HER2 puzzle pieces: Non-Coding RNAs as keys to mechanisms, chemoresistance, and clinical outcomes in Ovarian cancer.

Ovarian cancer (OC) presents significant challenges, characterized by limited treatment options and therapy resistance often attributed to dysregulation of the HER2 signaling pathway. Non-coding RNAs (ncRNAs) have emerged as key players in regulating gene expression in OC. This comprehensive review underscores the pivotal role of ncRNAs in modulating HER2 signaling, with a specific focus on their mechanisms, impact on chemoresistance, and prognostic/diagnostic implications. MicroRNAs, long non-coding RNAs, and circular RNAs have been identified as essential regulators in the modulation of the HER2 pathway. By directly targeting key components of the HER2 axis, these ncRNAs influence its activation and downstream signaling cascades. Dysregulated ncRNAs have been closely associated with chemoresistance, leading to treatment failures and disease progression in OC. Furthermore, distinct expression profiles of ncRNAs hold promise as reliable prognostic and diagnostic markers, facilitating personalized treatment strategies and enhancing disease outcome assessments. A comprehensive understanding of how ncRNAs intricately modulate HER2 signaling is imperative for the development of targeted therapies and the improvement of patient outcomes. The integration of ncRNA profiles into clinical practice has the potential to enhance prognostic and diagnostic accuracy in the management of ovarian cancer. Further research efforts are essential to validate the clinical utility of ncRNAs and elucidate their precise roles in the regulation of HER2 signaling. In conclusion, ncRNAs play a crucial role in governing HER2 signaling in ovarian cancer, impacting chemoresistance and providing valuable prognostic and diagnostic insights. The exploration of ncRNA-mediated HER2 modulation offers promising avenues for the development of personalized treatment approaches, ultimately advancing patient care and outcomes in OC.

Oxidative stress is two-sided in the treatment of acute myeloid leukemia.

INTRODUCTION: Oxidative stress caused by elevated ROS, as a novel therapeutic mechanism, has been implicated in various tumors including AML. AML cells are chronically under oxidative stress, yet overreliance on ROS production makes tumor cells increasingly vulnerable to further damage. Reducing the cytotoxic effect of ROS on normal cells while killing leukemia stem cell (LSC) with high levels of reactive oxygen species is a new challenge for oxidative stress therapy in leukemia. METHODS: By searching literature databases, we summarized recent relevant studies. The relationship of ROS on AML genes, signaling pathways, and transcription factors, and the correlation of ROS with AML bone marrow microenvironment and autophagy were summarized. In addition, we summarize the current status of research on ROS and AML therapeutics. Finally, we discuss the research progress on redox resistance in AML. RESULTS: This review discusses the evidence showing the link between redox reactions and the progression of AML and compiles the latest research findings that will facilitate future biological studies of redox effects associated with AML treatment. CONCLUSION: We believe that exploiting this unique oxidative stress property of AML cells may provide a new way to prevent relapse and drug resistance.

Clinical Prognostic Factors During the Last One Month of Life in Terminally Ill Cancer Patients: A Retrospective Observational Study.

OBJECTIVE: To explore the trajectory of clinical symptoms and biomarkers in the last four weeks of life in terminally ill cancer patients. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Oncology, Shijingshan hospital, Shijingshan Teaching Hospital of Capital Medical University, Beijing, China, between January 2017 and January 2020. METHODOLOGY: This study evaluated 173 terminally ill cancer patients. Seventeen symptoms and fifteen biomarkers were identified. For sequential analysis, the authors divided the final four weeks of life into four time periods from the date of death. Ordinal multiple logistic regression analysis was used to explore the association between the changes in clinical parameters and the risk of death in a given period. Changes in clinical parameters across different time periods were evaluated using the Wilcoxon signed rank test. RESULTS: Abnormal consciousness; elevated ECOG (Eastern Cooperative Oncology Group) scores, neutrophil-to-lymphocyte ratio (NLR), blood urea nitrogen (BUN) to creatinine ratio, C-reactive protein (CRP)-to-albumin ratio; and decreased platelet (PLT) counts were independent factors (p<0.05) for predicting closer death in the final month of life. All parameters above showed significant changes over time in the last month, although the starting time points for these changes varied. CONCLUSION: Abnormal consciousness, elevated ECOG scores, NLR, BUN-to-creatinine ratio, CRP-to-albumin ratio, and decreased PLT counts are potentially useful markers for approaching death in terminally ill cancer patients. These findings are valuable for understanding the biology of death in terminally ill cancer patients. And to some extent, they may help clinicians recognise that a patient will die in the near future. KEY WORDS: Cancer, Ordinal regression analysis, Death, Terminal illness, Biomarkers.

Transmission of SARS-CoV-2 in a primary school setting with and without public health measures using real-world contact data: A modelling study.

Background: Stringent public health measures have been shown to influence the transmission of SARS-CoV-2 within school environments. We investigated the potential transmission of SARS-CoV-2 in a primary school setting with and without public health measures, using fine-grained physical positioning traces captured before the COVID-19 pandemic. Methods: Approximately 172.63 million position data from 98 students and six teachers from an open-plan primary school were used to predict a potential transmission of SARS-CoV-2 in primary school settings. We first estimated the daily average number of contacts of students and teachers with an infected individual during the incubation period. We then used the Reed-Frost model to estimate the probability of transmission per contact for the SARS-CoV-2 Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron variant (B.1.1.529). Finally, we built a binomial distribution model to estimate the probability of onward transmission in schools with and without public health measures, including face masks and physical distancing. Results: An infectious student would have 49.1 (95% confidence interval (CI) = 46.1-52.1) contacts with their peers and 2.00 (95% CI = 1.82-2.18) contacts with teachers per day. An infectious teacher would have 47.6 (95% CI = 45.1-50.0) contacts with students and 1.70 (95% CI = 1.48-1.92) contacts with their colleague teachers per day. While the probability of onward SARS-CoV-2 transmission was relatively low for the Alpha and Delta variants, the risk increased for the Omicron variant, especially in the absence of public health measures. Onward teacher-to-student transmission (88.9%, 95% CI = 88.6%-89.1%) and teacher-to-teacher SARS-CoV-2 transmission (98.4%, 95% CI = 98.5%-98.6%) were significantly higher for the Omicron variant without public health measures in place. Conclusions: Our findings illustrate that, despite a lower frequency of close contacts, teacher-to-teacher close contacts demonstrated a higher risk of transmission per contact of SARS-CoV-2 compared to student-to-student close contacts. This was especially significant with the Omicron variant, with onward transmission more likely occurring from teacher index cases than student index cases. Public health measures (eg, face masks and physical distance) seem essential in reducing the risk of onward transmission within school environments.

Prevalence and molecular characterization of alpha and beta-Thalassemia mutations among Hakka people in southern China.

Our aim was to investigate molecular features of thalassemia for proper clinical consultation and prevention in Heyuan. In our research, a total of 25,437 positive screening subjects were further subjected to a genetic analysis of α-thalassemia (α-thal) and ß-thalassemia (ß-thal). The deletion of α-thal mutation was tested by Gap-PCR, while the non-deletion of α-thal and ß-thal mutation were identified by the PCR-reverse dot blot (PCR-RDB) technique. Nested PCR detected Hkαα/-- SEA and Hkαα/αα. Among the 25,437 positive screening subjects, 44.09% (11216/25437) subjects were bearers of thalassemia variations, and 30.85% (7847/25437) subjects showed α-thal changes alone. Among the 23 genotypes with α-thal mutation alone, the three common genotypes were --SEA/αα(68.34%), -α3.7/αα(16.44%), and -α4.2/αα(6.38%). Of the 11.50% (2924/25437) subjects and 29 genotypes with ß-thal mutation alone, the three common genotypes were ßCD41-42/ßN(36.22%), ßIVS-II-654/ßN(30.88%), and ß-28/ßN(13.47%). Additionally, of the 1.75% (445/25437) subjects and 55 genotypes showed both α- and ß-thal mutations. We also identified 269 cases of Hb H and six patients of Hkαα. Furthermore, the common genotypes of α-thal and ß-thal mutations were consistent with allele frequencies of mutations. Our study establishes molecular features of thalassemia among Hakka people in Heyuan. It will be useful for developing strategies to prevent thalassemia.

Effects of Comprehensive Swallowing Intervention on Obstructive Sleep Apnea and Dysphagia After Stroke: A Randomized Controlled Trial.

OBJECTIVE: This study aims to explore the effects of comprehensive swallowing intervention on obstructive sleep apnea (OSA) and dysphagia in stroke patients. METHODS: We performed a randomized controlled trial in stroke patients with obstructive sleep apnea (OSA) complicated by dysphagia, divided into treatment group and control group. The treatment group underwent comprehensive swallowing intervention and received swallowing care for 4 weeks, while the control group received only swallowing care. Outcome measurements were obtained at baseline and after the 4-week intervention, evaluated by polysomnography (PSG), videoendoscopic swallowing study (VFSS) synchronized surface electromyography (sEMG), oropharyngeal magnetic resonance imaging (MRI) and swallowing assessment scales. RESULTS: Sixty patients with stroke (30 treatment and 30 control) were eligible to participate in this study. There were no significant differences in any assessment between two groups at baseline. After a 4-week intervention, compared with to control group, there was a significant decrease in the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), and increased mean and minimal oxygen saturation (SaO2), amplitudes of suprahyoid muscle group (ASUPMG) and subhyoid muscle group (ASUBMG). Moreover, the posterior palatal distance (PPD), posterior lingual distance (PLD) and minimal cross-sectional area (MCSA) were obviously elevated in the treatment group. Additionally, the scores of Gugging swallowing screen (GUSS) and VFSS were significantly increased in the treatment group, compared to control group. CONCLUSIONS: The comprehensive swallowing intervention had therapeutic effects on OSA and dysphagia after stroke, and the mechanism was related to enhancing oropharyngeal muscle strength and changing upper airway structure.

Efficacy and follow-up of humanized anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma patients with extramedullary-extraosseous, extramedullary-bone related, and without extramedullary disease.

The prognosis of patients with multiple myeloma (MM) with extramedullary disease (EMD) remains poor. A high overall response rate (ORR) has been reported following anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory (R/R) patients with MM; however, data on patients with EMD remain limited. Herein, we compared and analyzed the efficacy and long-term follow-up of anti-BCMA CAR-T cell therapy in R/R MM patients with extramedullary-extraosseous (EM-E), extramedullary-bone related (EM-B), and without extramedullary disease. No difference in the ORR was observed between the three groups. The long-term efficacy of anti-BCMA CAR-T cell therapy in the EM-E group was worse than that in patients without EMD and with EM-B. In the EM-E group, disease progression was the reappearance of extramedullary lesions without an increase in the MM cell percentage or M protein level. Although no difference in the proportion of CAR-T cells was detected among the three groups, the EM-E group might exhibit a relatively high grade of cytokine release syndrome following anti-BCMA CAR-T therapy. Interleukin-6 levels in the without EMD group were lower than those in the EM-E and EM-B groups. However, given the small number of cases in the three groups, statistical analysis was not performed.(ChiCTR1800017051 and ChiCTR2000033925).

Effect of Finely Ground Limestone and Dolomite on Compression Strength and Reduction Swelling of Vanadium-Titanium Pellets.

Vanadium-titanium magnetite (VTM) is an important raw material for ironmaking under the situation of increasingly demanding scarce resources. To further improve the metallurgical properties of pellets, and to satisfy the requirements of blast furnace slag basicity, finely ground dolomite and limestone have been added to the pellet. In this study, the effect of finely ground dolomite and limestone on the metallurgical properties (green pellet drop strength, cold compression strength, reduction swelling index, and microscopic mineral structure) of VTM pellets were investigated. With the addition of finely ground dolomite and limestone, the drop strength of the green pellet was improved. The effect of adding finely ground limestone was greater than adding finely ground dolomite. Adding more finely ground dolomite and limestone compared to pellets without limestone and dolomite, the cold compression strength was decreased, which was attributed to the decomposition of limestone and dolomite during the induration of pellets. With the addition of dolomite, the reduction swelling index (RSI) increased firstly and then decreased. When the basicity of the pellet was 0.54 to 0.94, the slag phase with the lowest melting point was formed, corresponding to the maximum of the reduction swelling index. For the pellets with added limestone, the reduction swelling of the pellets deteriorated. The reduction index of the pellets increased and reached the maximum (26.6%) at a basicity of 1.54, which belongs to abnormal swelling.

Students' experience of online learning during the COVID-19 pandemic: A province-wide survey study.

Online learning is currently adopted by educational institutions worldwide to provide students with ongoing education during the COVID-19 pandemic. Even though online learning research has been advancing in uncovering student experiences in various settings (i.e., tertiary, adult, and professional education), very little progress has been achieved in understanding the experience of the K-12 student population, especially when narrowed down to different school-year segments (i.e., primary and secondary school students). This study explores how students at different stages of their K-12 education reacted to the mandatory full-time online learning during the COVID-19 pandemic. For this purpose, we conducted a province-wide survey study in which the online learning experience of 1,170,769 Chinese students was collected from the Guangdong Province of China. We performed cross-tabulation and Chi-square analysis to compare students' online learning conditions, experiences, and expectations. Results from this survey study provide evidence that students' online learning experiences are significantly different across school years. Foremost, policy implications were made to advise government authorises and schools on improving the delivery of online learning, and potential directions were identified for future research into K-12 online learning.

Study of an Organic Binder of Cold-Bonded Briquettes with Two Different Iron Bearing Materials.

The aim of this study was to investigate the properties of an organic binder used in cold-bonded briquettes (CBBs) prepared from two different iron bearing materials. The applied binder is a type of starch as indicated by chemical analysis, iodine-starch staining and Fourier transform infrared analyses. Thermogravimetric differential scanning calorimetry showed that the binder pyrolysis undergoes four stages: moisture desorption, ash volatilization, pyrolysis of organic matter and decomposition of materials with high activation energy. The difference between the dry and heat-treated samples during the macroscopic failure process is the instability propagation of the crack. The CBB shows a low decrepitation index at 700 °C. The returned fines of CBBs used with the organic binder were applied in two blast furnaces. The industrial trials showed that the CBBs do not influence the performance of the blast furnace and can reduce the fuel consumption rate. The curing rate of the binder decreases, and the growth rate of compressive strength decreases during the curing process. Iron ore particles are bonded together and exist in the form of aggregation after mixing with water and binder. The edges and corners of the particles become blurred, and the original surfaces of the particles are covered with binder film, the surface of which is covered with fine particles. The multi-branched structure of amylopectin provides omnibearing adhesion sites, thus forming binder agglomeration and film leading to a strong adhesion between binder and iron ore particles. Binder film and binder agglomeration work together to make the CBB perform well.

[Effectiveness of arthroscopic microfracture combined with osteochondral autologous transplantation for large area cartilage injury of femoral condyle of knee].

OBJECTIVE: To explore the effectiveness of arthroscopic microfracture combined with osteochondral autologous transplantation (OAT) in treatment of large area (4-6 cm 2) cartilage injury of the femoral condyle of knee. METHODS: Between March 2016 and June 2017, 22 patients of large area cartilage injury of the femoral condyle of knee were treated with arthroscopic microfracture combined with OAT. There were 16 males and 6 females with an average age of 22-60 years (mean, 38.6 years). The cause of injury was traffic accident in 8 cases and sports injuries in 14 cases. The disease duration was 1-6 months (mean, 3.4 months). There were 15 cases of medial femoral condyle injuries and 7 cases of lateral condyle injuries. The area of cartilage defect was 4-6 cm 2 (mean, 4.98 cm 2). According to the International Cartilage Repair Society (ICRS) classification, 9 cases were rated as grade Ⅲ and 13 cases as grade Ⅳ. Eighteen cases were combined with meniscus injuries. Preoperative visual analogue scale (VAS) score was 6.36±1.25 and Lysholm score was 36.00±7.77. RESULTS: All incisions healed by first intention. All patients were followed up 2-3 years with an average of 2.3 years. At 2 years after operation, the VAS score was 1.27±0.94 and the Lysholm score was 77.82±6.21, which were significantly improved when compared with those before operation ( t=16.595, P=0.000; t=21.895, P=0.000). At 2 years after operation, MRI showed that the cartilage defect was repaired well. CONCLUSION: Arthroscopic microfracture combined with OAT can be used to treat large area cartilage injury of the femoral condyle of knee, and the good early effectiveness can be obtained.

Yi-qi-yang-yin-tang increases the sensitivity of KG1a leukemia stem cells to daunorubicin by promoting cell cycle progression and regulating the expression of PTEN, TOPOII and mTOR.

The present study aimed to investigate the effects of serum containing a combination of yi-qi-yang-yin-tang (YQYYT) and daunorubicin (DNR) on multidrug resistance in KG1a leukemia stem cells (LSCs). The effects of YQYYT and DNR on proliferation, cell cycle progression and the expression of phosphatase and tensin homolog (PTEN), topoisomerase II (Topo II) and mechanistic target of rapamycin (mTOR) in KG1a cells were investigated in vitro using cell counting kit-8 assay, flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. It was revealed that YQYYT-containing serum did not affect proliferation of KG1a cells compared with the blank group. Furthermore, there were no significant differences on the inhibition of proliferation among different groups at various concentrations of YQYYT. Treatment with YQYYT-containing serum (volume, 20 and 40 µl) and DNR was able to significantly inhibit the proliferation of KG1a cells compared with the blank group. The inhibition rate in the treatment group with YQYYT-containing serum (40 µl) and DNR for 48 h (72.5%) was higher compared with treatment for 24 h (60.4%, P<0.01). Treatment with YQYYT-containing serum was able to promote G0 phase of KG1a cells into cell cycle in a dose- and time-dependent manner, and significantly upregulated the mRNA expression of PTEN and Topo II, but did not affect mTOR expression compared with the blank group. Treatment with serum containing YQYYT alone did not directly affect the proliferation of KG1a cells, but when the cells were treated with a combination of YQYYT-containing serum and DNR, the proliferation of KG1a cells was significantly inhibited in a dose- and time-dependent manner. Furthermore, treatment with YQYYT-containing serum was able to promote cell cycle progression of KG1a cells in the G0 phase and upregulate the expression of the negative regulatory genes PTEN and Topo II. These results indicated the potential of YQYYT to reverse multidrug resistance in LSCs.

The Yiqi and Yangyin Formula ameliorates injury to the hematopoietic system induced by total body irradiation.

In this study, we examined whether the Yiqi and Yangyin Formula (YYF), used in traditional Chinese medicine, could ameliorate damage to the hematopoietic system induced by total body irradiation (TBI). Treatment with 15 g/kg of YYF increased the survival rate of Institute of Cancer Research (ICR) mice exposed to 7.5 Gy TBI. Furthermore, YYF treatment increased the white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and hematocrit (HCT) counts in ICR mice exposed to 2 Gy or 4 Gy TBI. Treatment with YYF also increased the number of bone marrow cells, hematopoietic progenitor cells (HPCs), hematopoietic stem cells (HSCs) and the colony-forming ability of granulocyte-macrophage cells. YYF alleviated TBI-induced suppression of the differentiation ability of HPCs and HSCs and decreased the reactive oxygen species (ROS) levels in bone marrow mononuclear cells (BMMNCs), HPCs and HSCs from mice exposed to 2 Gy or 4 Gy TBI. Overall, our data suggest that YYF can ameliorate myelosuppression by reducing the intracellular ROS levels in hematopoietic cells after TBI at doses of 2 Gy and 4 Gy.

Prevalence and genotype distribution of human papillomavirus among Hakka women in China.

BACKGROUND: Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. HPV genotypes are associated with varying degrees of pathogenicity. To better formulate strategies for cervical cancer prevention, we investigated the population-specific distribution of HPV genotypes, including those with high carcinogenicity. METHODS: From January to December 2012, a cervical cancer-screening program for HPV infection in Hakka women of Heyuan City Guangdong province was conducted. Of 736,000 women residents, 8,284 volunteers were recruited. The cytology specimens of 107 women were not adequate and excluded. Thus, 8,177 women submitted to polymerase chain reaction (PCR) sequencing of 16 HPV genotypes via MassARRAY spectrometry. RESULTS: Risk stratification based on genotypes indicated that the prevalence of overall, high-risk, and low-risk HPV infections was 12.27%, 14.20%, and 0.79%, respectively. Of the 1,003 women positively infected, 82.75% were infected with a single HPV type; 17.25% were infected with ≥2 types. Analysis revealed a U-shaped curve in HPV prevalence that correlated with age group, with peaks at ages 18-24 y (22.03%) and 60-65 y (25%). The most frequently detected HPV genotype was HPV-52 (26.81%), and then HPV-16 (17.54%), HPV-58 (14.25%), HPV-18 (10.16%), HPV-68 (8.27%), HPV-39 (5.68%), and HPV-51 (5.38%). CONCLUSIONS: HPV-52 is the most prevalent genotype infecting Hakka women. Therefore, vaccination against HPV-52 is imperative. The prevalence of HPV infection is highest in the younger (18-24 y) and older (60-65 y) age groups, indicating that screening for HPV in Hakka women should be performed early and maintained in the elderly.

[Reversion Mechanism Study of PESV to Multidrug Resistance at Leukemia Stem Cell Level].

OBJECTIVE: To explore the effect of peptide extract from scorpion venom (PESV) to multidrug resistance (MDR) of leukemic stem cell (LSC) in vivo. METHODS: K562/A02 cells were cultured and collected in the logarithmic phase. K562/A02 stem cells were screened using immunomagnetic beads for reserve. K562/A02 LSC was injected to 5 of 40 BABL/c nude mice for preparing subcutaneous tumor. The rest 35 nude mice were then randomly divided into 7 groups, i.e., the normal control group, the model group, the Adriamycin (ADM) group, the PESV group, the ADM +high dose PESV group, the ADM + middle dose PESV group, the ADM +low dose PESV group, 5 in each group. Tumor tissue was embedded in all groups except the normal control group. One milliliter normal saline was peritoneally injected to mice in the model group after modeling, once per day. ADM 0. 05 mg was peritoneally injected to mice in the ADM group, once per other day. PESV 2 µg was peritoneally injected to mice in the PESV group, once per day. Mice in 3 ADM + PESV groups were peritoneally injected with ADM 0. 05 mg (once per other day) plus PESV (5, 2, and 1 µg respectively, once per day). All medication lasted for 14 days. P-glycoprotein (P-gp) was detected using flow cytometry. Breast cancer resistance protein (BCRP) and mRNA expression of multidrug resistance 1 (MDR1) were measured using RT-PCR. Aldehyde dehydrogenase 1 (ALDH1) was detected using immunohistochemistry. Phosphoinositide 3-kinase (PI3K) was detected using Western blot. NF-κB content was detected using ELISA. RESULTS: CD34 + CD38-ratio was 31.5% and IC50 was (60.33 ± 10. 68) µg/mL before K562/A02 cells were screened with immunomagnetic beads, while they were 92. 8% and (58. 33 ±9. 72) µg/mL after screen. The tumor formation rate was 100% in modeling mice. Compared with the model group, no statistical difference of each index occurred in the ADM group (P <0. 05). There was statistical difference in BCRP, MDR1 mRNA, or NF-κB factor between the model group and the PESV group (P <0. 05). The expression level of P-gp obviously decreased and the protein expression of P13K was down-regulated in 3 ADM + PESV groups (P <0. 05); mRNA expression of BCRP decreased and mRNA ex- pression of MDR1 obviously increased in the ADM + high dose PESV group and the ADM + middle dose PESV group, with statistical difference (P <0. 05). Protein expression of P13K was down-regulated in the ADM+ high dose PESV group, with statistical difference (P <0. 05). P-gp value, BCRP mRNA expression, MDR1 mRNA expression, PI3K, and NF-κB factor were all obviously down-regulated in the ADM +high dose PESV group, as compared with the ADM group and the PESV group respectively (P <0. 05). There was no statistical difference in ALDH1 positive rate among all groups (P >0. 05). Conclusion PESV combined ADM could down-regulate expression levels of P-gp, BCRP, MDR1, P13K, and NF-κB, strengthen the sensitivity of K562/A02 LSC to ADM in vivo, and reverse MDR of LSC.

Income-based drug coverage in British Columbia: the impact on private and public expenditures.

BACKGROUND AND OBJECTIVES: In May 2003, the government of British Columbia adopted income-based pharmacare, replacing an age-based program. Stated policy goals included the reduction and reallocation of government spending. It was also hoped that income-based deductibles would increase consumer price sensitivity in decision-making. This analysis measured policy impacts on private and public expenditure and on expenditure drivers. METHODS: We employed a longitudinal research design using PharmaNet records of every prescription dispensed in the province from January 1996 to December 2004. Expenditure dynamics were analyzed using non-stochastic decompositions of trends. Analyses were stratified by five age categories and five socio-economic quintiles. The effect of the policy on expenditure trends and their sources was assessed using time series analysis. Additional analyses, using equivalent methods, were conducted using market-level data to compare per capita expenditure in British Columbia to the Canadian average over the period 1998-2004. RESULTS: The BC Ministry of Health was successful in reducing the public share of drug expenditure through the introduction of seniors' co-payments in 2002 and then income-based pharmacare in 2003. The policy change did not have major effects on aggregate expenditure trends in the province. While several statistically significant changes in expenditure dynamics occurred during the period of study, only an increase in seasonal "stockpiling" of medicines by seniors can reasonably be attributed to the policy changes. DISCUSSION: The lack of large and differential policy impacts on drug expenditure and utilization rates across age and income groups suggests that changes in the BC PharmaCare Program were designed in a manner that ensured continued access to medicines for the populations previously served by the drug plan (e.g., senior citizens). It also indicates that the policy did not significantly increase access to medicines by populations that might have been better served under the new policy (e.g., non-seniors). Finally, although it was hoped that income-based pharmacare might increase consumer cost consciousness, changes in the relative cost of certain drugs purchased following the policy change appear to have stemmed from other policies directly targeting the expenditure impact of therapeutic choices.

Income-based drug coverage in British Columbia: the impact on access to medicines.

BACKGROUND AND OBJECTIVES: In May 2003, the government of British Columbia adopted income-based pharmacare, replacing an age-based program. Stated policy goals included the maintenance or enhancement of access to necessary medicines. This study examines the policy impact on access to two widely used drugs for chronic risk factors (antihypertensives and statins). METHODS: Data on incident antihypertensive and statin prescriptions between 1997 and 2004 were extracted from PharmaNet. Incident antihypertensive users were those who filled a first prescription after residing in the province for at least two years prior to the initial prescription date. The number of patients who ceased to fill a contiguous series of prescriptions (within 120 days of one another) was used as a measure of apparent discontinuation or interruption of therapy. We used time series analysis to test for changes in incident use and discontinuation. RESULTS: Between 1997 and 2004, 530,167 BC residents initiated therapy with an antihypertensive, and 264,904 BC residents initiated therapy with a statin. The 2003 policy change had no statistically significant impact on incident use of antihypertensives or statins, when stratified by age or income. Similarly, the 2003 policy did not change the rate of apparent discontinuations of therapy across age and income groups. However, a co-payment introduced in 2002 did increase end-of-year seasonality in apparent discontinuations in seniors--a finding that deserves further research. DISCUSSION: The 2003 transition to income-based pharmacare in British Columbia did not result in significant changes in access to, or continuation of, prescriptions to treat two leading chronic risk factors.

Income-based drug coverage in British Columbia: the impact on the distribution of financial burden.

BACKGROUND AND OBJECTIVES: In May 2003, the government of British Columbia adopted an income-based pharmacare program, replacing the previous age-based program. Stated policy goals included improving the distribution of pharmaceutical payments across incomes. This analysis assesses the policy's effect on the distribution across incomes of both private payments and public subsidy for prescription drugs. METHODS: This analysis focuses on how the 2003 policy change affected the extent to which higher-income households pay a larger share of private drug expenditures and/or receive a smaller share of available public subsidies. Demographic information and drug spending data were extracted from BC PharmaNet and the BC PharmaCare Program for the years 2001-2004. These data were then graphed to assess (using concentration curves) changes in the progressivity of private and public pharmaceutical financing. RESULTS: Overall, the move to Fair PharmaCare resulted in larger but slightly less regressive private payments and smaller but slightly more progressive public subsidies. Because total drug spending increased while the total subsidy available decreased, average private household spending as a proportion of household income increased across virtually all age and income levels. DISCUSSION: The PharmaCare Program redistributed public subsidies in a manner that was more progressive than previous programs; this reduced the regressivity of private pharmaceutical payments. However, total public subsidy decreased, and private spending increased by a commensurate amount. This makes the program's overall financial impact on BC households somewhat ambiguous. Income-based pharmacare could improve financial equity unambiguously if public shares of drug spending are expanded.

First-line first? Trends in thiazide prescribing for hypertensive seniors.

BACKGROUND: Evidence of reduced cardiovascular morbidity and mortality as well as cost support thiazide diuretics as the first-line choice for treatment of hypertension. The purpose of this study was to determine the proportion of senior hypertensives that received thiazide diuretics as first-line treatment, and to determine if cardiovascular and other potentially relevant comorbidities predict the choice of first-line therapy. METHODS AND FINDINGS: British Columbia PharmaCare data were used to determine the cohort of seniors (residents aged 65 or older) who received their first reimbursed hypertension drug during the period 1993 to 2000. These individual records were linked to medical and hospital claims data using the British Columbia Linked Health Database to find the subset that had diagnoses indicating the presence of hypertension as well as cardiovascular and other relevant comorbidities. Rates of first-line thiazide prescribing as proportion of all first-line treatment were analysed, accounting for patient age, sex, overall clinical complexity, and potentially relevant comorbidities. For the period 1993 to 2000, 82,824 seniors who had diagnoses of hypertension were identified as new users of hypertension drugs. The overall rate at which thiazides were used as first-line treatment varied from 38% among senior hypertensives without any potentially relevant comorbidity to 9% among hypertensives with previous acute myocardial infarction. The rate of first-line thiazide diuretic prescribing for patients with and without potentially relevant comorbidities increased over the study period. Women were more likely than men, and older patients were more likely than younger, to receive first-line thiazide therapy. CONCLUSIONS: Findings indicate that first-line prescribing practices for hypertension are not consistent with the evidence from randomized control trials measuring morbidity and mortality. The health and financial cost of not selecting the most effective and least costly therapeutic options are significant.

Persistence with hypertension treatment among community-dwelling BC seniors.

BACKGROUND: Previous research has documented low levels of persistence with prescribed hypertension treatment in Canada. With growing recognition of the value of appropriate drug therapy, rates of persistence may be improving over time. The purpose of this study was to examine persistence with prescribed hypertension treatment among newly treated community-dwelling seniors in British Columbia. METHODS: BC PharmaCare data was used to determine the cohort of seniors who were newly-treated hypertensives over the period 1993 to 2000. Medical and hospital claims from the BCLHD were searched for diagnoses indicating the presence of essential hypertension and potentially confounding conditions. Rates of persistence with drug therapy were analysed, accounting for patient, age, sex, clinical complexity, the existence of potentially confounding conditions, and type of drug first prescribed. RESULTS: For the period 1993 to 2000, 82,824 seniors were identified as new users of hypertension drugs with diagnosed essential hypertension. Fifty-one percent of these newly-treated hypertensives filled a contiguous series of hypertension prescriptions for at least one full year. There was a slight improvement in the rate of persistence over time (p<0.001). Evidence of specific co-morbidities that potentially complicate essential hypertension increased the likelihood of persistence among first-time users (p<0.001), whereas greater overall clinical complexity decreased the likelihood of persistence (p<0.001). Persistence was highest amongst patients initiated on newer anti-hypertensive drug therapies. CONCLUSIONS: Despite modest improvement, persistence with hypertension treatment among the elderly is very low. Further research into the reasons for non-persistence would be advanced through primary data collection, including survey-based research. New policies and practices are needed to encourage persistence with evidence-based therapies.