs 69% [95% CI 59-78]). Conclusions: This study represents the first contemporary randomized controlled trial in patients with recurrent prostate cancer treated with early SRT without ADT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and radiotherapy dose, patients with a high-GC were more than twice as likely than a lower GC score to experience biochemical and clinical progression and receive salvage ADT. This data confirms the clinical value of Decipher GC for tailoring treatment in the postoperative salvage setting.

Abstract 16709: Contrasting Influences of Renal Function on Blood Pressure and HbA1c Reductions With Empagliflozin in Patients With Type 2 Diabetes and Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
David Cherney ◽  
Mark Cooper ◽  
Ilkka Tikkanen ◽  
Susanne Crowe ◽  
Odd Erik Johansen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Renal Function ◽  
Controlled Trial ◽  
Phase Iii ◽  
Vascular Effects ◽  
Antihypertensive Medications ◽  
Urinary Glucose ◽  
The Impact

The sodium glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces HbA1c, weight and blood pressure (BP) in patients with type 2 diabetes (T2D). While glucose lowering with EMPA is dependent on renal function, the impact of chronic kidney disease (CKD) on BP reduction with EMPA is less well understood. Our aim was to determine if impaired renal function attenuates antihypertensive effects of EMPA. A Phase III randomized placebo (PBO)-controlled trial (EMPA-REG BP™) investigated the efficacy and safety of EMPA in patients with T2D and hypertension (defined as mean seated office systolic BP [SBP] 130-159 mmHg and diastolic BP [DBP] 80-99 mmHg at screening). Patients (mean [SD] age 60.2 [9.0] years, HbA1c 7.90 [0.74] %, 24-hour SBP 131.4 [12.3] and 24-hour DBP 75.0 [7.8] mmHg) received EMPA 10 mg (n=276), EMPA 25 mg (n=276) or PBO (n=271) once daily for 12 weeks. We assessed changes from baseline in mean ambulatory 24-hour SBP and HbA1c in subgroups by baseline eGFR (MDRD equation), adjusting for differences in baseline mean 24-hour SBP (for SBP analyses only), HbA1c, region, number of antihypertensive medications, treatment, eGFR and treatment by eGFR interaction between groups. In patients with normal renal function, or stage 2 or 3 CKD, EMPA significantly reduced HbA1c and mean 24-hour SBP vs PBO (Table). As expected, PBO-corrected HbA1c reductions with EMPA appeared to decrease with decreasing eGFR (Table). In contrast, PBO-corrected reductions in mean 24-hour SBP with EMPA mostly appeared to increase with decreasing eGFR (Table). Unlike HbA1c, mean 24-hour SBP reductions with EMPA in patients with T2D and hypertension appear to be greater in patients with lower eGFR, indicating that SBP modulation with EMPA may involve pathways other than urinary glucose excretion such as diuretic effects, weight loss, improved glycemic control, reduced arterial stiffness or direct vascular effects.

Low-Dose Aspirin for the Prevention and Treatment of Preeclampsia

2021 ◽  
pp. 7-12
Author(s):  
Danielle M. Panelli ◽  
Deirdre J. Lyell
Keyword(s):  
Lower Risk ◽  
Low Dose ◽  
Controlled Trial ◽  
Entire Cohort ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Prevention And Treatment ◽  
Double Blinded ◽  
The Impact ◽  
To Receive

“CLASP: A Randomized Trial of Low-Dose Aspirin for the Prevention and Treatment of Preeclampsia Among 9364 Pregnant Women” was a double-blinded, placebo-controlled trial that evaluated the impact of antenatal aspirin administration on development of preeclampsia and intrauterine growth restriction (IUGR). A total of 9364 women either at risk for preeclampsia or currently experiencing preeclampsia or IUGR were enrolled between 12 and 32 weeks and randomized to receive 60mg aspirin daily or placebo. While a nonsignificant 12% reduction in the odds of preeclampsia was found among the entire cohort, the reduction in preeclampsia with aspirin use was more pronounced for those who began prophylaxis prior to 20 weeks (22% reduction, p = 0.06). There was also a lower risk of preterm birth before 37 weeks in those who received aspirin at any time (19.7% vs. 22.2%, p = 0.003) but no difference in IUGR infants. In conclusion, 60mg aspirin daily did not significantly reduce the risk of preeclampsia or IUGR among the women included in this study.

scholarly journals Impact of HIV-1 Diversity on Its Sensitivity to Neutralization

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 74 ◽  
Author(s):  
Karl Stefic ◽  
Mélanie Bouvin-Pley ◽  
Martine Braibant ◽  
Francis Barin
Keyword(s):  
Public Health ◽  
Envelope Protein ◽  
Neutralizing Antibodies ◽  
Continuous Process ◽  
Population Level ◽  
Global Public Health ◽  
Broadly Neutralizing Antibodies ◽  
The Many ◽  
The Impact ◽  
Hiv 1

The HIV-1 pandemic remains a major burden on global public health and a vaccine to prevent HIV-1 infection is highly desirable but has not yet been developed. Among the many roadblocks to achieve this goal, the high antigenic diversity of the HIV-1 envelope protein (Env) is one of the most important and challenging to overcome. The recent development of broadly neutralizing antibodies has considerably improved our knowledge on Env structure and its interplay with neutralizing antibodies. This review aims at highlighting how the genetic diversity of HIV-1 thwarts current, and possibly future, vaccine developments. We will focus on the impact of HIV-1 Env diversification on the sensitivity to neutralizing antibodies and the repercussions of this continuous process at a population level.

scholarly journals TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030731 ◽  
Author(s):  
Jarad Martin ◽  
Paul Keall ◽  
Shankar Siva ◽  
Peter Greer ◽  
David Christie ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Performance Status ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
High Dose ◽  
The Novel ◽  
Ecog Performance Status ◽  
Initial Portion ◽  
The Impact

IntroductionStereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration ofNew prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality.Methods and analysisEligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial.Ethics and disseminationNINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study.Trial registration numberANZCTN 12615000223538.

scholarly journals Impact of Rotavirus Vaccine Introduction in Children Less Than 2 Years of Age Presenting for Medical Care With Diarrhea in Rural Matlab, Bangladesh

2019 ◽  
Vol 69 (12) ◽  
pp. 2059-2070 ◽  
Author(s):  
Lauren M Schwartz ◽  
K Zaman ◽  
Md Yunus ◽  
Ahasan-ul H Basunia ◽  
Abu Syed Golam Faruque ◽  
...  
Keyword(s):  
Vaccine Coverage ◽  
Controlled Trial ◽  
Population Level ◽  
Diarrhoeal Disease ◽  
Incidence Rates ◽  
Service Area ◽  
Rotavirus Vaccine ◽  
Rotavirus Vaccines ◽  
Time Period ◽  
The Impact

Abstract Background Following the conclusion of a human rotavirus vaccine (HRV) cluster-randomized, controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab’s routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age. Methods Interrupted time series were used to estimate the impact of HRV introduction. We used diarrheal surveillance collected between 2000 and 2014 within the 2 service delivery areas (International Centre for Diarrhoeal Disease Research, Bangladesh [icddr,b] service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System, administered by icddr,b. Age group–specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV–) diarrhea diagnoses of any severity presenting to the hospital. We used 2 models to assess the impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV– and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period, using outcomes from control-only villages. Results Both models demonstrated a downward trend in RV+ diarrheal incidences in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impacts of HRV on RV+ diarrhea incidences in GSA villages were not observed in either model. Differences in population-level impacts between the 2 delivery areas may be due to the varied rotavirus vaccine coverage and presentation rates to the hospital. Conclusions This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies are needed of the rotavirus vaccine impact after the nationwide introduction in Bangladesh.

Pharmacoepidemiology of psychotropic drugs: examples of current research challenges on major public health issues

2009 ◽  
Vol 18 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Hélène Verdoux ◽  
Marie Tournier ◽  
Bernard Bégaud
Keyword(s):  
Public Health ◽  
Prenatal Exposure ◽  
Psychotropic Drugs ◽  
Antipsychotic Drugs ◽  
Population Level ◽  
Health Issues ◽  
Review Of The Literature ◽  
Research Challenges ◽  
The Impact

SummaryBackground– As a large number of persons are exposed to prescribed psychotropic drugs, their utilisation and impact should be further explored at the population level.Aims– To illustrate the interest of pharmacoepidemiological studies of psychotropic drugs by selected examples of major public health issues.Method– Selective review of the literature. Results – Many questions remain unsolved regarding the behavioural teratogenicity of prenatal exposure to psychotropic drugs, the impact of their increasing use in children, the long-term cognitive consequences of exposure to benzodiazepines, and the risks associated with extension of indications of antipsychotic drugs.Conclusion– Pharmacoepidemiological studies need to be further developed owing to the large number of public health questions raised by the extensive and expanding use of psychotropic drugs.

scholarly journals Comparison of the impact of bovine milk β-casein variants on digestive comfort in females self-reporting dairy intolerance: a randomized controlled trial

2019 ◽  
Vol 111 (1) ◽  
pp. 149-160 ◽  
Author(s):  
Amber M Milan ◽  
Aahana Shrestha ◽  
Helga J Karlström ◽  
Jakob A Martinsson ◽  
Nils J Nilsson ◽  
...  
Keyword(s):  
Ad Hoc ◽  
Controlled Trial ◽  
Bovine Milk ◽  
Abdominal Distension ◽  
Rapid Onset ◽  
Breath Hydrogen ◽  
Lactose Malabsorption ◽  
Double Blinded ◽  
The Impact ◽  
Conventional Milk

ABSTRACT Background Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy products. Recently, a role for bovine β-casein A1 has been proposed. Objectives We examined whether there are distinct symptoms of digestive discomfort due to either lactose or differing bovine β-casein types. Methods Women (n = 40; age: 25.2 ± 0.5 y) with self-reported varying dairy tolerance underwent a 50-g lactose challenge. Based on postchallenge LM and digestive discomfort, participants were classified as either lactose intolerant (LI; n = 10, self-reported intolerant, diagnosed lactose intolerant), nonlactose dairy intolerant (NLDI; n = 20, self-reported intolerant, diagnosed lactose tolerant), or dairy tolerant (DT; n = 10, self-reported tolerant, diagnosed lactose tolerant). In a double-blinded randomized sequence, participants consumed 750 mL conventional milk (CON; containing A1 and A2 β-casein and lactose), a2 Milk (A2M; exclusively containing A2 β-casein with lactose), or lactose-free conventional milk (LF-CON; containing A1 and A2 β-casein without lactose). Subjective digestive symptoms and breath hydrogen (measuring LM) were recorded regularly over 3 h, and further ad hoc digestive symptoms over 12 h. Results LI subjects experienced prolonged digestive discomfort with CON milk. A2M reduced (P &lt; 0.05) some symptoms (nausea: A2M 8 ± 3 mm compared with CON 15 ± 3mm; fecal urgency: A2M 4 ± 1 compared with CON 10 ± 3 mm), and attenuated the rise in breath hydrogen over 3 h, relative to CON milk (A2M 59 ± 23 compared with CON 98 ± 25 ppm at 150 min; P &lt; 0.01). In contrast, NLDI subjects experienced rapid-onset, transient symptoms (abdominal distension, bloating, and flatulence) without increased breath hydrogen, irrespective of milk type. Conclusions In LI individuals, LM and digestive comfort with lactose-containing milks was improved with milk containing exclusively A2 β-casein. Furthermore, self-reported dairy intolerance without LM (NLDI) is characterized by early-onset digestive discomfort following milk ingestion, irrespective of lactose content or β-casein type. This trial was registered at www.anzctr.org.au as ACTRN12616001694404.

An updated overall survival analysis with correction for protocol-planned crossover of the international, phase III, randomized, placebo-controlled trial of regorafenib in advanced gastrointestinal stromal tumors after failure of imatinib and sunitinib (GRID).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 110-110 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Failure Time ◽  
Cox Model ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Primary Analysis ◽  
Significant Difference ◽  
The Impact

110 Background: The GRID study showed that regorafenib improves progression-free survival compared with placebo in patients with advanced GIST after failure of at least imatinib and sunitinib (HR 0.27; 1-sided p<0.0001; Demetri 2013). At the time of the primary analysis, no significant difference in the secondary endpoint of overall survival (OS) was observed (HR 0.77; p=0.199), but this result may have been confounded by the high rate of crossover to regorafenib (85%) of placebo patients at progression. We conducted exploratory analyses of updated OS data to assess the effect of correcting for this protocol-planned crossover. Methods: The data cut-off for this updated OS analysis was 31 January 2014 (2 years after the primary analysis). OS was corrected using two randomization-based methods: rank preserving structural failure time (RPSFT) and iterative parameter estimation (IPE); both methods are considered as best choice among all correction analytics. Hazard ratios and 95% CI were derived using the Cox model. Results: A total of 139 deaths had occurred at the time of data cut-off: 91 events (68.4% of patients) in the regorafenib group and 48 (72.7%) in the placebo group. A total of 22 patients remained on regorafenib treatment (median duration 2.1 years, range 0.9–2.4). The updated hazard ratio for OS favored regorafenib (0.85, 95% CI: 0.60 - 1.21; p=0.18). Median OS was estimated as 17.4 months in both groups, with crossover from placebo. The corrected HRs for OS are less than the uncorrected HR (Table). Conclusions: The updated analysis of OS in the GRID trial is consistent with the primary analysis. An exploratory analysis correcting for the impact of cross-over on OS suggests a survival benefit for regorafenib in GIST. Clinical trial information: NCT01271712. [Table: see text]

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