Negative Treatment Effects Research Articles

Review on Tropical Carriers of Antifungal Drug Therapy

Among the most prevalent conditions affecting the skin are fungus infections. OTC and oral antifungal medications are used in treatment regimens. Considering the potential negative effects of oral treatment, the topical method is usually favoured. Soon, traditional products like gels, ointments, and creams may become obsolete due to advancements made in formulation. When used to treat cutaneous fungal infections, a number of carrier systems that are packed with antifungal medications have shown encouraging outcomes. These more recent carriers include liposomes, ethosomes, liposomes, Microemulsion, and lipid systems such solid lipid nanoparticles and nanostructured lipid carriers. Penetration enhancer vesicles are another example of these newer carriers. Compared to cream and ointment, gel and composition have superior stability and application qualities. Among the most prevalent dermatology issues are skin interactions resulting from fungal infections. The most effective treatment for cutaneous infections is topical medication.

Timeliness of Cold Plasma Treatment on Surface Modification of Polylactic Acid Fibers

Polylactic acid (PLA) fiber is a promising material due to its biodegradability, excellent mechanical properties, and good biocompatibility. However, its surface is chemically inert and has poor interfacial compatibility with gases due to a low number of polar groups. To address this issue, this study utilized cold plasma and solution wet pretreatment with varying pH levels to modify the surface of PLA fibers. The use of solution wet pretreatment helped mitigate the negative effects of plasma treatment on the timeliness, which improved the long-term stability of the PLA fibers surface properties. These modifications increased the suitability of the material for various applications. The surface of PLA fibers was modified using cold plasma and wet pretreatment with pH solutions of varying degrees. The surface chemical composition and hydrophilicity of modified fibers remained relatively stable for up to 120 days. Conversely, unpretreated fibers reverted to their original chemically inert state after 14 days.

Can diffusion tensor imaging unlock the secrets of the growth plate?

"How tall will I be?" Every paediatrician has been asked this during their career. The growth plate is the main site of longitudinal growth of the long bones. The chondrocytes in the growth plate have a columnar pattern detectable by diffusion tensor imaging (DTI). DTI shows the diffusion of water in a tissue and whether it is iso- or anisotropic. By detecting direction and magnitude of diffusion, DTI gives information about the microstructure of the tissue. DTI metrics include tract volume, length, and number, fractional anisotropy (FA), and mean diffusivity. DTI metrics, particularly tract volume, provide quantitative data regarding skeletal growth and, in conjunction with the fractional anisotropy, be used to determine whether a growth plate is normal. Tractography is a visual display of the diffusion, depicting its direction and amplitude. Tractography gives a more qualitative visualization of cellular orientation in a tissue and reflects the activity in the growth plate. These two components of DTI can be used to assess the growth plate without ionizing radiation or pain. Further refinements in DTI will improve prediction of post-imaging growth and growth plate closure, and assessment of the positive and negative effect of treatments like cis-retinoic acid and growth hormone administration.

Do “Likes” in a Brand Community Always Make You Buy More?

Online brand communities often use social plug-in features, such as the Like button, to facilitate social interactions and engage users with the brands. However, whether and how such a community feature affects users’ purchases remain open questions. Analysis of user behavior following the adoption of the Like feature indicates a surprising downturn in purchases, with a 4.1% decrease in orders and a 25.0% reduction in expenditure. Notably, online purchases dip by 3.4% in order numbers and 21.1% in expenditure, with a slighter offline decrease. The treatment effect of the adoption is not always negative but varies over time and across users. First, the Like feature adoption has a positive effect on users’ purchases in the first two months (primarily through enhancing their community participation), and the treatment effect turns negative in subsequent months, leading to the overall negative treatment effect on purchases. Second, the negative treatment effect likely stems from unflattering social comparison and can become weaker or even positive when users accrue more Likes. However, only a small proportion of users receive sufficient Likes to be motivated to purchase more. Our results caution against potential downsides of the Like feature in online communities and provide valuable managerial implications.

A Controlled Clinical Study of Accelerated High-Dose Theta Burst Stimulation in Patients with Obsessive–Compulsive Disorder

Background. Obsessive–compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method. Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS). Results. After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups ( p < 0.001 ), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90, p = 0.18 ). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion. Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.

Patulin induces ROS-dependent cardiac cell toxicity by inducing DNA damage and activating endoplasmic reticulum stress apoptotic pathway

Patulin (PAT) is one of the mycotoxins commonly found in agricultural products and fruits, and has obvious toxic effects on animals and humans. PAT has been found to cause myocardial toxicity and oxidative damage, but the mechanism of myocardial toxicity remained to be elucidated. We investigated the toxic effects and potential mechanisms of PAT on human cardiomyocytes and explored the effects of reactive oxygen species (ROS) on them. The study showed that treatment with PAT for 24 h decreased cell viability and superoxide dismutase (SOD) activity, and increased ROS and lactate dehydrogenase (LDH) levels. Moreover, in addition to detecting increased γ-H2AX expression and observing nuclear damage, the comet assay also showed increased DNA tail distance in the PAT-treated group, followed by an increase in phosphorylation of the p53 protein and p21 protein expression, and a decrease in CDK1 and Cyclin B1 protein expression, and G2/M phase arrest. In addition, PAT induced endoplasmic reticulum stress (ERS) and induced apoptosis, as evidenced by Ca2+ increase, ER enlargement and swelling, and upregulation of ERS-related genes and proteins expression, and increased expression of three apoptotic pathway proteins under ERS, including CHOP, JNK, and caspase-12. Meanwhile, N-acetylcysteine (NAC, a ROS scavenger) reversed the negative effects of PAT treatment on cells. These results clarify that excessive ROS production by PAT-treated AC16 cells not only causes DNA damage, leading to cell cycle arrest, but also causes ERS, which triggers apoptotic pathways to cause apoptosis.

Factors influencing preferential treatment on academic performance of private universities in Mogadishu

This study aims to explore how favoritism affects students' grades at private universities in Mogadishu. It uses a quantitative approach involving interviews with 98 faculty members. The research team carefully collected data to ensure the results were reliable. They then analyzed the data using statistical software like SPSS and Smart PLS. The findings show that favoritism, along with nepotism and cronyism, negatively impacts students' academic achievements in these universities. This research adds to what we already know about the negative effects of preferential treatment, especially regarding nepotism, favoritism, and cronyism. It makes a significant contribution to discussions on how favoritism affects education, highlighting its harmful effects. The study also suggests that future research in Somalia could look at this issue in other cities to better understand its wider effects. While this study focused on how favoritism influences students' grades, it points out that future research could examine other factors like trust within the organization, employee commitment, the tendency of employees to remain silent, and staff turnover. These factors could offer further insights into the complex environment of private universities in Mogadishu and similar institutions around the world.

Research on treatment-related aspects of depression from India in the preceding decade (2014-2023): An updated systematic review.

The National Mental Health Survey reports a prevalence of 2.7% for depressive disorders in India. The services for depression patients may be organized differently in India as compared to Western countries. It is important to consider studies conducted in India to determine effective interventions for depression catered specifically to the needs of the Indian population. We intended to systematically review the articles studying the usefulness of various treatment modalities in the management of depression in the Indian context. We searched PubMed, Google Scholar, and ScienceDirect to identify studies published in peer-reviewed English language journals. All articles from India evaluating the clinical efficacy of anti-depressants, electro-convulsive therapy, repetitive transcranial magnetic stimulation, and psychological interventions for the management of depression were evaluated. Data were extracted using standard procedures. A total of 36 studies were included in the review. Out of those, 15 were studies on drug efficacy, five on neuro-modulation, nine on psycho-social interventions, four on adverse effects, and three on miscellaneous studies. Innovations were seen in the field of neuro-modulation and psycho-social intervention. Trials on drug efficacy and adverse drug reactions require larger sample sizes, more studies on newer agents, and more robust study designs. More research is needed to understand the effectiveness and potential negative effects of depression treatments in India. Studies on ketamine have been inconclusive, and existing research on pharmacological agents is limited. Neuro-modulation studies show promise, but larger-scale studies are needed. Innovative psychological interventions tailored to the Indian population include community-based and digital technology-driven care.

Identification of ACHE as the hub gene targeting solasonine associated with non-small cell lung cancer (NSCLC) using integrated bioinformatics analysis.

Solasonine, as a major biological component of Solanum nigrum L., has demonstrated anticancer effects against several malignancies. However, little is understood regarding its biological target and mechanism in non-small cell lung cancer (NSCLC). We conducted an analysis on transcriptomic data to identify differentially expressed genes (DEGs), and employed an artificial intelligence (AI) strategy to predict the target protein for solasonine. Subsequently, genetic dependency analysis and molecular docking were performed, with Acetylcholinesterase (ACHE) selected as a pivotal marker for solasonine. We then employed a range of bioinformatic approaches to explore the relationship between ACHE and solasonine. Furthermore, we investigated the impact of solasonine on A549 cells, a human lung cancer cell line. Cell inhibition of A549 cells following solasonine treatment was analyzed using the CCK8 assay. Additionally, we assessed the protein expression of ACHE, as well as markers associated with apoptosis and inflammation, using western blotting. To investigate their functions, we employed a plasmid-based ACHE overexpression system. Finally, we performed dynamics simulations to simulate the interaction mode between solasonine and ACHE. The results of the genetic dependency analysis revealed that ACHE could be identified as the pivotal target with the highest docking affinity. The cell experiments yielded significant findings, as evidenced by the negative regulatory effect of solasonine treatment on tumor cells, as demonstrated by the CCK8 assay. Western blotting analysis revealed that solasonine treatment resulted in the downregulation of the Bcl-2/Bax ratio and upregulation of cleaved caspase-3 protein expression levels. Moreover, we observed that ACHE overexpression promoted the expression of the Bcl-2/Bax ratio and decreased cleaved caspase-3 expression in the OE-ACHE group. Notably, solasonine treatment rescued the Bcl-2/Bax ratio and cleaved caspase-3 expression in OE-ACHE cells compared to OE-ACHE cells without solasonine treatment, suggesting that solasonine induces apoptosis. Besides, solasonine exhibited its anti-inflammatory effects by inhibiting P38 MAPK. This was supported by the decline in protein levels of IL-1β and TNF-α, as well as the phosphorylated forms of JNK and P38 MAPK. The results from the molecular docking and dynamics simulations further confirmed the potent binding affinity and effective inhibitory action between solasonine and ACHE. The findings of the current investigation show that solasonine exerts its pro-apoptosis and anti-inflammatory effects by suppressing the expression of ACHE.

Complex skin care for psoriasis: effective control with modern dermatocosmetic products

Introduction. Recent decades have witnessed significant progress in the dermatocosmetic industry, driven by increased knowledge of skin physiology, development of new active ingredients and products based on well-studied action mechanisms. Dermatovenerologists actively use dermatocosmetics in inflammatory skin diseases, which include psoriasis. Even in mild forms, psoriatic rashes can be accompanied by itching and flaking. A significant proportion of patients have lesions on exposed skin, and the disease has a severe psychosocial burden. Full and successful control of psoriasis requires the use of adjuvant agents, which can be used alone to maintain remission or as an adjunct to medication, also reducing the negative effects of treatment. The Kertyol P.S.O. Ducray range is represented by products containing active components with anti-inflammatory, antipruritic, keratoregulatory action.Aim. To evaluate the effectiveness of including the Kertyol P.S.O. Ducray range of products in the treatment regimen of patients with psoriasis.Materials and methods. 20 patients with localization of psoriatic rashes on smooth skin and scalp were included in the study. Kertyol P.S.O. Ducray concentrate in combination with calcipotriol was recommended for smooth skin rashes, and daily skin care was corrected; Kertyol P.S.O. Ducray concentrate and regenerating shampoo in combination with calcipotriol/betamethasone dipropionate were recommended for scalp skin.Results. At the 4th week of therapy the average reduction of PASI index in the complex evaluation of clinical manifestations amounted to 89.6%; antipruritic effect was determined by the dynamics of VAS – the average reduction of the index at the 4th week amounted to 90.6%. Dermatologic life quality index (DLQI) decreased by 89.5% at the 4th week of therapy.Conclusion. Kertyol P.S.O. Ducray products can be recommended as an effective adjuvant therapy for smooth skin and scalp psoriasis.

Pain and quality of life in nursing home residents with dementia after admission – a longitudinal study

BackgroundPain in nursing home (NH) residents with dementia is commonly reported and may affect Quality of Life (QoL) negatively. Few longitudinal studies have explored how pain and QoL develop in NH residents with dementia starting from their admission to the NH.AimThe aim was to explore pain, QoL, and the association between pain and QoL over time in persons with dementia admitted to a NH.MethodsA convenience sample, drawn from 68 non-profit NHs, included a total of 996 Norwegian NH residents with dementia (mean age 84.5 years, SD 7.6, 36.1% men) at NH admission (A1), with annual follow-ups for two years (A2 and A3). Pain and QoL were assessed using the Mobilization-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) Pain Scale and the Quality of Life in Late-Stage Dementia (QUALID) scale, respectively, at all assessments. Severity of dementia, personal level of activities of daily living, general medical health, neuropsychiatric symptoms, and the prescription of psychotropic drugs and analgesics (opioids and/or paracetamol) were also assessed at all assessments.ResultsMean (SD) MOBID-2 pain intensity scores were 2.1 (2.1), 2.2 (2.2), and 2.4 (2.1) at A1, A2, and A3, respectively. Participants who were prescribed analgesics had higher pain intensity scores at all assessments than participants not prescribed analgesics. The mean (SD) QUALID scores at each assessment were 19.8 (7.1), 20.8 (7.2), and 22.1 (7.5) at A1, A2, and A3, respectively. In the adjusted linear mixed model, higher pain intensity score, prescription of opioids, and prescription of paracetamol were associated with poorer QoL (higher QUALID total score and higher scores in the QoL dimensions of sadness and tension) when assessed simultaneously. No time trend in QoL was found in these adjusted analyses.ConclusionNH residents with dementia who have higher pain intensity scores or are prescribed analgesics are more likely to have poorer QoL. Clinicians, NH administrators, and national healthcare authorities need to look into strategies and actions for pharmacological and non-pharmacological pain treatment to reduce pain intensity while simultaneously avoiding negative side effects of pain treatment that hamper QoL.

Informing patients about possible negative effects of psychological treatment: A survey of Swedish clinical psychologists’ attitudes and practices

Objective: The present study explored Swedish clinical psychologists’ attitudes and practices of informing patients about possible negative effects of psychological treatment. Method: An anonymous online survey with closed and open-ended questions was distributed via Facebook and two mailing lists. In total, 320 clinical psychologists (age M = 38.6, SD = 10.3; 76% women; 77.3% Cognitive Behavior Therapy) completed the survey. Responses were analyzed using χ2, binominal regression analysis, and thematic analysis. Results: No significant associations were identified between demographic variables selected a priori and informing patients about possible negative effects, i.e., years in practice, therapeutic orientation, age, and male gender. The thematic analysis resulted in several positive (e.g., creating realistic expectations of treatment and increasing resilience) and negative attitudes (e.g., causing excessive worry) of sharing patients with information about possible negative effects. It also revealed various factors that prevent an open discussion on the topic, despite being seen as important. Conclusion: The need to offer patients information about possible negative effects should be included in ethical guidelines, codes of conduct, and taught during clinical training. Lack of knowledge, fear, lack of time, and patient characteristics however seem to prevent therapists from discussing the issue during the informed consent procedure.

Altered expression of activated induced hepatocellular carcinoma markers (HCCmk) in murine model treated with Portulaca oleracea L.

Hepatocellular carcinoma (HCC) is a wan prognosis and is highly resistant to cancer therapy, pushing the search for safe drugs as an essential issue. Plant-based bioproducts may reduce the negative side effects of cancer treatment. By the present study, we evaluated the ability of a defatted methanol and hexane extracts from Portulaca oleracea to regulate HCC in an animal model. The anticancer activity of Portulaca oleraceae L. (PO) extract was evaluated against HepG2 cell line where IC50 was 241.79 µg/ml for PO MeOH extract and 122.19 µg/ml for PO Hex extract. Overall, treatment with DEN+ PO Hex 200 mg/kg shows 100% survival rate. Furthermore, it improved the preservation of hepatocyte architecture in animals with small hepatocyte alterations but interspersed with foci of hepatocyte apoptosis as well as liver enzymes ALP (11.77±4.02 IU/L), AST (114.15±11.79 IU/L), ALT (22.11±2.66 IU/L) and TBILR (0.4±0.20 IU/L). The relative expression of serum TNF-α was significantly up-regulated in DEN induced HCC mice to reach (322.44±11.2) compared to normal mice (0.07±0.02). Besides the TNF-α in DEN/ PO groups were significantly down-regulated to be (73.98±2.7), so the relative expression level of tumor markers BCl-2 and AFP. In addition, apoptotic markers BAX and Cas-8 were significantly increased in DEN/ P. oleracea treated mice. Chemical profiling of methanol and hexan extracts using GC–MS and HPLC analysis revealed that 9,12,15 octadecatrienoic acid, (2-phenyl-1,3-dioxolan-4-yl) methyl ester, mesitylene, 2-Hydroxy-3-[(9E)-9-octadec-enoylox] propyl(9E) octadecenoate, and 2-(phenymethylene) octanal are the major compounds that were identified by GC_MS analysis of PO Hex extract. While, HPLC clarified the presence of pyrogallol, Syringenic acid, Caffeic acid, P-coumaric acid and Cinnamic acid as major phenolic compounds besides Catechin, Luteolin, and rutin as major flavonoid compounds in PO MeOH extract. Taken together, these results provide the first visualization of the action effects of several compounds in PO and represent potential anti HCC therapy.

Celebrity Endorsement and Fan Economy in China: Warm Glow or Pure Altruism?

The use of a celebrity's stature or social standing to promote a product, service, or problem is known as celebrity endorsement. Is such consumption motivated by genuine compassion or a pleasant glow? In this paper, the researchers created an online experiment that distinguishes between two categories of fan consumption: those who worry seriously about their idols' wealth and wellbeing, and those who love contributing to their idols' income because it gives them a warm glow. Specifically, assessing the effect of reminders regarding celebrities' riches to differentiate between two potential channels: pure altruism toward the celebrity and warm glow. In conclusion, the data indicate negative treatment effects: reminders decrease the willingness to pay and reduce the inclination to spend, hence supporting the altruism channel rather than the pure warm glow channel.

Life Experience of Women with Breast Cancer Undergoing Chemotherapy at Jayapura General Hospital, Indonesia

Introduction: Breast cancer is the second most common cancer in the world and is the most common cancer among women. Cancer is a term used for malignant tumors, which are tumors that grow rapidly, infiltrate surrounding tissues, metastasize, and can cause death if they don't get proper treatment and therapy. One of the treatments for cancer is chemotherapy; the negative effects of chemotherapy treatment for patients can affect life. This study aimed to find out in depth the life experiences of women with breast cancer undergoing chemotherapy.
 Methods: The research design used is qualitative research using a phenomenological approach. The technique used is purposive sampling, with a total of 10 participants. This research was carried out at the Jayapura General Hospital in April 2023 using the in-depth interview method. 
 Results: Subjects felt the side effects during chemotherapy, the impact during chemotherapy, adapting to reduce physical changes after chemotherapy, the support received during chemotherapy, and expectations of chemotherapy.
 Conclusion: Chemotherapy provides hope for patients but also causes uncomfortable side effects for patients. Efforts to educate and strengthen chemotherapy patients are important.

Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension.

Long-term prescription of proton pump inhibitors (PPIs) in patients with cirrhosis is common practice. However, in recent years, several observational studies have reported increased complications and negative prognostic effects of PPI treatment in these patients. Judging the significance of these associations is complicated by the fact that a plausible underlying pathomechanism has not been identified so far. In the present study, we address this important issue by investigating the impact of PPI treatment on subclinical bacterial translocation from the gut into the blood stream in patients with advanced cirrhosis and portal hypertension. Indeed, we report significantly aggravated bacterial translocation in cirrhosis patients receiving PPI treatment. This finding is highly relevant, as bacterial translocation is known to promote the development of complications and impair prognosis in patients with cirrhosis. Hence, the present study could establish a plausible link between PPI treatment and adverse effects in cirrhosis.

Metabolites of Xenorhabdus bacteria are potent candidates for mitigating amphibian chytridiomycosis

Chytridiomycosis, caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), has caused extreme losses in amphibian biodiversity. Finding bacteria that produce metabolites with antifungal properties may turn out to be invaluable in the fight against this devastating disease. The entomopathogenic bacteria, Xenorhabdus szentirmaii and X. budapestensis produce secondary metabolites that are effective against a wide range of fungal plant pathogens. To assess whether they may also be effective against Bd, we extracted cell-free culture media (CFCM) from liquid cultures of X. szentirmaii and X. budapestensis and tested their ability to inhibit Bd growth in vitro. As a second step, using juvenile common toads (Bufo bufo) experimentally infected with Bd we also tested the in vivo antifungal efficacy of X. szentirmaii CFCM diluted to 2 and 10% (v/v), while also assessing possible malign side effects on amphibians. Results of the in vitro experiment documented highly effective growth inhibition by CFCMs of both Xenorhabdus species. The in vivo experiment showed that treatment with CFCM of X. szentirmaii applied at a dilution of 10% resulted in infection intensities reduced by ca. 73% compared to controls and to juvenile toads treated with CFCM applied at a dilution of 2%. At the same time, we detected no negative side effects of treatment with CFCM on toad survival and development. Our results clearly support the idea that metabolites of X. szentirmaii, and perhaps of several other Xenorhabdus species as well, may prove highly useful for the treatment of Bd infected amphibians.

Microalgae as Biofertilizers: A Sustainable Way to Improve Soil Fertility and Plant Growth

The intensification of agricultural production in response to the global population increase and the growing demand for food has raised significant concerns regarding environmental impacts over the past few decades. Currently, modern agriculture aims to improve the quantity and quality of crop yield, minimizing the negative effects of treatments on the environment. Recently, microalgae have found extensive application as a valuable biological resource across multiple industries, including the food sector, biofuel production, and the pharmaceutical industry. In agriculture, microalgae have been seen as a promising and sustainable alternative to agrochemicals, offering a range of benefits to improve soil fertility, optimize nutrient management, and reduce reliance on synthetic fertilizers. In general, microalgae have demonstrated efficient nutrient cycling abilities, assimilating and converting essential nutrients, such as nitrogen, phosphorus, and potassium, into forms readily available for plants. Additionally, they produce bioactive substances, including phytohormones, which have a direct impact on the physiological processes of plants and promote their growth. Microalgae can also establish beneficial interactions with other soil microorganisms, supporting the growth of beneficial bacteria and fungi, thus promoting a healthy soil microbiome. On the other hand, as photosynthetic microorganisms, microalgae harness sunlight to convert carbon dioxide (CO2) into organic matter through photosynthesis. This ability allows them to sequester carbon and contribute to sustainable agriculture by reducing greenhouse gas emissions. The present work provides an overview of the potential of microalgae as biofertilizers, highlighting their unique characteristics, benefits, and main limitations for effective implementation in agriculturally sustainable practices.

Stochastic curtailment tests for phase II trial with time-to-event outcome using the concept of relative time in the case of non-proportional hazards

ABSTRACT As part of the drug development process, interim analysis is frequently used to design efficient phase II clinical trials. A stochastic curtailment framework is often deployed wherein a decision to continue or curtail the trial is taken at each interim look based on the likelihood of observing a positive or negative treatment effect if the trial were to continue to its anticipated end. Thus, curtailment can take place due to evidence of early efficacy or futility. Traditionally, in the case of time-to-event endpoints, interim monitoring is conducted in a two-arm clinical trial using the log-rank test, often with the assumption of proportional hazards. However, when this is violated, the log-rank test may not be appropriate, resulting in loss of power and subsequently inaccurate sample sizes. In this paper, we propose stochastic curtailment methods for two-arm phase II trial with the flexibility to allow non-proportional hazards. The proposed methods are built utilizing the concept of relative time assuming that the survival times in the two treatment arms follow two different Weibull distributions. Three methods – conditional power, predictive power and Bayesian predictive probability – are discussed along with corresponding sample size calculations. The monitoring strategy is discussed with a real-life example.

Silver diamine fluoride and resin-dentin bonding: Optimization of application protocols

ObjectiveTo evaluate the effect of SDF-based treatments following delayed bonding and surface treatment approaches on resin-dentin bonding efficiency of a universal adhesive under different application modes. MethodsMid-coronal dentin surfaces from sound third molars were randomly treated with 38% silver diamine fluoride (SDF) and/or additionally with potassium iodide (SDF/KI). Untreated dentin served as control. SDF-treated teeth were assigned to groups according to surface treatment approaches (air-abrasion and water rinsing), the application mode of a mild universal adhesive (etch-and-rinse or self-etch) and delayed bonding (immediate, 7, 15 or 30 days). Microtensile bond strength (n = 5), SEM analyses of hybrid layer formation and dentin etching patterns and dentin permeability were evaluated. Data were analyzed with factorial ANOVA. ResultsSDF-based treatments affected dentin bonding depending on application mode and surface treatment approaches (p<0.001). Etch-and-rinse bonding was not affected by SDF-based treatments (p<0.05), producing more homogenous hybrid layers. While dentin etching patterns of etch-and-rinse application were not affected by SDF-based treatments, self-etching presented limitations. Bond strength reductions of self-etched dentin were restored by silver-removal strategies containing a water-rinsing step (p<0.05). Delayed bonding additionally reduced dentin permeability (p<0.05), further decreasing with longer periods (p<0.05). ConclusionAlthough the negative effect of SDF-based treatments on resin-dentin bonding can be avoided by strategies incorporating water-rinsing before hybridization, delayed bonding brings additional advantages due to higher mineral deposition. Clinical significanceWhile the etch-and-rinse technique avoids major bonding drawbacks to SDF-treated dentin, self-etch bonding requires removal of excess silver deposits before hybridization. Performing SDF-based treatments and dentin hybridization in separate sessions (>15 days apart) potentialize mineral deposition improving caries control and service life of composite restorations.