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61, CI [0.42, 0.80] P less then 0.0001 for a fixed-effects model), while a four-point scoring scale self-assessment by patients was significantly high (RR = 1.44, CI [1.17, 1.76] P = 0.0004 for a fixed-effects model). CONCLUSION Our meta-analysis showed that IPL-based combination therapy for melasma can effectively reduce the MASI score and result in higher satisfaction among patients, indicating an effective method for treatment of the condition. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.Bladder neck stenosis (BNS) after simple prostatectomy and vesicourethral anastomosis stenosis (VUAS) after radical prostatectomy for prostate cancer are common sequelae. However, the two entities differ in their pathology, anatomy and their surgical results. VUAS has an incidence of 0.2-28%. Commonly, VUAS occurs within the first 2 years after surgery. Initial therapy should be performed endourologically dilatation, (laser) incision or resection. After three unsuccessful treatment attempts, open reconstruction should be considered. Different surgical approaches (abdominal, perineal, abdominoperineal) have been described. All are associated with good success rates. However, they are accompanied by high rates of urinary incontinence. Incontinence can be treated safely by implantation of an artificial urinary sphincter. The incidence of BNS is around 5% for all types of surgery for benign prostate hyperplasia. It occurs within the first 2 years after surgery. Initial treatment should be performed endourologically. In case of recalcitrant BNS, open reconstruction is indicated. The YV-plasty is an established procedure, and the T‑plasty represents a modification. Success rates of both procedures are high. Folinic Robot-assisted reconstructive procedures have been described for both VUAS and BNS.The cost of prescription drugs has increased at rates far exceeding general inflation in recent history, with topical drugs increasing at a disproportionate rate compared to other routes of administration. We assessed the relationship between net changes in the number of therapeutic options, defined as any approved drug or therapeutic equivalent on the market, and prescription topical drug spending. Drugs were divided based on the category of use through pairing of Medicare Part D Prescriber Public Use and Food and Drug Administration (FDA) approved drug products databases. Across drug classes, we modeled the log of the ratio of total spending per unit in 2015 to total spending per unit in 2011 as a linear function of net number of topical therapeutic options over this time period. Primary outcomes include total Medicaid Part D spending on topical drugs and net change in the number of available therapeutic options within each category of use. Total spending on topical drugs increased by 61%, while the number of units dispensed increased by only 18% from 2011-2015. The greatest total spending increases were in categories with few new therapeutic options, such as topical corticosteroid and antifungal medications. Each net additional therapeutic option during 2011-2015 was associated with an reduction in how much relative spending per unit increased (95% CI 2.5%-14.4%, p = 0.013). Stimulating greater competition through increasing the net number of therapeutic options within each major topical category of use may place downward pressure on topical prescription drug spending under medicare Part D.Skin cancers are the most common malignancies diagnosed worldwide. In Gulf Cooperation Council (GCC) countries, skin cancer remains a significant health burden. Multiple studies have attempted to elucidate patient knowledge and attitudes regarding skin cancer risks and behavioral interventions to reduce risks. A systematic literature search of relevant articles was conducted in PubMed, ScienceDirect, and the Saudi Digital Library databases. A narrative analysis of relevant study results was conducted. A total of 12 studies were reviewed across GCC. These studies revealed common themes among GCC populations. Many study participants were aware that excess sun exposure represents a threat to health and increases cancer risk. Several studies reported sun exposure, with a mean of 19.13 h per week. More studies reported patients engaging in lower or no sunscreen use rather than regular sunscreen use. There are discrepancies in the understanding of sun exposure risk and risk mitigation practices among the study populations. Skin cancer poses a significant burden to patients in GCC countries and improved patient education will enhance population health.OBJECTIVE Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. METHODS Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1-14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. RESULTS 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. CONCLUSIONS The RP2D is 200 mg veliparib BID on days 1-14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.
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