An economic evaluation of radiotherapy for patients with symptomatic Ledderhose disease

BACKGROUND: Evidence for effectiveness of radiotherapy for Ledderhose disease was demonstrated in the LedRad-study. However, the health economic impact of Ledderhose disease is unclear. Therefore, an economic evaluation alongside the LedRad-study was planned.METHODS: The economic evaluation was performed as a cost-effectiveness and cost-utility analysis from the societal perspective. Primary outcome parameters were pain burden and Quality Adjusted Life Years (QALY), until 12 months after the end of treatment. Secondary analyses were performed with outcomes until 18 months. Incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) were calculated to express costs per unit improvement in pain burden and costs per QALY gained, for radiotherapy compared to sham-radiotherapy. Bootstrap replication was used to assess uncertainty surrounding the ratios and to construct cost-effectiveness acceptability curves for QALY gain.RESULTS: Previous analysis showed a statistically significant improvement in pain- and QoL scores in favour of radiotherapy at 12 and 18 months. At these timepoints and excluding treatment costs, cumulative total costs were considerably lower in the radiotherapy group. The ICER until 12 months after treatment was 4987 euro per unit of pain burden reduction. The ICUR was 14249 euro per QALY gained. Most of the bootstrap replications were in the upper right quadrant, indicating that health gain can be achieved at higher costs. At increasing levels of willingness to pay for a gain in QALY, the probability of cost-utility gradually increased to approximately 85%.CONCLUSIONS: In patients with symptomatic Ledderhose disease, radiotherapy, at a moderate threshold for willingness to pay, is cost-effective in terms of QoL gain.TRIAL REGISTRATION NUMBERS: NCT03507010, NL62429.042.17.</p

Cardiac allograft vasculopathy and donor age affecting permanent pacemaker implantation after heart transplantation

AIMS: The need for permanent pacemakers (PMs) after heart transplantation (HT) is increasing. The aim was to determine the influence of cardiac allograft vasculopathy (CAV), donor age, and other risk factors on PM implantations early and late after HT and its effect on survival. METHODS AND RESULTS: A retrospective, single‐centre study was performed including HTs from 1984 to July 2018. Early PM was defined as PM implantation ≤90 days and late PM as PM > 90 days. Risk factors for PM and survival after PM were determined with (time‐dependent) multivariable Cox regression. Out of 720 HTs performed, 62 were excluded (55 mortalities ≤30 days and 7 retransplantations). Of the remaining 658 patients, 95 (14%) needed a PM: 38 (6%) early and 57 (9%) late during follow‐up (median 9.3 years). Early PM risk factors were donor age [hazard ratio (HR) 1.06, P < 0.001], ischaemic time (HR 1.01, P < 0.001), and in adults amiodarone use before HT (HR 2.02, P = 0.045). Late PM risk factors were donor age (HR 1.03, P = 0.024) and CAV (HR 3.59, P < 0.001). Late PM compromised survival (HR 2.05, P < 0.001), while early PM did not (HR 0.77, P = 0.41). CONCLUSIONS: Risk factors for early PM implantation were donor age, ischaemic time, and in adults amiodarone use before HT. Late PM implantation risk factors were donor age and CAV. Late PM diminished survival, which is probably a surrogate marker for underlying progressive cardiac disease

Radiotherapy for Ledderhose disease:Results of the LedRad-study, a prospective multicentre randomised double-blind phase 3 trial

Background and purpose: Radiotherapy is considered a treatment option for Ledderhose disease. However, its benefits have never been confirmed in a randomised controlled trial. Therefore, the LedRad-study was conducted. Materials and methods: The LedRad-study is a prospective multicentre randomised double-blind phase three trial. Patients were randomised to sham-radiotherapy (placebo) or radiotherapy. The primary endpoint was pain reduction at 12 months after treatment, measured with the Numeric Rating Scale (NRS). Secondary endpoints were pain reduction at 6 and 18 months after treatment, quality of life (QoL), walking abilities and toxicity.Results: A total of 84 patients were enrolled. At 12 and 18 months, patients in the radiotherapy group had a lower mean pain score compared to patients in the sham-radiotherapy group (2.5 versus 3.6 (p = 0.03) and 2.1 versus 3.4 (p = 0.008), respectively). Pain relief at 12 months was 74% in the radiotherapy group and 56% in the sham-radiotherapy group (p = 0.002). Multilevel testing for QoL scores showed higher QoL scores in the radiotherapy group compared to the sham-radiotherapy group (p &lt; 0.001). Moreover, patients in the radiotherapy group had a higher mean walking speed and step rate with barefoot speed walking (p = 0.02). Erythema, skin dryness, burning sensations and increased pain were the most frequently reported side effects. These side effects were generally graded as mild (95%) and the majority (87%) were resolved at 18 months follow-up.Conclusion: Radiotherapy for symptomatic Ledderhose disease is an effective treatment resulting in a significant pain reduction, improvement of QoL scores and bare feet walking abilities, in comparison to sham-radiotherapy.</p

The History of Makassan Trepang Fishing and Trade

The Malayan term trepang describes a variety of edible holothurians commonly known as sea cucumbers. Although found in temperate and tropical marine waters all over the world, the centre of species diversity and abundance are the shallow coastal waters of Island Southeast Asia. For at least 300 years, trepang has been a highly priced commodity in the Chinese market. Originally, its fishing and trade was a specialized business, centred on the town of Makassar in South Sulawesi (Indonesia). The rise of trepang fishing in the 17th century added valuable export merchandize to the rich shallow seas surrounding the islands of Southeast Asia. This enabled local communities to become part of large trading networks and greatly supported their economic development. In this article, we follow Makassan trepang fishing and trading from its beginning until the industrialization of the fishery and worldwide depletion of sea cucumbers in the 20th century. Thereby, we identify a number of characteristics which trepang fishing shares with the exploitation of other marine resources, including (1) a strong influence of international markets, (2) the role of patron-client relationships which heavily influence the resource selection, and (3) the roving-bandit-syndrome, where fishermen exploit local stocks of valuable resources until they are depleted, and then move to another area. We suggest that understanding the similarities and differences between historical and recent exploitation of marine resources is an important step towards effective management solutions

How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property

The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe

Pottery production and trade in the Banda zone, Indonesia: the Kei tradition in its spatial and historical context

This paper provides the first comprehensive description of pottery production in the Kei islands of eastern Indonesia, based on field data collected mainly in 1981 and on Museum collections in the UK and The Netherlands. The account is situated in what we know of the dynamics of trading systems that existed in the Moluccan islands between 1500 and 2000. Kei pottery is widely thought to be the successor of a tradition established in the Banda islands that was extinguished with the 1621 Dutch massacre of Bandanese, but re-established at several sites in the Kei islands by Bandanese migrants after this date. These claims are critically examined using ethnographic and archaeological data, and an attempt made to compare the production and trading patterns of pottery in the ‘Banda zone’ before and after 1621

Globally, songs and instrumental melodies are slower and higher and use more stable pitches than speech: A Registered Report

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a “musi-linguistic” continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech

Globally, songs and instrumental melodies are slower, higher, and use more stable pitches than speech: a registered report

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a “musi-linguistic” continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech