Switching to or Add-on Peginterferon in Patients on Nucleos(t)ide Analogues for Chronic Hepatitis B: The SWAP RCT.

BACKGROUND & AIMS: The optimal therapeutic strategy in nucleoside analogue (NA) experienced chronic hepatitis B (CHB) using peginterferon is still unclear; hence we explored a switch to or add-on peginterferon strategy versus continued NA. METHODS: We conducted a randomized controlled trial of CHB patients on NA >12 months with HBV DNA(-) randomized to switch or add-on peginterferon-alpha2b (1.5 µg/kg/weekly) for 48 weeks versus continuing NA (controls) (allocation 2:2:1; Clinicaltrial.gov: NCT01928511) in tertiary Singapore hospitals. The primary composite endpoint at week 72 was hepatitis B e antigen (HBeAg) loss or quantitative HBsAg (qHBsAg) >1 log IU/mL reduction, and secondary endpoints were HBsAg loss, HBsAg seroconversion, qHBsAg <200 IU/mL, qHBsAg <100 IU/mL, HBV DNA(-), viral relapse, and safety. Analysis was by intention-to-treat (ITT). RESULTS: A total of 253 patients (controls 51, switch 103, add-on 99) were randomized. The primary ITT endpoint was achieved in 3.9% of controls, 33.3% of switch, and 26.7% of add-on (P < .0001, switch/add-on versus controls). HBsAg loss occurred in 0% of controls, 7.8% of switch, and 10.1% of add-on (ITT, P < .001, switch/add-on versus controls). HBeAg(+) patients on peginterferon had higher HBeAg loss than controls but poor HBsAg responses, whereas HBeAg(-) patients on peginterferon achieved better HBsAg responses than controls. Reduction in qHBsAg in HBeAg(+) was 0.14 log IU/mL versus 0.51 log IU/mL in HBeAg(-) (P < .0001) in peginterferon-treated patients. Clinical relapse was higher in switch (13.6% overall, 27% in HBeAg(+)) versus 1% add-on and 0% controls. Adverse events were typically interferon-related symptoms, with one death (myocardial infarction unrelated to therapy). CONCLUSIONS: ITT analysis showed that either peginterferon strategies were superior to NA for the primary endpoint and HBsAg loss, but add-on peginterferon is preferred to switch due to improved safety and similar efficacy. ClincialTrials.gov number: NCT01928511.

Use of a dental surveyor to ensure optimal seating of implant overdenture attachments.

Many implant overdenture attachments accommodate divergent abutments. However, there can be instances where the denture base resin surrounding the abutment may impede seating by binding on the axial surface(s) of the abutment. This article describes the use of a dental surveyor to aid clinicians in determining where the resin denture base might be preventing the seating of overdenture attachments. The surveyor can be used for judicious adjustment to allow optimal seating of the attachments.

Digital scanning to aid guiding plane and rest seat preparations for removable partial dentures.

This article describes the use of a digital intraoral scanner to aid clinicians making rest seat and guiding plane preparations, simplifying the procedure and reducing the time needed to analyze the abutment modifications. No additional equipment is required other than a diagnostic cast and a digital scanner with preparation comparison software.

Superlinear composition-dependent photocurrent in CVD-grown monolayer MoS2(1-x)Se2x alloy devices.

Transition metal dichalcogenides (TMDs) have emerged as a new class of two-dimensional materials that are promising for electronics and photonics. To date, optoelectronic measurements in these materials have shown the conventional behavior expected from photoconductors such as a linear or sublinear dependence of the photocurrent on light intensity. Here, we report the observation of a new regime of operation where the photocurrent depends superlinearly on light intensity. We use spatially resolved photocurrent measurements on devices consisting of CVD-grown monolayers of TMD alloys spanning MoS2 to MoSe2 to show the photoconductive nature of the photoresponse, with the photocurrent dominated by recombination and field-induced carrier separation in the channel. Time-dependent photoconductivity measurements show the presence of persistent photoconductivity for the S-rich alloys, while photocurrent measurements at fixed wavelength for devices of different alloy compositions show a systematic decrease of the responsivity with increasing Se content associated with increased linearity of the current-voltage characteristics. A model based on the presence of different types of recombination centers is presented to explain the origin of the superlinear dependence on light intensity, which emerges when the nonequilibrium occupancy of initially empty fast recombination centers becomes comparable to that of slow recombination centers.

Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon.

BACKGROUND: HBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy. AIM: To evaluate the use of serum biomarkers to predict HBeAg loss. METHODS: HBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated. RESULTS: HBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03-0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67-374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18-0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm. CONCLUSIONS: Baseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon.

Effect of instruction on dental students’ ability to light-cure a simulated restoration.

OBJECTIVE: To measure the light energy that dental students delivered to a simulated Class I restoration before training, immediately after training and 4 months after training. METHODS: Thirty-eight (38) dental students used a single light-emitting diode curing light (SmartLite iQ2, Dentsply) to cure, for 10 seconds, a simulated Class I restoration positioned in the Managing Accurate Resin Curing - Patient Simulator (BlueLight analytics inc.). The students then attended an instructional lecture and received individualized instruction on optimizing their light-curing technique. The students were retested immediately after instruction and again 4 months later (without further instruction). The irradiance and energy delivered during light-curing were calculated for each student at all 3 time points. Mean values were calculated and compared. RESULTS: Before instruction, the students delivered between 0.1 and 7.2 J/cm2 of energy (mean ± standard deviation [SD] 4.1 ± 1.7 J/cm2). After instruction, the same students delivered between 5.8 and 7.5 J/cm2 of energy (mean ± SD 6.7 ± 0.4 J/cm2). Analysis of variance and Fisher's Protected Least Significant Difference tests showed that instruction with the patient simulator led to a significant improvement in the amount of energy delivered and that the students retained this information. When retested 4 months later, the students delivered between 4.2 and 7.9 J/cm2 of energy (mean ± SD 6.1 ±1.1 J/cm2). Although this was less energy than immediately after instruction, the decline was not significant (p = 0.44). CONCLUSIONS: Provision of immediate feedback on light-curing technique and instruction on how to avoid mistakes led to a significant and lasting improvement in the amount of energy delivered by the students.

Neuropathy Mimicking Dental Pain in a Patient Diagnosed with Lyme Disease.

This report documents the case of a patient who developed neuropathy that presented as dental pain and was later diagnosed with Lyme disease. A healthy female patient presented to the endodontist with toothache symptoms. Her symptoms included intense pain in the left mandible irradiating into the temporalis area and through her neck and tingling on the lower left lip and left side of her tongue. She also reported feeling of sweats and chills the night before, as well as an altered sensation in her shoulder and arm. The pain was not alleviated by over-the-counter analgesics. Both intraoral and radiographic examinations did not reveal any abnormalities, and the patient was presented with the following differential diagnoses: cardiac issues, trigeminal neuralgia, and temporomandibular dysfunction. She presented to the emergency department at the local hospital for assessment on the same day. After some tests were performed, both a stroke and myocardial infarction were ruled out. The following morning, she noticed a bump in the posterior area of her left upper thigh where an erythema with a bull's-eye appearance was observed. She presented to her family doctor's office on the same day and was diagnosed with Lyme disease. Because Lyme disease can present with symptoms similar to a toothache, dentists should be knowledgeable of its manifestations. Lyme disease should be considered as differential diagnosis in patients who present with compatible symptoms and signs, which may occur in the orofacial region.

Experiences of Left-Handed Dental Students in Australia.

This article was migrated. The article was marked as recommended. Background: The aim of this study is to understand how left-handed (LH) dental students perceive their education and identify areas for improvement in their training. Methods: All LH students in their senior clinical years of their programs, at the nine Australian dental schools, were invited to participate in the study, by completing an online questionnaire. Results: A total of 40 students responded to the survey. The clinical disciplines ranked most often in the top 3 for difficulty were operative (restorative) dentistry (73%), followed by similar percentages for periodontics (49%), prosthodontics (46%), oral surgery (45%) and endodontics (44%). Areas for improvement that ranked highest were instructors and supervisors, and dental chair orientation (both at 26%). Operating tools and equipment, and dental chair orientation (68%) were most often ranked in the top 3, followed by the interior design of the room (63%) and instructors and supervisors (61%). Keywords: dental education, left-handed dental students, perceived difficulties, improvements Conclusion: The findings suggest that LH students perceived greater difficulty from the inconvenience caused by inadequate design of the surgery and chair, and due to a lack of personalised teaching. The findings of this study support a need for alterations to learning environment to better support LH students in learning specific procedures and increasing access to individualised teaching approaches.

Towards characterization and identification of solid state pharmaceutical mixtures through second harmonic generation.

In this paper, we report improvements to a previously developed method based on optical nonlinearity for characterizing polymorphism and concentration of pharmaceuticals in powdered and tablet form. An apparatus that measures the nonlinear optical response of a sample through second harmonic generation (SHG) is described. The response of several enalapril maleate-polyvinylpyrrolidone (PVP) tablets was measured, the results of which were used to determine the concentration of the drug. The current limit of detection of the apparatus was found to be approximately 1%-2%. Ranitidine hydrochloride (RN) polymorph forms I and II were also characterized using SHG. It was found that pure samples of forms I and II could be clearly and rapidly distinguished. Mixtures consisting of 50% form I and 50% form II were also distinguishable from the respective pure forms. An investigation was performed into the size dependence of the SHG response for crystalline lactose. It was found that the SHG response was a slowly decreasing monotonic function of particle size. Additional investigation into the angular dependence of the scattered SHG light was also undertaken for crystalline lactose. This new technique based on optical nonlinearity offers promise for application in monitoring of pharmaceutical manufacturing processes.

The effectiveness of using a patient simulator to teach light-curing skills.

BACKGROUND: The authors evaluated the effectiveness of using a patient simulator (MARC Patient Simulator [MARC PS], BlueLight analytics, Halifax, Nova Scotia, Canada), to instruct dental students (DS) on how to deliver energy optimally to a restoration from a curing light. Five months later, the authors evaluated the retention of the instruction provided to the DS. METHODS: Toward the end of the DS' first year of dental education, the authors evaluated the light-curing techniques of one-half of the class of first-year DS (Group 1) before and after receiving instruction by means of the patient simulator. Five months later, they retested DS in Group 1 and tested the remaining first-year DS who were then second-year DS and who had received no instruction by means of the patient simulator (Group 2). They gave DS in Group 1 and Group 2 MARC PS instruction and retested them. The authors also the tested fourth-year DS (Group 3) and dentists (Group 4) by using the MARC PS before giving any instruction by means of the MARC PS. RESULTS: The results of one-way analysis of variance (ANOVA) showed that there were no significant differences in the ability of dentists and DS to light cure a simulated restoration before they received instruction by means of the patient simulator (P = .26). The results of two-way ANOVA and Fisher protected least significant difference tests showed that after receiving instruction by means of the patient simulator, DS delivered significantly more energy to a simulated restoration, and this skill was retained. There were no significant differences between DS in Group 1 and Group 2 after they had received instruction by means of the patient simulator. CONCLUSIONS: The abilities of dentists and DS to light cure a simulated restoration were not significantly different. Hands-on teaching using a patient simulator enhanced the ability of DS to use a curing light. This skill was retained for at least five months. PRACTICAL IMPLICATIONS: The education provided to dentists and DS is insufficient to teach them how to deliver the optimum amount of energy from a curing light. Better teaching and understanding of the importance of light curing is required.

A phase II, open label, monotherapy study of liposomal doxorubicin in patients with metastatic malignant melanoma.

PURPOSE: This phase II study explored the efficacy and tolerability of pegylated liposomal doxorubicin (PLD) given on a 2 week schedule in patients with advanced malignant melanoma previously untreated by chemotherapy. PATIENTS AND METHODS: Patients with inoperable, advanced melanoma were treated with Pegylated liposomal doxorubicin (Caelyx) at a dose of 20 mg/m(2) every 2 weeks. Treatment cycles were repeated every 4 weeks for a maximum of 6 cycles. Patients with responding or stable disease at the end of study treatment, as assessed by using NCI CTG criteria, could continue PLD off-study. RESULTS: PLD administered as a 2 weekly IV infusion was well tolerated with mild infusion reactions usually associated with the first infusion. Myelosuppression was mild, as was nausea and vomiting. Palmar plantar erythrodysesthesia was also uncommon using this schedule. There were no objective responses seen in the 14 evaluable patients. Enrollment was stopped as per protocol, due to lack of activity. CONCLUSION: PLD was well tolerated using a 2 week schedule but failed to show any activity in chemotherapy naive patients with advanced malignant melanoma.