Published Efficacy Studies Research Articles

Evaluation and comparison of three virucidal agents on inactivation of Nipah virus

Modern human activity is profoundly changing our relationship with microorganisms with the startling rise in the rate of emerging infectious diseases. Nipah virus together with Ebola virus and SARS-CoV-2 are prominent examples. Since COVID-19 and the West African Ebola virus disease outbreak, different chemical disinfectants have been developed for preventing the direct spread of viruses and their efficacy has also been evaluated. However, there are currently no published efficacy studies for the chemical disinfection of Nipah virus. In this study, the virucidal efficacy of three disinfectants (Micro-Chem Plus detergent disinfectant cleaner, FWD and Medical EtOH) against Nipah virus was evaluated in quantitative suspension tests including. Our results showed that the > 4 log reduction achieved for all products in inactivating Nipah virus in 15 s. Even, 19% ethanol was able to inactivate Nipah virus when applied for at least 8 min contact time. Comparative analysis displayed virucidal efficacy of each of the evaluated disinfectants against SARS-CoV-2, Ebola virus and Nipah virus, with only minor differences in working concentrations and contact times required for complete inactivation. We expect that our study can assist in decontamination in healthcare settings and high level biosafety laboratories and can be beneficial to control for emerging enveloped viruses.

EHealth and mHealth Psychosocial Interventions for Youths With Chronic Illnesses: Systematic Review.

BackgroundAn estimated 12.8% of children and adolescents experience chronic health conditions that lead to poor quality of life, adjustment and coping issues, and concurrent mental health problems. Digital health deployment of psychosocial interventions to support youth with chronic illness has become increasingly popular with the advent of the technological advances in the digital age.ObjectiveOur objectives were to systematically review published efficacy studies of eHealth and mHealth (mobile health) psychosocial interventions for youths with chronic illnesses and review intervention theory and treatment components.MethodsPubMed, Embase, Web of Science, PsycInfo, and Cochrane Database of Systematic Reviews were searched for studies published from 2008 to 2019 of eHealth and mHealth psychosocial interventions designed for children and adolescents with chronic illnesses in which efficacy outcomes were reported. We excluded studies of interventions for caregivers, healthy youth, disease and medication management, and telehealth interventions that function solely as a platform to connect patients to providers via phone, text, or videoconference.ResultsWe screened 2551 articles and 133 relevant full-text articles. Sixteen efficacy studies with psychosocial and health outcomes representing 12 unique interventions met the inclusion criteria. Of the included studies, 12 were randomized controlled trials and 4 were prospective cohort studies with no comparison group. Most interventions were based in cognitive behavioral theory and designed as eHealth interventions; only 2 were designed as mHealth interventions. All but 2 interventions provided access to support staff via text, phone, email, or discussion forums. The significant heterogeneity in intervention content, intervention structure, medical diagnoses, and outcomes precluded meta-analysis. For example, measurement time points ranged from immediately postcompletion of the mHealth program to 18 months later, and we identified 39 unique outcomes of interest. The majority of included studies (11/16, 69%) reported significant changes in measured health and/or psychosocial posttreatment outcomes, with small to large effect sizes.ConclusionsAlthough the available literature on the efficacy of eHealth and mHealth psychosocial interventions for youth with chronic illnesses is limited, preliminary research suggests some evidence of positive treatment responses. Future studies should continue to evaluate whether digital health platforms may be a viable alternative model of delivery to traditional face-to-face approaches.

Moderators of Treatment for Adolescent Depression

ABSTRACT Objective: This brief report reviews the literature on moderators of treatment for adolescent depression. Treatment moderators can help to guide the process of personalizing intervention to individual patient characteristics. Method: We conducted a systematic search in PsycInfo and PubMed. We also reviewed references of previous reviews and searched for moderator analyses conducted secondary to published efficacy studies. Results: We review 27 studies that address the following categories of moderators: demographics, severity indices, comorbidity, contextual factors, history of abuse or trauma, and cognition and coping. We found limited evidence that demographic, contextual, or cognitive variables consistently moderated treatment for adolescent depression. There was some indication of moderation by race/ethnicity, presence of some comorbid disorders, greater depression severity, and a history of trauma. Conclusion: Our review found inconsistent findings across studies, likely due to the strong impact of predictors relative to moderators and limited statistical power. More research using innovative statistical approaches is necessary before treatment tailoring can be an empirically-based process.

Cenobamate for focal seizures - a game changer?

In the first published efficacy study of cenobamate for treatment-resistant focal seizures, high doses produced high seizure-free rates, suggesting cenobamate can outperform existing options. A risk of serious rash and low tolerability at higher doses means further safety studies and clinical experience are needed to determine its clinical value.

Randomized controlled trial evaluating the antimicrobial efficacy of chlorhexidine gluconate and para-chloro-meta-xylenol handwash formulations in real-world doses

Chlorhexidine gluconate-based soaps have become the gold standard for handwashing in critical care settings and para-chloro-meta-xylenol is an effective alternative antibacterial active ingredient. This study benchmarked 2 novel foaming handwashes, compared to a bland soap for antimicrobial effectiveness using the health care personnel handwash method at realistic soap doses (0.9 mL and 2.0 mL). To our knowledge, this is the first published efficacy study on realistic soap doses. Both soaps met Food and Drug Administration success criteria.

Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection.

Each year, thousands of patients are at risk of cerebral ischemic injury, due to iatrogenic responses to surgical procedures. Prophylactic treatment of these patients as standard care could minimize potential neurological complications. We have shown that protection of brain tissue, in a non-human primate model of cerebral ischemic injury, is possible through pharmacological preconditioning using the immune activator D192935. We postulate that preconditioning with D192935 results in neuroprotective reprogramming that is evident in the brain following experimentally induced cerebral ischemia. We performed quantitative proteomic analysis of cerebral spinal fluid (CSF) collected post-stroke from our previously published efficacy study to determine whether CSF protein profiles correlated with induced protection. Four groups of animals were examined: naïve animals (no treatment or stroke); animals treated with vehicle prior to stroke; D192935 treated and stroked animals, further delineated into two groups, ones that were protected (small infarcts) and those that were not protected (large infarcts). We found that distinct protein clusters defined the protected and non-protected animal groups, with a 16-member cluster of proteins induced exclusively in D192935 protected animals. Seventy percent of the proteins induced in the protected animals have functions that would enhance neuroprotection and tissue repair, including several members associated with M2 macrophages, a macrophage phenotype shown to contribute to neuroprotection and repair during ischemic injury. These studies highlight the translational importance of CSF biomarkers in defining mechanism and monitoring responses to treatment in development of stroke therapeutics.

Topical polyhydroxy acid treatment for autosomal recessive congenital ichthyosis in the golden retriever: a prospective pilot study.

Autosomal recessive congenital ichthyosis (ARCI) in golden retrievers is due to a PNPLA1 gene mutation, which plays a role in epidermal lipid organization and metabolism. Topical therapies are used to reduce scaling; however, there are few published efficacy studies. To examine the efficacy of topical treatment based on gluconolactone, a polyhydroxy acid with known beneficial effects on stratum corneum structure. Sixteen golden retriever dogs with clinical signs of ARCI and PCR-confirmed PNPLA1 gene mutation. This was a prospective, multicentre, noncontrolled study. Dogs were treated with a shampoo and lotion containing gluconolactone and other hydroxyl acids. Treatments were administered initially twice weekly for two weeks, then once weekly for two weeks and finally once monthly. Examinations were performed prior to and at 14 and 30 days of treatment to assess scaling, presence of other skin lesions and pruritus. In two dogs, pre- and 30 day post-treatment, skin biopsies were obtained. The extent and size of the scales were reduced by 60% and 75% after 14 and 30 days of treatment, respectively (P < 0.001). In 20% of the dogs, scaling was no longer observed after the first 30 days of treatment. No other skin lesions or pruritus were observed in any dog. Post-treatment biopsies showed normalization of the stratum corneum morphology and reduced hyperpigmentation. The frequent use of a shampoo and lotion containing gluconolactone may be an effective measure to improve skin scaling in golden retrievers with ARCI.

Acoustic measures versus crowdsourced listeners’ ratings: Evaluating the efficacy of treatment for hypokinetic dysarthria

Clinical interventions for speech disorders aim to produce changes that are not only acoustically measurable or perceptible to trained professionals, but are also apparent to naïve listeners. Due to the difficulty of collecting ratings from a suitably large sample, few researchers evaluate speech interventions relative to this criterion. Crowdsourcing technologies could enable a shift toward a more naturalistic standard to evaluate speech interventions. This project compared 35 naïve crowdsourced listeners’ ratings against acoustic measures of speech samples collected from patients with hypokinetic dysarthria secondary to Parkinson’s Disease. The data come from a published efficacy study (Sapir et al., 2007) that documented significant acoustic changes after a period of intensive treatment, Lee Silverman Voice Treatment. Specifically, the ratio of mean F2 in /i/ versus /u/, calculated for each subject, was greater in post-treatment relative to pre-treatment samples. Mixed-effects logistic regression indicated that words elicited post-treatment, presented in randomly ordered pairs with words elicited pre-treatment, were significantly more likely to be rated “more clear” (beta = 1.24, SE =.46, p &amp;lt;.01). This result supports the original conclusion of Sapir et al. (2007); it also supports the validity of crowdsourcing as a means to obtain ratings of disordered speech data.

Evidence vs. efficacy in allergen-specific immunotherapy: Considerations using the example of tradable products in Germany.

The recently published S2k-guideline on (allergen-) specific immunotherapy (AIT) provides an excellent overview of the evidence on allergen preparations available for AIT in Germany based on the published efficacy studies. Publications based on the guideline are currently being used by the German associations of statutory health insurance physicians and German health insurance funds to open a discussion on the reimbursement status of allergen preparations. In our view, calling the reimbursement status of perscribable and tradable AIT preparations into question on the basis of an assessment of the current body of evidence in the guideline is to be rigidly opposed. In Germany the Paul Ehrlich Institute (PEI) is the only authority empowered to decide on the marketability of AIT preparations, and decisions on the reimbursement status of AIT products need to be based on cost-benefit analyses and not solely on an evaluation of the evidence. The present article aims to examine the relationship between the evidence, efficacy, tradability, and reimbursability of AIT preparations.

Pharmacokinetics of Inhaled Rifampicin Porous Particles for Tuberculosis Treatment: Insight into Rifampicin Absorption from the Lungs of Guinea Pigs.

Tuberculosis (TB) is a life-threatening infection that requires a lengthy treatment process that is often associated with adverse effects. Pulmonary delivery of anti-TB drugs has the potential to increase efficacy of treatment by increasing drug concentrations at the lungs, the primary site of infection. The aim of the present study is to evaluate the disposition of rifampicin (RIF) after its pulmonary administration as porous particles (PPs) to guinea pigs and contrast it to that after oral administration. RIF microparticles were prepared by spray drying a solution of RIF and L-leucine (9:1), and the resulting particles were characterized for their physicochemical properties. Animals received RIF either as intravenous solution (iv), as oral suspension of micronized RIF (ORS) and RIF-PPs (ORPP), or by insufflation of the PPs (IRPP). Plasma samples were collected at preselected time points, and bronchoalveolar lavage (BAL) was performed at the end of the study. RIF concentrations in biological samples were analyzed by HPLC. Plasma concentration versus time data was analyzed by compartmental and noncompartmental methods. RIF PPs were thin walled porous particles with mass median aerodynamic diameter (MMAD) of 4.8±0.1 μm, GSD=1.29±0.03, and fine particle fraction below 5.8 μm of 52.9±2.0%. RIF content in the resulting particles was 91.8±0.1%. Plasma concentration vs time profiles revealed that the terminal slope of the iv group was different from that of the oral or pulmonary groups, indicating the possibility of flip-flop kinetics. RIF from IRPP appeared to be absorbed faster than that of ORPP or ORS as evidenced by higher RIF plasma concentrations up until 2 h. Notably, similar AUC (when corrected by dose), similar CL, λ, and half-life were obtained after oral administration of RIF at 40 mg/kg and pulmonary administration of RIF at 20 mg/kg. However, RIF in the IRPP group had a shorter Tmax and higher bioavailability than orally dosed groups. In addition, RIF concentrations in the BAL of animals in the IRPP group were 3-4-fold larger than those in the orally dosed groups. The disposition in ORS and ORPP were best described by a model with two sequential compartments, whereas the disposition of IRPP was best described by a two parallel compartment model. The advantages of delivering RIF by the pulmonary route are demonstrated in the present study. These include achieving higher RIF concentrations in the lungs and similar systemic levels after pulmonary delivery of one-half of the oral nominal dose. This is expected to result in a more effective treatment of pulmonary TB, as shown previously in published efficacy studies.

Achilles tendinopathy: A prospective study on the effect of active rehabilitation and steroid injections in a clinical setting.

In published efficacy studies on Achilles tendinopathy (AT) exercise alone results in improvement in 60-90% of the cases. However, this high success rate cannot be expected in usual clinical practice. We prospectively investigated the effectiveness of a treatment regimen consisting of home-based exercises (concentric, eccentric, and stretching) and optional glucocorticosteroid (GCS) injections in patients with (AT) in a usual clinical setting. Patients unable to commence or progress in exercise were offered GCS, hypothesizing that the GCS would facilitate exercise. Ninety-three consecutive patients with AT referred to two outpatient rheumatology clinics were registered, and seen at five visits over a 6-month period. Exercises seemed to have a slow, but long-lasting effect with GCS having a dramatic short-term effect on symptoms. Twenty-six percent of the patients could proceed with training alone, the remainder received one to three supplementary GCS. There were significant improvements on all outcome variables over time (P ≤ 0.001). At follow-up, 42 had no more symptoms, 29 good result, 16 slightly improved, 4 unchanged, and 2 slightly worse. Overall, 94% of the patients had improved, and we thus recommend the use of GCS injections in AT patients if training alone does not lead to improvement.

Late, never or non-existent: the inaccessibility of preclinical evidence for new drugs.

Animal studies establish much of the evidence used to support clinical development of new drugs. Recent studies suggest that many preclinical investigations are withheld from publication, leading to exaggerated estimates of clinical utility. We sought to estimate the volume and properties of all published animal efficacy studies for a cohort of novel drugs. We searched biomedical databases to identify 47 novel drugs whose first trials were reported between 2000 and 2003, inclusive. Next, we searched for all published animal studies testing the same drug, regardless of publication date. We then extracted items from titles and abstracts of eligible studies. We identified 2462 efficacy studies, representing an average of 52 studies per drug. No published efficacy studies were available for three drugs in our sample. The volume of efficacy studies was related to how far the drug had progressed in clinical development (Spearman's correlation coefficient = 0.66, P < 0.0001). Most (87%) accessible animal efficacy studies were reported after publication of the first trial, and for 17% of the drugs in our sample, no efficacy studies were published before the first trial report. Disease indications used in trials often did not match those modelled in efficacy studies; for 35% of indications tested in trials, we were unable to identify any published efficacy studies in models of the same indication. The volume of published efficacy studies is large, although numerous gaps reflect non-publication, publication delay or non-performance of efficacy studies supporting trials.

Self-managing mental health: The WRAP approach

Despite increasing popularity, the Wellness Recovery Action Plan (WRAP) has few published efficacy studies. WRAP aims to support participants to take ownership of their mental health and wellbeing through facilitated groups. Bandura's (1977) self-efficacy mechanism framework proposed that a person's belief in their ability to use coping skills is predictive of future behaviour. This project focused on evaluating the effectiveness of WRAP for improving coping self-efficacy, confidence and clinical outcomes for adults with mental health difficulties supported through NHS community mental health teams. 17 participants took part and showed significant mean differences between their pre- and post-scores for coping self-efficacy, mental health confidence, depression and overall distress. These findings suggest that WRAP improves coping self-efficacy and confidence in ability to self-manage, and reduces levels of distress and low mood. Improvements in ability to seek support and cope related to improvements in all but one of the clinical outcomes. Further research with larger samples, follow-up data, comparison and control groups is suggested to identify key variables for enhancing change.

Effectiveness of Cognitive-Behavioral Treatment for Major Depressive Disorder in a University Psychology Clinic

Major Depressive Disorder (MDD) is the most prevalent mental disorder in our environment, and one of the main causes of disability. While several empirically supported treatments (ESTs) for MDD exist, some doubts have been cast on the applicability--in time, components, and effectiveness--of these ESTs in routine clinical practice. A few attempts have been made to contrast the effectiveness of ESTs, but usually the precise components of the treatment developed are not considered in detail. The purpose of this study is to analyze the components of an EST-based treatment on a sample of 69 MDD cases from a University Psychology Clinic, and to benchmark them against the results of published efficacy studies on ESTs (behavioral activation, cognitive therapy, interpersonal therapy). Results show that treatments delivered at this clinical facility are similar in components, length, and effectiveness (in effect size, completers and improved ratio) to the benchmarked studies. Cognitive restructuring is the most frequent component of the delivered treatments. Therapy results show a 3.12 effect size, and a 55.1% improved ratio over initial sample, an 80% of completers. Results and limitations of the current study, especially those related to sample and center characteristics, are discussed.

Meta‐analysis of clinical trials on traditional Chinese herbal medicine for treatment of persistent allergic rhinitis

Chinese herbal medicine (CHM) has been used for the prevention and treatment of persistent allergic rhinitis (PAR), but results are still equivocal. This study was to assess the clinical effectiveness of CHM in patients with PAR. Databases searched included articles published in the Cochrane library, MEDLINE, EMBASE, China National Knowledge Infrastructure, and Wanfang database from 1999 to 2011. The studies included were randomized controlled trials (RCTs) comparing CHM to placebo if they included patients with PAR. The main outcomes were the changes in the standardized mean difference (SMD) of nasal symptom scores and total serum IgE level. Methodological quality was assessed by the modified Jadad's scale. Seven RCTs with 533 patients were identified and analyzed. In the meta-analysis, CHM reduced the total nasal symptom scores compared to placebo (SMD, -1.82; 95% confidence interval [CI], -3.03 to -0.62; P = 0.003). The effect estimate was in favor of the CHM intervention (SMD, -1.09; 95% CI, -2.74 to 0.55) in reducing the total serum IgE level, although this was not significant (P = 0.19). CHM interventions appear to have beneficial effects in patients with PAR. However, the published efficacy studies are too small to draw firm conclusion.

Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2)

Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer. Patients with > or =3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and 8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate. A total of 451 patients were randomised. Results for AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy. Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.

Informed Consent and Investigational New Drug Abuses in the U.S. Military

Objective: The focal point of this investigation was to research the ethical issues surrounding the military's requests for informed consent waivers when using investigational drugs, and the recent debate surrounding the anthrax vaccine as an investigational new drug (IND). Design: The military's management of the informed consent process was examined using documents obtained through the Freedom of Information Act, Institutional Review Board (IRB) minutes, consent forms, legal pleadings, and protocols for specific investigational drugs. Results: In December 1990, prior to Operation Desert Storm, the Federal Drug Administration (FDA) granted the Department of Defense (DoD) an unprecedented waiver to the federally mandated informed-consent requirement for the use of investigational drugs. However, the waiver approval was conditional, and the FDA insisted on several safeguards. Partially in response to the subsequent Gulf War Syndrome debate, the FDA recently evaluated the military's use of investigational drugs during the Gulf War. The FDA cited the military for significant deviations from the originally approved protocols. Most notably, the military was found to be abusing the IRB process by convening a second IRB when the first IRB concluded that waiving informed consent was unethical. In addition, there was a gross lack of documentation and no monitoring of adverse reactions. The DoD's plan to use the current anthrax vaccine on all 2.4 million troops against inhalation anthrax has kindled an additional investigational drug controversy. The safety and efficacy of the use of the anthrax vaccine as a prophylactic against inhalation anthrax have been questioned by both military and medical organizations. There have never been any published studies of human efficacy or long-term effects for the anthrax vaccine. In addition, the military is not using the vaccine for its intended purpose, and it is also not adhering to prescribed dosing schedules. There is clear evidence to support the claim that, in fact, the military's use of the anthrax vaccine should be considered experimental. Conclusions: I argue that in medical situations, the military is obligated to treat its troops as autonomous persons entitled to basic rights and protections. The DoD is currently using an approved drug, the anthrax vaccine, for an unapproved purpose and in an unapproved manner. In doing so, the DoD is not only violating the FDA's regulations against such practices, it is also violating an executive order which only allows the president to authorize the use of INDs on service members without their consent.

Eye Movement Desensitization and Reprocessing: An Analysis of Specific versus Nonspecific Treatment Factors

Incremental validity and incremental efficacy have become important issues in the evaluation of psychological assessment and intervention procedures. Incremental validity in assessment is that shown by novel measures over and above established ones. Incremental efficacy is that shown by novel treatments over and above nonspecific and established treatment effects. In this paper, we critically examine the question of whether Eye Movement Desensitization and Reprocessing (EMDR) possesses efficacy above and beyond nonspecific treatment effects and components that are shared with well-established interventions. A review of recently published efficacy studies reveals that (a) the effects of EMDR are largely limited to verbal report indices, (b) eye movements and other movements appear to be unnecessary, and (c) reported effects are consistent with nonspecific treatment features. Examination of individual studies shows that control procedures for nonspecific features have been minimal. We analyze EMDR for nonspecific treatment features and suggest experimental controls to examine the incremental efficacy of EMDR.