Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Subjective Well-Being and Aversion to Macroeconomic Losses: New Evidence.

This work analyses the existence of asymmetric effects on the subjective well-being of the population of different countries in response to changes in the levels of aggregate income. Microdata from the Eurobarometer and the World Values Survey are used for the period 2000-2019. This period includes several economic changes, among which are the strong expansion at the beginning of the century, the Great Recession, and the subsequent recovery. Our study includes several groups of countries. In the broadest case, the study comprises a group of 83 countries and analyses the issue both from a global perspective as well as focusing particular attention on European countries. These asymmetric effects of economic activity are in line with behavioural economics and previous literature and allow us to determine a macroeconomic aversion to losses. The results obtained support the existence of asymmetric effects of changes in aggregate income on subjective well-being, and show that losses generated in recessions require a far more vigorous recovery if they are to be compensated for, and that they might even have permanent effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-021-00401-5.

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.

Oral status of older people in medium to long-stay health and social care setting: a systematic review.

BACKGROUND: Older patients who spend long periods hospitalized or those who are in a situation of institutionalization represent a risk group in this regard, as many of them suffer a degree of dependence and need help to perform the basic tasks of personal care. It is therefore important to learn more of the oral health status of this group of patients in order to make a proper assessment of the situation and to develop protocols for its management. The purpose of the study was to conduct a systematic review to ascertain the oral health status of older people patients admitted to institutions or hospitalized for a long period of time. METHODS: a systematic review of the literature published in two different databases (PubMed, Embase and Cochrane Library) was carried out, with 12 different combinations of keywords based on the following selection criteria: studies published in the last 5 years, in English and/or Spanish and/or Portuguese, with samples of ≥30 patients, performed in patients older than 65 years, admitted to any type of institution and/or hospital center for at least 7 days and in which the state of hard and/or soft tissues of the oral cavity were evaluated in some way. The selected articles were subjected to a thorough analysis. RESULTS: The search strategy covered 1.014 articles: 689 from Pubmed and 325 from Cochrane Library. After applying the eligibility criteria, five articles were selected for our review. The level of evidence of the articles was, a sample of 773 patients most of them were women with an average age older than 70 years old. CONCLUSIONS: The oral health of patients aged more than 65 is worse than that of the rest population. Long hospital stays or being institutionalized in a residence makes this group susceptible to a worsening of their oral health status. It is necessary to develop protocols for the oral health care of these patients, accompanied by training programs for the personnel responsible.

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Abstract analysis method facilitates filtering low-methodological quality and high-bias risk systematic reviews on psoriasis interventions.

BACKGROUND: Article summaries' information and structure may influence researchers/clinicians' decisions to conduct deeper full-text analyses. Specifically, abstracts of systematic reviews (SRs) and meta-analyses (MA) should provide structured summaries for quick assessment. This study explored a method for determining the methodological quality and bias risk of full-text reviews using abstract information alone. METHODS: Systematic literature searches for SRs and/or MA about psoriasis were undertaken on MEDLINE, EMBASE, and Cochrane database. For each review, quality, abstract-reporting completeness, full-text methodological quality, and bias risk were evaluated using Preferred Reporting Items for Systematic Reviews and Meta-analyses for abstracts (PRISMA-A), Assessing the Methodological Quality of Systematic Reviews (AMSTAR), and ROBIS tools, respectively. Article-, author-, and journal-derived metadata were systematically extracted from eligible studies using a piloted template, and explanatory variables concerning abstract-reporting quality were assessed using univariate and multivariate-regression models. Two classification models concerning SRs' methodological quality and bias risk were developed based on per-item and total PRISMA-A scores and decision-tree algorithms. This work was supported, in part, by project ICI1400136 (JR). No funding was received from any pharmaceutical company. RESULTS: This study analysed 139 SRs on psoriasis interventions. On average, they featured 56.7% of PRISMA-A items. The mean total PRISMA-A score was significantly higher for high-methodological-quality SRs than for moderate- and low-methodological-quality reviews. SRs with low-bias risk showed higher total PRISMA-A values than reviews with high-bias risk. In the final model, only 'authors per review > 6' (OR: 1.098; 95%CI: 1.012-1.194), 'academic source of funding' (OR: 3.630; 95%CI: 1.788-7.542), and 'PRISMA-endorsed journal' (OR: 4.370; 95%CI: 1.785-10.98) predicted PRISMA-A variability. Reviews with a total PRISMA-A score < 6, lacking identification as SR or MA in the title, and lacking explanation concerning bias risk assessment methods were classified as low-methodological quality. Abstracts with a total PRISMA-A score ≥ 9, including main outcomes results and explanation bias risk assessment method were classified as having low-bias risk. CONCLUSIONS: The methodological quality and bias risk of SRs may be determined by abstract's quality and completeness analyses. Our proposal aimed to facilitate synthesis of evidence evaluation by clinical professionals lacking methodological skills. External validation is necessary.

The therapeutic effects of apigenin and dexamethasone on 5-fluorouracil-induced oral mucositis - a pilot study using a Syrian hamster model.

OBJECTIVE: Oral mucositis (OM) is a common complication of chemotherapy and radiotherapy. The aim of this study was to evaluate the effects of treating 5-fluorouracil-induced OM with apigenin and dexamethasone. METHODS: Thirty-six male Syrian hamsters were randomly assigned to one of three groups: control (50% acetic acid + 5-FU), 50% acetic acid + 5-FU + potassium Apigenin (KA), and 50% acetic acid + 5-FU + dexamethasone. The animals from each group were sacrificed 5, 7, 10, and 14 days after inducing the mucositis, and two samples collected from each animal, accounting a total of 72 samples. Macroscopic changes were assessed by histomorphometric analysis, with ulcers being assessed by imaging analysis and the number of inflammatory cells in the ulcerated region quantified in all periods through histomorphometric analysis (H&E). Furthermore, immunohistochemical changes were evaluated by proliferating cell nuclear antigen. RESULTS: All groups presented an increased inflammatory infiltrate after 7 days, compared to other evaluation times (P ≥ 0.05). There was significant difference between apigenin and control group in the 10-days period. Lower quantity of inflammatory cells in the apigenin-treated group in comparison with control group in the 7- and 10-days periods was observed (P < 0.05). No statistically significant difference was verified among the groups in 5- and 14-days periods. The healing process of the control group was slower than that of apigenin and dexamethasone-treated groups, with an overall significant difference between apigenin and the control group in the 10-days period. CONCLUSIONS: Apigenin treatment may enhance healing of OM induced by 5-fluorouracil, thus suggesting that more extensive research in this area may be useful to assess the role of agents of natural origin capable of preventing OM. Hence, further studies involving broader samples are need to confirm the therapeutic potential shown by this study.

Effects of potassium apigenin and verbena extract on the wound healing process of SKH-1 mouse skin.

Tissue repair is a complex process, which may be favoured or inhibited by different factors. Potassium apigenin (AP) and other flavonoids present in verbena extract (PLX(®) ) possess powerful anti-inflammatory properties. The aim of this study was to evaluate the effects of topical treatment with AP and PLX gels on wounds inflicted on SKH-1/CRL mice. Forty-eight SKH-1 mice were used (4 groups with 12 animals each), which were subjected to wound excision with a round scalpel, 4 mm in diameter, on the dorsal skin. The animals were divided into four groups: Group I received topical applications of apigenin gel; Group II received PLX gel; Group III received vehicle gel; Group IV acted as control. Wound contraction, reepithelialisation, inflammation and neovascularisation (by means of immunohistochemical staining with anti-laminin) were recorded at study periods established at 2, 7 and 14 days. Reepithelialisation was faster in Groups I and II at 7 days (56·25% grade 3 and 43·75% grade 4) compared with the other groups. The degree of inflammation showed improvement with a tendency towards statistical significance in Groups I and II at 2 and 7 days. Anti-laminin staining was more intense in the group treated with PLX at the 2- and 7-day periods. Topical treatment with PLX gel improved the degree of reepithelialisation and inflammation, and favoured neo-vascularisation of the wounds at 2 and 7 days following surgery.

Femoroplasty: a new option for femur metastasis.

Bone metastases are very frequent in patients with cancer and usually are located in the patient's long bones and spine. Various approaches to pain relief and stability to the affected bone have been used. The aim of the study is to report our experience with a new minimally invasive percutaneous technique in patients with bone metastases located in the head, neck, and proximal femur. The technique is performed under fluoroscopic guidance through the application of polymethylmethacrylate bone cement. Our descriptive, retrospective, longitudinal case series included 15 patients who underwent femoroplasty. All patients reported pain reduction and improved mobility, with no complications observed. The femoroplasty procedure caused pain relief by stabilizing the bone through the consolidation of the microfractures because of bone metastases.

Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review.

Introduction: This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations. Methods: Our methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Reviews. The review included studies reporting on IL-1 pathway inhibitor use in PAID patients. Results: From an initial pool of 5,225 articles, 36 studies involving 43 patients were selected. The studies predominantly used observational designs and exhibited diversity in patient demographics, treatment approaches, and outcomes. Anakinra and canakinumab demonstrated promise in treating sterile pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and PSTPIP1-associated myeloid-related-proteinemia inflammatory (PAMI) syndromes, with scant data on other syndromes. Notably, there was a paucity of information on the adverse effects of these treatments, necessitating cautious interpretation of their safety profile. Conclusion: Current evidence on IL-1 pathway inhibitors for PAID is primarily from observational studies and remains limited. Rigorous research with larger patient cohorts is imperative for more definitive conclusions. Collaborative efforts among specialized research centers and international health initiatives are key to advancing this field.

Effect of Photobiomodulation on Atrophic-Erosive Clinical Forms of Oral Lichen Planus: A Systematic Review.

INTRODUCTION: Oral lichen planus is a chronic autoimmune inflammatory disease of unknown origin, characterized by various clinical forms of which the atrophic-erosive causes patients the greatest symptomatology. For this reason, there are different treatments that improve the associated signs and symptoms. One of these therapies is photobiomodulation (PBM), which, although new, has a high level of acceptance in dentistry based on evidence. However, there are inconsistent results in its application against lichen planus. The aim of this review was to evaluate the effect of photobiomodulation and its effectiveness as a therapeutic alternative for atrophic-erosive lesions. MATERIAL AND METHODS: The databases PubMed, Google Scholar and Cochrane Library were searched to identify studies investigating the photobiomodulation treatment in atrophic-erosive lesions of oral lichen planus. A total of 294 articles were identified, published between 2017 and 2022, and then evaluated; 7 articles that met all the inclusion criteria were included in this study. RESULTS: The type of laser light source used in PBM was the diode laser (four cases), the Nd-YAG laser at the same wavelength of 1064 nm (two cases) and the He-Ne laser (one case). The minimum and maximum wavelengths used were 630 nm and 1064 nm, respectively. Most studies used lesions treated with topical corticosteroids as a control group. The follow-up times of the studies were highly variable. CONCLUSIONS: Photobiomodulation is a treatment that competently combats oral lichen planus lesions by improving signs and symptoms, with no known adverse reactions so far, which makes it more beneficial compared to more conventional therapies, such as corticosteroids, for which side effects have been found.

Use of the Fractal Dimension to Differentiate Epithelium and Connective Tissue in Oral Leukoplakias.

BACKGROUND: Oral leukoplakia (OL) is considered one of the most common potentially malignant oral disorders (OPMD), with a verified increased risk of developing oral cancer. The identification of the dysplasia grade (low-high) is the only consolidated factor used to evaluate this risk. The objective of this study was to verify the role of the fractal dimension (FD) in assessing this dysplasia. METHODS: To begin, 29 OL and 10 normal oral mucosa (NOM) biopsies were retrieved for FD analysis of the epithelial (dime) and the connective (dimc) tissue. RESULTS: In the OL group, the median value of dime is higher (1.67, IQR = 0.12) than for the NOM group (1.56, IQR = 0.08), with statistically significant differences (Wilcoxon test, p = 0.0031). There were no differences in relation to dimc. Significant differences were observed between the non-dysplasia vs. high-grade (p = 0.0156) and low-grade vs. high-grade (p = 0.0049) groups. No significant differences were identified in relation to dimc for the different degrees of dysplasia. For a cut-off point of 1.44 of dime, a specificity of 96.6% was obtained, a sensitivity of 100%, and an AUC = 0.819 (p = 0.003). CONCLUSIONS: FD at the level of the epithelium may be used as a diagnostic tool in OL.

Study of the Effect of Photobiomodulation on a Skin Repair Model in SKH-1 Mice.

Background and objective: Laser applied at low power (400-1100 nm), currently named photobiomodulation (PBM), is a noninvasive therapy to speed up wound healing. The purpose of this study was whether two different laser PBM delivery protocols would impact the skin wound healing in a mouse model. Materials and methods: A total of 24 SKH-1 mice were divided into three groups: Group 1 (control: untreated ulcers), Group 2 (a single postsurgical laser application), and Group 3 (laser each other day for 10 days; total five applications). Laser parameters were 940 nm, 0.4 W, 10 mm spot size, 0.008 J/cm2, 300 sec/wound. Each animal received two skin wounds which were photographed on days 0, 5, and 10 to determine wound closure (ImageJ). Half of the animals in each group were sacrificed on day 5 and the other half on day 10. Samples were routinely processed for histological analysis (re-epithelization, angiogenesis, granulation tissue formation, inflammation, and collagen deposition). Results: The closure of the wounds at the end of the experiment in the animals photobiostimulated each other day was more advanced than in the controls and in those treated only once, in both the macroscopic and microscopic studies. Angiogenesis was higher in both treated groups than in the control in the first study time (day 5). However, inflammation, maturation of the granulation tissue, and collagen deposition only improved when the laser was applied each other day. Conclusions: In our study, with the parameters used, PBM improved the healing of skin wounds when applied every other day and not in a single dose.

A Stimulator of the Salivary Excretion Based on Physical Vibration of the Parotid Glands.

Oral dryness causes significant health problems both functional (difficulty speaking, chewing and swallowing) and structural in teeth (increased number of infections) and oral mucosa. The main objective of this study is to show an alternative treatment to help stimulate the salivary secretion thus improving the quality of life of the patient. In this study, a salivary stimulation equipment using vibrotactile stimuli is shown. The system has been placed bilaterally in the parotid glands and assessed the efficacy of the salivary secretion by sialometry before and after the stimulation. The new proposal is capable of stimulating salivary secretion, in a significative way after 7 minutes of use, at least in the cases analyzed, and fulfills low-cost, easy-to-use, and safe technical restrictions. In this setting, this paper suggests the performance of a deep clinical trial to measure the exact efficacy of the prototype and the times and frequencies needed to state the optimal treatment depending in each case.

A Scoping Review on Use of Drugs Targeting the JAK/STAT Pathway in Psoriasis.

Introduction: The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway are known to be involved in inflammatory immune-mediated skin diseases, including psoriasis. The development of drugs targeting the JAK/STAT signaling pathway presents new treatment opportunities for psoriasis. However, the application of JAK inhibitors for the treatment of dermatological disorders is still in its early stages of development. This review summarizes available evidence in an attempt to identify knowledge gaps for conducting further research studies and improving clinical decision-making. Objective: The objective of this study is to conduct a scoping review of the use of drugs targeting the JAK/STAT pathway in the treatment of psoriasis. Methods: A priori protocol for scoping review was published in 2019. The Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Review were used for the review. MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science databases and ClinicalTrials registry were referred to in April 2019 and March 2021, respectively. References in English involving evidence on the use of drugs targeting the JAK/STAT pathway in patients with psoriasis were included. Data charting was performed by two authors using tables and figures. Results: The evidence found on the efficacy and safety of drugs targeting the JAK/STAT pathway in patients with psoriasis comes from 118 articles reporting the results of 34 randomized clinical trials (RCTs). Nine different drugs administered through various routes were identified (systemic: peficitinib, baricitinib, solcitinib, itacitinib, abrocitinib, deucravacitinib, and brepocitinib; topical: ruxolitinib; and both: tofacitinib). Knowledge articles are mainly created and published by pharmaceutical companies and authors through their own funding or by those related to them. Only tofacitinib and deucravacitinib have undergone phase III clinical trials, being the only ones tested with active comparators etanercept and apremilast, respectively. Proportions of Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) were the efficacy variables most frequently studied in systemic treatments. Only two RCTs declared the safety data collected by systematic assessment; the only systemic drug with phase III data was tofacitinib. Tofacitinib 5 mg two times daily (BID)/10 mg BID efficacy was compared with etanercept 50 mg/week and a placebo. At 12-16 weeks, PASI 75/PGA 01 ranges were as follows: 38.07-80%/37.16-67.4% for tofacitinib 5 mg BID; 54.79-100%/50-75.6% for tofacitinib 10 mg BID; 58.8/66.8% for etanercept, date from one only study; and 0-33.3%/9.04-33.3% for the placebo group. Other drugs in earlier stages of development showed values within these ranges. The most frequent adverse events (AEs) were nasopharyngitis and upper respiratory tract infections in all treatment groups. Conclusion: There is increasing evidence on the use of drugs targeting the JAK/STAT pathway as a treatment for psoriasis, although they are in the early phases of development. The trials conducted to date have been financed directly or indirectly by the pharmaceutical industry, which must be taken into account when interpreting the results of the trials. Psoriasis treatment is currently symptomatic and could potentially present a significant risk of toxicity. Therefore, the design of principal efficacy outcome measures considering the impact of the outcome on quality of life and a drug assessment methodology aimed at improving safety would probably strengthen the evidence and decision-making process.

Photodynamic Therapy, Photobiomodulation and Acetonide Triamcinolone 0.1% in the Treatment of Oral Lichen Planus: A Randomized Clinical Trial.

Objective: To evaluate the efficacy of photodynamic therapy (PDT) and photobiomodulation (PBM) in the treatment of oral lichen planus (OLP) in comparison with the use of topical corticosteroids. Material and methods: Sixty patients with OLP were randomized to three groups: group 1 photodynamic therapy applied once a week for four sessions, with orabase cream; group 2 low-power laser application with orabase cream; and group 3 inactive laser with triamcinolone acetonide 0.1%. Patient pain was evaluated, and the Thongprasom severity score, the Oral Health Impact Profile-14 (OHIP-14), and the Hamilton anxiety and depression scale at one and three months of follow-up. (ClinicalTrials.gov Identifier: NCT05127083). Results: Pain decreased significantly over time in all groups, though the symptoms relapsed over follow-up at one and three months in group 3. The OHIP-14 score improved significantly in groups 1 and 2 (p < 0.05), and this improvement was maintained after three months. Lesion resolution evaluated by the Thongprasom score at one month showed significant differences between groups 1 and 3 (p = 0.032) and between groups 2 and 3 (p = 0.024). Conclusions: Photodynamic therapy and photobiomodulation once a week for four weeks are safe and non-invasive treatment options, with the important advantage of lacking adverse effects. Further studies are needed to confirm it.

The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry.

BACKGROUND: Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES: To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS: All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS: Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS: Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Perioperative antibiotic regimen in rats treated with pamidronate plus dexamethasone and subjected to dental extraction: a study of the changes in the jaws.

PURPOSE: Osteonecrosis of the jaws is a well-known condition associated with long-term bisphosphonate use. This study analyzed the prophylactic effect of antibiotic treatment in Sprague-Dawley rats treated with pamidronate plus dexamethasone and subjected to oral surgery in the form of dental extraction. MATERIALS AND METHODS: One hundred twenty animals were included in a randomized prospective study. Animals in group I (n = 60) were treated with dexamethasone 1 mg/kg and pamidronate 3 mg/kg 3 times per week for 7, 14, and 21 days. All were subjected to right mandibular or maxillary molar extraction 8, 15, and 22 days after the start of dosing. Animals in group II (n = 60) received the same treatment except for the addition of penicillin 0.1 mL/kg per day for 3 days before and 4 days after extraction. Rats in the 2 groups were sacrificed 14 and 28 days after extraction. A clinical and histologic evaluation was performed. RESULTS: In group I, osteonecrosis was documented in 18 cases (34.6%; affecting the upper and lower jaws in 10 and 8 cases, respectively). In group II, osteonecrosis was documented in 5 cases (9.61%; affecting the upper and lower jaws in 3 and 2 cases, respectively). The difference between the 2 groups was statistically significant (P = .002). CONCLUSIONS: The adoption of preventive measures (antibiotic prophylaxis) in invasive dental procedures results in a significant decrease in osteonecrosis of the jaws associated with bisphosphonate use.

Effect of curcumin and irradiation in PE/CA-PJ15 oral squamous cell carcinoma.

OBJECTIVE: An in vitro study was made to evaluate the effect of curcumin and irradiation upon oral squamous cell carcinoma. MATERIALS AND METHOD: Curcumin was administered at doses of 3, 3.75, 4.50 and 5.25 µM in PE/CA-PJ15 oral squamous cell carcinoma cultures irradiated with different doses (1, 2.5 and 5 Gy), followed by evaluation of the effects upon cell viability after 24, 48 and 72 h, based on the MTT colorimetric test. RESULTS: The application of curcumin to the PECA/PJ15 tumor cells during 24, 48 and 72 h of incubation without irradiation exerted an inhibitor effect upon cell viability. The curcumin concentration at which the inhibition of cell viability proved maximum was 5.25 µM, with statistically significant differences for 24 h (p = 0.002), 48 h (p < 0.001) and 72 h of incubation (p < 0.001). In contrast, the combination of curcumin and irradiation exerted a synergic effect-the greatest effects in relation to cell viability being recorded with a curcumin concentration of 3.75 µM and 5 Gy of irradiation, in the studied cell line. CONCLUSIONS: Curcumin increases cytotoxic activity in the PE/CA PJ15 cell line, while the combination of curcumin and irradiation exerts a synergic effect.