Infectious Middle Ear Disease (IMED) is a group of infections that frequently afflict individuals across all age groups worldwide. Although in today’s clinical practice IMED is efficiently managed,... Show moreInfectious Middle Ear Disease (IMED) is a group of infections that frequently afflict individuals across all age groups worldwide. Although in today’s clinical practice IMED is efficiently managed, in the past it probably caused severe complications (e.g., hearing loss, balance problems, and facial nerve paralysis), heavily impacting the everyday life of many people. However, despite the valuable insights that studying ear infections in the past can bring, bioarcheology presently lacks a standardized methodology to assess their prevalence in skeletal populations. This can lead to several issues, including incomparability of results, difficulties in replications, and methodological biases.Recently, straightforward and accessible criteria for the observation of the cochlear promontory were presented to successfully assess IMED on skeletal remains. Yet, as otologists rarely examine the impact of ear infections on the bony structures of the middle ear, the results were not supported clinically, and could therefore not be validated. To fill this gap, we propose a study in which computed tomography (CT) of the mastoid process was utilized on the skulls of 50 individuals to verify the results obtained through gross observation of the cochlear promontory. Statistical analysis revealed significant correlation between hypopneumatization (indicative of childhood IMED) and bony changes of the promontory at the level of the individual. This suggests a potential correlation that warrants further investigation to determine whether the observation of the cochlear promontory should be used as a method for IMED assessment. Overall, our study contributes to the study of IMED in past populations, and underscores the importance of clear, standardized scoring criteria in paleopathology. Show less
Casna, M.; Schats, R.; Hoogland, M.L.P.; Schrader, S.A. 2023
Objective: This paper presents the current state of the art in the investigation of past malaria by providing an extensive review of previous studies and identifying research possibilities for the... Show moreObjective: This paper presents the current state of the art in the investigation of past malaria by providing an extensive review of previous studies and identifying research possibilities for the future. Materials: All previous research on the detection of malaria in human skeletal material using macroscopic and biomolecular approaches is considered.Methods: The approaches and methods used by scholars and the results they obtained are evaluated and the limitations discussed.Results: There is a link between malaria and porous lesions with significantly higher prevalence in malaria-endemic areas, however, they are not pathognomonic or specific for malaria. Malaria can be identified using biomolecular techniques, yet, to date there is no completely satisfactory method that is able to consistently diagnose the disease.Conclusions: Using macroscopic and biomolecular techniques, malaria can be investigated in past populations and the impact of the disease studied. Yet, this is not a straightforward process and the use of multiple lines of evidence is necessary to obtain the best results.Significance: The extensive discussion on ways malaria can and cannot be identified in past populations and the suggestions for new approaches provide a stepping stone for future research into this debilitating, global disease. Limitations: Malaria is a difficult disease to study archaeologically and successful identification depends on many intrinsic and extrinsic factors.Suggestions for further research: More large-scale spatial analyses of porous lesions as well as targeting different tissues or molecules for biomolecular identification may improve the archaeological understanding of malaria. Show less
STUDY QUESTION: Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian stimulation in women... Show moreSTUDY QUESTION: Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian stimulation in women with breast cancer who undergo fertility preservation? SUMMARY ANSWER: Alternative ovarian stimulation protocols with tamoxifen or letrozole did not affect the number of COCs retrieved at follicle aspiration in women with breast cancer. WHAT IS KNOWN ALREADY: Alternative ovarian stimulation protocols have been introduced for women with breast cancer who opt for fertility preservation by means of banking of oocytes or embryos. How these ovarian stimulation protocols compare to standard ovarian stimulation in terms of COC yield is unknown. STUDY DESIGN, SIZE, DURATION: This multicentre, open-label randomized controlled superiority trial was carried out in 10 hospitals in the Netherlands and 1 hospital in Belgium between January 2014 and December 2018. We randomly assigned women with breast cancer, aged 18-43 years, who opted for banking of oocytes or embryos to one of three study arms; ovarian stimulation plus tamoxifen, ovarian stimulation plus letrozole or standard ovarian stimulation. Standard ovarian stimulation included GnRH antagonist, recombinant FSH and GnRH agonist trigger. Randomization was performed with a web-based system in a 1:1:1 ratio, stratified for oral contraception usage at start of ovarian stimulation, positive estrogen receptor (ER) status and positive lymph nodes. Patients and caregivers were not blinded to the assigned treatment. The primary outcome was number of COCs retrieved at follicle aspiration. PARTICIPANTS/MATERIALS, SETTING, METHODS: During the study period, 162 women were randomly assigned to one of three interventions. Fifty-four underwent ovarian stimulation plus tamoxifen, 53 ovarian stimulation plus letrozole and 55 standard ovarian stimulation. Analysis was according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: No differences among groups were observed in the mean (+/- SD) number of COCs retrieved: 12.5 (10.4) after ovarian stimulation plus tamoxifen, 14.2 (9.4) after ovarian stimulation plus letrozole and 13.6 (11.6) after standard ovarian stimulation (mean difference -1.13, 95% CI -5.70 to 3.43 for tamoxifen versus standard ovarian stimulation and 0.58, 95% CI -4.03 to 5.20 for letrozole versus standard ovarian stimulation). After adjusting for oral contraception usage at the start of ovarian stimulation, positive ER status and positive lymph nodes, the mean difference was -1.11 (95% CI -5.58 to 3.35) after ovarian stimulation plus tamoxifen versus standard ovarian stimulation and 0.30 (95% CI -4.19 to 4.78) after ovarian stimulation plus letrozole versus standard ovarian stimulation. There were also no differences in the number of oocytes or embryos banked. There was one serious adverse event after standard ovarian stimulation: one woman was admitted to the hospital because of ovarian hyperstimulation syndrome. LIMITATIONS, REASONS FOR CAUTION: The available literature on which we based our hypothesis, power analysis and sample size calculation was scarce and studies were of low quality. Our study did not have sufficient power to perform subgroup analysis on follicular, luteal or random start of ovarian stimulation.WIDER IMPLICATIONS OF THE FINDINGS: Our study showed that adding tamoxifen or letrozole to a standard ovarian stimulation protocol in women with breast cancer does not impact the effectiveness of fertility preservation and paves the way for high-quality long-term follow-up on breast cancer treatment outcomes and women's future pregnancy outcomes. Our study also highlights the need for high-quality studies for all women opting for fertility preservation, as alternative ovarian stimulation protocols have been introduced to clinical practice without proper evidence. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant (2011.WO23.C129) of 'Stichting Pink Ribbon', a breast cancer fundraising charity organization in the Netherlands. M.G., C.B.L. and R.S. declared that the Center for Reproductive Medicine, Amsterdam UMC (location VUMC) has received unconditional research and educational grants from Guerbet, Merck and Ferring, not related to the presented work. C.B.L. declared a speakers fee for Inmed and Yingming. S.C.L. reports grants and non-financial support from Agendia, grants, non-financial support and other from AstraZeneca, grants from Eurocept-pharmaceuticals, grants and non-financial support from Genentech/Roche and Novartis, grants from Pfizer, grants and non-financial support from Tesaro and Immunomedics, other from Cergentis, IBM, Bayer, and Daiichi-Sankyo, outside the submitted work; In addition, S.C.L. has a patent UN23A01/P-EP pending that is unrelated to the present work. J.M.J.S. reported payments and travel grants from Merck and Ferring. C.C.M.B. reports her role as unpaid president of the National guideline committee on Fertility Preservation in women with cancer. K.F. received unrestricted grants from Merck Serono, Good Life and Ferring not related to present work. K.F. declared paid lectures for Ferring. D.S. declared former employment from Merck Sharp & Dohme (MSD). K.F. declared paid lectures for Ferring. D.S. reports grants from MSD, Gedeon Richter and Ferring paid to his institution; consulting fee payments from MSD and Merck Serono paid to his institution; speaker honoraria from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono paid to his institution. D.S. has also received travel and meeting support from MSD, Gedeon Richter, Ferring Pharmaceuticals and Merck Serono. No payments are related to present work. Show less
IntroductionOsteoarthritis (OA) is a common disease that degrades the cartilage in synovial joints, eventually leading to the direct destruction of bone. Today, OA is often observed in the hands... Show moreIntroductionOsteoarthritis (OA) is a common disease that degrades the cartilage in synovial joints, eventually leading to the direct destruction of bone. Today, OA is often observed in the hands and wrists, yet there have been few dedicated studies in past populations. This research aims to investigate how the living environment impacts the occurrence and patterning of hand and wrist OA in the medieval Netherlands.Materials & MethodsThe skeletal remains of 226 adult individuals from three sites (urban Alkmaar, rural Klaaskinderkerke, and urban hospital Kampen) were analysed to shed light on past prevalence and variation in affected joints between contextually different populations. The operational definition from Waldron (2009) was used to diagnose OA. ResultsExpectedly, a significant relationship between age and OA prevalence was found, χ2(2, N=226)=26.72, p<.001), with older individuals being more affected. Sex did not influence OA prevalence, χ2(2, N=226)=.75, p=0.68). Interestingly, even though the age distribution between the sites was similar, a clear interpopulation difference in overall hand and wrist OA prevalence was observed: hospital (32%), urban (12%) and rural (5%). Joint-specific patterning also showed variation between the sites, with OA predominance in the lateral wrist (thumb-base/wrist joint complex) in the urban hospital population, and in the medial wrist (piso-triquetral) in the urban population. ConclusionsThese results suggest that population context plays a significant role in OA occurrence. Differences in OA prevalence and patterning may suggest different activities or risk factors depending on the environment, which need to be explored further and on a larger scale. Show less
In the late medieval period, Holland experienced substantial socio-economic change. While the region was largely undeveloped prior to 1200 CE, the period after was characterised by extensive... Show moreIn the late medieval period, Holland experienced substantial socio-economic change. While the region was largely undeveloped prior to 1200 CE, the period after was characterised by extensive urbanisation and flourishing international trade, changes that would have impacted many aspects of life. This paper investigates the effect of these changes on diet by comparing skeletal collections from the early/central medieval rural village of Blokhuizen (800–1200 CE) to the late medieval urban town of Alkmaar (1448–1572 CE) using a combination of the prevalence and location of carious lesions (nteeth = 3475) and stable carbon and nitrogen isotope data (n = 50). Results show that the urban Alkmaar population had a significantly higher caries frequency (7.4% vs. 16.1%), starting at a younger age. Moreover, Alkmaar had significantly more approximal caries. These results point to increased consumption of cariogenic products, such as sugars and starches, by the urban citizens. Dietary differences are also demonstrated by the stable isotope data. Alkmaar individuals have significantly enriched δ15N ratios and more variable δ13C ratios compared with rural Blokhuizen. The elevated δ15N values may be due to increased consumption of fish or animals such as omnivorous pigs and chickens. The combination of caries and isotopic data points to clear changes in diet suggesting that urban individuals in the late medieval period had a substantially different diet compared with early rural inhabitants from the same area. Specifically, an increase in market dependence, availability of international trade products, and the growth of commercial fishing in the late medieval period may have contributed to this dietary shift. Future research should include a late medieval rural population to better understand the effects of late medieval socio-economic developments outside of the urban environment. This study demonstrates that the integration of palaeopathology and stable isotopic research provides a more complete understanding of dietary changes in medieval Holland. Show less
Spaan, M.; Belt-Dusebout, A.W. van den; Lambalk, C.B.; H.H. van boven; Schats, R.; Kortman, M.; ... ; Leeuwen, F.E. van 2021
Background: Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown. Methods: This nationwide cohort study comprises 30 625 women who received ovarian... Show moreBackground: Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown. Methods: This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided. Results: After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time. Conclusions: Increased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed. Show less
Cribra orbitalia, orbital roof porosity, is one of the most frequently scored skeletal lesions in archaeological remains from the Netherlands. Cribra orbitalia is generally associated with... Show moreCribra orbitalia, orbital roof porosity, is one of the most frequently scored skeletal lesions in archaeological remains from the Netherlands. Cribra orbitalia is generally associated with childhood anaemia, but the underlying cause of this red blood cell disorder is still debated. Gowland and Westen (2012) showed a clear correlation between cribra orbitalia prevalence and certain geographic areas in the UK, linking this to malaria. As the Netherlands was plagued by malaria as well, this parasitic infection may have been an important contributing factor to the prevalence of anaemia in the medieval period. To contribute to this complex debate on the aetiology, and to study the hypothesis of malaria as an important causative agent, this research investigates the spatial distribution of cribra orbitalia in the medieval Netherlands. In total, 1629 individuals from 19 different medieval sites have been studied for the presence or absence of cribra orbitalia and severity of the lesions (1 to 3, Stuart-Macadam 1985). Results show a greater prevalence of cribra orbitalia in the areas deemed malarial based on palaeogeographic and 20th century malaria distribution data (10.9% vs. 23.1%, p<0.001). Yet, even though the mean scores are slightly higher in the malarial area, the severity of the lesions does not significantly vary. This study suggests that malaria may have been an important contributing factor to the prevalence of cribra orbitalia and that it was likely an influential disease in the low-lying coastal areas of the Netherlands with a substantial impact on health and life expectancy. Show less
ObjectiveThis paper studies the prevalence, co-occurrence, and association of cribra orbitalia, cribra humeri, and cribra femora to contribute to the complex debate on cribriotic lesions and their... Show moreObjectiveThis paper studies the prevalence, co-occurrence, and association of cribra orbitalia, cribra humeri, and cribra femora to contribute to the complex debate on cribriotic lesions and their relationship with one another.Materials179 adults and 53 non-adults from the medieval/early modern Netherlands (800–1600 CE) for whom all three lesions could be observed are included in this study.MethodsPresence or absence of cribriotic lesions was studied macroscopically. Prevalence, co-occurrence, and association of lesions and their link to sex and age-at-death were assessed.ResultsA clear link between prevalence of the lesions and age-at-death is found. Co-occurrence and association of all three lesions is uncommon. There is a significant moderate correlation for cribra humeri-femora in non-adults.ConclusionsLesion prevalence is connected to age-at-death. However, while a similar age distribution and associations between pairs of lesions are noted, due to limited co-occurrence of the three lesions, the presence of a ‘cribrous syndrome’ cannot supported.SignificanceThis is the first study investigating the prevalence, co-occurrence and association of cribra orbitalia, cribra humeri, and cribra femora in non-adults and adults contributing to discussions about the nature and the much-debated aetiology of these commonly encountered skeletal lesions.LimitationsThe number of non-adults in this study is limited, potentially obscuring meaningful patterns, as the cribrous lesions are significantly more common in younger individuals.Suggestions for further researchMore research into the prevalence of the post-cranial lesions and their co-occurrence as well as into bone growth and remodelling is warranted. Show less
Casna, M.; Burrell, C. L.; Schats, R.; Hoogland, M. L. P.; Schrader, S. A. 2021
The aim of this study was to investigate the relationship between urbanization and upper respiratory health in two early modern populations from the Netherlands. For this purpose, we analyzed the... Show moreThe aim of this study was to investigate the relationship between urbanization and upper respiratory health in two early modern populations from the Netherlands. For this purpose, we analyzed the prevalence of chronic maxillary sinusitis in the adult urban population of Arnhem (n = 83) and in the rural village of Middenbeemster (n = 74). A slightly higher prevalence of chronic maxillary sinusitis was observed in the Arnhem sample (55.4%) compared with the Middenbeemster sample (51.3%), and these variations were not statistically significantly different. Although historical sources attest to the fact that life in the postmedieval settlements of Arnhem and Middenbeemster greatly differed, our results suggest that both environments exposed people to certain respiratory hazards. Furthermore, sinusitis prevalence was also investigated in correlation to sex, as urbanization in the Netherlands often involved women in factory work in direct contrast to the traditional domestic role they kept covering in rural environments. No significant differences were observed between males and females, both in an intersite (Arnhem males vs. Middenbeemster males; Arnhem females vs. Middenbeemster females) and in an intrasite (males vs. females at Arnhem; males vs. females at Middenbemster) comparison. As men and women in Arnhem worked on similar tasks, our results confirm that they were both exposed to similar risk factors. In Middenbeemster, where women mainly stayed inside taking care of the house while men worked the fields, the adverse weather conditions and continuous exposure to pollens and allergens may have enhanced men's chances of contracting chronic maxillary sinusitis. This study suggests that urbanization in the early modern Netherlands was in fact not inherently more detrimental than rural living. Future research incorporating a larger sample from other Dutch sites is being considered to better frame the complex etiology of sinusitis within the present understanding of historic regional variation in urbanization patterns. Show less
ObjectivesThe objective of this study is to apply pubertal stage estimation methods to a sample from a rural community: the post‐medieval Dutch skeletal collection from Middenbeemster. Puberty is a... Show moreObjectivesThe objective of this study is to apply pubertal stage estimation methods to a sample from a rural community: the post‐medieval Dutch skeletal collection from Middenbeemster. Puberty is a key developmental period involving transition to physical adulthood with broad societal relevance through its impact on fertility, morbidity, and mortality.Materials and methodsIndividuals (n = 55), including 27 of known sex and age‐at‐death, between the ages of 8 and 25 years were assessed for six skeletal markers indicative of pubertal growth spurt. Recent novel osteoarchaeological methods from Shapland and Lewis are used to reconstruct the timing and duration of pubertal stages.ResultsPubertal acceleration occurred earlier in females (10.38 years, n = 8) than males (13.30 years, n = 6), whereas maturation occurred later in males (21.36 years, n = 11) than females (19.30 years, n = 5). Onset appears earlier and completion later compared to other archaeological skeletal samples with osteoarchaeological evidence of puberty. Age shortly after menarche was reconstructed at 20.45 years, substantially later than historic records and bioarchaeological research reports suggest.ConclusionThis early onset and late completion caused a “stretch” of the overall duration of puberty compared to other collections, especially of the last three stages. This prolonged development is reflected in historically known social expectations for the Netherlands, for example, that marriage and children should not occur before about 22–23 years of age. Increasing the range of past peoples with puberty stage reconstruction will permit more insightful interpretations of the biological and cultural patterns of this important life stage. Show less
Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel... Show moreSyphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis' potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidumin early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws-causing T. pallidum subspecies were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws- and bejel-causing lineages. These findings imply a more complex pattern of geographical distribution and etiology of early treponemal epidemics than previously understood. Show less
Using a variety of anti-malaria tools has resulted in a steady decline of malaria in several endemic countries worldwide. An effective vaccine will be critical to halt malaria or even succeed to... Show moreUsing a variety of anti-malaria tools has resulted in a steady decline of malaria in several endemic countries worldwide. An effective vaccine will be critical to halt malaria or even succeed to final eradication. In that perspective, we studied the potential of whole sporozoite immunization by bites of P. falciparum infected mosquitoes under chemoprophylaxis (CPS). In this thesis we further explored this CPS model and assessed different immunizing doses, type of chemoprophylaxis and immunological determinants of disease and protection. We found a clear dose dependent efficacy, independent of type of chemoprophylaxis, found CD107a and CD8 T cells producing granzyme B related to protective immunity. In the field many genetically different strains circulate and a future vaccine should be able to cover multiple strains. We re-challenged volunteers with a different strain and found modest heterologously protection.We retrospectively assessed the parasitological dynamics and adverse events using a positive qPCR rather than thick smear and found reduced the clinical symptoms of malaria for volunteers after challenge.Successful malaria eradication will be more likely to be achieved with a multi-disciplinary approach. Additionally, sufficient and continuous funds will proof to be of tremendous necessity. Show less
