A short-term economic evaluation of early insulin therapy compared to oral anti-diabetic drugs in order to reduce the major adverse events in type 2 diabetes patients in Iran.

OBJECTIVE: While there are some recommendations about early insulin therapy in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, there is not sufficient evidence on this strategy's cost-effectiveness. This study compared early insulin therapy versus oral anti-diabetic drugs (OADs) for managing T2DMusing a cost-effectiveness analysis approach in Iran. METHODS: In this economic evaluation, a decision analytic model was designed. The target population was newly diagnosed type 2 diabetic patients, and the study was carried out from the perspective of Iran's healthcare system with a one-year time horizon. Basal insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, and Thiazolidinediones (TZDs) were compared in this evaluation. The main outcome for assessing the effectiveness of each intervention was the reduction in the occurrence of diabetes complications. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and deterministic and probabilistic sensitivity analyses were carried out. RESULTS: The DPP-4 inhibitors strategy was the dominant strategy with the highest effectiveness and the lowest cost. Early insulin therapy was dominated (ICER: $-53,703.18), meaning that it was not cost-effective. The sensitivity analyses consistently affirmed the robustness of the base case findings. The probabilistic sensitivity analysis indicated probabilities of 77%, 22%, and 1% for DPP-4 inhibitors, TZDs strategies, and early insulin therapy, respectively, in terms of being cost-effective. CONCLUSION: In terms of cost-effectiveness, early insulin therapy was not cost-effective compared to OADs for managing newly diagnosed T2DM patients. Future studies in this regard, utilizing more comprehensive evidence, can yield more accurate results.

Obesity as an independent risk factor for COVID-19 severity and mortality.

BACKGROUND: Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES: To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS: MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA: We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate.  DATA COLLECTION AND ANALYSIS: Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis.  MAIN RESULTS: We identified 171 studies, 149 of which were included in meta-analyses.  As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS: Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.

Tenecteplase in managing acute ischemic stroke: a long-term cost-utility analysis in Iran.

BACKGROUND & AIMS: The advantage of tenecteplase (TNK) over alteplase (ALT) in managing acute ischemic stroke (AIS) has been reported, but the cost-effectiveness of these two strategies has not received as much attention. The objective of this study was to compare TNK and ALT for the management of AIS patients in Iran in terms of cost-effectiveness. METHODS: This study was carried out from the payer's perspective in Iran, with a lifetime horizon. A full economic evaluation model was designed as a decision tree and a Markov model. After defining different Markov states, each health state was assigned a utility value, and quality-adjusted life year (QALY) was estimated using that value. The incremental cost-effectiveness ratio (ICER) was ultimately used for evaluating the comparative cost-effectiveness. Both deterministic and probabilistic sensitivity analyses were carried out. RESULTS: Compared to ALT, TNK can save approximately 4333.81 USD, and is able to increase one unit of QALY while saving approximately 17,450.29 USD. So, Base-case results showed that TNK strongly dominates ALT. Moreover, the base case results were strongly confirmed by deterministic and probabilistic sensitivity analysis. CONCLUSIONS: Base-case and sensitivity analysis showed that TNK is the dominant strategy compared to ALT for the management of AIS patients.

A recombinant affitoxin derived from a HER3 affibody and diphteria-toxin has potent and selective antitumor activity.

High expression of receptor tyrosine-protein kinase erbB-3 (HER3) has been found in several malignancies such as breast cancer. In this study, we designed, produced and evaluated a new affitoxin consisting of a truncated form of diphtheria toxin and a HER3-binding affibody domains. The new affitoxin was expressed in Escherichia coli and purified by affinity chromatography. We evaluated the suitability of affitoxin to kill HER3 positive breast cancer cells with MTT and apoptosis assays. The protein synthesis inhibition was also evaluated. The IC50 value in HER3 negative cells is about 10 times more than HER3 positive cells in new design of affitoxin. The specificity of affitoxin for binding to HER3 positive cells was also investigated with binding assay with flow cytometry. The results show that, the new affitoxin is an anti-cancer molecule with specific binding to HER3 positive cells and may open a new window for the treatment of HER3-positive cancers.

Clinical Effectiveness of Erlova in EGFR-Mutated Non-Small Cell Lung Cancer: An Affordable Price with Clinical Benefit.

BACKGROUND: Thyrosin kinase inhibitors (TKIs) is approved for the first line treatment of non-small cell lung cancer (NSCLC) patients with  epidermal growth factor receptor (EGFR) mutation. This study performed to assess clinical effectiveness and safety of Erlova (generic form of Erlotinib). METHODS: Somatic mutations of EGFR gene were studied in tumor tissue by polymerase chain reaction (PCR) and bi-directional sequencing in 513 chemonaive and histologically verified lung adenocarcinoma Iranian patients. Patients  with EGFR mutation received Erlova at 150 mg/day  as first line treatment. Primary endpoint was progression free survival (PFS). RESULTS: About 21% (n=109) cases had EGFR mutation. Most EGFR mutations were  occurred at exon 19. Among them, sixty nine patients treated with Erlova. Median PFS was 11.4 months and objective response rate (ORR) was about  88%. Most frequent treatment related adverse events was  skin rash. CONCLUSION: Our findings showed Erlova had remarkable effectiveness. In  mutation-positive patients with EGFR, Erlova can be used  safely instead of  other tyrosine-kinase inhibitors.

Fractional CO2 laser is as effective as pulsed dye laser for the treatment of hypertrophic scars.

BACKGROUND: Both pulsed dye laser (PDL) and fractional CO2 laser (FCO2L) are used commonly for the treatment of hypertrophic scars. OBJECTIVE: To compare the efficacy of PDL and FCO2L on hypertrophic scars. PATIENTS AND METHODS: One part of each scar, or one of the two similar scars in 35 patients was treated with PDL and the other parts, or scars were treated with FCO2L. The parameters used for FCO2L were: power = 30 W, pulse energy = 50 mJ, density = 200 spots/cm2. The parameters used for 585 nm PDL were 9 J/cm2 with 5 mm spot size. The FCO2L side was treated for three passes to debulk the scar. The coagulated tissue was wiped out before the next pass. The PDL side was treated with two superimposed passes. The procedures were repeated every month for 4 months. RESULTS: After four sessions of laser therapy, both sides showed remarkable improvement but no meaningful difference was detected between two areas that were treated with PDL and FCO2Ls (p > .05). The mean Vancouver Scar Scale was 7.31 ± 1.93 in the beginning and 4.26 ± 1.48 for FCO2L and 4.33 ± 1.70 for PDL one months after the final session. CONCLUSIONS: Both PDL and FCO2Ls were equally effective on hypertrophic scars.

Comparing the efficacy of pulsed dye laser, Q-Switched Nd-YAG, CO2, and combined CO2 and Q-Switched Nd-YAG lasers for the treatment of cutaneous macular amyloidosis.

BACKGROUND: No topical and systemic treatment is proven to be effective on Cutaneous Macular Amyloidosis (CMA). The physical removal of the deposited protein by lasers may be a better choice. OBJECTIVE: To compare the efficacy of different lasers including Pulsed dye laser (PDL), 1064 mode of Q-Switched Nd-YAG, CO2, and combined CO2 and Q-Switched Nd:YAG lasers for the treatment of CMA. PATIENTS AND METHOD: 17 adult female patients with clinical CMA and histopathological confirmation were included in this study. Four close 1 by 1 cm2 areas were treated simultaneously with PDL, Q-Switched Nd-YAG, CO2 and combined CO2 and Nd-YAG Lasers. The energy used for 585 nm PDL were 9 J/cm2 with the spot size of 5 mm. The energy used for 1064 nm mode of Nd-YAG laser was 5 Joules/cm2, with the spot size of 4 mm, and the frequency of 10 hertz. The energies used for CO2 laser were 4 and 3.5 Micro Joules for the first and second Passes. RESULTS: No desirable result obtained after PDL therapy. The Q-Switched Nd-YAG was effective in only 3 patients. All areas treated with CO2 laser were cleared. CONCLUSION: The CO2 laser is seems to be the most effective laser treatment of CMA.

Combined pulsed dye laser and fiberoptic Nd-YAG laser for the treatment of hypertrophic port wine stain.

The hypertrophic Port Wine Stain (PWS) is only partially and superficially treated with the Pulsed dye laser (PDL) because of its limited depth of penetration. We used combined PDL and fiberoptic 1444-nm Nd-YAG laser to treat a case with hypertrophic PWS. METHOD: After tumescent anesthesia, few holes were made by a 16-gauge needle on different sides of the lesion. The fiberoptic tip of 1444-nm Nd-YAG laser was inserted within the holes and was pushed forward while triggering. In a fan pattern and by a back and forth movement, the subcutaneous and deep dermal areas were coagulated. The skin and outer mucosal surfaces were then treated by PDL. The fiberoptic system used was Accusculpt 1444-nm Nd-YAG laser (Lutronic lasers, South Korea), and the PDL used was 585 nm Nlite system (Chromogenex UK). The parameters used for PDL were fluence = 9 Joules/cm2 and the spot size was 5 mm. The parameters used for fiberoptic 1444-nm Nd-YAG laser were: Pulse rate = 30 Hz, pulse energy = 300 mJ, power = 6 W, and the total energy = 4000 J for the whole face and mucosa. RESULT: Little sign of regression and moderate purpura were detected immediately after combined fiberoptic Nd-YAG and PDL therapy. The lesion gradually regressed within 4 months with satisfactory color and volume change. CONCLUSION: Combined fiberoptic Nd-YAG laser and PDL can be used for the treatment of deeper and superficial layers of hypertrophic PWS.

Successful treatment of isolated venous malformation with 1444-nm fiberoptic Nd-YAG laser.

UNLABELLED: Two patients with isolated venous malformations on the face were treated with fiberoptic Nd-YAG laser (Lutronic laser company, South Korea). After nerve block anesthesia, the laser tip was pushed into the lesions either through a hole made by a 16 gauge needle or directly by inserting and triggering the laser tip few millimeters away from the lesions. The laser tip was pushed from one or few directions and moved back and forth, while triggering, in a fan pattern to cover the whole lesion. The procedure was continued till complete flattening of the lesions. The parameters used were pulse rate = 30 hertz, pulse energy = 300 mJoules, power = 6.0 watt, and total energy used for the first patient was 1000 Joules and for the second patient was 800 joules. RESULTS: The lesions flattened completely after whole tissue coagulation. Moderate redness disappeared in the first 48 hours. No persistent discoloration and no sign of cutaneous burning appeared after the procedures. No antibiotic or analgesic was prescribed after the procedure. The patients were followed for more than 2 years with no recurrence and good cosmetic results. CONCLUSION: The fiberoptic Nd-YAG laser can be used as an effective procedure for venous malformations.

Successful removal of polyacrylamide hydrogel by pulsed fiberoptic 1444-nm Nd-YAG laser.

BACKGROUND: Tissue augmentation by polyacrylamide gel (PAAG) may lead to displacement or complications several years later and necessitate its removal. OBJECTIVE: To use a fiberoptic 1444-nm neodymium-doped yttrium aluminum garnet (Nd-YAG) laser for removing polyacrylamide hydrogel augmentations. METHODS: Five patients with frontal and cheek augmentations were referred for gel removal. After nerve block anesthesia, a 600-µm optical fiber tip with a metallic cannula was inserted into a hole created by a 16-gauge needle, and the laser was triggered. The cannula was moved in a fan pattern in the augmented area and was then removed. The tissue was squeezed from its outermost region toward the hole to extrude the gel. The laser system used was a 1444-nm fiberoptic Nd-YAG, obtained from Lutronic lasers, South Korea. The parameters used were: pulse rate = 30, pulse energy = 150 J, power = 4.5 W, and total energy = 400-1200 J. RESULTS: The heat of the laser tip liquefies the gel and by coagulating the surrounding tissues, it produces multiple patent canals. These two factors facilitate gel removal by squeezing the tissues. No temporary or permanent complication, such as hematoma, burning, or fibrosis, was detected. CONCLUSION: The 1444-nm Nd-YAG laser is a safe and efficient method for removing subcutaneous polyacrylamide hydrogel.