An overview of Compassionate Use Programs in the European Union member states.

The past decade witnessed rapid development of novel drugs and therapeutic biological agents. The marketing authorization for novel therapies is often time consuming and distressing for patients. Earlier clinical trials were the only way to access new drugs under development. However, not every patient meets the enrolment criteria, and participation is difficult for patients with life-threatening, long-lasting or seriously debilitating diseases like rare diseases. Early access programs like "Compassionate Use Program (CUP)" have generated alternative channels for such patients. The European Medical Agency provides regulations and recommendations for compassionate use, upon which every European Union (EU) member state has developed its own rules and regulations. Despite previous reviews and studies, the available information is limited and gaps exist. This literature review explores CUP in 28 EU member states. Data was collected through literature review and use of country-specific search terms from the healthcare domain. Data sources were not limited to databases and articles published in journals, but also included grey literature. The results implied that CUP was present in 20 EU member states (71%). Of 28 EU states, 18 (∼64%) had nationalized regulations and processes were well-defined. Overall, this review identified CUP and its current status and legislation in 28 EU member states. The established legislation for CUP in the EU member states suggest their willingness to adopt processes that facilitate earlier and better access to new medicines. Further research and periodic reviews are warranted to understand the contemporary and future regulatory trends in early access programs.

Influenza and pregnancy: a review of the literature from India.

Maternal influenza infection is known to cause substantial morbidity and mortality among pregnant women and young children. Many professional healthcare bodies including the World Health Organization (WHO) have identified pregnant women as a priority risk group for receipt of inactivated seasonal influenza vaccination. However influenza prevention in this group is not yet a public health priority in India. This literature review was undertaken to examine the Indian studies of influenza among pregnant women. Eight Indian studies describing influenza burden and/or outcomes among pregnant women with influenza were identified. In most studies, influenza A (pH1N1) was associated with increased maternal mortality (25-75%), greater disease severity, and adverse fetal outcomes as compared to nonpregnant women. Surveillance for seasonal influenza infections along with higher quality prospective studies among pregnant women is needed to quantify disease burden, improve awareness among antenatal care providers, and formulate antenatal influenza vaccine policies.

Case of thyrotoxic periodic paralysis in a caucasian male and review of literature.

Objective. Thyrotoxic periodic paralysis (TPP), a known condition in Asian men, is becoming increasingly common in men from Western countries. Since suspicion for TPP as a differential in diagnosis is of utmost importance to avoid overcorrection of hypokalemia and other complications, we are reporting a case of TPP in a 25-year-old Caucasian male. Methods. The patient presented with intermittent lower extremity weakness after consumption of a large high-carbohydrate meal. Clinical examination revealed diffusely enlarged thyroid gland, no muscle power in lower extremities, tremors, and brisk deep tendon reflexes. Results. Clinical and laboratory findings were consistent with Graves' disease and the patient had hypokalemia. The patient responded to potassium repletion and was treated with propylthiouracil and propranolol. After treatment with radioactive iodine, the patient developed postablative hypothyroidism for which he was treated with levothyroxine. Conclusion. Since this condition is overlooked by physicians in Western countries, we present a case of TPP in a Caucasian male thus showing the importance of consideration of TPP in Caucasians despite its rare occurrence and the need for prompt diagnosis to avoid the danger of hyperkalemia in management of the paralytic attack in TPP patients.

Effect of medications on physical function and cognition in nursing home residents with dementia.

OBJECTIVES: To assess the effectiveness of medications used in the management of Alzheimer's disease and related dementias (ADRD) on cognition and activity of daily living (ADL) trajectories and to determine whether sex modifies these effects. DESIGN: Two-year (2007-2008) longitudinal study. SETTING: Medicare enrollment and claims data linked to the Minimum Dataset 2.0. PARTICIPANTS: Older nursing home (NH) residents with newly diagnosed ADRD (n = 18,950). MEASUREMENTS: Exposures included four medication classes: antidementia medications (ADMs), antipsychotics, antidepressants, and mood stabilizers. Outcomes included ADLs and cognition (Cognitive Performance Scale (CPS)). Marginal structural models were employed to account for time-dependent confounding. RESULTS: The mean age was 83.6, and 76% of the sample was female. Baseline use of ADMs was 15%, antidepressants was 40%, antipsychotics was 13%, and mood stabilizers was 3%. Mean baseline ADL and CPS scores were 16.6 and 2.1, respectively. ADM use was not associated with change in ADLs over time but was associated with a slower CPS decline (slope difference: -0.09 points/year, 99% confidence interval (CI) = -0.14 to -0.03). Antidepressant use was associated with slower declines in ADL (slope difference: -0.36 points/year, 99% CI = -0.58 to -0.14) and CPS (slope difference: -0.12 points/year, 99% CI = -0.17 to -0.08). Sex modified the effect of both antipsychotic and mood stabilizer use on ADLs; female users declined most quickly. Antipsychotic use was associated with slower CPS decline (slope difference: -0.11 points/year, 99% CI = -0.17 to -0.06), whereas mood stabilizer use had no effect. CONCLUSION: Despite the observed statistically significantly slower declines in cognition with ADMs, antidepressants, and antipsychotics and the slower ADL decline found with antidepressants, it is unlikely that these benefits are of clinical significance.

Adverse event reporting patterns of newly approved drugs in the USA in 2006: an analysis of FDA Adverse Event Reporting System data.

BACKGROUND: The Weber effect states that adverse event (AE) reporting tends to increase in the first 2 years after a new drug is placed onto the market, peaks at the end of the second year, and then declines. However, since the Weber effect was originally described, there has been improvement in the communication of safety information and new policies regarding the reporting of AEs by healthcare professionals and consumers, prompting reassessment of the existence of the Weber effect in the current AE reporting scenario. OBJECTIVES: To determine the AE reporting patterns for new molecular entity (NME) drugs and biologics approved in 2006 and to examine these patterns for the existence of the Weber effect. METHODS: Publicly available FDA Adverse Event Reporting System data were used to assess the AE reporting patterns for a 5-year period from the drug's approval date. The total number of annual reports from all sources, based on the report date, was plotted against time (in years). RESULTS: In the period from 2006 to 2011, a total of 91,187 AE reports were submitted for 19 NMEs approved in 2006. The highest number of AE reports were submitted for varenicline tartrate (N = 47,158) and the lowest number for anidulafungin (N = 161). Anidulafungin was reported to have the highest proportion of death reports (36 %) and varenicline tartrate the lowest proportion (1.7 %). The classic Weber pattern was not observed for any of the 19 NMEs approved in 2006. While there was no one predominant pattern of AE report volume, we grouped the drugs into four general categories; the majority of drugs had either a continued increase in reports (Category A 31.6 %) or an N-pattern with reporting reaching an initial peak in year 2 or 3, declining and then beginning to climb again (Category B 42.1 %). CONCLUSIONS AND RELEVANCE: There have been numerous changes in AE reporting, particularly a huge increase in overall annual report volume, since the Weber effect was first reported. Our results suggest that a Weber-type reporting pattern should not be assumed in the design or interpretation of analyses based on AE reports.

Pharmacotherapeutic management of dementia across settings of care.

OBJECTIVES: To describe population-based use of cognitive-enhancing and psychopharmacological medications across care settings in Medicare beneficiaries with dementia. DESIGN: One-year (2008) cross-sectional study. SETTING: Medicare administrative claims from a 5% random sample. PARTICIPANTS: Medicare beneficiaries with dementia aged 65 and older with continuous Medicare Parts A, B, and D coverage and alive throughout 2008. To ascertain dementia, one or more medical claims with a dementia International Classification of Diseases, Ninth Revision, Clinical Modification code was required before 2008, and an additional claim was required in 2008 to confirm active disease. MEASUREMENTS: Use of medications commonly prescribed in managing dementia (cognitive enhancers, antidepressants, antipsychotics, and mood stabilizers) was assessed using three measures: annual prevalence of use, consistency of use, and count of psychopharmacological medication classes. Care setting was determined using the number of months of nursing home (NH) residency: no NH (0 months), partial NH (1-11 months), and full NH (12 months). RESULTS: Community-dwellers represented 41.3% of the cohort, whereas 42.4% and 16.3% resided partially and fully in a NH, respectively. Annual prevalence of use was 57.1% for cognitive enhancers, 56.4% for antidepressants, 34.0% for antipsychotics, and 8.8% for mood stabilizers. Cognitive enhancer use was significantly lower in those with any NH stay (partial NH vs no NH, adjusted prevalence ratio (APR) = 0.84, 99% confidence interval (CI) = 0.83-0.86; full NH vs no NH, APR = 0.83, 99% CI = 0.81-0.85). In contrast, those with any NH residence had significantly higher use of all psychopharmacological medication classes than community-dwellers. More than half the cohort had consistent medication regimens during 2008 (64.8%). The number of psychopharmacological medication classes used increased with increasing NH stay duration. CONCLUSION: This population-based study documents significant differences in medication use for managing dementia between care settings and substantial use of psychopharmacological medications in older adults with dementia.

Novel adverse events of bevacizumab in the US FDA adverse event reporting system database: a disproportionality analysis.

BACKGROUND: Bevacizumab is the first in its class, vascular endothelial growth factor (VEGF) inhibitor that was initially approved by the US FDA in 2004 for the treatment of metastatic colon cancer and other solid tumors. Preapproval clinical trials, particularly for oncology drugs, are limited in their ability to detect certain adverse effects and, therefore, the FDA and pharmaceutical sponsors collect and monitor reports of adverse events (AEs) following approval. OBJECTIVE: The purpose of this study was to screen the FDA's Adverse Event Reporting System (AERS) database for novel AEs that may be attributed to bevacizumab. METHODS: The FDA AERS database was used to identify all AE reports for bevacizumab from February 2004 to September 2009. Disproportionality analysis was conducted for bevacizumab against all other drugs in the background by setting statistical significance at proportional reporting ratio (PRR) ≥2, observed case count ≥3 and chi-square ≥4. Subsequent clinical evaluation was performed to determine the clinical relevance of the findings and to group related events. RESULTS: A total of 523 Preferred Terms (PTs) were disproportionally reported; following clinical review 63 (12%) were found to be both unlabelled and of clinical importance. These PTs were grouped into 15 clinical disorder groups. Among the clinical disorders, electrolyte abnormalities had the greatest number of reports (n = 426) followed by cardiovascular events (n = 421), gastrointestinal events (n = 345), nervous system disorders (n = 106) and pneumonitis (n = 96). On sensitivity analysis, a number of clinically important unlabelled disorders, such as necrotizing fasciitis, vessel wall disorders, arrhythmia and conduction disorder and autoimmune thrombocytopenia still met the statistical significance criteria. CONCLUSIONS: During the study period, out of 12 010 AE reports mentioning bevacizumab, it was listed as the suspect drug in 94.2% of the reports. Our disproportionality analysis identified many events that are already recognized as AEs of bevacizumab, but it also identified a number of clinically important unlabelled terms, which if confirmed in future studies would have potential implications for use of bevacizumab in clinical practice.

The effect of dementia on medication use and adherence among Medicare beneficiaries with chronic heart failure.

BACKGROUND: Alzheimer's disease and related disorders (ADRD) are prevalent in older adults, increase the costs of chronic heart failure (CHF) management, and may be associated with undertreatment of cardiovascular disease. OBJECTIVE: The purpose of our study was to determine the relationship between comorbid ADRD and CHF medication use and adherence among Medicare beneficiaries with CHF. METHODS: This 2-year (1/1/2006-12/31/2007) cross-sectional study used data from the Chronic Condition Data Warehouse of the Centers for Medicare and Medicaid Services. Medicare beneficiaries with evidence of CHF who had systolic dysfunction and Medicare Parts A, B, and D coverage during the entire study period were included. ADRD was identified based on diagnostic codes using the Chronic Condition Data Warehouse algorithm. CHF evidence-based medications (EBMs) were selected based on published guidelines: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selected ß-blockers, aldosterone antagonists, and selected vasodilators. Measures of EBMs included a binary indicator of EBM use and medication possession ratio among users. RESULTS: Of 9827 beneficiaries with CHF and systolic dysfunction, 24.2% had a diagnosis of ADRD. Beneficiaries with ADRD were older (80.8 vs 73.6 years; P < 0.0001) and more likely to be female (69.3% vs 58.1%; P < 0.0001). Overall EBM use was lower in patients with CHF and ADRD compared with patients with CHF but no ADRD (85.3% vs 91.2%; P < 0.0001). Lower use among those with ADRD was consistent across all EBM classes except vasodilators. Among beneficiaries receiving EBM, those with ADRD had a slightly higher mean medication possession ratio for EBM compared with those without ADRD (0.86 vs 0.84; P = 0.0001). CONCLUSIONS: EBM medication adherence was high in this population, regardless of ADRD status. However, patients with ADRD had lower EBM use compared with those without ADRD. Low use of specific EBM medications such as ß-blockers was found in both groups. Therefore, interventions targeting increased treatment with specific EBMs for CHF, even among patients with ADRD, may be of benefit and could help reduce CHF-related hospitalizations.

Medication reconciliation during the transition to and from long-term care settings: a systematic review.

BACKGROUND: Medication reconciliation has been recognized as an important process in care transitions to prevent adverse health outcomes. Because older adults have multiple comorbid conditions and use multiple medications, they are more likely to experience complicated transitions between acute and long-term care settings. Hence, it is important to develop effective interventions to protect older adults at transition points of care. OBJECTIVE: To systematically review the literature and evaluate studies performing medication reconciliation interventions in patients transferred to and from long-term care settings. METHODS: The literature search focused on studies that evaluated an intervention involving medication reconciliation in patients transferred to and/or from long-term care settings, such as nursing homes, skilled nursing facilities, residential care facilities, assisted living facilities, homes for the aged, and hospice care. A search was conducted on Ovid MEDLINE (1950-August 2010), Ovid HealthSTAR (1966-August 2010), Cumulative Index to Nursing and Allied Health Literature (1982-August 2010), PubMed (1980-August 2010), The Cochrane Database of Systematic Reviews (2005-August 2010), the Agency for Healthcare Research and Quality website, and reference lists of relevant articles were hand-searched. Two reviewers screened the titles and abstracts for potentially relevant studies. Data abstraction from the included articles was performed independently by 4 reviewers. RESULTS: Seven studies met the inclusion criteria. Four studies were performed in the United States, whereas 3 studies were performed in other countries. A clinical pharmacist proved to be useful in providing medication reconciliation interventions by adopting specialized responsibilities such as serving as a transition pharmacist coordinator or working through a call center. Although improvement in the outcome(s) examined was shown in all of the studies, there were study design flaws. CONCLUSION: There is a need for well-designed studies demonstrating the effectiveness of medication reconciliation interventions in long-term care settings. Future studies should focus on employing appropriate methods so that their interventions can be evaluated more effectively.