Trends in the availability and prices of quality-assured tuberculosis drugs: a systematic analysis of Global Drug Facility Product Catalogs from 2001 to 2024.

BACKGROUND: The Global Drug Facility (GDF) of the Stop TB Partnership was launched in 2001 with the goal of increasing access to quality-assured tuberculosis (TB) drugs and products. We aimed to describe the TB drugs and prices available from the GDF over time and to assess trends. METHODS: We searched the internet, including an internet archive, for past and recent GDF Product Catalogs and extracted the listed TB drugs and prices. We calculated the lowest price for the most common drug formulations assuming drugs with similar active pharmaceutical ingredients (APIs) are substitutes for each other. We assessed time trends in the TB drugs and prices offered by the GDF in univariable regressions over the longest possible period. RESULTS: We identified 43 different GDF Product Catalogs published between November 2001 and May 2024. These product catalogs included 122 single medicines (31 APIs), 28 fixed-dose combinations (9 API combinations), and 8 patient kits (8 API regimens and other materials). The number of TB drugs listed in the GDF Product Catalog increased from 9 (8 APIs) to 55 (32 APIs). The price decreased for 17, increased for 19, and showed no trend for 12 APIs. The price of 15 (53.6%) of 28 APIs used against drug-resistant TB decreased, including the price of drugs used in new treatment regimens. The decreasing price trend was strongest for linezolid (-16.60 [95% CI: -26.35 to -6.85] percentage points [pp] per year), bedaquiline (-12.61 [95% CI: -18.00 to -7.22] pp per year), cycloserine (-11.20 [95% CI: -17.40 to -4.99] pp per year), pretomanid (-10.47 [95% CI: -15.06 to -5.89] pp per year), and rifapentine (-10.46 [95% CI: -12.86 to -8.06] pp per year). The prices of 16 (61.5%) of 23 APIs for standard drug-susceptible TB treatment increased, including rifampicin (23.70 [95% CI: 18.48 to 28.92] pp per year), isoniazid (20.95 [95% CI: 18.96 to 22.95] pp per year), ethambutol (9.85 [95% CI: 8.83 to 10.88] pp per year), and fixed-dose combinations thereof. CONCLUSIONS: The number of TB drugs available from the GDF has substantially increased during its first 23 years of operation. The prices of most APIs for new TB treatments decreased or remained stable. The prices of most APIs for standard drug-sensitive TB treatment increased.

Correction: The contribution of drug import to the cost of tuberculosis treatment: A cost analysis of longer, shorter, and short drug regimens for Karakalpakstan, Uzbekistan.

[This corrects the article DOI: 10.1371/journal.pgph.0000567.].

Depressive symptoms and their association with age, chronic conditions and health status among middle-aged and elderly people in peri-urban Tanzania.

Background: Depression is a global mental health challenge. We assessed the prevalence of depressive symptoms and their association with age, chronic conditions, and health status among middle-aged and elderly people in peri-urban Dar es Salaam, Tanzania. Methods: Depressive symptoms were measured in 2,220 adults aged over 40 years from two wards of Dar es Salaam using the ten-item version of the Center of Epidemiologic Studies Depression Scale (CES-D-10) and a cut-off score of 10 or higher. The associations of depressive symptoms with age, 13 common chronic conditions, multimorbidity, self-rated health and any limitation in six activities of daily living were examined in univariable and multivariable logistic regressions. Results: The estimated prevalence of depressive symptoms was 30.7% (95% CI 28.5-32.9). In univariable regressions, belonging to age groups 45-49 years (OR 1.35 [95% CI 1.04-1.75]) and over 70 years (OR 2.35 [95% CI 1.66-3.33]), chronic conditions, including ischemic heart disease (OR 3.43 [95% CI 2.64-4.46]), tuberculosis (OR 2.42 [95% CI 1.64-3.57]), signs of cognitive problems (OR 1.90 [95% CI 1.35-2.67]), stroke (OR 1.56 [95% CI 1.05-2.32]) and anemia (OR 1.32 [95% CI 1.01-1.71]) and limitations in activities of daily living (OR 1.35 [95% CI 1.07-1.70]) increased the odds of depressive symptoms. Reporting good or very good health was associated with lower odds of depressive symptoms (OR 0.48 [95% CI 0.35-0.66]). Ischemic heart disease and tuberculosis remained independent predictors of depressive symptoms in multivariable regressions. Conclusion: Depressive symptoms affected almost one in three people aged over 40 years. Their prevalence differed across age groups and was moderated by chronic conditions, health status and socioeconomic factors.

Out-of-pocket Expenses and Time Spent on Clinic Visits Among HIV Pre-exposure Prophylaxis Users and Other Clinic Attendees in Eswatini.

User costs constitute a barrier to the uptake of HIV pre-exposure prophylaxis (PrEP), but their magnitude appears rarely assessed. In this prospective observational study, we assessed self-reported out-of-pocket expenses (OOPE) and time spent on clinic visits during a PrEP demonstration project in Eswatini. At six public primary care clinics, 240 PrEP users and other clinic attendees were interviewed after a clinic visit. Among the 79.2% of clinic attendees reporting any medical OOPE (e.g., expenses for consultations or drugs) and/or non-medical OOPE (e.g., expenses for transport, food, or phone use), the median total OOPE was $1.36 (IQR 0.91-1.96). Non-medical OOPE occurred mostly due to transport expenses. The median travel time for a clinic visit was 1.0 h (IQR 0.67-2.0). The median time spent in the clinic was 2.0 h (IQR 1.15-3.0). The median opportunity cost of a clinic visit was $7.54 (IQR 5.42-11) when valuing time spent on a clinic visit with Eswatini's per-capita gross domestic product. Our findings can guide measures to reduce the user costs of PrEP in Eswatini and other contexts in which oral PrEP is provided through health care facilities.

RESUMEN: Los costes de los usuarios constituyen un obstáculo para la adopción de la profilaxis previa a la exposición al VIH (PrEP), pero su magnitud rara vez se evalúa. En este estudio observacional prospectivo, evaluamos los gastos de bolsillo (OOPE) declarados por los propios usuarios y el tiempo dedicado a las visitas clínicas durante un proyecto de demostración de la PrEP en Eswatini. En seis clínicas públicas de atención primaria, se entrevistó a 240 usuarios de la PrEP y a otros asistentes a la clínica después de una visita a la misma. Entre el 79,2% de los asistentes a las clínicas que declararon algún OOPE médico (por ejemplo, gastos por consultas o medicamentos) y/o OOPE no médico (por ejemplo, gastos de transporte, comida o uso del teléfono), la mediana del OOPE total fue de 1,36 dólares (IQR: 0,91­1,96). Los gastos no médicos se debieron principalmente a los gastos de transporte. La mediana del tiempo de viaje para una visita a la clínica fue de 1,0 horas (IQR 0,67­2,0). La mediana del tiempo empleado en la clínica fue de 2 horas (IQR 1,15­3,0). La mediana del coste de oportunidad de una visita a la clínica fue de 7,65 dólares (IQR 5,55­11) al valorar el tiempo dedicado a una visita a la clínica con el producto interior bruto per cápita de Eswatini. Nuestros resultados pueden orientar las medidas para reducir los costes de uso de la PrEP en Eswatini y en otros contextos en los que se suministra la PrEP oral a través de los centros de salud.

Costs and import costs of past, present, and future TB drug regimens: a case study for Karakalpakstan, Uzbekistan.

BACKGROUND: Tuberculosis (TB) drugs and their import are costly. We assessed how shorter TB drug regimens, which were non-inferior or superior in recent TB trials, can affect the costs for purchasing and importing TB drugs. METHODS: We estimated the drug costs and import costs of 39 longer and shorter TB drug regimens using TB drug prices from the Global Drug Facility and import cost estimates for a TB program in Karakalpakstan, Uzbekistan. Drug regimens from recent TB trials were compared with TB drug regimens following present or past World Health Organization recommendations. RESULTS: We estimated an import cost of $4.19 and a drug cost of $43 per standard 6-month drug-sensitive (DS)-TB regimen. A new 17-week DS-TB regimen from the TBTC Study 31 currently requires more tablets and is more expensive to import ($6.08) and purchase ($233). The TB program can substantially decrease import costs ($2.26-14) and drug costs ($391-2308) per multidrug-resistant (MDR)-TB regimen when using new 6-month or shorter drug regimens from the Nix-TB, NExT, TB PRACTECAL, ZeNix, or BEAT TB trials instead of 9-20-month regimens with import costs of $9.96-507 and drug costs of $354-15 028. For a commonly used 20-month all-oral, bedaquiline-containing MDR-TB regimen, we estimated costs of $41 for drug import and $1773 for drug purchase. CONCLUSIONS: The implementation of a new and shorter DS-TB regimen may increase the costs for drug purchase and import. The implementation of new and shorter MDR-TB regimens may decrease the costs for drug purchase and/or drug import.

Human resource needs and costs for HIV pre-exposure prophylaxis provision in nurse-led primary care in Eswatini and opportunities for task sharing.

BACKGROUND: The global expansion of HIV pre-exposure prophylaxis (PrEP) includes health systems that face a shortage of skilled health care workers (HCWs). We estimated the human resource needs and costs for providing PrEP in nurse-led primary care clinics in Eswatini. Furthermore, we assessed potential cost savings from task sharing between nurses and other HCW cadres. METHODS: We conducted a time-and-motion and costing study in a PrEP demonstration project between August 2017 and January 2019. A form for recording time and performed activities ("motion") was filled by HCWs of six primary care clinics. To estimate the human resource needs for specific PrEP activities, we allocated recorded times to performed PrEP activities using linear regression with and without adjusting for a workflow interruption, that is, if a client was seen by different HCWs or by the same HCW at different times. We assessed a base case in which a nurse provides all PrEP activities and five task shifting scenarios, of which four include workflow interruptions due to task sharing between different HCW cadres. RESULTS: On average, PrEP initiation required 29 min (95% CI 25-32) of HCW time and PrEP follow-up 16 min (95% CI 14-18). The HCW time cost $4.55 (uncertainty interval [UI] 1.52-9.69) for PrEP initiation and $2.54 (UI 1.07-4.64) for PrEP follow-up when all activities were performed by a nurse. Time costs were $2.30-4.25 (UI 0.62-9.19) for PrEP initiation and $1.06-2.60 (UI 0.30-5.44) for PrEP follow-up when nurses shared tasks with HCWs from lower cadres. Interruptions of the workflow added, on average, 3.4 min (95% CI 0.69-6.0) to the time HCWs needed for a given number of PrEP activities. The cost of an interrupted workflow was estimated at $0.048-0.87 (UI 0.0098-1.63) depending on whose time need increased. CONCLUSIONS: A global shortage of skilled HCWs could slow the expansion of PrEP. Task shifting to lower-cadre HCW in nurse-led PrEP provision can free up nurse time and reduce the cost of PrEP provision even if interruptions associated with task sharing increase the overall human resource need.

Costs and cost-effectiveness of HIV early infant diagnosis in low- and middle-income countries: a scoping review.

BACKGROUND: Continuing progress in the global pediatric human immunodeficiency virus (HIV) response depends on timely identification and care of infants with HIV. As countries scale-out improvements to HIV early infant diagnosis (EID), economic evaluations are needed to inform program design and implementation. This scoping review aimed to summarize the available evidence and discuss practical implications of cost and cost-effectiveness analyses of HIV EID. METHODS: We systematically searched bibliographic databases (Embase, MEDLINE and EconLit) and grey literature for economic analyses of HIV EID in low- and middle-income countries published between January 2008 and June 2021. We extracted data on unit costs, cost savings, and incremental cost-effectiveness ratios as well as outcomes related to health and the HIV EID care process and summarized results in narrative and tabular formats. We converted unit costs to 2021 USD for easier comparison of costs across studies. RESULTS: After title and abstract screening of 1278 records and full-text review of 99 records, we included 29 studies: 17 cost analyses and 12 model-based cost-effectiveness analyses. Unit costs were 21.46-51.80 USD for point-of-care EID tests and 16.21-42.73 USD for laboratory-based EID tests. All cost-effectiveness analyses stated at least one of the interventions evaluated to be cost-effective. Most studies reported costs of EID testing strategies; however, few studies assessed the same intervention or reported costs in the same way, making comparison of costs across studies challenging. Limited data availability of context-appropriate costs and outcomes of children with HIV as well as structural heterogeneity of cost-effectiveness modelling studies limits generalizability of economic analyses of HIV EID. CONCLUSIONS: The available cost and cost-effectiveness evidence for EID of HIV, while not directly comparable across studies, covers a broad range of interventions and suggests most interventions designed to improve EID are cost-effective or cost-saving. Further studies capturing costs and benefits of EID services as they are delivered in real-world settings are needed.

Programme costs of longer and shorter tuberculosis drug regimens and drug import: a modelling study for Karakalpakstan, Uzbekistan.

Background: The introduction of new and often shorter tuberculosis (TB) drug regimens affects the cost of TB programmes. Methods: We modelled drug purchase and import costs for 20-month, 9-month and 4- to 6-month TB drug regimens based on 2016-2020 treatment numbers from a TB programme in Karakalpakstan, Uzbekistan, and 2021 Global Drug Facility prices. Results: On average, 2225±374 (±sd) people per year started TB treatment, 30±2.1% of whom were diagnosed with drug-resistant forms of TB. Transitioning from a 6-month to a 4-month drug-susceptible (DS)-TB drug regimen increased the TB programme's annual DS-TB drug cost from USD 65±10 K to USD 357±56 K (p<0.001) and its drug import cost from USD 6.4±1.0 K to USD 9.3±1.4 K (p=0.008). Transitioning from a 20-month all-oral multidrug-resistant (MDR)-TB drug regimen to a 9-month MDR-TB drug regimen with an injectable antibiotic decreased the TB programme's annual MDR-TB drug cost from USD 1336±265 K to USD 266±53 K (p<0.001) and had no significant effect on the drug import cost (USD 28±5.5 K versus USD 27±5.4 K; p=0.88). Purchasing (USD 577±114 K) and importing (USD 3.0±0.59 K) the 6-month all-oral MDR-TB drug regimen cost more than procuring the 9-month MDR-TB drug regimen but less than the 20-month all-oral MDR-TB drug regimen (both p<0.01). Conclusion: Introducing new and shorter TB drug regimens could increase the cost of TB programmes with low drug resistance rates and decrease the cost of TB programmes with high drug resistance rates.

The contribution of drug import to the cost of tuberculosis treatment: A cost analysis of longer, shorter, and short drug regimens for Karakalpakstan, Uzbekistan.

Tuberculosis (TB) programs depend on a continuous supply of large amounts of high-quality TB drugs. When TB programs procure TB drugs from international suppliers, such as the Global Drug Facility, they can incur import costs for international transport, customs clearance, and national transport. We assessed the drug costs and import costs of 18 longer (≥18 months), 10 shorter (9-12 months), and 8 short (≤6 months) drug regimens for drug-sensitive (DS) and multidrug-resistant (MDR)-TB treatment. Costs per regimen were estimated by multiplying recommended drug amounts with 2021 Global Drug Facility prices and drug import costs of a TB program in Karakalpakstan, Uzbekistan. The standard short-course treatment of DS-TB requires taking 730 fixed-dose combination tablets, which weigh 0.79 kg and cause an import cost of $4.19 (9.8% of the regimen's drug cost of $43). A new 4-month DS-TB regimen requires taking 1358 tablets, which weigh 1.1 kg and cause an import cost of $6.07 (2.6% of the regimen's drug cost of $233). MDR-TB regimens that last between 24 weeks and 20 months involve 546-9368 tablets and injections. The drugs for these MDR-TB regimens were estimated to weigh 0.42-96 kg and cause an import cost of $2.26-507 per drug regimen (0.29-11% of a regimen's drug cost of $360-15,028). In a multivariable regression analysis, an additional treatment month increased the import cost of a drug regimen by $5.45 (95% CI: 1.65 to 9.26). Use of an injectable antibiotic in a regimen increased the import cost by $133 (95% CI: 47 to 219). The variable and potentially sizable import costs of TB regimens can affect the financial needs of TB programs. Drug regimens that are shorter and all-oral tend to reduce import costs compared to longer regimens and regimens including an injectable drug.

The Costs of Creatinine Testing in the Context of a HIV Pre-Exposure Prophylaxis Demonstration Project in Eswatini.

HIV treatment and prevention as well as other chronic disease care can require regular kidney function assessment based on a creatinine test. To assess the costs of creatinine testing in a public health care system, we conducted activity-based costing during a HIV pre-exposure prophylaxis (PrEP) demonstration project in the Hhohho region of Eswatini. Resource use was assessed by a laboratory technician and valued with government procurement prices, public sector salaries, and own cost estimates. Obtaining a blood sample in a clinic and performing a creatinine test in a high-throughput referral laboratory (> 660,000 blood tests, including > 120,000 creatinine tests, in 2018) were estimated to have cost, on average, $1.98 in 2018. Per test, $1.95 were variable costs ($1.38 personnel, ¢39 consumables, and ¢18 other costs) and ¢2.6 were allocated semi-fixed costs (¢1.1 laboratory equipment, ¢0.85 other, ¢0.45 consumables, and ¢1.3 personnel costs). Simulating different utilization of the laboratory indicated that semi-fixed costs of the laboratory (e.g., equipment purchase or daily calibration of the chemistry analyzer) contributed less than variable costs (e.g., per-test personnel time and test reagents) to the average creatinine test cost when certain minimum test numbers can be maintained. Our findings suggest, first, lower creatinine testing costs than previously used in cost and cost-effectiveness analyses of HIV services and, second, that investment in laboratory equipment imposed a relatively small additional cost on each performed test in the high-throughput referral laboratory.

RESUMEN: El tratamiento y la prevención del VIH, así como el cuidado de otras enfermedades crónicas, pueden requerir una evaluación periódica de la función renal basada en una prueba de creatinina. Para evaluar los costes de las pruebas de creatinina en un sistema de atención sanitaria público, realizamos un cálculo de costes basado en actividades durante un proyecto de demostración de profilaxis preexposición al VIH (PrEP) en la región de Hhohho de Eswatini. El uso de los recursos fue evaluado por un técnico de laboratorio y valorado con los precios de adquisición del gobierno, los salarios del sector público y las estimaciones de costes propias. La obtención de una muestra de sangre en una clínica y la realización de una prueba de creatinina en un laboratorio de referencia de alto rendimiento (> 660.000 pruebas de sangre, incluidas > 120.000 pruebas de creatinina, en 2018) se estimó que habían costado, en promedio, $1,98 en 2018. Por prueba, $1,95 eran costes variables ($1,38 de personal, ¢39 de consumibles y ¢18 de otros costes) y ¢2,6 eran costes semifijos asignados (¢1,1 de equipamiento de laboratorio, ¢0,85 de otros, ¢0,45 de consumibles y ¢1,3 de personal). La simulación de utilización diferente del laboratorio indicó que los costes semifijos del laboratorio (por ejemplo, la compra de equipos o la calibración diaria del analizador químico) contribuyeron menos que los costes variables (por ejemplo, el tiempo del personal por prueba y los reactivos de la prueba) al coste medio de la prueba de creatinina cuando se pueden mantener ciertos números mínimos de pruebas. Nuestros resultados sugieren, en primer lugar, que los costes de las pruebas de creatinina son inferiores a los utilizados anteriormente en los análisis de coste y costo-efectividad de los servicios de VIH y, en segundo lugar, que la inversión en equipos de laboratorio supuso un coste adicional relativamente pequeño en cada prueba realizada en el laboratorio de referencia de alto rendimiento.

A Framework for Assessing Import Costs of Medical Supplies and Results for a Tuberculosis Program in Karakalpakstan, Uzbekistan.

Background. Import of medical supplies is common, but limited knowledge about import costs and their structure introduces uncertainty to budget planning, cost management, and cost-effectiveness analysis of health programs. We aimed to estimate the import costs of a tuberculosis (TB) program in Uzbekistan, including the import costs of specific imported items.Methods. We developed a framework that applies costing and cost accounting to import costs. First, transport costs, customs-related costs, cargo weight, unit weights, and quantities ordered were gathered for a major shipment of medical supplies from the Médecins Sans Frontières (MSF) Procurement Unit in Amsterdam, the Netherlands, to a TB program in Karakalpakstan, Uzbekistan, in 2016. Second, air freight, land freight, and customs clearance cost totals were estimated. Third, total import costs were allocated to different cargos (standard, cool, and frozen), items (e.g., TB drugs), and units (e.g., one tablet) based on imported weight and quantity. Data sources were order invoices, waybills, the local MSF logistics department, and an MSF standard product list.Results. The shipment contained 1.8 million units of 85 medical items of standard, cool, and frozen cargo. The average import cost for the TB program was 9.0% of the shipment value. Import cost varied substantially between cargos (8.9-28% of the cargo value) and items (interquartile range 4.5-35% of the item value). The largest portion of the total import cost was caused by transport (82-99% of the cargo import cost) and allocated based on imported weight. Ten (14%) of the 69 items imported as standard cargo were associated with 85% of the standard cargo import cost. Standard cargo items could be grouped based on contributing to import costs predominantly through unit weight (e.g., fluids), imported quantity (e.g., tablets), or the combination of unit weight and imported quantity (e.g., items in powder form).Conclusion. The cost of importing medical supplies to a TB program in Karakalpakstan, Uzbekistan, was sizable, variable, and driven by a subset of imported items. The framework used to measure and account import costs can be adapted to other health programs.

Global matching and fluency attribution in familiarity assessment.

In the integrative memory model proposed by Bastin et al., familiarity is thought to arise from attribution of fluency signals. We suggest that, from a computational and anatomical perspective, this conceptualization converges with a global-matching account of familiarity assessment. We also argue that consideration of global matching and evidence accumulation in decision making could help further our understanding of the proposed attribution system.

Usage of a German prevention and health promotion web portal and cost per pageview: A life-cycle assessment.

BACKGROUND: Web portals providing health information online have the potential to reach large numbers of people. Yet few studies have assessed usage and costs of health portals, especially over an extended period of time. OBJECTIVES: First, to assess the usage of a web portal on prevention and health promotion that was initiated by the German states of Berlin and Brandenburg. Second, to estimate average cost per pageview over the full web portal life-cycle. METHODS: Usage data were gathered through Google Analytics. The main usage metric assessed was pageviews originating from an IP address in Berlin or Brandenburg. Project cost data were reported by the local government and from own records. Descriptive and regression analyses were used to determine time trends in pageviews. RESULTS: The redesigned web portal Praeventionsatlas.de launched August 2011 and was discontinued March 2018. Analyzing the full calendar years only, the annual pageview number increased from 2012 (8492) to its peak in 2014 (11,876) and steadily decreased to its minimum in 2017 (7232). Pages of the web portal were most often viewed around lunchtime (12 to 1 p.m.), in the middle of the week (Wed to Thu), and at the beginning of the year (Jan to Feb). Adjusting for year, month, and weekday, the number of daily pageviews dropped on major public holidays (Easter -9, Pentecost -12, Christmas -12 and New Year's Eve and Day -20; p < .001) and increased during the fasting period before Easter (+6; p < .001). Average cost per page viewed from relaunch until the web portal went offline was estimated to be €0.38 (€0.33 to €1.67) per pageview. CONCLUSION: Usage of the web portal showed temporal variation and peaked before the middle of its 6.5 year life-cycle. Development and need for updates may require substantial investment in a web portal, such that a pageview can come at a considerable expense, even in small-scale projects. Assessing and discussing the cost-effectiveness of a web portal is therefore desirable.

Impaired assessment of cumulative lifetime familiarity for object concepts after left anterior temporal-lobe resection that includes perirhinal cortex but spares the hippocampus.

The ability to recognize the prior occurrence of objects can operate effectively even in the absence of successful recollection of episodic contextual detail about a relevant past object encounter. The pertinent process, familiarity assessment, is typically probed in humans with recognition-memory tasks that include an experimentally controlled study phase for a list of items. When meaningful stimuli such as words or pictures of common objects are employed, participants must judge familiarity with reference to the recent experimental encounter rather than their lifetime of autobiographical experience, which may have involved hundreds or thousands of exposures across numerous episodic contexts. Humans can, however, also judge the cumulative familiarity of objects concepts they have encountered over their lifetime. At present, little is known about the cognitive and neural mechanisms that support this ability. Here, we tested an individual (NB) with a rare left anterior temporal-lobe lesion that included perirhinal cortex but spared the hippocampus, who had previously been found to exhibit selective impairments in familiarity assessment on verbal recognition-memory tasks. As NB exhibits normal recollection abilities, her case presents a unique opportunity to examine potential links between both types of familiarity. In Experiment 1, we demonstrated that NB's impairment in making recognition judgments affects cumulative frequency judgments for exposure to concept names in a recent study episode. Experiments 2 and 3 revealed, with a task borrowed from the semantic-memory literature, that NB's impairments do indeed extend to abnormalities in judging cumulative lifetime familiarity for object concepts. These abnormalities were not limited to verbal processing, and were present even when pictures were offered as additional cues. Moreover, they showed sensitivity to concept structure as reflected in semantic feature norms; we only observed them for judgments on object concepts with high feature overlap. In Experiment 4, we found that an amnesic patient (HC) with previously established deficits in autobiographical recollection, due to a selective lesion of the extended hippocampal system, does not exhibit any abnormalities in assessing lifetime familiarity. Together, these findings provide support for a functional link between the assessment of recent changes in familiarity, as probed with experimental study-test paradigms, and cumulative lifetime familiarity based on autobiographical experience accrued outside the laboratory. They argue in favor of the notion that familiarity is closely related to the representation of concept knowledge, likely through computations in perirhinal cortex.

Smoke-free laws and direct democracy initiatives on smoking bans in Germany: a systematic review and quantitative assessment.

BACKGROUND: Germany's 16 states regulate smoking differently within health protection principles laid down in the federal law. All state smoke-free laws in Germany have undergone at least one change since taking effect. METHODS: We systematically review federal and state laws regulating smoking, as well as petitions, popular initiatives and referenda that aimed at changing statutory smoking bans. Data generated through the systematic review were correlated with state smoking rates. RESULTS: The protection from the dangers of secondhand smoke is the primary motive for smoking bans in Germany. The first smoke-free laws affecting smoking in pubs, restaurants and several other public places were introduced in 2007. In 2008, the Federal Constitutional Court of Germany ruled in a leading decision on the smoke-free laws of two states that some common smoking ban exemptions of the introduced smoke-free laws violate the basic right to freely exercise a profession and mandated revisions. All states but Bavaria and Saarland, whose smoking bans were more and less comprehensive than those judged by the constitutional court, respectively, needed to change the smoking ban exemptions to reconcile their smoke-free laws with the constitution. Direct democracy initiatives to change smoking bans were only successful in Bavaria in 2010, but a total of 15 initiatives by citizens' or interest groups attempted to influence non-smokers protection legislation through direct democratic procedures. Early ratification of a smoking ban in a federal state correlates with a higher reduction in the smoking rate from 2005 to 2009 (Spearman's ρ = 0.51, p = 0.04). CONCLUSIONS: The federal government structure and direct democratic participation in smoke-free legislation in Germany has produced a diversity of local smoking bans and exemptions.

Cost effectiveness of antiarrhythmic medications in patients suffering from atrial fibrillation.

Atrial fibrillation (AF), a supraventricular tachycardia disorder, is the most common sustained cardiac arrhythmia affecting 1-2 % of the general population. Prevalence is highly related to age, with every fourth individual older than 40 years old developing AF during his lifetime. Due to an aging population, the prevalence of AF is estimated to at least double within the next 50 years. This article presents AF-related cost-of-illness studies and reviews 19 cost-effectiveness studies and six cost studies published roughly over the past decade, which have compared different antiarrhythmic medications for AF. A systematic literature search for studies published between June 2000 and December 2011 was conducted in PubMed using the combination of keywords ((atrial fibrillation OR atrial flutter) AND cost). Current cost-effectiveness analyses of dronedarone and the pill-in-the-pocket strategy are subject to substantial uncertainties with regard to clinical benefit. Comparing rate control with rhythm control, a cost-effectiveness advantage for rate control was shown in several but not all studies. Within antiarrhythmic drug treatments, magnesium added onto ibutilide was shown to be more cost effective than ibutilide alone. Comparing chemical and electrical cardioversion, the latter was recommended as more cost effective from the healthcare system perspective in all reviewed studies but one. Catheter ablation appeared more cost effective than antiarrhythmic drugs in the medium to long run after 3.2-63.9 years. Admissions to hospital, inpatient care and interventional procedures as well as mortality benefit are key drivers for the cost effectiveness of AF medications. No clear cost-effectiveness advantage emerged for one specific antiarrhythmic drug from the studies that compared antiarrhythmic agents. Rate control as well as catheter ablation appear more cost effective than rhythm control in the treatment of AF. Rate control treatment also seems more cost effective than electrical cardioversion in AF patients.