Specialty drugs are identified by high monthly costs and complexity of administration. Payers use utilization management strategies, including prior authorization and separate tiers with higher cost ...sharing, to control spending. These strategies can negatively impact patients' health outcomes through treatment initiation delays, medication abandonment, and nonadherence.
To examine the effect of patient cost sharing on specialty drug utilization and the effect of prior authorization on treatment delay and specialty drug utilization.
We conducted a literature search in the period between February 2021 and April 2022 using PubMed for articles published in English without restriction on date of publication. We included research papers with prior authorization and cost sharing for specialty drugs as exposure variables and specialty drug utilization as the outcome variable. Studies were reviewed by 2 independent reviewers and relevant information from eligible studies was extracted using a standardized form and approved by 2 reviewers. Review papers, opinion pieces, and projects without data were excluded.
Forty-four studies were included in this review after screening and exclusions, 9 on prior authorization and 35 on cost sharing. Patients with lower cost sharing via patient support programs experienced higher adherence, fewer days to fill prescriptions, and lower discontinuation rates. Similar outcomes were noted for patients on low-income subsidy programs. Increasing cost sharing above $100 was associated with up to 75% abandonment rate for certain specialty drugs. This increased level of cost sharing was also associated with higher discontinuation rates and odds. At the same time, decreasing out-of-pocket costs increased initiation of specialty drugs. However, inconsistent results on impact of cost sharing on medication possession ratio (MPR) and proportion of days covered (PDC) were reported. Some studies reported a negative association between higher costs and MPR and PDC; however, MPR and PDC of cancer specialty drugs did not decrease with higher costs. Significant delays in prescription initiation were reported when prior authorization was needed.
Higher levels of patient cost sharing reduce specialty drug use by increasing medication abandonment while generally decreasing initiation and persistence. Similarly, programs that reduce patient cost sharing increase initiation and persistence. In contrast, cost sharing had an inconsistent and bidirectional effect on MPR and PDC. Prior authorization caused treatment delays, but its effects on specialty drug use varied. More research is needed to examine the effect of cost sharing and prior authorization on long-term health outcomes.
Background
Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma ...(AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single‐center data suggests that 5%–15% of adult TSC patients are kidney transplant recipients.
Methods
This retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC‐associated kidney failure. We utilized descriptive statistics to characterize the frequency of first‐time kidney transplant waitlisting and transplantation among persons with TSC and the Fine‐Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist.
Results
We identified 200 TSC‐associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two‐thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 95% CI: 0.96–0.99). 91.8% of kidney transplant recipients survived 1‐year post‐transplant with a functioning allograft.
Conclusions
The majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1‐year post transplant patient and allograft survival.
Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single‐center data suggests that 5%–15% of adult TSC patients are kidney transplant recipients.
Background/aim: Cisplatin-induced nephrotoxicity in large proportion of patients. The aim of this work is to clarify the effect of combination of sildenafil and gemfibrozil on cisplatin-induced ...nephrotoxicity either before or after cisplatin treatment and determination of nephrotoxicity predictors among the measured tissue markers.
Methods: Thirty two adult male albino rats were divided into four equal groups (G) GI control, GII received cisplatin, GIII received sildenafil and gemfibrozil before cisplatin, GIV received sildenafil and gemfibrozil after cisplatin. Creatinine and urea were measured and animals were sacrificed and kidney was taken for histopathology. The following tissue markers were measured, heme oxygenase-1 (HO-1) activity, reduced glutathione, quantitative (real-time polymerase chain reaction) RT-PCR for gene expression of tumor necrosis factor alpha (TNF-α) and endothelial nitric oxide synthase (ENOS) level.
Results: GII developed AKI demonstrated by significantly high urea and creatinine and severe diffuse (80-90%) tubular necrosis. TNF-α was highly and significantly elevated while the rest of tissue markers were significantly reduced in GI1 compared to other groups. GIV showed better results compared to GIII. There was a significant positive correlation between creatinine and TNF-α when combining GI and GII while there were significant negative correlation between creatinine and other tissue markers in same groups. Linear regression analysis demonstrated that HO-1 was the independent predictor of AKI demonstrated by elevated creatinine among GI and GII.
Conclusions: Combination of sildenafil and gemfibrozil can be used in treatment of cisplatin-induced nephrotoxicity. HO-1 is a promising target for prevention and/or treatment of cisplatin-induced nephrotoxicity.
We conducted this study to assess the real-world prevalence, nature, predictors, and clinical necessity of apixaban pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions in patients with ...non-valvular atrial fibrillation (NVAF) at a tertiary medical institution in Saudi Arabia.
An observational retrospective cohort analysis was conducted in adult patients diagnosed with NVAF receiving apixaban for stroke prevention from the period of June 2015 to May 2019.
Of the 1271 patients included in the analysis, 611 (48.1%) patients had potential PD- or PK-drug interactions with apixaban. Of those, 490 (38.6%) patients had potential PD drug-drug interactions (DDIs) and 121 (9.5%) patients had potential PK-DDIs. PD-DDIs with apixaban were mainly with antiplatelet therapy followed by non-steroidal anti-inflammatory drugs and antidepressants. PK-DDIs with apixaban were mainly with combined P-gp/CYP3A4 inhibitors or inducers. History of minor bleeding was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.455 (OR 1.58; 95% CI 1.01-2.45); p<0.05. History of acute coronary syndrome was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.515 (OR 1.60; 95% CI 1.36-1.99); p<0.05. History of heart failure was positively correlated with PK-DDIs with apixaban, ß coefficient = 0.459 (OR 1.58; 95% CI 1.07-2.35); p<0.05. Almost 15% of the included patients had no clinical indication to receive the potential interacting drug with apixaban and about 20% of them were assuming an inappropriate apixaban dose according to the product package insert.
Pharmacodynamics and pharmacokinetics interactions are common in more than half of the patients with NVAF receiving apixaban for stroke prevention in this real-world analysis. Some of these interacting medications are not indicated. Drug-drug interactions should always be considered and monitored with apixaban with a regular assessment of the need for any interacting medication.
Metformin is widely used for the treatment of type 2 diabetes mellitus and found to have a crucial rule in the induction of apoptosis in several cancer types including pancreatic cell carcinoma, ...epithelial ovarian cancer, breast cancer, and renal cell carcinoma. In this study, we propose to explore the potential role of metformin as an adjuvant of irinotecan to target colorectal cancer (CRC) cell lines, exploring the effects underlying the anticancer properties of metformin on CRC cell lines.
HCT116 and SW480 cell lines were treated with metformin, irinotecan and their combination. The effect of metformin on cell viability was evaluated using MTT assay. Flow cytometry technique was used to analyze apoptosis and cell cycle progression. While, detection of protein expression was analyzed by Western blot.
Metformin was found to inhibit growth in both HCT1116 and SW480 cell lines. On combination with irinotecan, it has been revealed that metformin sensitized CRC cells to irinotecan-induced cytotoxicity. Flow cytometry analysis showed that metformin did not induce apoptosis, but blocked cell cycle in G1 and S phases. This blockage was accompanied by decreased cyclin E and Cdk2 levels and increased p21 level.
Combination of metformin with irinotecan may be an effective treatment strategy for targeting colorectal cancer that are resistant to irinotecan monotherapy.
Background: Bladder cancer is the most common malignancy of the urinary tract. Calcitriol 1,25 (OH)2vitamin D3 has anticancer effects mediated through binding to vitamin D receptor (VDR). The ...expression of VDR is present in many normal and cancer tissues. But, there is little information about its expression in urinary bladder carcinoma. This study aimed to analyze VDR immunohistochemical expression in 74 Egyptian patients with urinary bladder carcinoma and to evaluate its association with different clinicopathological parameters. Methods: Sections from formalin-fixed, paraffin-embedded tumor blocks were stained immunohistochemically using monoclonal anti-VDR antibody. VDR protein expression as well as its immunostaining patterns were recorded and scored separately in each case using semi-quantitative immunoreactive score. Results: VDR was consistently expressed in the included histologically normal urothelium while tumor cells showed variable degrees of expression. Cytoplasmic/membranous VDR expression was common among the studied cases especially those with urothelial morphology (p = 0.076). While, the mean nuclear VDR was significantly (p = 0.007) higher in non-urothelial tumors. Nuclear VDR was significantly associated with muscle invasion (p = 0.000) and tumor stage (p = 0.001) in urothelial carcinoma. It was also statistically related to tumor grade, stage and muscle invasion in non-urothelial tumors (p = 0.002, 0.003 and 0.012, respectively). Conclusion: there was a significant relation between nuclear VDR expression and prognostic markers suggesting its decrease as an indicator of a poorer prognosis. Vitamin D supplementation may represent a new treatment option for patients with bladder cancer.
Background/Aims: Liver transplantation (LT) is a life-saving intervention for patients with liver failure. LT recipients' adherence to their therapeutic regimen is an essential element for graft ...survival. According to WHO, the impact of medication non-adherence in solid organ transplantation has shown to cost $15-100 million annually. The aim of the present study was to identify the factors that best predict medication adherence and to explore the relationship between treatment satisfaction and medication adherence in liver transplant recipients. Patients and Methods: Adult liver transplant patients at King Abdulaziz Medical City were included in the study. Patients completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4) in addition to several socio-demographic and transplant-related data. Results: A total of 154 patients were included in the study and of these 59.7% were adherent. Older age was a significant predictor of adherence (P < 0.05). The mean treatment satisfaction score was 91.9 ± 12.7 in Effectiveness, 80.0 ± 25.9 in Side Effects, 83.5 ± 15.7 in Convenience, and 94.6 ± 8.6 in Global Satisfaction. Further analysis indicated that patients in the adherent group had reported significantly higher satisfaction scores than those in the non-adherent group (P < 0.05) in all treatment satisfaction domains: Effectiveness (94.4 ± 10.4 vs. 88.6 ± 14.8), Side Effects (83.9 ± 22.0 vs. 74.2 ± 30.1), Convenience (87.0 ± 13.9 vs. 77.2 ± 16.1), and Global Satisfaction (96.9 ± 6.6 vs. 91.2 ± 8.6). Conclusion: Older patients and those who were more satisfied with their treatment tend to have better adherence to the prescribed medications. Therefore, increasing patients' satisfaction with their treatment should be an integral element of future care plans designed to improve treatment outcomes in liver transplant recipients.
The International Committee of Medical Journal Editors has published clear guidelines on the authorship of scientific papers. It is the research team's responsibility to review and ensure those ...guidelines are met. Authorship ethics and practices have been examined among healthcare professionals or among particular health science students such as medical students. However, there is limited evidence to assess the knowledge of authorship roles and practices among health science students.
We conducted a cross-sectional study to assess the knowledge of authorship guidelines practices among health science students at King Saud bin Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia. A survey was developed and distributed. It covered several domains, including demographic characteristics, participant's knowledge and attitude of authorship practices, knowledge and experience with ghost and guest authorships, and knowledge of institutional authorship policies. Moreover, a score was computed to reflect the respondents' knowledge about authorship practices.
Among the 321 participants who agreed to take the survey, two-thirds agreed with and supported that multi-authored articles' credit allocation should be based on the most significant contribution and contributions to the manuscript writing. Almost 47% agreed that team relationships would influence authorship allocation. The majority of the participants were not aware of their institutional research and publication policies. Also, around 50% of participants were not aware of guest or ghost authorships. Finally, the knowledge score about authorship credits, allocation, contribution, order, and guidelines was higher among students who were assigned as corresponding authors and those who were aware of their institutional authorship guidelines and policies.
In conclusion, our findings suggest that health science students may have limited knowledge about authorship guidelines and unethical behaviors involved in a scientific publication. Universities and research centers should make more efforts to raise the awareness of health science students regarding authorship guidelines while ensuring that they comply with those guidelines.
Abstract
Background and Aims
Observational studies suggest that acute kidney injury may occur in up to 15% of patients treated with sofosbuvir based regimens. Histological findings show features of ...acute interstitial nephritis (AIN) or acute tubular necrosis (ATN). Here, we report the first case of small vessel vasculitis following sofosbuvir treatment.
Method
A 65-year-old female with controlled T2DM was recently diagnosed with HCV. She attained sustained viral response (SVR) after a three-month course of (sofosbuvir + daclatasvir + ribavirin). Kidney functions were normal pre and post treatment. Three months later, she presented with puffiness, bilateral lower extremities edema (no rash) and vomiting. Labs showed acute kidney injury (AKI), nephrotic proteinuria and haematuria (table 1). Immunological investigations (C3, C4, ANA, ANCA and anti-GBM), paraproteinemia workup and cryoglobulins were all negative. Renal US was also normal. Kidney biopsy revealed focal necrotizing glomerulonephritis with 70% crescents (figure 3,4). No chronic changes were detected in the glomeruli, interstitium or tubules. The patient received pulse methylprednisolone 0.5 gm for 3 days followed by oral prednisolone 60 mg/day. Oral cyclophosphamide was initiated at 150 mg after biopsy result was obtained. Our patient showed clinical and laboratory improvement (figure 1,2), however, she developed bone marrow suppression that required cessation of cyclophosphamide. Valsartan initiated to control proteinuria with slight increase in serum creatinine to 1.4 mg/dl. The patient is still under close follow up every two weeks, with a plan to introduce rituximab if serum creatinine continued to increase.
Results
AKI following HCV treatment with DAA has been reported. Explanation includes AIN, ATN and cryoglobulinemic vasculitis (CV). AIN and ATN usually occur during the treatment course, which is not the case in our patient as she developed AKI three months following the end of the treatment, and the biopsy did not show signs of either ATN or AIN. New onset CV has been reported previously in 3 case reports following SVR after DAA treatment. Previous reports explained that HCV can induce B-cell clonal proliferation that may persist independent of viral eradication and produce IgM kappa which will result in cryoglobulinemic GN, again this is not true in our case. Our patient did not have a rash, her serum cryoglobulin was negative and complement levels (C3 and C4) were normal and biopsy did not show evidence of CV. As far as we know, this is the first case with suspected sofosbuvir associated small vessel vasculitis to be reported. Despite the patient had a negative serum ANCA levels, we suspect that this is a case of drug induced vasculitis. Drug induced vasculitis has been reported with hydralazine, propylthiouracil and cocaine, none of these drugs were used in our case. Also, there is no reported case of vasculitis associated with ribavirin or daclatasvir. Thus, we suspect Sofosbuvir is the cause of drug induced vasculitis in this patient.
Conclusion
Crescentic GN following HCV treatment using DAA is a serious complication that should be promptly diagnosed and managed. Physicians treating HCV infected patients should be aware of this possible complication and monitor for kidney function even after achieving SVR.
Figure 1:
Treatment course against serum creatinine over time
Figure 2:
Proteinuria level against treatment and time
Figure 3:
H&E stain of kidney biopsy
Figure 4:
PAS stain of kidney biopsy
Table 1:
Laboratory investigations of the patient
4.2019
9.2019
10.2019
11.2019
12.2019
Urea (mg/dl)
25
86
112
62
53
Creatinine (mg/dl)
0.9
2.4
3.2
1.5
1.1
Uric acid (mg/dl)
4
6.5
7.1
5
5
Na (mEq/l)
140
122
133
127
133
K (mEq/l)
3.8
5.5
5
5.1
4.6
U-ACR (mg/g)
7000
2800
1403
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