Discontinue Drug Therapy Research Articles

Critical care pharmacy practice advancement recommendations on direct patient care activities: An opinion of the American College of Clinical Pharmacy Critical Care Practice and Research Network

AbstractAn updated position paper on critical care pharmacy services recommends the development of new clinical programs. However, proposed pragmatic strategies for critical care pharmacy practice advancement are lacking. The purpose of this position paper is to develop consensus recommendations aimed at direct patient care activities for the advancement of critical care pharmacy practice. A 24‐member task force of critical care pharmacists, physicians, and nurses participated in a Recommendation Development Phase and Consensus‐building Phase (using a Delphi method) to produce the final critical care practice advancement recommendations. Proposed recommendations of pragmatic medication management opportunities with an advanced scope of practice involving pharmacist prescriptive authority for initiating, modifying, or discontinuing drug therapy and medication monitoring were developed. Task force participants anonymously voted on each proposed recommendation using a five‐point Likert scale (1 = strongly agree, 2 = agree, 3 = neutral, 4 = disagree, and 5 = strongly disagree). Recommendations failing to achieve consensus (≥70% agreement on “strongly agree”/“agree” votes) were revised for subsequent voting. Task force response rates during the first and second voting rounds were 71% (n = 17) and 79% (n = 19), respectively. A total of 57 (93.4%) of the 61 proposed practice advancement recommendations achieved consensus of which 88.5% (n = 54) met consensus after the first round. Consensus recommendations involved the critical care pharmacist initiating (n = 15), modifying (n = 22), or discontinuing (n = 9) drug therapy, and ordering relevant laboratory values or tests to optimize drug therapy (n = 11). One recommendation failing consensus was not revised for additional voting given the impracticality of achieving agreement. Fifty‐seven of the proposed 61 recommendation statements (93%) achieved the consensus threshold after two rounds of voting by an interprofessional expert panel. These recommendations provide a conceptual framework for promoting novel critical care pharmacist prescriptive authority over specific aspects of direct patient care. Implementation challenges and barriers, further described in this paper, must be explored at the institutional level for acceptance.

Real-word adrenocorticotropic hormone treatment for childhood-onset nephrotic syndrome.

Current first-line anti-proteinuric treatments do not produce a satisfactory therapeutic effect in a considerable number of patients with nephrotic syndrome (NS). Interest in adrenocorticotropic hormone (ACTH) for the treatment of NS has recently been revived. The present study investigated the efficacy and safety of ACTH treatment in children with frequent relapsing NS (FRNS), steroid-dependent NS (SDNS), and steroid-resistant NS (SRNS). The ACTH treatment group was comprised of NS patients receiving ACTH treatment. Patients with serum cortisol concentrations <85.3 nmol/L and who had not received ACTH treatment previously were enrolled in the control group from January 2018 to January 2021. The maintenance dose of prednisone, the number of disease recurrences, the time of first disease relapse, immunosuppressant use, serum cortisol levels, and adverse events were recorded in both groups. Fifty-one patients were included in the ACTH group, and twenty-one patients were enrolled in the control group. Concurrent treatment with one or more immunosuppressive and/or cytotoxic treatments occurred in 92.2% and 85.7% of patients in the ACTH and control groups, respectively, throughout the study period. A greater reduction in the prednisone maintenance dose was observed in the ACTH group compared with the control group after 1 year of follow up (0.603 ± 0.445 mg/kg vs. 0.267 ± 0.500 mg/kg, p = 0.006). During the one-year study period, fewer participants experienced one or more disease relapses in the ACTH group (45.1%) compared to the control group (76.2%, odds ratio = 3.896, p = 0.016). The number of disease recurrences per patient in the ACTH group was less than that in the control group (median difference = -1, p = 0.006). The mean length of remission was 8.902 m and 7.905 m in the ACTH group and control group, respectively. A log-rank test showed a longer relapse free survival for patients in the ACTH group (p = 0.046), but the Breslow test showed no significant difference between groups (p = 0.104). Ten patients in the ACTH group successfully discontinued all drug therapies. No patients in the control group were able to discontinue drug therapy as of February 2022. ACTH, combined with multiple drugs, is effective at reducing the prednisone maintenance dose and may effectively prevent disease relapses in childhood NS.

Drug-induced crystalluria attributable to tosufloxacin in children.

Drug-induced crystalluria is reportedly caused by a large number of drugs. Tosufloxacin (TFLX), a second-generation fluoroquinolone antibiotic, is reported to cause kidney injury and crystalluria. We retrospectively analyzed patients with crystalluria caused by TFLX to clarify the clinical course of TFLX-induced crystalluria in children. This study was designed as a retrospective case series using the database of the National Center for Global Medicine covering the period from January 1, 2020 to March 31, 2021. We enrolled pediatric patients aged 15 years or younger with crystalluria attributable to TFLX treated in our pediatric department and collected clinical data. Thirteen patients were diagnosed with crystalluria attributable to TFLX. The median age of the patients at diagnosis was 4.0 years (range, 0.8-15 years; interquartile range=1.2-8.8 years), and five patients (38%) were male. Six patients (46%) had gastrointestinal symptoms such as vomiting and abdominal pain, and 12 patients (92%) had decreased oral intake. The median time to diagnosis after TFLX administration was 4 days (range, 2-7 days; interquartile range=3-6 days). All patients received TFLX at the appropriate dose. Two patients (17%) were diagnosed with acute kidney injury, and both had gastrointestinal symptoms such as vomiting and abdominal pain. Crystalluria induced by TFLX occurred despite administration of the appropriate dose of TFLX. Physicians should recognize crystalluria and renal injury attributable to TFLX. It may be possible to prevent renal injury by discontinuing drug therapy.

New insight into the CATIE study by constrained confidence partitioning. An innovative technique towards personalized antipsychotic drug therapy in schizophrenia treatment

The CATIE schizophrenia trial was a very influential randomized controlled trial in patients with chronic schizophrenia. Patients were followed for up to 18 months under treatment with a randomly assigned antipsychotic. The primary endpoint, time to discontinuation of treatment for any reason, is influenced by individual patient characteristics, external factors as well as effects of drug treatment. New insight is obtained by applying an innovative survival analysis based on constrained confidence partitioning (SA-C2P). Through this data-driven approach we identify homogeneous collectives of patients with similar patient characteristics differing from the study population in the primary endpoint, enabling us to predict patient individual outcome more precisely. A subgroup of patients treated with olanzapine featuring neither an anxiety disorder in the past month, drug abuse in the past five years nor hospitalizations in the past year discontinued drug therapy substantially later compared to patients meeting at least one of the named parameters. Moreover, differences in the primary outcome between second-generation antipsychotics increased compared to the original CATIE analysis when looking into this subgroup in the entire study sample. Our findings suggest that SA-C2P may assist in identifying relevant responder subgroups, probably missed by conventional statistical methods, making it a potential tool for personalized medicine.

Pharmacist Interventions in Improving Clinical Outcomes in Patients with Type 2 Diabetes Mellitus Among the Underrepresented Population: A Collaborative Ambulatory Care Pharmacy Practice (CAPP) Approach.

Objective:The objective of this study was to evaluate the impact of pharmacist's interventions through a collaborative ambulatory care pharmacy practice (CAPP) model in patients with type 2 diabetes mellitus (T2DM) among the underrepresented population.Methods:Eligible patients were 18 years and older with a diagnosis of T2DM with or without comorbid cardiovascular disease risk factors. Patients were enrolled through routine primary care provider referrals. During a one-on-one, face-to-face scheduled clinic visit, the pharmacist provided a comprehensive medication management by reviewing vital signs and laboratory values, provided medication reconciliation and management, followed by medication counseling through a CAPP approach in a primary care setting. The pharmacist worked in close collaboration with the primary care provider to intervene on medication therapy through recommendations to initiate, adjust, modify, or discontinue drug therapy and order laboratory tests and drug concentration levels as appropriate. Each visit was documented as a “PharmD Progress Note” in the patient's electronic medical record. Follow-up visits were scheduled until patients' targeted treatment goals were achieved. Primary and secondary outcome data were collected and then analyzed.Findings:A pharmacist saw 47 patients over 12 months. Sixty-four percent of the participating patients were able to achieve targeted treatment goals. A statistically significant decrease in the mean change in hemoglobin A1c, diastolic blood pressure, fasting blood glucose, and triglyceride levels was observed from the baseline which was −2.3%, −7.75 mmHg, −76.1 mg/dL, and −55.5 mg/dL, respectively. No significant changes in other clinical outcomes were observed.Conclusion:The CAPP model demonstrated a significant reduction in clinical endpoints in patients with T2DM among the high-risk underrepresented population.

Initiation and Persistence of Pharmacotherapy for Youths with Attention Deficit Hyperactivity Disorder in Taiwan.

BackgroundPharmacotherapy is an effective therapeutic option for attention deficit hyperactivity disorder (ADHD). Understanding the patterns of medication treatment is crucial for clinical practice. This study employed nationwide population-based data to elucidate the initiation and persistence of pharmacotherapy (immediate-release methylphenidate [IR–MPH], osmotic controlled-release formulations of methylphenidate [OROS–MPH] and atomoxetine [ATX]) for youths with ADHD in Taiwan.MethodsPatients first receiving an ADHD diagnosis at age 18 or younger between January 2000 and December 2009 (n = 112,140; mean age at ADHD diagnosis: 7.7 years) were selected from Taiwan’s National Health Insurance database. All patients were monitored through December 31, 2011, with an average follow-up time of 5.8 years. The initiation of ADHD drug therapy was defined as the first patient prescription, and discontinuation was defined as the cessation of ADHD medication for 180 days or longer.ResultsWithin the first year after ADHD diagnosis, 47.3%, 14.4%, and 0.8% of the patients were prescribed IR–MPH, OROS–MPH, and ATX, respectively. Regarding the patients prescribed IR–MPH, OROS–MPH, and ATX, 17.8%, 12.6%, and 18.8%, respectively, received the prescription only once and never returned for a drug refill, and 51.0%, 38.9%, and 58.8%, respectively, discontinued drug therapy within 1 year after the first prescription. Male sex and neuropsychiatric comorbidities were associated with higher probabilities of being prescribed one of the medications. An older age at first prescription and a higher daily dose of prescription were significant predictors of early discontinuation of ADHD medication.ConclusionsThe current findings suggest that IR–MPH is the most frequently prescribed drug for ADHD treatment in Taiwan. Patients treated with OROS–MPH possessed the highest persistence rate, whereas those treated with ATX had the lowest persistence rate. The results provide insight into the delivery of pediatric mental health services and have crucial implications for ADHD medication treatment in real clinical settings.

Spinal hydatidosis relapse: a case report.

Human cystic echinococcosis (CE) is a zoonosis caused by the larval stage of the Echinococcus granulosus and the most common sites affected are the liver and lung in approximately 80–90% of cases. The hydatid bone represents the 0.5–2.5% of all cases and localization cord is present about 50% of the time. This benign and commonly asymptomatic disease may simulate an aggressive malignancy because of osseous destruction and aggressive extension. We report a case of a 42-year-old male patient, presented with an unusual spinal hydatidosis relapse, related to anthelmintic drug therapy withdrawal after 10-year treatment. The man had previous excision of chest and hepatic hydatid cysts (resp., 10 and 3 years ago) and after primary mediastinal and spinal involvement (3 years ago) he was lost to follow-up and discontinued drug therapy. The patient underwent surgery and the postoperative histopathology confirmed the diagnosis. The patient recovered with no complications. Despite significant progress in diagnostic imaging, pharmacological and surgical therapy, spinal CE remains associated with high morbidity.

California provider status bill heads to governor

California provider status bill heads to governor

Antipsychotic Medication During the Critical Period Following Remission From First-Episode Psychosis

Theperson recovering froma first episodeofpsychosis (FEP), the family, and the treating clinical teamhaveuntil now faced a real dilemma. Having reached the base camp of remission of psychotic symptoms, how long should antipsychoticmedication be continued? Most guidelines propose a trial of dose reduction anddiscontinuation, all beingwell, after 12months of treatment with careful monitoring subsequently. However, it is only recently that studies have been carried out to derive evidence regarding this decision. In theearly 21st century, thegoal of treatment inFEPmust be to pursue as full a functional recovery as possible. This means ameaningful lifewith vocational recovery, positive relationships, social inclusion, and good physical health. The worldwide development of specialized early psychosis care is based on these goals. Aswith cancer, and chronic disease generally, early detection and sophisticated use of the existing therapeutic armamentarium,evenwithoutdramaticbreakthroughs,cannotonlysave and extend lives but also facilitatemanymore recoveries. The “soft bigotry of low expectations” in psychosis is under seriouschallenge.Manywouldnowcontend thatmuchof thepoor outcome inpsychosis is anartifact of latedetection, crudeand reactive pharmacotherapy, sparse psychosocial care, and social neglect. Despite 60 years of use of antipsychotic medications, it is only now becoming clearer how best to use these medications to maximize recovery. A key issue in the management of FEP is relapse prevention in the early years after diagnosis when relapse rates are known to peak. Clinicians understandably want to safeguard a hard-won remission, influenced by the fact that the strongest predictor of relapse is medication nonadherence (relative risk, 4) (although there are several other environmental risk factors, notably, substance misuse and family climate1). Furthermore, discontinuation studies have shown increased relapse rates in patients who discontinue drug therapy, approaching 80% to 100%within 5 years inmainstreampsychiatric care (nonspecialized for FEP) if sensitive positive symptom–based definitions of relapse are used.2-4 Relapse has beenvariously defined fromsimply readmission to a hospital at one extreme to temporary exacerbation of positive symptoms with minimal functional impact at the other extreme. The former is too insensitive, but the latter might be too sensitive to serve as a basis for treatment decisions. Until now it has been assumed that relapse prevention is the top priority in treatment and a prerequisite for functional recovery, since genuine relapses are risky and distressing, setting back recovery in all domains. Although relapses were appropriately seenas agenuine threat to recovery, all too often, in research and clinical practice, prevention of relapse becameanend in itself rather thanan intermediate goal on the path to recovery. The data reported byWunderink et al5 highlight these issues and pose a challenge to linear thinking in relationship to relapse. They appear to put relapse in perspective. Although certainly not desirable, a contained relapse is rarely the end of the world. Modest exacerbations of symptoms, which are more common in the3 to5years afterdiagnosis,maybeaprice worth paying for better longer-term functional recovery. A trade-off may be available. Wunderink andcolleagues5 randomized 128patientswith remissionofpsychosis todose reduction/discontinuation (DR) ormaintenance treatment (MT) for 18months. At 18months, there had been twice the rate of relapse in the DR group (43% vs 21%)6 yet no more than a trend for better functional outcomes, consistent with both conventional wisdom and other recent data showing discontinuation to be an unwise course even in patients with remission.2 However, at 7 years’ follow-up byWunderink et al, the picture had changed dramatically. Patients assigned to DR manifested no increased relapse rates (the excess was confined to the first 3 years) yet achieved twice the level of functional recovery (40.4% vs 17.6%).Randomassignment toDRhad in fact resulted inminimal or very low-dose use of antipsychotic medications more frequently than didMT. That this was done randomlymeans that the 7-year results are very unlikely to be confounded. Ultimately, this studydemonstrates thatwithantipsychoticmedication in the critical period of FEP, “less is more.”

Pharmacogenetics of response to methylphenidate in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD): A systematic review

Methylphenidate (MPH) is a first line option in the psychopharmacologic treatment of adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, there is a considerable proportion of adult patients who do not respond to treatment with MPH or discontinue drug therapy. Since effects of genetic variants in the response to MPH treatment might explain these negative outcomes, we conducted an electronic systematic search of MEDLINE-indexed literature looking for articles containing information about pharmacogenetics of ADHD in adults published until January, 2012. The keywords used were 'ADHD', 'Attention-Deficit/Hyperactivity Disorder' and 'gene' in combination with methylphenidate, amphetamine or atomoxetine. Only 5 pharmacogenetic studies on adult ADHD met inclusion criteria. The results evidenced that most findings obtained so far are negative, and all studies focused on MPH response. There is only one positive result, for a polymorphism at the dopamine transporter gene (DAT1) gene. The current state of the art in adult ADHD implies that pharmacogenetic tests are far from routine clinical practice. However, the integration of these studies with neuroimaging and neuropsychological tests may help to understand mechanisms of drug action and the pathophysiology of ADHD.

The importance of patient clubs in the management of osteoporotic patients

AbstractAlthough the significance of osteoporosis is well known worldwide, the number of patients undergoing therapy for this disease corresponds to a fraction only of the optimal proportion. In many countries, patients at a high risk of fracture — including those who have in fact sustained a typical fracture — do not receive therapy at all. Unawareness of the population, difficulties in accessing specialist care, as well as insufficient communications all contribute to the fact that a substantial percentage of patients discontinue drug therapy prematurely. Using information from a survey conducted in a club of osteoporotic patients, this paper discusses the achievements and substantiates the existence of patient associations, as well as emphasizes the need for establishing new patient clubs in Hungary.

Psychiatric Pharmacist and Primary Care Collaboration at a Skid-Row Safety-Net Clinic

There is limited access to psychiatric medication follow-up services at safety-net clinics serving the largely homeless minority population of Los Angeles' skid-row district. This paper describes the process of establishing a pharmacist-run psychiatric medication management service, the types of interventions provided by the psychiatric pharmacist, and patient and provider satisfaction with the service. The establishment of a collaborative practice agreement between primary care physicians and psychiatric pharmacists is described along with the patient demographics and types of pharmacist interventions. Primary care physicians were surveyed regarding their comfort level with managing psychiatric illness and prescribing psychotropic medications. They were also asked about their opinion of psychiatric pharmacist medication management services. An anonymous patient satisfaction survey was also administered. The development of psychiatric pharmacy services is described. The types of interventions included initiating drug therapy, adjusting dosages, discontinuing drug therapy, and providing medication education. Primary care providers were not comfortable in providing psychiatric medication follow-up for patients beyond uncomplicated depression and anxiety disorders. They expressed an overall positive view of psychiatric pharmacist services for their patients with established psychiatric diagnoses. Patient satisfaction ratings were high. A psychiatric pharmacist-run medication management service in collaboration with primary care providers can improve access to mental health services in safety-net clinics with good provider and patient satisfaction.

Monitoring the long‐term safety of therapies for children with juvenile idiopathic arthritis: Time for a consolidated patient registry

Introduction Juvenile idiopathic arthritis (JIA; formerly juvenile rheumatoid arthritis) is a chronic rheumatic disease characterized by persistent joint inflammation and an onset prior to age 16 years. The JIA phenotype consists of 7 categories: oligoarticular (up to 4 affected joints), polyarticular (more than 4 joints) rheumatoid factor (RF) positive, polyarticular RF negative, systemic, enthesitis-related arthritis, psoriatic, and undifferentiated. JIA is an uncommon disease with an estimated incidence of 1.3 to 22.6 new cases per 100,000 person-years (1–7). Treatment for JIA includes simple analgesics and nonsteroidal antiinflammatory drugs to reduce pain and inflammation, and intraarticular and oral corticosteroids, traditional disease-modifying antirheumatic drugs (DMARDs), and biologic agents, such as tumor necrosis factor antagonists, to prevent joint destruction. The goal of therapy for JIA is clinical remission (i.e., the absence of the signs and symptoms over time). Although many children do achieve remission while receiving medication, the majority experiences disease reoccurrence within 2–3 years of discontinuing drug therapy (8). Therefore, most children with JIA are typically treated with one or more medications over the long term. However, there are critical gaps in medical knowledge on the effectiveness and safety of existing JIA drug regimens used over an extended period of time, the long-term impact of such medications on children’s growth and development, and which drug or drug combinations are most efficacious for which particular categories of JIA. In addition, certain key questions have not been addressed, including the use of medications in the outpatient setting, optimal dosing regimens, and toxicity rates compared with background rates of adverse events in children with JIA. Longitudinal data for many patients with JIA are urgently needed to guide clinicians in the optimal selection of JIA medications and the management of their risks and toxicities to improve the overall quality of care of children with JIA. At present, the long-term safety of traditional DMARDs and biologic agents used in the treatment of JIA is monitored in two ways: through passive adverse event surveillance systems (e.g., the US Federal Adverse Event Reporting System), and via product-specific observational registry studies conducted by pharmaceutical industry sponsors to fulfill mandatory Food and Drug Administration (FDA) postmarketing commitments. Both approaches, however, have significant limitations. Passive adverse event surveillance systems are known to substantially underestimate the true incidence rate of adverse event occurrence, are subject to reporting bias, and often do not provide reliable denominator data (9). Similarly, for an uncommon condition such as JIA, single-drug registries have inherent limitations of scale, thus making it difficult to identify rarer safety signals. Existing product-based registries result in competing and duplicative efforts by multiple biopharmaceutical companies to collect similar information on a small patient population. Furthermore, current registries typically have restrictive enrollment criteria and limited sample sizes, and are usually not designed to capture data on background rates of diseaserelated adverse events and medication switching. In contrast, a consolidated registry with broad sponsorship by industry, federal agencies, research networks, and patient advocacy groups would offer a unique alternative approach to monitoring the long-term safety of pediatric rheumatology treatments, one that does not have the shortcomings of either of the two foregoing options. The topic of a consolidated registry was addressed in a public workshop sponsored by the FDA on May 12–13, 2009, in BeDr. Wallace’s work was supported by grants from Amgen, Centocor, and Pfizer. Meredith Y. Smith, PhD, MPA: Abbott Laboratories, Abbott Park, Illinois; Rachel E. Sobel, DrPH: Pfizer, New York, New York; Carol A. Wallace, MD: University of Washington and Seattle Children’s Hospital, Seattle. Dr. Smith owns stock and/or holds stock options in Abbott Laboratories. Dr. Sobel owns stock and/or holds stock options in Pfizer. Address correspondence to Carol A. Wallace, MD, University of Washington School of Medicine, Division of Rheumatology–Pediatrics, Seattle Children’s Hospital, 4800 Sand Point Way NE R-5420, Seattle, WA 98104. E-mail: cwallace@ u.washington.edu. Submitted for publication October 12, 2009; accepted in revised form February 4, 2010. Arthritis Care & Research Vol. 62, No. 6, June 2010, pp 800–804 DOI 10.1002/acr.20128 © 2010, American College of Rheumatology

Effects of Prior Authorization on Medication Discontinuation Among Medicaid Beneficiaries With Bipolar Disorder

Few data exist on the cost and quality effects of increased use of prior-authorization policies to control psychoactive drug spending among persons with serious mental illness. This study examined the impact of a prior-authorization policy in Maine on second-generation antipsychotic and anticonvulsant utilization, discontinuations in therapy, and pharmacy costs among Medicaid beneficiaries with bipolar disorder. Using Medicaid and Medicare utilization data for 2001-2004, the authors identified 5,336 patients with bipolar disorder in Maine (study state) and 1,376 in New Hampshire (comparison state). With an interrupted time-series and comparison group design, longitudinal changes were measured in second-generation antipsychotic and anticonvulsant use; survival analysis was used to examine treatment discontinuations and rates of switching medications. The prior-authorization policy resulted in an 8-percentage point reduction in the prevalence of use of nonpreferred second-generation antipsychotic and anticonvulsant medications (those requiring prior authorization) but did not increase use of preferred agents (no prior authorization) or rates of switching. The prior-authorization policy reduced total pharmacy reimbursements for bipolar disorder by $27 per patient during the eight-month policy period. However, the hazard rate of treatment discontinuation (all bipolar drugs) while the policy was in effect was 2.28 (95% confidence interval=1.36-4.33) higher than during the prepolicy period, with adjustment for trends in the comparison state. The small reduction in pharmacy spending for bipolar treatment after the policy was implemented may have resulted from higher rates of medication discontinuation rather than switching. The findings indicate that the prior-authorization policy in Maine may have increased patient risk without appreciable cost savings to the state.

Two dogs with iatrogenic discospondylitis caused by meticillin‐resistantStaphylococcus aureus

Two dogs developed discospondylitis caused by meticillin-resistant Staphylococcus aureus following thoracolumbar hemilaminectomy. Diagnoses were established by magnetic resonance imaging and radiography, respectively, in conjunction with culturing of microbial swabs. Treatment with beta-lactam antibiotics was first initiated. As soon as culturing results, confirming meticillin-resistant Staphylococcus aureus infection, and antibiograms became available, antimicrobial therapy was changed to gentamicin and trimethoprim/sulphadiazine. One dog, however, deteriorated further and was euthanased. The other dog improved on appropriate therapy. The first attempt to discontinue drug therapy four months after surgery led to a relapse. Antimicrobial therapy with chloramphenicol was then initiated and maintained for an additional four months. This dog is free of any relapses for 2.5 years. The veterinary surgeon should be aware of the possible involvement of meticillin-resistant Staphylococcus aureus in postsurgical discospondylitis when choosing an antibiotic for initial antimicrobial therapy while culturing results are still pending.

α2δ Modulators for management of compression neuropathic pain: A review of three case series

Context:The α2δ modulators gabapentin and pregabalin are effective against neuropathic pain. Numerous brands of α2δ modulators are available in India, and are expected to have equivalent clinical effects. They are routinely used for management of neuropathic pain associated with radiculopathy.Aim:To describe clinical outcomes in three series of cases of neuropathic pain treated with three available brands of α2δ modulators.Settings and Design:Retrospective analysis of clinical outcomes in patients attending an interventional pain clinicPatients and Methods:One hundred and ninety-four consecutive patients with neuropathic pain secondary to Magnetic Resonance Imaging (MRI)-documented compression radiculopathy received either LYRICA (LYR), a locally available generic brand of pregabalin (PGN), or a locally available generic brand of gabapentin (GBN), respectively. Drug treatment was continued till adequate pain relief was achieved. In each of the three groups, mean pain scores were analyzed at Days 0, 15, 60 and 90, and daytime sedation scores at Days 1, 15, 60 and 90.Statistical Analysis Used:Analysis of variance (ANOVA) followed by pair-wise comparison using two-tailed unpaired t-test (if P value was significant).Results:Mean pain score was significantly lower in the LYR series as compared to the PGN and GBN series at Days 15, 60 and 90. As compared to the PGN and GBN series, a greater proportion of patients in the LYR series could discontinue drug therapy following adequate pain relief, by Day 90. Daytime sedation scores were significantly lower in the LYR series as compared to the PGN and GBN series at Days 1, 15 and 60, and as compared to the PGN series at Day 90.Conclusion:These results indicate the effectiveness of α2δ modulators for management of neuropathic pain secondary to compression radiculopathy. The results also suggest a possible therapeutic superiority of LYRICA over locally available generic brands of pregabalin and gabapentin. These findings need to be further examined in randomized, controlled trials.

Behavioral Therapy to Enable Women with Urge Incontinence to Discontinue Drug Treatment

Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy. To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy. 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006. 9 university-affiliated outpatient clinics. 307 women with urge-predominant incontinence. 10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months. The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment. 237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% CI, -12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [CI, -0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P <0.001) at both time points for patient satisfaction and perceived improvement but not health-related quality of life. Adverse events were uncommon (12 events in 6 participants [3 in each group]). Behavioral therapy components (daily bladder diary and recommendations for fluid management) in the group receiving drug therapy alone may have attenuated between-group differences. Assigned treatment was completed by 68% of participants, whereas 8-month outcome status was assessed on 77%. The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence. Combination therapy has a beneficial effect on patient satisfaction, perceived improvement, and reduction of other bladder symptoms.

Risk factors for discontinuing drug therapy among children with ADHD

Compliance with drug therapy is of major concern to clinicians as well as policy makers since uncontrolled symptoms due to noncompliance present health risks for patients and may lead to social costs. Noncompliance comes in the form of skipped dosages as well as discontinuation well before a clinician deems it appropriate. The problem is especially severe in behavioral disorders among children where the symptoms can last well beyond adolescence. We use pharmacy dispensing and clinical diagnosis data on children diagnosed with attention-deficit hyperactivity disorder (ADHD) and who are on ADHD-related medications. The paper shows how the pharmacy refill data fit naturally into a discrete time hazard rate framework, and then compares estimates from alternative definitions of discontinuation. We use a long follow-up period (up to 6 years), allow for a flexible duration dependence and account for unobserved heterogeneity. The expected duration is about 18 months with significant differences across race, gender, copays, medication switching, and seasonality. We find that African-American, Hispanic and, Asian children are about 39% more likely, on average, to quit therapy in a given month than white children. Similarly, compared to a child that initiates drug therapy at age 9, a child that starts therapy at age 10 is 26.4% more likely to discontinue at any given time. Earlier literature using the hazard approach reports smaller associations between these covariates and durations. We show that this could be because of ignored unobserved heterogeneity, use of a relatively short follow-up study design and monotonic duration dependence. Finally, our results are of particular relevance to clinicians as well as to policy makers given recent changes in federal and state policies that may make early detection and diagnosis of ADHD among children less likely.

Fracture incidence and changes in quality of life in women with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO)

In this observational study of women with an inadequate clinical outcome to osteoporosis therapy, those with a fracture at baseline were more likely to sustain an incident fracture and have a worse health-related quality of life than those without prior fracture. The Observational Study of Severe Osteoporosis (OSSO) was designed to assess the fracture incidence and health-related quality of life (HRQoL) in women with an inadequate clinical outcome to osteoporosis therapy. Post-menopausal women (N=1,885) with established osteoporosis and an inadequate clinical response to osteoporosis drug therapy defined as: a) a fragility fracture despite therapy for one year (index fracture, N=988), or b) discontinued drug therapy due to adverse effects and/or non-compliance (N=897), were assessed during one year for HRQoL using the EQ-5D and the QUALEFFO questionnaires. One hundred and sixty-six (8.8%) women had a total of 209 incident fractures (1,139 fractures/10,000 women-years). Women with an index fracture were more likely to sustain an incident fracture than those without prior fractures (hazard ratio 1.91; 95% CI: 1.37-2.66; p<0.001). Co-morbidities or antidepressant use at baseline also increased the risk of incident fracture. Median total EQ-5D Health State Values and QUALEFFO scores were worse in women with an incident fracture regardless of index fracture status. The worst scores were reported in the EQ-5D sub-domains of self-care, usual activities and pain/discomfort. Women with an inadequate response to osteoporosis therapy had a high rate of incident fracture which had an adverse impact on HRQoL.

Design of the Behavior Enhances Drug Reduction of Incontinence (BE-DRI) study

PurposeTo describe the design of a multi-center randomized clinical trial of behavioral training combined with drug therapy for the treatment of urge incontinence. The study aims are to determine whether adding behavioral training will increase the number of women who can discontinue drug therapy and sustain a significant reduction of incontinence; to test whether the short-term effectiveness of drug therapy can be enhanced by combining it with behavioral training; and to determine the cost-effectiveness of combined therapy. DesignTwo-stage randomized clinical trial currently being conducted by the Urinary Incontinence Treatment Network, a clinical trials network established by the National Institutes of Health. MethodsParticipants are 307 community-dwelling women with pure or predominant urge incontinence. Stage 1 consists of 10 weeks of drug therapy with sustained-release tolterodine alone or combined with behavioral training (pelvic floor muscle exercise training, bladder control techniques, fluid management). In stage 2, drug is withdrawn and behavioral training stopped. The primary outcome, measured at 8 months, is a composite of two endpoints (1) successful drug withdrawal (i.e. not requesting any other treatment for incontinence) and (2) achieving and maintaining ≥70% reduction in the frequency of incontinence episodes on bladder diary. The effects of treatment and drug withdrawal are measured at week 10 and months 4, 6, 8, 14, 20, and 26. Assessments include: the Medical Epidemiological and Social Aspects of Aging (MESA) incontinence questionnaire, pelvic floor muscle strength assessment, Incontinence Impact Questionnaire, Urogenital Distress Inventory, Overactive Bladder Questionnaire, Short-Form Health Survey (SF-12), costs associated with incontinence care, Health Utility Index Mark 3, Willingness to Pay Scale, and Patient Satisfaction Questionnaire. SignificanceThe BE-DRI study is the first clinical trial to investigate the use of drug therapy combined with behavioral therapy with the pre-established goal of discontinuing the medication. The concept of drug cessation represents a new paradigm in this field of research and has important implications for future treatment approaches to urge incontinence.