Extended-Release Versus Immediate-Release Triamcinolone Acetonide in Patients Who Have Knee Osteoarthritis and Type 2 Diabetes Mellitus.

BACKGROUND: Intra-articular (IA) corticosteroid injections may cause hyperglycemia (glucose level > 180 mg/dL). In a phase 2 study of 33 patients who had osteoarthritis of the knee (OAK) and type 2 diabetes mellitus (T2D), triamcinolone acetonide extended-release (TA-ER) was associated with minimal glycemic control disruption compared with triamcinolone acetonide immediate-release (TA-IR). This post hoc analysis characterizes the clinical relevance of these results. METHODS: Patients who had symptomatic OAK for ≥ 6 months, T2D for ≥ 1 year, and hemoglobin A1c ≥ 6.5 and ≤ 9.0% were randomized to receive an IA injection of either TA-ER or TA-IR. Changes in continuous glucose monitor daily glucose level, percentage of time in or above the target glucose range (> 70 to 180 mg/dL), time to glucose level 250 mg/dL and maximum glucose level > 250 mg/dL, and glycemic variability were evaluated. RESULTS: Across postinjection days 1 to 3, the TA-ER group (n = 18) had a lower median change from baseline in maximum glucose level (92.3 versus 169.1 mg/dL), a reduced percentage of time with a glucose level > 250 mg/dL (12 versus 26%), a smaller proportion of patients who had a maximum glucose level > 250 mg/dL (50 versus 93%), and a greater percentage of time in the target glucose range (62 versus 48%) versus the TA-IR group (n = 15). There was less glycemic variability and lower glucose spikes in the TA-ER versus TA-IR group. Median times to glucose level 250 mg/dL (44 versus 6 hours) and maximum glucose level (34 versus 13 hours) were significantly longer in the TA-ER versus TA-IR group. CONCLUSIONS: Use of TA-ER was associated with a clinically meaningful reduction in hyperglycemia versus TA-IR.

Study of Antimicrobial Utilization and Cost of Therapy in Medicine Intensive Care Unit of a Tertiary Care Hospital in Eastern India.

INTRODUCTION: High utilization of antimicrobial agent (AMA) and inappropriate usage in an intensive care unit (ICU) intensifies resistant organism, morbidity, mortality, and treatment cost. Prescription audit and active feedback are a proven method to check the irrational prescription. To analyze and compare the utilization of drugs, the World Health Organization (WHO) proposed daily defined dose (DDD)/100 patient days and days of therapy (DOT)/100 patient days to measure utilization of AMAs. Data of AMAs utilization are required for planning an antibiotic policy and for follow-up of intervention strategies. MATERIALS AND METHODS: A prospective observational study was conducted for 1 year from July 2018 to June 2019 and the data obtained from ICU of a tertiary care hospital. The demographic data, the disease data, and the utilization of different classes of AMAs [WHO-Anatomical Therapeutic Chemical (ATC) classification] as well as their cost were recorded. Total number of patient days, DDD, DDD/100 patient days, and DOT/100 patient days were calculated as proposed by the WHO. Statistical analysis was performed using statistical software SPSS version 25.0. The descriptive analysis was performed using summary statistics median [interquartile range (IQR)]. RESULTS: A total 939 patients were included, out of them 332 (35.4%) were female. The median age of the total patients was 58 (45-70). The median length of stay in ICU was 3 days. Mortality rate during our study period was 38.6%. The highly utilized AMAs in our study was ceftriaxone (36.95 DDD/100 patient days) followed by piperacillin/tazobactam (31.57), meropenem (26.4), doxycycline (21.53), and polymyxin B (21.38). The association between APACHE II and SOFA score with use of restricted antibiotics found to be statistical significant (p value 0.018 and 0.000, respectively). The cost of antibiotics per patient and patient days were $449.97 and $93.77, respectively, while median value of total cost was $2,343.26. CONCLUSION: Ceftriaxone was the highest utilized AMA. The risk of receiving restricted antibiotics intensified with increasing prevalence of multidrug resistance bacteria and associated comorbidities. High treatment cost is responsible for higher utilization of restricted antibiotics in ICU. HOW TO CITE THIS ARTICLE: Patra SK, Mishra SB, Rath A, Samal S, Iqbal SN. Study of Antimicrobial Utilization and Cost of Therapy in Medicine Intensive Care Unit of a Tertiary Care Hospital in Eastern India. Indian J Crit Care Med 2020;24(10):938-942.

Characterisation and monitoring of postoperative respiratory depression: current approaches and future considerations.

Respiratory depression is common in patients recovering from surgery and anaesthesia. Failure to recognise and lack of timely institution of intervention can lead to catastrophic cardiorespiratory arrest, anoxic brain injury, and mortality. Opioid-induced respiratory depression (OIRD) is a common and often under-diagnosed cause of postoperative respiratory depression. Other causes include residual anaesthesia, residual muscle paralysis, concurrent use of other sedatives, splinting from inadequate pain control, and obstructive sleep apnoea. Currently used methods to identify and monitor respiratory safety events in the post-surgical setting have serious limitations leading to lack of universal adoption. New tools and technologies currently under development are expected to improve the prediction of respiratory depression especially in patients requiring opioids to alleviate acute postoperative pain. In this narrative review, we discuss the various causes of postoperative respiratory depression, and highlight the advances in monitoring and early recognition of patients who develop this condition with an emphasis on OIRD.

A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI.

BACKGROUND: The VELOUR study demonstrated a survival benefit for FOLFIRI + aflibercept versus FOLFIRI + placebo in metastatic colorectal cancer (mCRC) patients who progressed on oxaliplatin-based chemotherapy. Continued divergence of overall survival (OS) curves in the intension to treat (ITT) population, with the survival advantage persisting beyond median survival time, suggested subpopulations might have different magnitudes of survival gain. Additionally, 10% of patients within VELOUR had recurrence during or within 6 months of completing oxaliplatin-based adjuvant therapy (adjuvant fast relapsers)--previously identified as having poorer survival outcomes. METHODS: To determine which patients received the greatest benefit from FOLFIRI-aflibercept, a post hoc multivariate analysis of the VELOUR ITT population was conducted. Prognostic factors identified were applied to the ITT population, excluding adjuvant fast relapsers, to derive OS prognostic profiles. RESULTS: The better efficacy subgroup was identified as patients within VELOUR exclusive of adjuvant fast relapsers and had performance status (PS) 0 with any number of metastatic site or PS 1 with <2 metastatic site. A significant improvement in efficacy outcome was observed with aflibercept in the better efficacy subgroup. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo:16.2 and 13.1 months (adjusted Hazard Ratio [HR] = 0.73; 95% confidence interval [CI]: 0.61-0.86); median progression free survival (PFS): 7.2 and 4.8 months (adjusted HR = 0.68; 95% CI: 0.57-0.80); and objective response rate (ORR): 24% versus 11% respectively. Poorer efficacy subgroup comprised of adjuvant fast relapsers or patients with PS2 or PS1 with ≥ 2 metastatic sites. In poorer efficacy subgroup, no benefit was seen with aflibercept. Median OS for FOLFIRI-aflibercept and FOLFIRI-placebo: 10.4 and 9.6 months (adjusted HR = 0.97; 95% CI: 0.78-1.21) respectively with no improvement in PFS or ORR. CONCLUSION: This analysis suggests that within VELOUR, patients in the better efficacy subgroup may derive enhanced benefit from treatment with FOLFIRI-aflibercept. These prognostic criteria may guide practitioners toward optimal use of targeted biologicals in appropriate second-line mCRC patients.

A wearable telehealth system for the monitoring of parameters related to heart failure.

Heart failure is a cardiovascular disease in which heart fails to pump sufficient blood required by the body. Significant signs of worsening heart failure include decreased thoracic impedance, increased heart rate, irregular electrocardiogram (ECG), and lack of motion activity of the patient. Heart failure can be better managed if monitored continuously and in real-time. The existing solutions for continuous monitoring of these parameters are invasive and hence are not only expensive but can also cause serious health risks. This paper discusses the development of a telehealth system that consists of an Internet of Things including a wearable device connected to a cloud-based database and a mobile application using Wi-Fi. The wearable device is a noninvasive monitor that consists of different sensors embedded with a microcontroller and can be a potential solution for better management of heart failure. It continuously monitors the above-mentioned parameters and sends data to the mobile application using a cloud-based system. The mobile application has separate portals for patients and doctors where doctor can monitor a specific patient enrolled under his profile. The performance of the developed device is validated in 10 healthy individuals.

Development of a wearable belt with integrated sensors for measuring multiple physiological parameters related to heart failure.

Heart failure is a chronic disease, the symptoms of which occur due to a lack of cardiac output. It can be better managed with continuous and real time monitoring. Some efforts have been made in the past for the management of heart failure. Most of these efforts were based on a single parameter for example thoracic impedance or heart rate alone. Herein, we report a wearable device that can provide monitoring of multiple physiological parameters related to heart failure. It is based on the sensing of multiple parameters simultaneously including thoracic impedance, heart rate, electrocardiogram and motion activity. These parameters are measured using different sensors which are embedded in a wearable belt for their continuous and real time monitoring. The healthcare wearable device has been tested in different conditions including sitting, standing, laying, and walking. Results demonstrate that the reported wearable device keeps track of the aforementioned parameters in all conditions.

A meta-analysis of osteoporotic fracture risk with medication nonadherence.

OBJECTIVES: Therapy for osteoporosis reduces the risk of fracture in clinical trials; real-world adherence to therapy is suboptimal and may reduce the effectiveness of intervention. The objective was to assess the fracture risk among patients nonadherent versus adherent to therapy for osteoporosis. METHODS: Medline, Embase, and CINAHL were searched for English-language publications of observational studies (January 1998-February 2009). Proceedings from two recent meetings of five relevant conferences were hand searched. Prospective and retrospective observational studies of patients with osteoporosis receiving bisphosphonates, parathyroid hormone, or selective estrogen receptor modulators denosumab were included. Studies were required to consider both fracture risk and adherence (compliance and/or persistence); any definition of adherence/fracture was acceptable. Data were analyzed using pooled comparisons of the odds and hazard ratios of fracture in noncompliance versus compliance and nonpersistence versus persistence. Sensitivity analyses were conducted to determine the effect of clinical heterogeneity on the results. RESULTS: Twenty-seven citations were identified, the majority of which were retrospective database analyses considering the effect of adherence to bisphosphonate therapy on fracture at any skeletal site. The absolute frequency of fracture ranged from 6% to 38% with noncompliance and from 5% to 19% with nonpersistence (104-159 weeks). Meta-analysis indicates that fracture risk increases by approximately 30% with noncompliance (odds ratio [95% confidence interval] 1.29 [1.22-1.38]; hazard ratio 1.28 [1.18-1.38]) and by 30% to 40% with nonpersistence (odds ratio 1.40 [1.29-1.52]; hazard ratio 1.32 [1.23-1.42]). CONCLUSIONS: Poor medication adherence is associated with a significantly increased risk of fracture versus optimal adherence. Improving medication adherence in patients with osteoporosis may lead to a greater reduction in fracture.

Advances in CSF shunt devices and their assessment for the treatment of hydrocephalus.

INTRODUCTION: Hydrocephalus is a neurological disorder caused by excessive accumulation of the cerebrospinal fluid (CSF) in the ventricles of the brain. It can be treated by diverting the extra fluid to different parts of the body using a device called a shunt. This paper reviews different shunt devices that are used for this purpose. AREAS COVERED: Shunts have high failure rates either due to infection or mechanical failure, therefore there is still ongoing work to address these two main handicaps. They require additional devices for performance assessment. Here, the paper also reviews different approaches for assessing shunt limitations. Moreover, future prospects are also discussed. EXPERT OPINION: This study shows that shunt devices still remain an important treatment option for hydrocephalus. However, further efforts are required to design more advanced shunts, to eliminate high failure rates in clinical use. Sophisticated sensor systems that can accurately detect and regulate changes in CSF drainage to optimize drainage for individual needs. Moreover, shunt infection problem is still present despite recent improvements such as antibiotic impregnated catheters.

Diagnosis for COVID-19: current status and future prospects.

Introduction: Coronavirus disease 2019 (COVID-19), a respiratory illness caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had its first detection in December 2019 in Wuhan (China) and spread across the world. In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic disease. The utilization of prompt and accurate molecular diagnosis of SARS-CoV-2 virus, isolating the infected patients, and treating them are the keys to managing this unprecedented pandemic. International travel acted as a catalyst for the widespread transmission of the virus.Areas covered: This review discusses phenotype, structural, and molecular evolution of recognition elements and primers, its detection in the laboratory, and at point of care. Further, market analysis of commercial products and their performance are also evaluated, providing new ways to confront the ongoing global public health emergency.Expert commentary: The outbreak for COVID-19 created mammoth chaos in the healthcare sector, and still, day by day, new epicenters for the outbreak are being reported. Emphasis should be placed on developing more effective, rapid, and early diagnostic devices. The testing laboratories should invest more in clinically relevant multiplexed and scalable detection tools to fight against a pandemic like this where massive demand for testing exists.

Management of COVID-19: current status and future prospects.

COVID-19, a highly transmissible pandemic disease, is affecting millions of lives around the world. Severely infected patients show acute respiratory distress symptoms. Sustainable management strategies are required to save lives of the infected people and further preventing spread of the virus. Diagnosis, treatment, and vaccination development initiatives are already exhibited from the scientific community to fight against this virus. In this review, we primarily discuss the management strategies including prevention of spread, prophylaxis, vaccinations, and treatment for COVID-19. Further, analysis of vaccine development status and performance are also briefly discussed. Global socioeconomic impact of COVID-19 is also analyzed as part of this review.

Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden.

Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs). Utilizing the Premier Healthcare Database, we identified patients > 18 years old, who underwent at least one surgical procedure of interest (i.e., cardiothoracic/vascular, general/colorectal, obstetric/gynecologic, orthopedic, or urologic), and received at least one dose of intravenous morphine, hydromorphone, or fentanyl for acute postoperative pain. The incidence of OIRD and PONV using ICD-9 codes, factors influencing these AEs, length of stay (LOS) and related costs were analyzed. Among 592,127 inpatient stays, rates of respiratory depression ranged from 3% (obstetric/gynecologic) to 17% (cardiothoracic/vascular) and nausea/vomiting from 44% (obstetric/gynecologic) to 72% (general/colorectal). Increased odds of OIRD were associated with older age (cardiothoracic/vascular, general/colorectal, obstetric/gynecologic); obesity, respiratory conditions, and sleep apnea (all surgery groups); opioid dose (cardiothoracic/vascular, general/colorectal, orthopedic); and sedative use after day 1. Increased odds of PONV were associated with younger age, female sex, and major disease severity. When respiratory depression or nausea/vomiting was present versus absent, LOS was significantly longer, and hospital costs were higher. In this analysis, OIRD and PONV were more prevalent than previously reported, were associated with identifiable risk factors, and had substantial effects on resource utilization and costs.

Practice Patterns and Treatment Challenges in Acute Postoperative Pain Management: A Survey of Practicing Physicians.

INTRODUCTION: The management of acute postoperative pain remains a significant challenge for physicians. Poorly controlled postoperative pain is associated with poorer overall outcomes. METHODS: Between April and May 2017, physicians from an online database who regularly prescribe intravenous (IV) medications for acute postoperative pain completed a 47-question survey on topics such as patient demographics, IV analgesia preferences, factors that influence prescribing decisions, and the challenges and unmet needs for the treatment of acute postoperative pain. RESULTS: Of 501 surveyed physicians, 55% practiced in community hospitals, 60% had been in practice for > 10 years, and 60% were surgeons. The three categories of IV pain medications most likely to be prescribed to patients with moderate-to-severe pain immediately after surgery were morphine, hydromorphone, or fentanyl (95.8% of respondents); COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (73.7%); and acetaminophen (60.5%). Past clinical experience (81.6%), surgery type (78.2%), and onset of analgesia (67.1%) were practice-related factors that most determined their medication choice. Key patient-related risk factors, such as avoidance of medication-related adverse events (AEs), each influenced prescription decisions in > 75.0% of physicians. Nausea and vomiting were among the most common challenges associated with postoperative pain management (76.2 and 60.3%, respectively), and avoidance of analgesic medication-related AEs was among the three most influential patient-related factors that determined prescribing decision (75%). Physicians reported the top unmet need for acute pain management in patients experiencing moderate-to-severe postoperative pain was more medications with fewer side effects (i.e., nausea, vomiting, and respiratory depression; 80.7%). CONCLUSIONS: Opioids remain an integral component of multimodal acute analgesic therapy for acute postoperative pain in hospitalized patients. The use of all IV analgesic medications is limited by concerns over AEs, particularly with opioids and in high-risk patients. There remains a key unmet need for effective analgesic medications that are associated with a lower risk of AEs. FUNDING: Trevena, Inc.

The Early Engagement Model in Product Development: Linking "Proof of Concept" to "Proof of Medical Value".

In a rapidly changing health care environment, it is more important than ever that pharmaceutical manufacturers improve the quality and efficiency of their research and development efforts in order to help ensure the right drug gets to the right patient at the right time. The evolving role of the Medical Affairs, Health Economics & Outcomes Research (HEOR) and other functions engaged in evidence generation within the pharmaceutical industry is leading to earlier involvement in the clinical development process so that the proof of concept for new therapies can be more strongly linked to the proof of medical value. In this article, the authors outline key components of an Early Engagement Model that connects the proof of concept to proof of medical value through a systematic approach linking molecular profile with early insights on disease, unmet needs, stakeholder requirements, and patient-centric differentiation.

Using Certification to Promote Uptake of Real-World Evidence by Payers.

Most randomized controlled trials are unable to generate information about a product's real-world effectiveness. Therefore, payers use real-world evidence (RWE) generated in observational studies to make decisions regarding formulary inclusion and coverage. While some payers generate their own RWE, most cautiously rely on RWE produced by manufacturers who have a strong financial interest in obtaining coverage for their products. We propose a process by which an independent body would certify observational studies as generating valid and unbiased estimates of the effectiveness of the intervention under consideration. This proposed process includes (a) establishing transparent criteria for assessment, (b) implementing a process for receipt and review of observational study protocols from interested parties, (c) reviewing the submitted protocol and requesting any necessary revisions, (d) reviewing the study results, (e) assigning a certification status to the submitted evidence, and (f) communicating the certification status to all who seek to use this evidence for decision making. Accrediting organizations such as the National Center for Quality Assurance and the Joint Commission have comparable goals of providing assurance about quality to those who look to their accreditation results. Although we recognize potential barriers, including a slowing of evidence generation and costs, we anticipate that processes can be streamlined, such as when familiar methods or familiar datasets are used. The financial backing for such activities remains uncertain, as does identification of organizations that might serve this certification function. We suggest that the rigor and transparency that will be required with such a process, and the unassailable evidence that it will produce, will be valuable to decision makers.

Pharmacoeconomic evaluation of antidepressants : a critical appraisal of methods.

In recent years, there has been much debate regarding the real cost effectiveness of new antidepressants. This review is an attempt to identify key contentious methodological issues that can impact the reliability, validity and quality of the research on this subject. There are inherent complexities between inputs and outcomes related to depression, and the choice of pharmacoeconomic methodology requires a crucial balance between the study design and its ability to capture relevant information. Knowledge of the real efficiency of antidepressants should always be ascertained with reference to the real-world setting. Studies that show a corresponding balance between internal and external validity, coupled with sound methodology and standardised reporting, have the potential to translate pharmacoeconomics research into real-world, time-relevant decision-making.

Health services research in rheumatology: a great deal accomplished, a great deal left to do.

Although rheumatology has been on the cutting edge of health services research for decades, there are many unresolved issues for patients, clinicians, insurers, and policy makers. This article explore three areas in which methodologic controversies present tradeoffs to a health care system that is grappling with larger issues around cost and access to care. Specifically, we examine issues around the use of large databases, the appropriate instruments for measuring patient-centered outcomes, and the questions that are raised from cost effectiveness studies of new treatments for rheumatoid arthritis. The issues are presented in the context of a need to provide better information to those who are providing care and those who are paying for it.

Epidemiology of myeloproliferative neoplasms in the United States.

Myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET) are three classic BCR ABL fusion gene-negative chronic myeloproliferative neoplasms (MPNs). Though rare, it is important to understand the burden of illness of these disorders for public health planning, healthcare insurers and pharmaceutical manufacturers. Therefore, we have described the incidence of MF and prevalence of MF, ET and PV in the United States between 2008 and 2010 based on data from two large health plans. The incidence of primary MF was about 1 per 100 000 per year and did not vary over the study years. The prevalence of PV (44-57 per 100 000) and ET (38-57 per 100 000) was much higher than that of MF (4-6 per 100 000) or subgroups containing MF (post-PV MF = 0.3-0.7 per 100 000; post-ET MF = 0.5-1.1 per 100 000). Additional research using other national databases and/or study designs is needed to substantiate these findings.

Health resource utilization and cost associated with myeloproliferative neoplasms in a large United States health plan.

Myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET) may lead to bone marrow fibrosis. Because the disease course of ET and PV are long and the disease course of MF may be fatal, healthcare resource utilization (HRU) associated costs of these neoplasms are especially important to understand. We used a large US health insurance claim database to describe the costs of these diseases. Compared to age-gender matched comparisons without myeloproliferative neoplasms (MPN), all aspects of HRU that we examined, including inpatient, outpatient and emergency room visits and pharmacy, as well as overall healthcare expenditures, were significantly higher in patients with MF, PV and ET (e.g. MF total costs = $54 168 vs. $10 203; PV = $14 903 vs. $7913; ET = $29 553 vs. $8026) than in matched comparisons. In order to reduce the burden of illness associated with these diseases, continued efforts in the development of more efficacious treatments for these disorders are needed.

The association of adherence to osteoporosis therapies with fracture, all-cause medical costs, and all-cause hospitalizations: a retrospective claims analysis of female health plan enrollees with osteoporosis.

BACKGROUND: Osteoporosis affects approximately 10 million people in the United States and is associated with increased fracture risk and fracture-related costs. Poor adherence to osteoporosis medications is associated with higher general burden of illness compared with optimal adherence. OBJECTIVE: To examine the associations of adherence to osteoporosis therapies with (a) occurrence of closed fracture, (b) all-cause medical costs, and (c) all-cause hospitalizations. METHODS: This retrospective analysis of administrative claims data examined women with osteoporosis initiating therapy with alendronate, risedronate, ibandronate, or raloxifene from July 1, 2002, to March 10, 2006. Data were from a large, geographically diverse U.S. health plan that covered about 12.6 million females during the identification period. Commercially insured and Medicare Advantage plan enrollees were observed for 1 year before (baseline period) and 540 days after therapy initiation (follow-up period). Outcomes included closed fractures, all-cause medical costs, and all-cause hospitalizations; all outcomes were measured starting 180 days after therapy initiation through follow-up. All subjects had at least 2 pharmacy claims for any of the targeted osteoporosis medications. Adherence was measured with a medication possession ratio (MPR) and accounted for all osteoporosis treatment. High adherence was MPR of at least 0.80; low adherence was MPR less than 0.50. Covariates included baseline fracture, "early" fracture (in the first 180 days of follow-up), baseline corticosteroid or thyroid hormone use, health status indicators, and demographic characteristics. Outcome fractures were modeled with Cox survival regression with time-dependent cumulative MPR. All-cause medical costs and all-cause hospitalizations were modeled, respectively, with generalized linear model regression (gamma distribution, log link) and negative binomial regression. RESULTS: The sample comprised 21,655 patients--16,295 (75.2%) commercial and 5,360 (24.8%) Medicare Advantage. During the entire follow-up period, 5,406 (33.2%) and 2,253 (42.0%) of commercial and Medicare Advantage patients, respectively, had low adherence. Adherence tended to decrease over the follow-up period. The Cox regression showed that commercial plan patients with low versus high adherence had 37% higher risk of fracture (hazard ratio = 1.37, 95% CI = 1.12-1.68). Adherence was not significantly associated with fracture in the Medicare Advantage cohort. Commercial and Medicare Advantage patients with low versus high adherence had 12% (exponentiated coefficient = 1.12, 95% CI = 1.02-1.24) and 18% (exponentiated coefficient = 1.18, 95% CI = 1.04-1.35) higher all-cause medical costs during months 7 through 18 of follow-up. Commercial and Medicare Advantage patients with low versus high adherence had 59% (incidence rate ratio [IRR] = 1.59, 95% CI = 1.38-1.83) and 34% (IRR = 1.34, 95% CI = 1.13-1.58) more all-cause hospitalizations during months 7 through 18 of follow-up, respectively. CONCLUSIONS: Low adherence to osteoporosis pharmacotherapy was associated with higher risk of fracture for commercially insured but not Medicare Advantage patients and with higher all-cause medical costs and more all-cause hospitalizations in both groups. These results are consistent with the literature and highlight the importance of promoting better adherence among patients with osteoporosis.

H+-L-proline cotransport by vesicles from pars convoluta of rabbit proximal tubule.

The mechanism of renal transport of L-proline by luminal-membrane vesicles isolated from proximal convoluted tubules of rabbit kidney was studied. It was found that H+ gradient (extravesicular greater than intravesicular) can drive the transport of L-proline into the vesicles both in the presence and absence of Na+. The stimulation of L-proline uptake by a pH gradient was additive with that produced by Na+. Saturation kinetic experiments revealed that pH gradient, in addition to Na+, increased the maximal uptake of L-proline by twofold. This is the first demonstration of H+-L-proline cotransport across luminal membrane of rabbit kidney proximal convoluted tubule. The physiological importance of this system is briefly discussed.