Background: This project originated from the study of an 18th century manuscript found in Valle Imagna  which contains 200 plant-based medicinal remedies. A first comparison with published books concerning 20th century folk medicine in the Valley led to the designing of an ethnobotanical investigation, aimed at making a thorough comparison between past and current phytotherapy knowledge in this territory. Methods: The field investigation was conducted through semi-structured interviews. All data collected was entered in a database and subsequently processed. A diachronic comparison between the field results, the manuscript, and a 20th century book was then performed. Results: A total of 109 interviews were conducted and the use of 103 medicinal plants, belonging to 46 families, was noted. A decrease in number of plant taxa and uses was observed over time, with only 42 taxa and 34 uses reported in the manuscript being currently known by the people of the valley. A thorough comparison with the remedies in the manuscript highlighted similar recipes for 12 species. Specifically, the use of agrimony in Valle Imagna for the treatment of deep wounds calls back to an ancient remedy against leg ulcers based on this species. Conclusions: The preliminary results of this study allow us to outline the partial passage through time fragments of ancient plant-based remedies once used in the investigated area. Diachronic approach in ethnobotanical studies has recently gained the attention of several authors. The use of historical sources allows researchers to collect valuable information about the mechanisms of transmission of Local Ecological Knowledge (LEK) and the nature of its transformation over time ,2,3. HowRaccolta di diversi rimedj a varj mali’ (Collection of various remedies to various pathologies), an in-depth ethnobotanical study of a pocket-size 18th century manuscript found in Valle Imagna  which contains approximately 200 plant-based complex recipes with therapeutic purposes collected and written down by an anonymous author [In 2021, Milani and Fico published a book titled ‘s author   [The remedies were considered useful to treat almost 80 different types of pathologies that were recognized by the official Western Medicine of that time  and were made of plant, mineral, animal, and human ingredients. Specifically, 205 plant species (21 of which are still unidentified) belonging to 70 botanical families were mentioned in the book, either used as they were or as derivatives. Today, most of these preparations can only be considered picturesque at best, because of the medical theories that the remedies were based on, the mix of ingredients used, the steps described for the preparations , and the way of administering them to the patients. For example, in order to ‘gredient . Howevergredient . Admittegredient . However Imagna) . As a fafil rouge across the centuries, from the 18th century medicine to the 21st century folk medicine of Valle Imagna.The results obtained from the analyses of the manuscript prompted us to deepen our investigation on traditional uses of spontaneous medicinal species still surviving nowadays in Valle Imagna, and on whether part of this knowledge could be potentially traced back to centuries past. Thus, we conducted an ethnobotanical survey to investigate current knowledge of medicinal plants in the upper Valle Imagna. Then, we performed a thorough comparison between the plants and their traditional uses currently known and possibly practiced by the people of the valley and the ancient remedies included in the 18th century manuscript described in Milani and Fico (2021). The book by Maconi (2006) was considered too, in the attempt to sketch a potential Between November 2021 and November 2022, a total of 109 informants were interviewed in the field, 93 of whom provided information concerning the medicinal use of spontaneous and cultivated plants of Valle Imagna. Out of the total 3849 citations, 669 referred to the Medicinal sector and involved 103 plant species, belonging to 46 botanical families. Four of these species were recalled only by their vernacular name and the descriptions provided by the informants during the interviews were not sufficient to allow for prompt identification. For this purpose, further investigation, both on the field and bibliographic, is currently taking place.Malva sylvestris L., which is commonly found spontaneous in Valle Imagna, but was also sometimes grown by the informants in their own gardens). Finally, 5% of the citations referred to species that could not be found throughout the territory, but that were usually kept in the house and became common ingredients for herbal remedies  Merr. & L.M.Perry dried flower buds and Zingiber officinale Roscoe rhizomes).Seventy-eight percent of the citations involved species collected in the wild, 17% cultivated species, and 1% species that were collected both spontaneous and cultivated , Tilia cordata Mill. , Taraxacum sect. Taraxacum , Hypericum perforatum L. , Sambucus nigra L. , Laurus nobilis L. , Rosa canina L. , Agrimonia eupatoria L. , Rosmarinus officinalis L. , and Citrus x limon (L.) Osbeck. fil. . It can be observed that Malvaceae was the most mentioned family only due to the high number of citations concerning M. sylvestris and, to a lesser extent, T. cordata, while the citations for the others were distributed among a higher number of different plant species. It is interesting to highlight that during the preliminary bibliographic research conducted on the territory and the local flora [The most recurrent botanical families were Malvaceae , Asteraceae , Lamiaceae , and Rosaceae , while the most cited species were a L. 12; , Laurus araxacum ; 26, Hypal flora ,23, AsteConcerning the 103 plant species mentioned by the informants, they were prepared mainly as infusions (n. citations = 340), used raw , macerated in oil (n = 62), or boiled in decoctions (n = 48). Leaves  and flowers/inflorescences/flowered aerial parts  were the most recurrent plant parts. Mostly, the reported uses were personally experienced (84.0% of citations) and still currently of concern (94.0%).The species were distributed among different categories of pathologies, according to their use see .Hypericum perforatum (n. citations = 21) were macerated for at least 3 weeks in vegetable oil. This oleolite was then applied on skin as an anti-inflammatory, wound healing, and soothing agent for wounds, sunburn, and burns. Compresses prepared with the leaves of Malva sylvestris (n = 11) were used mainly as anti-inflammatory and soothing for skin irritations. Leaves of Agrimonia eupatoria (n = 10) were applied fresh externally or as compresses of the infusion, mainly as a wound healing agent for wounds that were, as some of the informants reported, ‘hard to treat otherwise’.Among the 35 species used for the treatment of skin problems, flowers and aerial parts of Malva sylvestris (n = 38) was drunk for its general anti-inflammatory properties on the whole body, while the infusion of rosehips  was considered rich in vitamin C and useful as tonic and for the prevention of colds. The infusion of leaves and flowers of Salvia officinalis L. (n = 8) was drunk or added to the bath water as a tonic agent.In the category General condition, the infusion of leaves of M. sylvestris (n = 20) was drunk as laxative, or to ease abdominal pain. The leaves, rarely the flowerheads or the underground parts, of Taraxacum spp. (n = 16) were drunk in infusion or eaten mainly as liver depurative. The juice of Citrus x limon fruits (n = 7) was added to an infusion of Thymus spp., Lavandula angustifolia Mill., and Zingiber officinale to improve its digestive and antispastic properties. The juice was once added to Ricinus communis L. seeds oil and sugar as a laxative preparation. Finally, the infusion of leaves of Artemisia absinthium L. (n = 5) was taken for its digestive and carminative activities.For the treatment of digestive problems, the infusion of leaves or flowers, or sometimes the whole above ground parts of Tilia cordata (n = 30): its flowers were commonly collected and mainly used in infusions once dried for the treatment of cough, colds, and sore throat. Syrups of flowers (sometimes fruits) or infusions of flowers of Sambucus nigra (n = 13) were administered against cough for their expectorant properties, while a syrup of pinecones or fresh tops of Pinus mugo Turra (n = 8) was prepared for cough and sore throat. It is important to note that this last species can rarely be found throughout the territory of Valle Imagna and grows mainly at the higher altitudes of Mount Resegone . For this reason, the informants who mentioned this use often collected the herbal ingredients for this preparation in the neighboring valleys, such as Val Taleggio and Val Brembana.As for the category of respiratory tract infections, the most cited species was Arnica montana L. (n = 9). Its flowerheads were macerated in oil or in alcohol and the preparation used as it was or mixed with fat  and rubbed externally on contusions or aching joints or muscles. For the same purpose, fresh leaves of Brassica oleracea L. (n = 7) were applied on the affected area. Moreover, the macerated oil of flowered aerial parts of Achillea millefolium L. (n = 5) was massaged (sometimes after mixing it with bee wax to obtain an ointment) on joints or on contusions and bruises.Among the 30 species used for musculoskeletal pains and inflammations, the most cited one was T. cordata (n = 11), flowered aerial parts of L. angustifolia (n = 8), and leaves of Melissa officinalis L. (n = 7) were the most mentioned preparations for the treatment of nervous system disorders, specifically as sedative remedies to facilitate and improve sleep. Additionally, the oleolite of lavender was massaged on the temples for the same purpose.The infusions of flowers of M. sylvestris (n = 21). The infusion of its leaves was drunk or used as vaginal douche for diuretic or anti-inflammatory purposes, specifically for cystitis and irritations. Another remedy against cystitis was the decoction of the whole above ground parts of A. eupatoria (n = 5), also drunk (in this case with the addition of cherry seeds) or used externally. The informants who reported this specific use of agrimony emphasized the fact that this remedy was once recommended by the midwives of the valley.The most used species for the urinary tract was without doubt M. sylvestris (n = 30). Its infusion was commonly used as anti-inflammatory mouthwashes. Less common was the similar use of the whole above ground parts of A. eupatoria , the leaves of Blitum bonus-henricus (L.) Rchb. , and the leaves of Salvia officinalis .For the treatment of gingivitis and other inflammations of the oropharyngeal tract, the most used remedy was prepared once again with leaves  of Laurus nobilis (n = 5) were considered useful mainly as a hypotensive, while the infusion of Crataegus monogyna Jacq. (n = 3) was drunk as a hypotensive as well, but also as an antiarrhythmic. Finally, decoctions of Taraxacum (n = 3) leaves or sometimes the leaves and underground parts eaten raw were considered a powerful blood depurative.Concerning the circulatory system, leaves infusions of Achillea millefolium, Calendula officinalis L., Malva sylvestris, and Sambucus nigra, the literature concerning the active compounds involved in their activity and their potential mechanisms of action was relatively extensive, while in most cases the information was limited. The complete results of this research can be found in Finally, extensive bibliographic research in scientific literature was conducted on the 99 identified medicinal species mentioned by the informants in order to validate or refute their traditional uses. This bibliographic research highlighted that scientific evidence could be found for at least one of the uses concerning 62 taxa and detected during the field work, though it is important to note that the part of the plant and preparations analysed in literature rarely matched the traditional ones. Moreover, in vitro and in vivo studies could be more easily found, while clinical trials performed on human subjects were definitely lacking. Phytochemical investigations related to the potential biological activities were found only for 42 out of the 62 aforementioned taxa. For some of these, for example p < 0.01) and uses   . This fiThe age of informants ranged from 20 to 96 years with 70–79 years being the most frequent age class (32 informants) . No signDelphinium consolida L. for the treatment of fractures, or the macerated oil of Hedera helix L. leaves used to improve legs circulation against cellulitis). Others combined family reminiscences with new understanding gained through schools and university courses, upon deciding to return to their home territory with innovative agropastoral activities. An explanation of the low rate of knowledge owned by the older informants could be found in the history that distinguished the XIX century Valle Imagna. During the post World War II era, this valley was in fact characterized by sheer poverty, while its inhabitants were barely surviving through their rural lives with what the territory would offer [Allium sativum L. underground organs and pork fat against contusions, the use of leaves of Agrimonia eupatoria externally applied fresh to treat deep wounds, or the aerial parts of agrimony drunk in anti-inflammatory infusions for the digestive and urinary tract. Additionally, it is interesting to note that these occurrences may have partly thwarted the intergenerational knowledge transfer of these traditional uses in Valle Imagna.The same pattern was observed by Bruschi et al. (2019)  in an Alld offer . From thBefore focusing on the plant species, it is important to note that some of the ancient non-herbal remedies described in the booklet and the ones from 20th centuries referred by Maconi are interestingly similar. Prolapsed hemorrhoids, for example, were usually treated with herbal or non-herbal ointments in order to slide them back and were then kept in position with a balled up linen cloth . Maconi Prospectus Phamaceuticus sub quo Antidotario Mediolanense”, published in 1668 and updated until 1729; “Pratica universale nella Medicina”, dated 1693 and written by friar Felice Passera from Bergamo; and “De Secreti del Reverendo Donno Alessio Piemontese”, dated 1557 and written by Girolamo Ruscelli. Even the high number of exotic species reported in the manuscript  compared to Maconi  and the fieldwork  can further explain the observed differences. Since the 16th to 18th century, Bergamo was part of the “Repubblica Serenissima di Venezia”, one of the most important centers of trade in Europe at that time. For this reason, doctors and apothecaries could obtain a wide variety of spices and exotic ingredients.In order to explain the observed differences between the manuscript and the other considered sources, it has to be highlighted that the manuscript includes remedies taken from other sources, even from earlier times to 18th century, not always connected with the territory of Valle Imagna. For example, among these “external” sources identified by Milani and Fico (2021), “The comparison between Maconi’s book and the results of our fieldwork show that in a few decades, information on 73 taxa 58.4%) and on 240 uses (77%) was lost. A rapid loss of ethnomedicinal knowledge has been detected in many industrialized countries .4% and o,26 and hTaking into consideration the categories of use, skin and digestive tract diseases are the ones with the highest number of taxa with a homogeneous distribution in the three datasets .ponta’, ‘brossole’, ‘tarlo’, which cannot be translated). Taxa reported in all the three data sources were found in the following categories: skin diseases and traumas , respiratory tract diseases , digestive tract diseases , circulatory system disorders (1: Urtica spp.), urinary tract diseases (1: M. syslvestris), nervous system diseases (1: M. chamomilla), gynaecological disorders, obstetric, and puerperal problems (1: M. sylvestris), general condition . A constant decrease in the number of the recorded taxa over time can be observed in the categories fever (20:10:3), gynaecological disorders, obstetric, and puerperal problems (25:22:3), nervous system diseases (29:22:15), ophthalmic ailments (27:16:3), and urinary tract diseases (34:24:14). Skin diseases (40:43:35) and digestive tract diseases (30:50:31) categories showed a more heterogeneous pattern but always with a reduction in the more recent years. Similar findings were observed by Söukand et al. (2022) [Regarding the manuscript, “others” is the most represented category with 97 recorded taxa; it mostly includes diseases or symptoms which are not easily interpretable and classifiable in accordance with Western nosologies  . On the ailments :16:3, anM. sylvestris used to treat skin problems and urinary tract diseases; T. cordata used to treat respiratory tract diseases; S. nigra used to treat skin problems; R. canina used to treat respiratory tract diseases; Citrus x limon used to treat skin problems; R. officinalis used to treat respiratory tract diseases), the use was the same in the three sources. Fourteen percent of the uses were reported only in Maconi and in the fieldwork. Twenty-seven percent were new . In particular, new uses were recorded in the category general condition, a finding further confirming the increasing importance of preventive plants in the current herbal medicine. Although the use of Taraxacum as remedy to treat digestive, urinary, respiratory diseases, and as a blood purifier has been known since ancient times [M. sylvestris, H. perforatum, S. nigra, R. canina, and A. eupatoria to those reported in Dal Cero et al. (2023) for the same species, we found a Jaccard similarity index of 0.72.nt times ,30, no rnt times  for Centnt times  for SwitOut of the 42 species shared between the manuscript and our field investigation, 12 were used in remedies that were at least comparable, sometimes even almost identical. All information regarding the comparison can be found in Chelidonium majus, Linum usitatissimum, Plantago spp., Salvia officinalis, and Vitis vinifera) the 18th century remedies and the traditional uses in Valle Imagna were similar not only in terms of part of the plant used, but also of methods of preparation and administration, and the same uses were reported by Maconi in his book.More specifically, for 5 species , while in 18th century the mucilaginous water obtained by boiling the flaxseeds was added to fresh butter and then applied on the chest, specifically in children. As for Plantago spp., our informants, in accordance with what was written by Maconi, reported the use of leaves of plantain applied externally on burns and as a wound healing and anti-inflammatory remedy. For similar purposes, the author of the manuscript described the preparation of two different ointments, both obtained by mixing a poultice of plantain leaves with butter and other ingredients.A similar consistency with the data reported by Maconi could also be found in the cases of Agrimonia eupatoria. In the manuscript, the author referred to a complex remedy to treat leg ulcers. Specifically, they wrote: “Alle Piaghe: D’ogni sorte nelle Gambe, sebbene la Gamba fosse scoperta e mangiata fino all’osso”  [Erba del Vinil’, as not even the Italian common name was known to them. Furthermore, the primary data of our field investigation revealed that A. eupatoria was used in this fashion mainly until the 1960s–1970s, coinciding with the great migration of people from rural areas to the big cities and foreign countries. Finally, extensive bibliographic research conducted on ethnobotanical published works on neighboring areas has shown that in Lombardy, A. eupatoria was either used to treat different pathologies  . This reryngitis ; Vitalinryngitis ), or notryngitis ,35,36,37faggio’ and the vernacular name ‘fó’. Concerning herbaceous plant species, among the most abundant we cite Achillea millefolium L., Agrimonia eupatoria L., Arctium lappa L., Artemisia L. spp, Carum carvi L., Chelidonium majus L., Cichorium intybus L., Equisetum arvense L., Polypodium vulgare L., Filipendula ulmaria (L.) Maxim., Foeniculum vulgare Mill., Gentiana L. spp, Hedera helix L., Hypericum perforatum L., Malva sylvestris L., Ruta graveolens L., Salvia L. spp, Urtica dioica L., and Vaccinium myrtillus L. [Valle Imagna is located in the western area of Orobic Prealps, in the province of Bergamo, Lombardy, Northern Italy . The higillus L. For our investigation, we focused on upper Valle Imagna, specifically on the municipalities of Berbenno (675 m a.s.l.), Brumano (911 m a.s.l.), Corna Imagna (736 m a.s.l.), Costa Valle Imagna (1.014 m a.s.l.), Fuipiano Valle Imagna (1.055 m a.s.l.), Rota d’Imagna (690 m a.s.l.), and Sant’Omobono Terme (427 m a.s.l.).In preparation of the field work, preliminary bibliographic research on the territory and the spontaneous flora of Valle Imagna was performed through the consultation of local botany textbooks ,21,22,23TM files : an ‘Informant Sheet’ for data concerning the informants and a ‘Species Sheet’ for data concerning the plant species cited and their traditional uses throughout the Valley. Specifically, the “Species Sheet” consisted of a 7-column table arranged as follows: Species (common and vernacular name), Field of use, Detailed use, Preparation form, Administration form, Part of the plant, Other information. Each “Informant Sheet” was then matched to the corresponding “Species Sheet” through a one-to-one identification code. Identification of the species was performed by Professor Gelsomina Fico, Professor Claudia Giuliani, and Dr. Paola Sira Colombo following Pignatti et al., 2017 [http://www.worldfloraonline.org/ (accessed on 14 July 2023) [Subsequently, open- and semi-structured interviews were conducted. All the information gathered during the interviews was archived in Microsoft Wordl., 2017 . Plant sly 2023)  for the TM spreadsheet  where each row represents a ‘citation’, defined as ‘a single use reported for a single species by a single informant’. Every citation was considered as ‘distinct’, when differing from one another in at least one of the following fields: species, informant id code, category of use, part of the plant, preparation, and administration form. Data was processed and analysed by means of Pivot tables.All data was filed away in a database, organized in an ExcelSpearman’s correlation test was carried out to detect a relationship between the age of informants and their plant-related knowledge. Mann–Whitney was performed to check for statistical significance between sex of informants and their ethnobotanical knowledge. To measure the similarity of the different data sources in terms of reported taxa and uses, we performed the Jaccard Similarity Index , in order to account for artefacts due to the difference in diversity between the considered data sources) .For the comparisons among the different sources, we defined ‘use’ as ‘category of use’, namely the affected organ groups, such as ‘digestive tract disorders’, ‘urinary tract disorders’, etc. The followed criterion for the classification of the different categories of use was based on previous published works ,41,42,43For the comparison between the 18th and 20th century remedies and the 21st century ones, we consulted Milani and Fico, 2021  and MacoArtemisia absinthium AND digestive system, Agrimonia eupatoria AND skin) and then the specific pathology or activity . We focused our attention particularly on systematic reviews and meta-analyses, if possible, or on single in vitro, in vivo, and clinical trials studies, and we applied no time filters. Extensive bibliographic research in the ethnobotanical, phytochemical, and concerning the biological activities of the 99 identified species mentioned during the interviews was carried out through search engines and online databases, such as PubMed, MEDLINE, Google Scholar, and the bibliographic research online tool known as J.A.N.E. Concerning the ethnobotanical research, the scientific or English common name of the species was combined with the keywords ‘ethnobotany’, ‘ethnopharmacology’, ‘traditional medicine’, or ‘folk medicine’. Special attention was paid to Italian ethnobotanical works published and, specifically, the ones concerning the neighboring areas to Valle Imagna. As for phytochemistry and biological activities, we paired the scientific or English common name with specific keywords concerning the category of use cited in Valle Imagna (i.e., Our previous analysis of a little 18th century manuscript found in Valle Imagna was the starting point of the case study reported in this paper. The library where the manuscript was retrieved was part of a private 17th century house, stocked with historical documents related to the valley, and the presence in the text of vernacular words from the province of Bergamo could be indication of the provenance of the author. As for the purpose of such a piece, the personal and professional notes that the anonymous author added to various remedies would suggest that the work was considered more than a mere copy from other sources. Even the size of the booklet hinted at its practicality to be carried around and produced when a consultation was needed, maybe even by a medical practitioner of the territory.The first comparison with published books concerning 20th centuries folk medicine in the valley prompted us to deepen our understanding of the traditional knowledge still surviving nowadays in Valle Imagna, specifically on the uses of plant species. Our survey revealed that, especially after the 1960s and 1970s great migrations from the valley, this knowledge was almost completely lost to the passage of time and the fading of memories. However, a few older people of the valley could still recall some of the traditional uses of spontaneous plant species and being able to retrieve this information and partly stop the loss of memories was certainly an important step.The diachronic comparison among the historical sources involved in this analysis confirmed a general pattern of decline in the information concerning both number of taxa and their uses across the centuries, from the 1700s, represented by the manuscript, through the early 1900s, described by Maconi, to the first two decades of the 2000s, highlighted by our field investigation. Another clear example of the pending loss of knowledge concerns the uses of the first 10 frequently mentioned species during the fieldwork, compared to the ones of the historical sources.Agrimonia eupatoria undoubtedly piqued our interest, due not only to the shared purpose of use and desired outcome of the remedies, but also to some similarities concerning the part of the plant used and their administration form. Moreover, although some of the other species are commonly used throughout Lombardy, the bibliographic investigation concerning the ethnobotanical studies conducted in neighboring areas underlined the specific and identifiable use of agrimony in Valle Imagna.However, among the similar uses, the 18th and 21st century preparations regarding fil rouge across centuries of traditional knowledge of Valle Imagna, with unfortunately only slivers of the ancient remedies of the 18th century surviving the passage of time.Further investigation is certainly mandatory but ultimately, our analysis of the sources allowed us to likely sketch a


Adequate saliva flow and salivary urea concentration are important parameters for a healthy periodontium. In this study, the relationship between Periodontal Diseases and the History of opioid addiction was investigated by measuring the Salivary Urea and Stimulated Saliva Concentration.P-value <0.05 was considered as the significance level.This case-control study was conducted on 240 patients (120 cases and 120 controls) in 2021 referred to addiction treatment centers and the dental clinic in Iran, Birjand. The control and case groups were matched in terms of age. Demographic, base data, and clinical examination results were collected by a checklist. Data were analyzed using SPSS 19 and one-way ANOVA and chi-square tests. P-value = 0/000). Salivary urea concentration significantly increased in both case and control groups with an increase in periodontitis severity , but there was no significant relationship between the stimulated saliva flow rate and the severity of periodontitis in these two groups .Periodontitis severity was significantly higher in the case group than in the control group (Following the use of opioids, the flow of saliva decreases, and with the exacerbation of the periodontal disease, the concentration of urea in saliva increases. Therefore, it seems that the analysis of saliva parameters, including urea concentration, can be useful for the diagnosis of periodontal disease, and saliva urea concentration is not directly related to opioid use. Opioids cause oral dryness, discoloration of oral tissues and periodontal diseases .The primary cause of periodontal diseases is microbial plaque, and factors such as lack of oral hygiene, smoking and opioid addiction. In addition, oral dryness and tooth decay can accelerate microbial plaque formation and disease progression . A higheThe saliva volume depends on various factors such as stimulation, circadian rhythm, diet, age, drugs and hydrogen ion concentration, and these factors can change due to pathological conditions such as periodontitis . Clinica2), which are very destructive to periodontal tissues; therefore, the analysis of salivary urea concentration reflects the disease activity and severity [A sufficient salivary flow rate is a prerequisite for oral health, and the salivary urea concentration is an important parameter for tooth and gingiva health ,15. The severity .Although several epidemiological studies have shown the relationship between periodontitis and opioid addiction, there is little information about the mechanisms of occurrence and severity of periodontitis in opioid addicts. Therefore, the salivary urea concentration as one of the salivary biomarkers affecting periodontium was investigated in the present study to evaluate its effect on the periodontal status of opioid addicts and the control group.22.1In the present case-control study, 120 people were assigned to the case group and were selected from patients referred to addiction treatment centers and 120 people were also assigned to the control group and were selected from patients who visited the Periodontology Department of the Faculty of Dentistry and Samen Dental Clinic in Birjand in 2021.2.2Inclusion criteria included the mean age of 20–40 years and addiction to opioids in the case group for at least one year. Exclusion criteria also included patients with underlying diseases such as diabetes, immunodeficiency, leukemia, hepatitis, Human Immunodeficiency Virus (HIV), upper respiratory infection, necrotizing ulcerative gingivitis (NUG) mucosal lesions and invasive periodontitis or undergoing periodontitis treatment, a history of regular use of mouthwashes and taking antibacterial or anti-inflammatory drugs in the last three months and taking vitamin supplements, a history of chemotherapy and radiotherapy that caused xerostomia (17).2.3Data was collected by a checklist which included demographic, baseline data and clinical exam results. Demographic information included age, gender, place of residence, occupation, level of education, and base data included opioid addiction, type of opioid , route of abuse, , and duration of opioid addiction .2.4Then periodontal tissue examination was carried out by measuring clinical attachment loss (CAL) at six sites and recorded on each tooth, except third molars using William's probe and the results were recorded in the information form and calibrated by a senior dental student (17). According to the degree of attachment loss, the samples were divided into four groups: no periodontitis, mild periodontitis (CAL = 1–2 mm), moderate periodontitis (CAL = 3–4 mm), and severe periodontitis (CAL = 5 mm and more) .2.5To collect stimulated saliva, each participant was asked to chew a piece of unflavored rubber dam for 1 min to collect his/her saliva in a calibrated falcon tube between 9.00 a.m. and 12.00 p.m. Saliva samples were refrigerated at 4 °C for salivary urea (17). The stimulated salivary concentration was observed and recorded on the calibrated falcon. Salivary samples were analyzed to assess the salivary urea .2.6This study was approved by the ethics committee of the Birjand University of Medical Sciences with the ethics code number IR.BUMS.REC.1399.300. Before participating in the study, patients completed an informed consent form. In addition, they were assured of the confidentiality of their information.2.7P-value<0.05 was considered as the significance level.The results of the evaluations were recorded in the information form and entered into SPSS ver. 19. Data analysis was carried out using Chi-square and one way ANOVA tests and a 3P-value<0.05), but there was no significant relationship between the stimulated saliva flow rate and the severity of periodontitis in these two groups . More details was presented in Prevalence of higher degrees of periodontitis is higher in the case group; moderate periodontitis 32.5 vs. 20.8% and severe periodontitis 27.5 vs. 9.2% . The resP-value<0.05) but there was no significant relationship between periodontitis severity with the route of abuse (smoking-non-smoking), type of opioid  and the duration of addiction  (The results of the Chi-square test showed that the periodontitis severity in drug addicts is significantly higher than in the control group (ue>0.05) .Table 2T4Different salivary biomarkers are used for screening and predicting early changes in periodontal tissues and for determining the effectiveness of treatment because they enable rapid screening as well as an accurate and valid assessment of periodontitis severity .In the present study, there was no significant relationship between the stimulated saliva flow rate and the periodontitis severity in both case and control groups; however, the saliva flow rate increased in the case group with an increase in the periodontitis severity, but this relationship was not significant. Idrees et al. (2018) and Rajesh et al. (2015) found that unstimulated saliva secretion increased significantly with increasing severity of periodontitis ,23. Hiro2 by bacterial urease enzymes, which is an important way to increase pH in the oral cavity. Ammonia, which is potentially cytotoxic, increases the epithelium permeability to other antigenic and toxic substances and plays a fundamental role in the initiation of periodontitis [The present study revealed a significant increase in the saliva urea concentration of both groups with an increase in the periodontitis severity, which is consistent with the results of the study by Patil et al. (2020). Patil et al. reported a statistically significant increase in urine analysis (UA) levels in smokers with severe periodontitis compared to other groups  . Bezerradontitis . Luke etdontitis .Gaál Kovalčíková (2019) showed that periodontitis increases the salivary urea concentration, but it is most likely not a result of blood contamination. In this study, blood was artificially added to the saliva of a group of patients, and tests showed that salivary urea increased only with very high levels of blood contamination , which was not normally present in the patients .The results revealed that periodontitis was significantly more severe in drug addicts compared to the control group, which is consistent with the study by Saini et al. 2013). Saini reported a high prevalence of periodontitis with severe plaque build-up, which is characterized by attachment loss. Most addicts have a high rate of plaque accumulation, deposits due to the neglect of oral hygiene, dry mouth, and changes in the microbial profile. The use of drugs such as opioids leads to the suppression of pain responses and causes the patient to ignore the symptoms of tooth decay, periodontal diseases and limited access to dental care 013. Sain.The result of a meta-analysis study showed that drug type was associated with periodontal disease  and pooled estimates showed that type of drug used increased the odds of the number of decayed, missed and filled teeth (DMFT)  respectively . Also, tThere was no significant relationship between periodontitis and the type of opioid (smoking-non-smoking), routes of abuse  and the duration of addiction. Ye et al. (2014) stated that community periodontal index (CPI) scores were higher in people with four-year opioid abuse than those with shorter addiction durations . In a lo4.1During the collection of saliva, saliva could flow out of the falcon in 1 min, so the amount of stimulated saliva was measured approximately.Also at first, our goal was to investigate salivary urea in opium, marijuana, hashish, heroin, amphetamine, methamphetamine, and cocaine users. Since marijuana users did not go to the addiction treatment center for withdrawal, and cocaine, heroin, and hashish use was rare in Birjand city, the study samples were selected from opium, methadone, and methamphetamine users.5Following the use of opioids, the flow of saliva decreases, and with the exacerbation of the periodontal disease, the concentration of urea in saliva increases; therefore, it seems that the analysis of saliva parameters, including urea concentration, can be useful for the diagnosis of periodontal disease, and saliva urea concentration is not directly related to opioids use.Marzie Eydzadeh: Performed the experiments; Contributed reagents, materials, analysis tools or data; Wrote the paper.Parvin Parvaei: Conceived and designed the experiments; Performed the experiments.Freshteh Osmani: Analyzed and interpreted the data.Data associated with this study has been deposited at birjand university medical science under the accession number 09105477044.The authors declare no conflict of interest.


Background and Objectives: Few studies have investigated the relationship between female reproductive hormones, especially estrogen, and the incidence of cataracts. This study sought to evaluate the effects of hysterectomy on the risk of lens opacity in Korean women. Materials and Methods: This retrospective cohort study utilized data collected from 2007 to 2020 for 255,576 postmenopausal women in the Korean National Health Insurance database. Participants were divided into those who did and did not undergo hysterectomy. The hysterectomy group was further divided into two subgroups according to the type of adnexal surgery performed. The prevalence of cataracts was then compared among the control, hysterectomy alone, and hysterectomy with adnexal surgery groups. Results: The control group included 137,999 participants who did not undergo hysterectomy, while the treatment group included 93,719 women who underwent hysterectomy alone or in combination with adnexal surgery. The incidence of cataracts was higher in the control group than in the treatment group, as demonstrated in a 1:1 propensity score-matching analysis adjusted for potential confounding variables. Conclusions: The incidence of cataracts was significantly lower in the group with hysterectomy than in the control group, but the difference was subtle. The current findings may aid in identifying the role of female reproductive hormones in cataract development. Cataracts are among the major causes of blindness in older adults worldwide . Given tEstrogen is one of the most important reproductive hormones in women. Endogenous exposure to female reproductive hormones starts with the release of estrogen from the ovary , which iIn an experimental rat model, estrogen exerted a protective effect against the apoptosis of lens epithelial cells . Estroge+ [+ in the lens was associated with cataract generation [Some studies suggest different effects of estrogen on cataracts. There was a study that showed that progesterone and 17-estradiol induced an increase in Ca2+ , and a sneration ,17,18. Ineration ,20, and neration . Hysterectomy, one of the most common gynecological surgeries , has beeTo address these issues, the present retrospective cohort study analyzed Korean National Health Insurance data collected from 2007 to 2020 to identify the relationship between hysterectomy and the incidence of cataracts in Korean women.All citizens of South Korea are legally obliged to enroll in the country’s health insurance program, The National Health Insurance Service (NHIS). The NHIS has medical information for 51 million Koreans, such as age, sex, diagnosis, drug prescription, type of surgery, type of medical insurance, hospitalizations, and outpatient examinations. The NHIS shares most of this information with the Health Insurance Review and Assessment Service (HIRA), which was established to examine the suitability of billed medical expenses to prevent disputes between the NHIS and hospitals over insurance payments. This population-based retrospective cohort study analyzed HIRA data collected between January 2007 and December 2020. This study used the International Classification of Diseases, 10th revision, and Korea Health Insurance Medical Care Expenses  for participant selection and statistical analysis. In this study, the hysterectomy group comprised women aged 40–59 years who underwent hysterectomy for uterine myoma or elective hysterectomy between 1 January 2011 and 31 December 2014. When adnexal surgery ; incision and drainage of ovarian cyst; ovarian wedge resection; and adhesional adnexectomy) was performed on the same day, the case was defined as hysterectomy with simultaneous adnexal surgery. The hysterectomy date was set as the day of inclusion. Cases of any cancer or benign lens disease (H25 (disorders of lens), H26 (other cataract), H27 (other disorders of lens), H28 (cataract and other disorders of lens in diseases classified elsewhere)) diagnosed within 180 days of inclusion were excluded from both groups. Among the hysterectomy and control groups, 1:1 propensity score matching was performed for factors such as age, year of inclusion, socioeconomic status (SES), region, Charlson Comorbidity Index (CCI), parity, adnexal surgery before inclusion, hypertension, diabetes mellitus, dyslipidemia, menopause, and menopausal hormone therapy (MHT) before inclusion.Patients who visited any hospital with cataract-related diagnostic codes  more than thrice were considered to have cataracts.Participants whose medical insurance was medical assistance were defined as having a low SES. Non-metropolitan regions were defined as rural areas. CCI was obtained in accordance with the method reported by Quan et al. , using dp-value < 0.05 was considered statistically significant. All statistical analyses were performed using SAS Enterprise Guide 7.15  and supplemented with R 3.5.1 . A The Cochran–Mantel–Haenszel test was used to analyze categorical variables, and the Wilcoxon signed-rank test was used to analyze continuous variables. Standardized differences were used to evaluate variables subjected to matching. Stratified Cox regression analysis was performed to determine the contribution of hysterectomy to cataract risk after adjusting for confounding factors. The first day for Cox analysis was set as the inclusion day for each group, and the last day was set as the date of the end of the study (31 December 2020). The listwise deletion method was used when the missing value was less than 10%. When the missing value was greater than 10%, a regression imputation method was applied. To confirm the robustness of our study, stratified Cox regression analysis was performed on participants who underwent laparotomic hysterectomy to analyze the risk of cataract formation. Continuous variables are expressed as median values , and categorical variables are expressed as numbers (percentages). Cox proportional hazards models were implemented to adjust for various confounding factors and as a sensitivity test after selecting cases prescribed by an obstetrician in the MHT group. All analyses were performed using two-sided tests. This study was approved by the Institutional Review Board (IRB) of Sanggye Paik Hospital . Before releasing the medical information to researchers, HIRA removes identifying variables for each patient. Furthermore, HIRA permits analysis only on closed servers, and only the anonymized resultant tables, figures, and numbers can be taken outside the server. Therefore, researchers are fundamentally unable to specify each patient, and there are no possible disadvantages for the participants. In accordance with the Bioethics and Safety Act of South Korea, these participants were not obliged to provide informed consent. Therefore, raw data could not be provided.Data were extracted for 255,576 patients who underwent national examinations by the Korean Health Insurance Corporation. Among these patients, 145,856 were classified into the non-hysterectomy group, while 93,179 were classified into the hysterectomy group. After 1:1 propensity score matching, 84,757 participants were included in the two groups  . The medp = 0.004) in the hysterectomy group, 0.924  in the hysterectomy alone group, and 0.844  in the hysterectomy with adnexal surgery group. After adjusting for hysterectomy, age, SES, region, CCI, parity, adnexal surgery, hypertension, diabetes mellitus, dyslipidemia, menopause, and MHT before inclusion, the hazard ratios for cataracts were 0.886  in the hysterectomy group, 0.91  in the hysterectomy alone group, and 0.822  in the hysterectomy with adnexal surgery group. After additional adjustment for MHT after inclusion with previous variables, the hazard ratios were 0.902  in the hysterectomy group, 0.924  in the hysterectomy alone group, and 0.842  in the hysterectomy with adnexal surgery group. Cataract formation was observed in 1787 (2.1%) patients in the non-hysterectomy group and 1648 (1.9%) patients in the hysterectomy group. In the subgroup analysis, the number of patients with cataract formation was 1235 (1.9%) in the hysterectomy alone group and 413 (2.2%) in the hysterectomy with adnexal surgery group . Before p = 0.034)  . p = 0.77) in the hysterectomy group, 0.998  in the hysterectomy alone group, and 0.919  in the hysterectomy with adnexal surgery group among participants aged 45–49 years; 0.845  in the hysterectomy group, 0.883  in the hysterectomy alone group, and 0.877  in the hysterectomy with adnexal surgery group among participants aged 50–54 years; and 0.813  in the hysterectomy group, 0.872  in the hysterectomy alone group, and 0.724  in the hysterectomy with adnexal surgery group among participants aged 55–59 years , both hysterectomy alone and hysterectomy with adnexal surgery were shown associated with a lower prevalence of cataracts. Estrogens released from the ovary play important roles in the reproductive system . HysterePrevious studies have reported compromised ovarian function after hysterectomy based on changes in estradiol levels, follicle-stimulating hormone, and anti-Mullerian hormone ,35. EstrSince surgical menopause occurs earlier when adnexal surgery is performed with hysterectomy, the risk of cataract incidence was compared by dividing the cohort into a hysterectomy alone group and a hysterectomy with adnexal surgery group. Adnexal surgery, including any kind of operation , affects ovarian function. Previous studies have indicated that unilateral oophorectomy may cause failure of the contralateral ovary independent of hysterectomy ,37. ConcHowever, after adjusting for variables including MHT, hysterectomy alone was not associated with the risk of cataracts. Previous studies on the relationship between MHT and cataract risk have reported limited and inconsistent results. In the Beaver Dam Eye Study, MHT was associated with a lower incidence of cataracts, and a later onset of menopause was associated with a protective effect against nuclear sclerosis of the lens . In contIn the present study, MHT after inclusion decreased the risk of cataracts. This result supports the hypothesis of previous studies that estrogen has a protective effect on cataract formation. However, the drug’s type, dose, and duration could not be identified because MHT after inclusion was used as a variable in this study. Additionally, MHT use was significantly more frequent in the hysterectomy group than in the non-hysterectomy group due to the development of surgical menopause after hysterectomy. This study could not verify the effect of MHT as a sole variable on cataract incidence because 1:1 propensity score matching was performed to compare the hysterectomy and non-hysterectomy groups. To our knowledge, this is the first large-scale, single-race study on the relationship between hysterectomy and cataract formation. Our study is also advantageous compared to previous studies, given that the data were acquired from the National Health Screening Program and NHIS; thus, this study included participants from all regions of Korea. Furthermore, analyses were adjusted for numerous variables , and 1:1 propensity score matching was performed.This study had several limitations. First, cataract types could not be identified because the cataract diagnostic codes used in this study did not differentiate between cataract types. Second, the effects of the type of adnexal surgery on cataract formation could not be identified because the number of surgeries performed was not available due to the policies of the NHIS. In addition, as “cataract” was identified by its diagnostic code in this study, the disease severity could not be diagnosed. It was, therefore, difficult to decide whether the cataract affects the visual function or requires surgery.The current findings indicate that the incidence of cataracts is lower among patients who have undergone total hysterectomy than among those who have not. Subgroup analysis further revealed that the hazard ratio for cataract formation was lower in the hysterectomy with adnexal surgery group than in the hysterectomy alone and non-hysterectomy groups. In this study, the incidence of cataracts decreased after surgical menopause, which conflicted with the effects of estrogen on cataract formation in majority of previous studies. The exact mechanism between estrogen and cataract, including surgical menopause, needs further research. This study analyzed the data of approximately 250,000 Korean Health Insurance Corporation participants and included 160,000 women in analyses adjusted for cataract risk factors. To the best of our knowledge, this is the first large-scale study to provide relevant findings that may be beneficial in understanding the effects of hysterectomy and estrogen on cataract progression.


The analysis included patients seen 6 months before or after Hurricanes Gustav and Ike in 2008 and who were diagnosed with HTN, DM, or anxiety. There was a statistically significant association between post-disaster and diagnosis of hypertension, X2  = 3.985, p = 0.04. There was no association post-disaster and diabetes X2  = 0.778, p = 0.378 or anxiety, X2  = 0.017, p = 0.898. The research showed that there was a change in the diagnosis of HTN after a disaster. Changes in HTN are an additional important consideration for clinicians in disaster-prone areas. Data about non-communicable diseases help healthcare disaster planners to include primary care needs and providers in the plans to prevent the long-term health impacts of disasters and expedite recovery efforts.People impacted by disasters may have adverse non-communicable disease health effects associated with the disaster. This research examined the independent and joint impacts of federally declared disasters on the diagnosis of hypertension (HTN), diabetes (DM), anxiety, and medication changes 6 months before and after a disaster. Patients seen in zip codes that received a federal disaster declaration for Hurricanes Gustave or Ike in 2008 and who had electronic health records captured by MarketScan The number and frequency of disasters increased by a factor of five in the last 50 years . DisasteThis study addresses gaps in existing research related to new onset metabolic and anxiety disorders following disasters and identifies the impact of the disasters on persons living with these disorders. An emphasis on linking data to social determinants of health (SDOH) and Census data in areas that received federal disaster declarations is included. It was established that the percentage of individuals who live with metabolic and anxiety disorders increased steadily. Among the increased conditions, this study addresses HTN, DM, and anxiety .Like other public health emergencies, African Americans, Latinx, Native Americans, Alaska Natives, and those with low income are disproportionately impacted. An analysis of the Federal Emergency Management Agency (FEMA) National Risk Index Score indicated that U.S. indigenous people are at the greatest risk from natural hazards, including hurricanes, volcanic activity, avalanches, extreme cold, drought, flooding, wildfires, and ice storms. The analysis also showed that Black or African Americans have the lowest overall risk from natural disasters, but they have the highest risk of negative impacts based on expected annual loss, social vulnerability, and community resilience ,11. FollThe number of people diagnosed with DM also grew from 6.4 million to 26.8 million from 1990 to 2018 , with 80It was documented that after 9/11, major earthquakes, and Hurricane Katrina, there was an increase in cardiovascular disease and deaths . Two sepa priori belief that because disasters are inherently stressful events, anxiety would rise.Anxiety disorders are characterized by “unpleasant feelings of stress, uneasiness, tension, and worry [and] is either the predominate disturbance or is expected in confronting a dreaded object or situation or is resisting obsessions or compulsions” . The impA frequent concern for people with non-communicable diseases is difficulty obtaining prescribed medications in the aftermath of a disaster. This may be exacerbated by the just-in-time resupply of medications and individuals not having more than a week of medication before the insurance company will pay for a refill. Jimmez-Mangual found that 77% of people in their study of Hurricane Maria survivors reported problems with medications, and 47.7% reported difficulty getting to the pharmacy . In addiPreliminary studies of mapping capabilities related to disaster risks indicated there is considerable publicly available data on environmental hazards and natural disasters, but a lack of knowledge of the risks and necessary response by healthcare providers ,33,34. FThe United Nations Office on Disaster Risk Reduction (UNDRR) noted the increased risk of disaster resulting from climate change and the growing number of deaths and persons impacted by disasters. “Between 2000 and 2019, 510,837 deaths and 3.9 billion people were affected by 6681 climate-related disasters” . This maAim 1. Determine the independent and joint impacts of federally declared disasters on metabolic and anxiety disorders 6 months after a disaster. The change will be evaluated to determine the impact of disasters on outcomes for patients with HTN, DM, and/or anxiety. We hypothesize, based on preliminary data, that disaster survivors will show an increased rate of metabolic and anxiety disorders 6 months after the disaster.Aim 2. Determine the independent and joint impacts of federally declared disasters on the medications prescribed for metabolic and anxiety disorders 6 months after a disaster. The change will be evaluated to determine the impact of disasters on medications. Using the medications prescribed, we hypothesize that disaster survivors diagnosed with metabolic or anxiety disorders have more medications ordered than controls.Aim 3. Examine regional  environmental hazard risk integrating hazard data and data about population vulnerabilities that would affect healthcare workers’ treatment approach. Begin to develop recommendations for provider and community education to mitigate potential disaster health-related risks.®  from patients seen in zip codes that received a federal disaster declaration because of either Hurricane Gustave or Ike and attempts to answer the proposed research questions. MarketScan® was selected because it has patient-level longitudinal data that maintain the exact date of service. Because pre- and post-disaster data were being compared, the precise dates of service were essential. Additionally, because their data included the lifespan, there was not an overrepresentation of those over 60 years old, which usually occurs with Medicare data.This longitudinal, population-based cohort study used electronic health records data reported in MarketScanThe conceptual framework of this study was based on the public health crisis conceptual model that was adapted from the crisis conceptual model and the social justice in nursing and public health preparedness human-centered structured analytical approach  33,37].,37.33,37In 2008, Hurricane Gustave a made la® data comes primarily from large employers; small employers may be underrepresented, and it does not include Medicare (except for those for retirees with employer-paid Medicare supplements). The study included individuals ≥18 who had a documented diagnosis of HTN, DM, or anxiety, with at least one visit to a primary care provider 6 months before and 6 months after a federally declared disaster, were treated in one of the declared regions in Louisiana, and whose healthcare data were captured in MarketScan®. As such, the sample was a convenience sample of those whose information is captured in the MarketScan® dataset.MarketScan® databases of de-identified patient-level health data, ICD-9 codes for HTN, DM, and anxiety were used to identify patients who were diagnosed with HTN, DM, or anxiety 6 months before and after the disasters. Working with the Center for Translational Science Center at the University of New Mexico, SAS Analytical Software was used to collect data from MarketScan®. Data were provided to the research team in Excel and imported into SPSS 26 for analysis.Using the MarketScanThere was a total of 13,681 patients who met the criteria of having a diagnosis of HTN, DM, or anxiety six months before  or after (14 September to 13 March 2009) Hurricanes Gustave and Ike, and who received care in an area that received a federal disaster designation.Noncommunicable chronic conditions  and medication data were analyzed, and trends were identified, looking for previously unidentified evidence that disaster can cause or exacerbate health conditions. Changes in disease-specific diagnosis and medication use rates were assessed between the pre-disaster and the post-disaster. This is significant because much of the policy related to disaster relief is specific to events caused by a disaster and does not cover events only exacerbated by a disaster.Demographic characteristics of patients were compared using Pearson’s chi-squared test for categorical variables and a t-test or Mann–Whitney U test for continuous variables. A patient diagnosis was included if their visit occurred within six months before or six months after the disaster. Individual patients could have more than one diagnosis.A binary logistic regression was conducted. Association between exposure to disaster (post-disaster) and diagnoses are shown as odds ratios (ORs) with 95% confidence intervals (CIs). No collinearity between variables was observed. The regression models showed an overall statistical significance of α < 0.05 and the goodness-of-fit of α > 0.05 (Hosmer–Lemeshow test). Therefore, the assumptions to conduct the analysis were met. All analyses were conducted using SPSS 26 .Study 22–215 was submitted to the University of New Mexico, Health Sciences Center IRB, and determined not to be human subjects research.Census estimates for 2008 for Louisiana were used to estimate the total population and population characteristics. FEMA disaster declarations were mapped for the USA from 2012 to 2022 as an estimate of the disaster by region and type. All mapped data were shared on GitHub. Additionally, declared counties were identified and mapped for comparison with the 10-year average.The overall number of unique patients diagnosed with HTN, DM, and/or anxiety within six months before and after the disaster was 13,681. During the control period before the disaster, 9567 (49.5%) unique patients were diagnosed with HTN, DM, or anxiety, and 9761 (50.5%) after the disaster.The analysis for medication included a total of 11,911 unique patients . There was no significant difference in medications before or after the disaster in patients diagnosed with HTN, DM, or anxiety.The patients’ characteristics were similar in the two periods . The mea2  = 3.985, p = 0.04. There was no association post-disaster and diabetes X2  = 0.778, p = 0.378 or anxiety, X2  = 0.017, p = 0.898.A chi-square test of independence was performed to examine the relationship between the diagnosis of hypertension, diabetes, and anxiety and exposure to the disaster. There was a statistically significant association between post-disaster and diagnosis of hypertension, XaOR 1.19, 95% CI: 1.09–1.30), DM , and anxiety    after adOur final analysis for prescribed medication included a total of 11,911 unique patients . A total of 11,911 unique patients were prescribed medications—a total of 8498 unique ones before the disaster and 8671 after the disaster. On average, 3.22 (SD = 2.88) medications per patient were prescribed during the six months preceding the disaster, and 3.21 (SD = 2.87) medications were prescribed after the disaster.t-test was conducted to compare the number of medications prescribed for hypertension, diabetes, and anxiety before and after the disaster. Levene’s test  = 0.039, p = 0.838; d = 0.003) between the two groups. The mean number of medications per patient prescribed before the disaster was 3.22 (SD = 2.88), which was similar to the mean number of medications prescribed after the disaster . The magnitude of the difference in the means was 0.009 (95% CI: −0.077 to 0.095). The effect size (strength of the relationship) for this analysis was (d = 0.003), which according to Cohen (1976), is considered a very small effect size.An independent sample e’s test  for equat-test was conducted to compare the number of medications prescribed for hypertension before and after the disaster. Levene’s test for equality of variances  = 0.017, p = 0.386; d = 0.019) between the two groups. The mean number of hypertension medications per patient prescribed before the disaster was 2.29 (SD = 1.65), which was similar to the mean number of medications prescribed after the disaster . The magnitude of the difference in the means was 0.031 (95% CI: −0.039 to 0.102).An independent sample ariances  was condt-test was conducted to compare the number of medications prescribed for diabetes before and after the disaster. Levene’s test for equality of variances  = −0.094, p = 0.925; d = −0.003) between the two groups. The mean number of diabetes medications per patient prescribed before the disaster was 4.68 (SD = 3.42), which was similar to the mean number of medications prescribed after the disaster . The magnitude of the difference in the means was −0.011 (95% CI: −0.235 to 0.214).An independent sample ariances  was condt-test was conducted to compare the number of medications prescribed for anxiety before and after the disaster. Levene’s test for equality of variances  = −0.239, p = 0.811; d = −0.007) between the two groups. The mean number of hypertension medications per patient prescribed before the disaster was 3.70 (SD = 3.45), which was similar to the mean number of medications prescribed after the disaster . The magnitude of the difference in the means was −0.023 (95% CI: −0.208 to 0.163).An independent sample ariances  was condAmong those diagnosed with hypertension, diabetes, and/or anxiety either before or after the disaster, data were not surprising. In all cases, most people continued their medications. Fewer people diagnosed with any of the conditions discontinued medications than those diagnosed before the disaster and more people diagnosed after the disaster started new medications .® did not include information on race and ethnicity. Therefore, the Census data on race and ethnicity is important.The study population consisted of fewer individuals under the age of 55 (62.6%) compared to the Census data on the general population  of LouisThe United Health Foundation (2008) data analysis ranked Louisiana as 48th for HTN and 44th for DM in the USA. . This inThe number of hurricanes from the FEMA database is represented in 2  = 3.985, p = 0.04. The finding of a significant difference in the post-disaster diagnosis of HTN is inconsistent with the work of Kairo [The first aim explored metabolic and anxiety disorders 6 months after a disaster. The change was evaluated to determine the impact of disasters on outcomes for patients with HTN, DM, and/or anxiety after Hurricanes Gustave and Ike. The number of unique patients diagnosed with HTN, DM, and/or anxiety was similar before (49.5%) and after (50.5%) the disaster. Likewise, the patients’ characteristics were similar in the two periods. The only statistically significant association was the post-disaster diagnosis of hypertension, Xof Kairo  who founof Kairo , who fouThe second aim was to determine the independent and joint impacts of federally declared disasters on the medications prescribed for metabolic and anxiety disorders 6 months after a disaster. There was no statistically significant difference in medications before and after the disaster. Still, there was an increase in the number of medications started post-disaster for those diagnosed with HTN, DM, and anxiety. This is consistent with a new diagnosis and not unexpected. The study did not examine difficulties obtaining the medications as our data were related to the prescription.® data did not include information on race and ethnicity, the Census data demonstrated that Louisiana is a highly diverse state, with 32.8% of the population being Black or African American, 1.2% American Indian and Alaska Native, and 1.8% Asian. Because there is a “differential recognition of medical need as a function of ethnicity” [The third aim examined regional  environmental hazard risks integrating hazard data and data about population vulnerabilities that would affect healthcare workers’ treatment approach. The study began a preliminary examination of existing FEMA and Census data to begin to identify interconnections with the post-disaster diagnosis of HTN, DM, and anxiety. The data clearly indicated that Louisiana is among the states most heavily impacted by hurricanes and with the most statewide impact. Because it is 48th in HTN and 44th in DM, their rate of HTN and DM was above the national average before the disaster. While the MarketScanhnicity”  it shoulWe are beginning to develop recommendations for provider education and practice and community education to mitigate potential disaster health-related risks. Clinicians should know the potential hazards in their community and be familiar with community resources to help patients access care, including medications. Recommendations for education and practice include the importance of identifying disaster and health hazards in a region and region specific characteristics. In addition to helping patients prepare for disasters, clinicians must also be alert to potential health hazards resulting from the disaster and aftereffects, e.g., mental health issues, inability to assess medications, and increased risk of non-communicable diseases. With the knowledge that there is a statistically significant association between the six months before and after a disaster and a diagnosis of hypertension, steps can be taken to educate clinicians to screen for hypertension after a disaster and monitor medication compliance, as well as other potential health issues. Additionally, because exposure to the disaster was significantly associated with increased odds of being diagnosed with HTN, DM, and anxiety after adjusting for age and sex, it is recommended that there be increased screening in the primary care setting for these conditions in areas impacted by a disaster.The Public Health Crisis Conceptual Model  provides® data. MarketScan®, unlike many data sets, uses the exact date of services rather than deidentifying information by date; individual patients are coded, making it possible to track a patient before and after a disaster. This is valuable for longitudinal studies that examine health diagnosis and treatment before and after a disaster.The study was a large retrospective population-based cohort study of people diagnosed with HTN, DM, and/or anxiety 6 months before or after Hurricanes Gustave and Ike and reflected the real-world setting before and after a disaster and served as a model for using the MarketScan® data set was somewhat limited in that it had diagnoses, medications, and tests but did not include all desirable demographic information, such as race and ethnicity, for much of the data.The MarketScan® data were obtained primarily from large employers; small employers may be underrepresented, and it did not include Medicare (except for those for retirees with employer-paid Medicare supplements), and as such, not all persons affected by hurricanes Gustave and Ike were included in the data set.MarketScan® is a claims database and, as such, is a convenience sample.MarketScanThis research has two important implications for science and practice. First, it was determined that there was a statically significant increase in the diagnosis of HTN but no statically significant changes in the diagnosis of DM, and anxiety after a disaster. It is important to note that there is a key distinction between statistical significance and clinical significance. Although there was no statistically significant increase in the diagnoses of diabetes, anxiety, or prescribed medications, the management of these chronic conditions and the ability to acquire the necessary medication remains critical to the health and well-being of patients, especially during a disaster when people may have been displaced from their homes. Until there is more evidence, it is recommended that increased screening for HTN occur in the 6 months after a disaster. Further studies to evaluate the clinical and statistical significance of different types of disasters in different geographic location on persons living with chronic conditions such as DM, HTN, and anxiety are needed. Further research is ongoing to assess five different types of disasters in five different geographic locations and whether medications were obtained by patients when prescribed.Second, non-communicable chronic diseases and access to medications are essential considerations for clinicians, educators, and emergency planners in disaster-prone areas. This study illuminated the need to provide guidance and training for healthcare providers, health professions students, and emergency planners ensure that primary care needs, including non-communicable chronic diseases, are addressed in response plans, especially related to long-term health impacts of disasters. The findings related to medications identified a gap in the literature. Specifically, do patients prescribed new medications after a disaster have access to them?Although the study specifically addressed the impact of natural disasters on HTN, DM, and anxiety, there may be policy implications for implementing primary care screening for metabolic and anxiety disorders following a disaster and changing policy related to what is considered “caused by” a disaster.


The COVID-19 pandemic has had major impact on the daily lives of adolescents. This study examined whether mental health outcomes had changed over the pandemic, and if such changes were related to changes in physical activity (PA), sedentary time, sleep, screen time, and participation in organized sports.In this longitudinal study, data were collected in autumn 2019 with follow-up measurements in spring 2021. In total, 558 schools were invited and 34 schools around Stockholm with a variation in socioeconomic background were included. Physical activity and sedentary time were measured for seven consecutive days by accelerometry (Actigraph). Anxiety, health-related quality of life (HRQoL), psychosomatic health, stress, sleep duration, screen time, and organized sports participation were self-reported in questionnaires. Linear models were applied to estimate associations between changes in mental health outcomes and exposures.p < 0.001], increase in psychosomatic health problems , and an increase in the number of participants with high stress . Weekly light PA and sleep duration decreased and weekly sedentary time and screen time increased unrelated to changes in mental health outcomes. An increase in sleep duration during weekdays was significantly related to both a decrease in anxiety  and an increase in HRQoL .From the baseline sample of 1,139 participants, 585 (55% girls), mean (SD) age 14.9 (0.3) years, participated in the follow-up. Between 2019 and 2021, there was a decrease in HRQoL [mean difference −1.7 , During the COVID-19 pandemic, mental health appears to have been impaired in Swedish adolescents, but unrelated to changes in PA, sedentary time, screen time, or participation in organized sports. However, increased sleep duration on weekdays was related to less anxiety and better HRQoL. The results may help policy makers and other stakeholders comprehend the differential effects of the COVID-19 pandemic on mental health outcomes and help guiding the planning of policy actions.ISRCTN15689873. There has been an increase in self-reported mental health and psychosomatic health problems in recent years among Swedish adolescents , 2. GlobThe COVID-19 pandemic restrictions may have had an influence on current and future mental health among adolescents. It is therefore important to assess the impact of the pandemic on mental health so relevant interventions can be developed to mitigate its effects. In Sweden, restrictions related to the pandemic were minimal compared to those in many other countries. There was no lockdown but there were recommendations to keep physical distance, avoid crowding and large gatherings and non-essential traveling, and to stay home and avoid close contact with others when ill. Organized physical activities continued, albeit with adapted forms of participation, but matches and competitions were not allowed for adolescents. A large proportion of the physical education classes were performed outdoors. There were no school closures for adolescents but most schools had distance learning to some degree.Global findings on changes in mental health during the pandemic are a cause of concern, suggesting an impact on mental health among adolescents , 9. In aThe first phase of this study was performed between September and December 2019, thus providing unique data from just before the pandemic started. The data include multiple measures of mental health outcomes, device-measured PA, sedentary time, and health behaviors with a mean (SD) follow-up 18.4 (1.0) months later during the pandemic. The aim of this study was therefore to examine potential changes in mental health outcomes  and if such changes were related to changes in PA, sedentary time, and health behaviors  before and during the COVID-19 pandemic among Swedish boys and girls.n = 1,139) and in a follow-up in the same sample (n = 585) in April–June 2021.This longitudinal study used data from the study “Physical activity for healthy brain functions in school youth”  collecteSchools situated within a 2-to-3-h drive from Stockholm, Sweden were invited to participate in the study. Schools with a sports profile , with fewer than 15 students in each class, or with a student population that did not speak Swedish, were excluded. In total, 558 schools with students in grade seven (aged 13–14 years) were invited to participate in the study and 84 schools agreed to participate at baseline  or by post to individual students (n = 157). The teacher or student was asked to report the first accelerometer wear-day and the participant wore the accelerometer for seven consecutive days. The accelerometers were sent back in pre-paid envelopes. Information on how to log in to complete the web-based questionnaire was distributed by the teachers or by post. The link was also sent to the e-mail address that the participant had provided at baseline. The teachers provided information regarding the degree of distance learning during the accelerometer wear period. Information from schools that declined to assist in the data collection was provided by the participating students in the questionnaire or by e-mail. The participants received a gift card as a compensation .At baseline, the measurements were conducted at GIH by trained researchers. Physical activity and sedentary time were measured by accelerometry. Anxiety, health-related quality of life (HRQoL), psychosomatic health, stress, sleep duration, screen time, and sports participation were self-reported in questionnaires. Further methodological details can be found elsewhere . At follAt both measurements, the students gave written consent. The study was conducted in accordance with the Declaration of Helsinki and the protocol was approved by the Ethical Review Agency in Stockholm, Sweden (Dnr: 2019-03579 and Dnr: 2021-01235). Trial registration: ISRCTN15689873.Anxiety was measured using a short version of the Spence Children's Anxiety Scale (SCAS-S). The questionnaire includes 19 items and each item is rated on a four-point scale with the options of “never,” “sometimes,” “often,” and “always.” The scores are summed with higher values reflecting more symptoms of anxiety .Health-related quality of life was measured using the questionnaire Kidscreen-10 . The scaPsychosomatic health was assessed using the questionnaire Psychosomatic Problems Scale (PSP) . The scaStress was measured with the Single Item Stress Question (SISQ) . ParticiChanges in the mental health variables were calculated by subtracting the baseline values from the follow-up values. Change in stress was derived by including only those who had low stress at baseline  and categorizing them as continuing to have low stress or changing to having high stress .Time spent in PA and sedentary was collected during 7 days using hip-worn accelerometers . The same method for data collection and data processing was used at baseline and at follow-up described in more detail elsewhere . The proSleep duration was calculated using bed-time and time for getting up reported by the participants in the questionnaire for weekdays and weekends. The response alternatives were in 30-min intervals. Change in sleep duration was calculated in hours.The amount of screen time outside school hours (not including schoolwork) on weekdays and weekends was self-reported by the participants. The response alternatives were: no time at all, < 1 h, 1–2 h, 3–4 h, 5–6 h, and 7 h or more, and were categorized into ≤ 2 h, 3–4 h, and ≥5 h. The responses from baseline and follow-up were coded to reflect either an increase or decrease in screen time or no change in screen time.The participants reported in the questionnaire if they were active in any sports organization (yes/no). The answers from baseline and follow-up were combined to reflect change in organized sports:  no changRegister data on parental education was collected from the Statistics of Sweden and dichotomized into ≤ 12 years (low) and >12 years (high) of education. The highest level of education attained by either of the parents was used. The participant's and their parents' country of birth were reported by the participants in the questionnaire. Parents' country of birth was classified as “both born in Sweden,” “one born outside Sweden and one born in Sweden,” and “both parents born outside Sweden.”Baseline data was used on body mass index (BMI). Underweight, normal weight, overweight and obesity were defined according to the International Obesity Task Force recommendations, with different cut-off values depending on age and sex .n = 27) reported full distance learning.The amount of distance learning was self-reported at follow-up by the participants by asking them “Did you have distance learning during January to April 2021?” The response alternatives were “no, not at all,” “yes partially distance,” and “yes fully distance.” The two last alternatives were combined as very few  were analyzed in separate models with ANCOVAs , reported as non-standardized betas with 95% confidence intervals. The binary outcome (change in stress) was modeled using multivariable logistic regression models, reported as odds ratios with 95% confidence intervals. As the outcome variables showed minimal influence of clusters (0–1%), all the models were on one level. The independent variables included in the models were checked for multi-collinearity, but none was detected. Homoscedasticity assumptions were checked through plotting of residuals against predicted values and all residuals were visually checked for normality of distribution. All models were adjusted for gender, parental education, parental country of birth as well as the baseline value of the outcome variable. Wear time was added in the initial analyses and did not alter the results and was therefore not included in the final analyses. No imputations for missing data or loss to follow-up were performed. All statistical tests were two-sided with a significance threshold of P < 0.05. The data analyses were performed in IBM SPSS Statistics, version 27 .Descriptive statistics are presented as percentages or means with standard deviations. Differences between girls and boys for the background variables were tested with chi-square tests and independent From the baseline sample of 1,139 participants, 585 (51%) participated in the follow-up measurements. The mean (SD) age was 14.9 (0.3) years and 263 were boys (45%) and 321 girls (55%), one participant did not reveal gender. There were significant differences between the baseline and follow-up in gender composition, the proportions of parental country of birth, and the proportions of stress, as shown in p < 0.001], increase in psychosomatic health problems , and an increase in the number of participants with high stress , in the total sample and also among both boys and girls when stratified , p = 0.005], between baseline and follow-up measurements.Between 2019 and 2021, there was a decrease in HRQoL [mean difference −1.7 , fied see . There wp = 0.31), HRQoL (p = 0.11), psychosomatic problems (p = 0.11), and stress (p = 0.44). Accelerometer wear-time at baseline compared to follow-up was higher for all participants, mean (SD) 803 (56) min/791 (71) min, p = 0.007 and girls 806 (55) min/793 (77) min, p = 0.02.In total, 264 participants had valid accelerometer registrations for the whole week, both at baseline and follow-up. There were no significant differences between participants with and without valid accelerometer registrations in anxiety (p < 0.001), for girls , and for boys  but there was no significant change in MVPA, as shown in p = 0.04) and for boys .Between baseline and follow-up measurements, there was a significant decrease of an average of 20 min/day in light PA for the whole sample (p < 0.001)/, and also significantly among girls and boys when stratified  and during weekends from 49% to 67.6% (girls 47.5% to 70% and boys 51.3% to 64.9%).There was no significant difference between baseline and follow-up in organized sports participation.At follow-up measurements, 433 participants (78.6%) reported that they had some amount of distance learning during the spring period.B = −0.71, CI: −1.36, −0.06) and an increase in HRQoL . No significant relationships were found between changes in mental health outcomes and changes in MVPA, light PA, sedentary time, organized sports participation, and screen time.Results from the multivariable logistic regression are presented in To the best of our knowledge, this is the first longitudinal study with data on mental health outcomes in relation to detailed device-measured PA, sedentary time, and health behaviors, just before and during the pandemic. Our findings show that self-reported HRQoL, psychosomatic health, and stress have worsened in adolescents in Sweden during the COVID-19 pandemic but unrelated to changes in PA, sedentary time, screen time, or participation in organized sports. Nonetheless, an increase in sleep duration during weekdays was related to better mental health.n = 3,752) (n = 248) (n = 584)   also foun = 584) . Similarn = 584) , 23. StuThe observational design prevented any control group. Therefore, the mean change in the prevalence of mental health in this study cannot be fully attributed to the COVID-19 pandemic, as no comparable data are available. However, the main question was to investigate if any such changes were related to changes in PA variables. The main result from these analyses were that only few such relations were found. To what extent these findings can be relevant for other situations, i.e., without a pandemic, is difficult to assess. However, as we identify temporal changes between baseline and follow-up but only few relations to changes in PA, it can be hypothesized that smaller changes in mental health (possibly found in non-pandemic situations) would also be unrelated to changes in PA.Several studies have shown that the impact on mental health outcomes has been worse for females compared to males , 20, 23.The findings in this study showed no decline in MVPA. However, there was a decline in light PA and an increase in sedentary time. In addition, there was an increase in screen time and no change in participation in organized sports. This might imply that Swedish adolescents have not stopped participating in organized activities outside school hours but may be moving less in their everyday lives since they spent more time at home due to distance education. Studies from other countries showed declines in PA levels and increases in sedentary behavior during the pandemic , 11.This study also showed a decrease in sleep duration during the pandemic. Furthermore, sleep duration during weekdays was related to mental health outcomes, suggesting that an increase in sleep duration during weekdays was related to better HRQoL and less anxiety. Other studies that have measured sleep before and during the pandemic showed mixed results, including increased sleep duration , fewer sIn a study with Chinese children and adolescents, it was reported that longer screen time before and during the pandemic was associated with a higher risk of psychological symptoms . In the The major strength of this study is the longitudinal design with baseline data collected just before the pandemic in late 2019 and follow-up in the spring of 2021. Another strength is the detailed device-measured PA in relation to several mental health outcomes. One limitation was the loss of valid accelerometer measurements due to insufficient wear time. However, there were no significant differences between participants with and without valid accelerometer measurements in mental health outcomes. Another limitation of the study is that the sample was non-representative and therefore caution with generalizability should be taken. In addition, the drop-out rate between baseline and follow-up might also have impacted the generalizability of the study. However, the recruitment of schools was based on a variation in type of municipality and socioeconomic background of parents and attrition bias may be limited as the results showed few differences in variables between participants and drop-outs. Another limitation, as mentioned above, is that the effects on mental health outcomes might have been confounded by an expected age-related increase in mental health problems within this group and this could have led to a slight overestimation of the changes in mental health outcomes.The results suggest that the COVID-19 pandemic has impaired the mental health of Swedish adolescents and that the decrease in mental health was not related to changes in PA, sedentary time, screen time, or participation in organized sports. However, increased sleep duration during weekdays was related to positive changes in anxiety and HRQoL. The results of this study may help policy makers and other stakeholders comprehend the differential effects of the COVID-19 pandemic on mental health outcomes and help guiding the planning of policy actions.gisela.nyberg@gih.se.The datasets are not available for download to protect the confidentiality of the participants. The data are held at The Swedish School of Sport and Health Sciences. Anonymous data for meta-analyses can be provided upon request from the corresponding author. Requests to access the datasets should be directed to The studies involving human participants were reviewed and approved by the Ethical Review Agency in Stockholm, Sweden (Dnr: 2019-03579 and Dnr: 2021-01235). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.GN, BH, and KK conducted the data collection. BH and KK cleaned, processed, accessed, and verified the data. GN, BH, and ÖE selected the design of the statistical model. BH performed the analyses. GN drafted the manuscript. All authors contributed to the design of the study and the interpretation of the results. All authors contributed to the article and approved the submitted version.