Background: This study aimed to investigate the early and longitudinal humoral response in Healthcare Workers (HCWs) after two doses of the BNT162b2 vaccine and to assess the association between metabolic and anthropometric parameters and the humoral response after vaccination. Methods: The study included 243 fully vaccinated HCWs: 25.50% previously infected with SARS-CoV-2 (with prior history of COVID-19—PH) and 74.40%—uninfected, seronegative before the first vaccination (with no prior history of COVID-19—NPH). IgG antibodies were measured, and sera were collected: prior to the vaccination, 21 days after the first dose, and 14 days and 8 months after the second dose. Results: 21 days after the first dose, 90.95% of individuals were seropositive; 14 days after the second dose, persistent immunity was observed in 99.18% HCWs, 8 months after complete vaccination—in 61.73%. Statistical analysis revealed that HCWs with PH had a greater chance of maintaining a humoral response beyond eight months after vaccination. Increased muscle mass, decreased fat mass, and younger age may positively affect long-term immunity. Smokers have a reduced chance of developing immunity compared to non-smokers. Conclusions: Fully vaccinated HCWs with PH are more likely to be seropositive than fully inoculated volunteers with NPH. Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus [Coronavirus disease 2019 (COVID-19) is an infectious zoonotic illness caused by a novel pathogen belonging to the broad and diverse family of The first case of SARS-CoV-2 infection was detected in December 2019 in Wuhan, Hubei Province, China. Two years after its emergence, the total number of confirmed SARS-CoV-2 infections exceeded 271 million, and the number of deaths—5.3 million [The first vaccines were administered in December 2020; as the vaccination program progressed, a temporal stabilization or even a downward trend in the range of newly recorded weekly COVID-19 cases and deaths was observed in many countries . HoweverSerological tests constitute a crucial element of SARS-CoV-2 infection prevention and control strategies. They provide an exemplary method for assessing the incidence of coronavirus infection and monitoring seroconversion and seroversion in the population ,8,9. By Routine serological testing takes on particular meaning in the context of healthcare workers (HCWs)—a group requiring a special concern and protection during the pandemic, for numerous reasons. First, as the front-line workers combat COVID-19, HCWs are at higher risk of contracting SARS-CoV-2 and transmitting the virus to others (workmates and patients) than other professional groups . The risThis prospective, observational single-center study aimed to assess early and longitudinal antibody response after COVID-19 vaccination among HCWs on the timeline: after receiving the first and second dose of BNT162b2 mRNA vaccine . Moreover, the study aimed to investigate a potential correlation between selected factors, such as gender, age, body mass index (BMI), smoking, body composition, being convalescent, and early- and long-term humoral response in this group.Furthermore, we tested the hypothesis that decreased fat tissue and increased muscle mass tissue may positively affect long-term immunity in fully vaccinated individuals.The study was conducted among HCWs working in a Regional Specialized Hospital no. 4 in Bytom in Upper Silesia—one of the Polish regions most severely affected by COVID-19. Before collecting the data and specimens, all participants provided their written informed consent. The study was approved by the Institutional Review Board of the Medical University of Silesia in Katowice (PCN/0022/KB1/50/20) and was conducted in accordance with the Helsinki Declaration. The inclusion and exclusion criteria are presented below .The vaccination program in the study group was conducted from 29 December to 15 January 2021 (first dose), from 20 January to 11 February 2021 (second dose). Following the study protocol, participants underwent four blood draws: two during the vaccination process, and two—post-vaccination  . AccordiParticipants’ demographics  and primary clinical data: smoking, self-reported presence of chronic diseases  and COVID-19 status before the study start , symptomatic vs. asymptomatic course of the disease) were obtained through an author questionnaire.Serum samples were analyzed using ACCESS SARS-CoV-2 —a two-step enzyme chemiluminescent immunoassay (CLIA), according to the manufacturer’s instructions . This asExcessive body mass has been considered one of the main risk factors for severe COVID-19 infection. To investigate whether it also impacted the level of humoral response, an analysis of potential correlations between those variables was conducted. Anthropometric parameters were measured, and body composition was analyzed using the TANITA Body Composition Analyzer MC-780MA . This non-invasive device, using an electrical bioimpedance analysis (BIA), is certified and approved for clinical use, with NAWI CLASS III standards for scales used for medical measurements, EU certification CE0122. It also complies with the Medical Device Directive (MDD) 93/42/EEC for medical devices.Participants with a physical disability, those pregnant, or those not consenting to undergo this part of the study, were excluded from the measurements. Body mass and height were measured, and BMI (Quetelet’s index) was assessed for consenting participants. It was calculated as a person’s weight in kilograms divided by the square of the person’s height in meters. Its results were interpreted according to the WHO classification: <18.50 means underweight, 18.50–24.99—normal body mass, 25.00–29.99—overweight, and ≥30.00—obesity . In addiMoreover, basal metabolic rate (BMR) was assessed based on weight and age parameters. Before the examination, the participant’s data  and clothing weight were entered into the GMON software . During the analysis, the examined individual was asked to stand in the appropriate position  and bare feet on the TANITA platform. Body composition was assessed for body fat mass (BFM), fat-free mass (FFM), visceral fat (VFAT), predicted muscle mass (PMM), and total body water (TBW). The adipose tissue and muscle mass analyses were performed separately for each arm, leg, and trunk. Five different impedance results of the right arm, right leg, left arm, left leg, and trunk were then quantified. Measurements were made following the device manufacturer’s instructions. They were performed by the same study team members during the fourth blood collection, eight months after the second vaccine dose.p values < 0.05 were considered significant. The R language with the GGplot library was used to analyze [Data were presented as the mean ± standard deviation for quantitative variables and counts and % values for qualitative variables. The normality of the distribution in the individual groups was assessed using a Q-Q plot. It was observed that for IgG titers in individual measurements, the distribution of the feature was right-skewed, and a better fit to the normal distribution was obtained through logarithmic transformation. Repeatable measures ANOVA was used to compare changes in IgG titers over time. The assumption of sphericity was verified using the Mauchly test; in case of failure, the Greenhouse–Geisser correction was applied. A paired t-test with the Bonferroni–Holm correction was used for post hoc comparisons. The comparison of pairs of variables was performed using the Student’s t-test to assess the homogeneity of variance using the Brown–Forsythe test. Comparisons of more than two groups at the one-time point were performed using a one-way analysis of variance with Tukey’s post hoc test. The relationship between the quantitative variables was analyzed using the Pearson correlation coefficient. A logistic regression multivariable model was built to assess the influence of examined variables on the chance of maintaining long-term seropositivity. The model was built using a stepwise backward method and presented as odds ratio (OR) and its 95% confidence interval (CI).  analyze ,22.Initially, 286 HCWs vaccinated with two BNT162b2 doses were enrolled in the study. Eventually, 243 individuals who met the inclusion criteria were included: 187 (76.95%) women and 56 men (23.05%). The mean age in this group was 47.42 years (range: 22.00–66.00 years). The demographic and clinical characteristics of the study cohort, as well as the TANITA results, are presented below .Of the study cohort, 62 HCWs (25.51%) were seropositive (IgG ≥ 10.00 AU/mL) before the first dose of the vaccine. Immediately before administration of the second dose of vaccine (21 days after receiving the first dose), 221 participants (90.95%) had IgG antibody levels ≥ 10.00 AU/mL. 14 days after receiving the second dose of vaccine, 241 participants (99.18%) were identified as seropositive.Fourteen days after receiving the second dose of the vaccine (early follow-up), a high titer of IgG (>350.00 AU/mL) was determined in 148 participants (60.91%), low—only in 3 individuals (1.23%). However, after eight months, a high titer of the IgG (>350.00 AU/mL) was detected only in 1 HCW (0.41%), while in 93 (38.27%) of the subjects, the level of antibodies was determined as seronegative (<10.00 AU/mL). Long-term follow-up indicated persistent immunity (IgG > 10.00 AU/mL) in 150 HCWs (61.73%). Antibody titers at each time interval are presented in p = 0.00). On the other hand, an age above 60 years reduces the chances of maintaining the appropriate amount of IgG antibodies after an 8-month follow-up . The performed analysis did not confirm the influence of such factors as gender, smoking, BMI, obesity, BFM, FFM, TBW, PMM, bone mass, impedance, or BMR on the chance of maintaining long-lasting immunity to SARS-CoV-2 (p > 0.05)  increases the 8-fold chances of developing a long-term humoral response to COVID-19  .Then, to confirm those observations and verify factors affecting the titer of anti-SARS-CoV-2 IgG antibodies , a multivariate analysis using a stepwise backward method was performed .p = 0.00). Gender impacted the chance of maintaining long-term immunity after full vaccination . Male gender was associated with a lower chance of preserving immunity after eight months, whereas females were 6-times more likely to keep the long-lasting immunity. In addition, our research demonstrated that both age and body composition  impact the durability of one’s humoral response and are good predictors of long-term immunity. PMM was an additional parameter that positively affected the long-term immune response. An increase in PMM by one kg raised the chance of maintaining a long-term immunity , whereas an increased BFM reduced the chance of longitudinal immune response . Furthermore, smokers also had a lower chance of developing long-lasting immunity after vaccination than non-smokers .The results of this analysis revealed that HCWs with PH before receiving the first dose of BNT162b2 vaccine had a 7-fold greater chance of maintaining a humoral response beyond eight months after a complete, two-dose vaccination course , left-hand FFM , and left-hand PMM  between seronegative and seropositive individuals. In addition, we performed correlation analyses between BFM and PMM in the study population, in the group of seropositive and seronegative HCWs, also divided into right and left arms. The results indicated a significant weak positive correlation in each of the analyzed subgroups . Data not included in the manuscript.Additionally, anthropometric parameters were compared between the seronegative and seropositive groups at the fourth time point of the study. There was a significant difference in right-hand FFM  revealed that before the first vaccination, at the study baseline, HCWs with PH had a naturally higher antibody titer than those with NPH; this phenomenon was also observed before the administration of the second dose (peri-vaccination draw). Fourteen days after the second dose, however, the maximum level of IgG in those two groups was comparable. Interestingly, eight months after the second dose, HCWs with PH again achieved significantly higher antibody titers than NPH volunteers. No significant interaction between antibody titer on the timeline and adipose tissue level was observed. Regardless of one’s fat tissue range, after the first and second dose of vaccine (early follow-up), a similar increase in antibody levels had been reported, and eight months after complete vaccination (late follow-up)—a similar decrease in IgG levels. Furthermore, smoking had no significant effect on the process of developing immunity after vaccination. Moreover, there was no significant effect of gender on changes in antibody titer after vaccination. Participants over 60 years of age had a similar chance of developing immunity as those under 60 years of age; no significant age-related interaction was observed. However, it was noted that the antibody titer in the group over 60 years was lower than in the younger cohort at each measurement point. In addition, there was no significant effect of obesity on the course of immunization after vaccination .Vaccination against SARS-CoV-2 has been considered one of the most effective strategies to keep the spread of the virus under control. Although since the beginning the fast-track of vaccine development, a short path from the lab to the market, has aroused many controversies among the public worldwide, epidemiological data confirm that inoculation against COVID-19 results in a lower number of hospitalizations and deaths.Vaccination against SARS-CoV-2 is highly recommended, especially in groups with high exposure risk, such as frontline responders or healthcare workers. In response to those guidelines, many countries, such as France, Greece, and Italy, have introduced mandatory vaccinations against COVID-19 for HCWs .Published systematic reviews and meta-analyses show a significant effect of vaccination against SARS-CoV-2 on the significant prevention of symptomatic and asymptomatic COVID-19 among HCWs ,25,26,27The primary objective of our study was to investigate early and late humoral responses following the administration of the BioNTech/Pfizer BNT162b2 COVID-19 vaccine. Our research demonstrated that 14 days after receiving the second dose of vaccine and finishing the complete vaccination course, almost all, i.e., 241 out of 243 HCWs (99.18%), became seropositive. These results indicate a vital immune system stimulation in response to secondary contact with the mRNA vaccine, manifested by increased IgG anti-SARS-CoV-2 antibody levels. These observations confirm the efficacy of vaccination and are in accordance with Liu et al.’s results presented in their systematic review and meta-analysis .However, our long-term follow-up results revealed a significant waning of the humoral response over time. Eight months after complete vaccination, only 150 individuals (61.73%) remained seropositive, which suggests a reduction in activation of B lymphocytes stimulated by SARS-CoV-2 virus S protein. A similar trend was observed in the study conducted by Levin et al., where they found a substantial decline in humoral response in study participants six months after receiving the second dose of the vaccine, noticeable especially among men, subjects aged 65 years or older, and those with immunosuppression . AdditioOur study also investigated a potential correlation between selected variables and humoral response following vaccination to identify which factors affect vaccination-induced immunity the most.Numerous studies indicate that gender affects immune system functions and that the female sex is associated with a more robust, faster, and more effective innate and adaptive  immune response ,32,33,34The adverse effect of age on the COVID-19 course and prognosis has already been reported in numerous studies ,37. AccoOur research revealed that people over 60 years of age have a lower chance of developing long-term immune responses. These observations are consistent with other studies investigating the correlation between age and COVID-19 vaccine-induced immunity. Levin et al., in their study on a large cohort of 4868 HCWs, found a significant association between the durability of the humoral response and age; six months after the second doses of BNT162b2 vaccine, older individuals had significantly lower IgG titers than their younger counterparts . LikewisConducted in our study, one-way logistic regression analysis did not confirm the influence of BMI, obesity, and body composition  on the chances of developing a long-lasting humoral response. However, different conclusions could be drawn from a multivariable analysis performed using backward stepwise regression. Using this method, we did not eliminate the variables manually, but allowed the computer to adjust the predictors optimally for the best model. The obtained results revealed that both age and selected body composition parameters (fat and muscle mass) affect the humoral response of tested HCWs, and could be considered good predictors of long-lasting immunity. Our findings suggest that in younger volunteers, increased muscle mass and decreased adipose tissue levels could enhance the effectiveness and durability of immunization. Additionally, seronegative HCWs had lower FFM in the right and left arms and lower left arm PMM compared to seropositive subjects. This observation is similar to the previous results showing that greater PMM has an impact on the process of long-term immunization. Due to the fact that this value was on the border of the significance of the test, further analysis should be conducted with the participation of a larger number of people.The current evidence shows that severe COVID-19 course in some individuals is associated with “a cytokine storm”, which could be a consequence of increased secretion of pro-inflammatory cytokines directly by adipose tissue of obese subjects. On the other hand, muscle cachexia (increased muscle protein catabolism) or malnutrition, common in older people, may negatively affect the vaccine-induced immunization process .Skeletal muscles are increasingly recognized as organs with endocrine properties. They regulate the function of the immune system through myokine signaling and the expression of surface molecules that modulate the immune system . It has The term ‘obesity’ describes the accumulation of excessive amounts of BFM in adipose tissue, subcutaneous tissue, or within selected organs . The maiDifferent methods are used to assess body mass, and BMI is a popular anthropometric indicator used for the overall assessment of body fat . It is aBioimpedance analysis constitutes a more reliable method of body fat assessment than BMI. Although the percent of body fat and body fat are predictable based on BMI score, the prediction accuracy is lower in the case of individuals with a BMI < 30.00. Frankenfield et al. reported that a significant number of people, despite having a BMI < 30.00, have obesity levels of body fat .The above-mentioned facts strongly suggest not considering BMI solely in the analysis of factors affecting humoral response to the SARS-CoV-2 vaccine. Therefore, in our study, we decided to assess body fat using two methods independently: BMI and bioimpedance analysis.2 higher BMI [Obesity is a recognized risk factor for severe COVID-19 outcomes ,37. Recegher BMI . One posgher BMI .Numerous studies have confirmed that obesity is linked to greater susceptibility to infections . ExcessiMoreover, obesity is associated with other conditions that are independent risk factors and predictors of mortality from COVID-19, including diabetes, chronic cardiovascular, cerebrovascular, and pulmonary diseases . As a reFurthermore, behavioral factors, such as smoking, can affect how individuals respond to vaccines. Toxic chemicals in cigarette smoke, such as carbon monoxide, nitrogen oxides, and cadmium, can influence the production of many immune mediators . In addiIn our study, smoking was one of the factors that negatively affected the production of IgG antibodies against SARS-CoV-2 in response to vaccination. Smokers, who accounted for 20% of the cohort, had a lower response in antibody titers at every measurement point than non-smokers. Similar observations were presented by Tsatsakis et al. The results of their research showed that non-smokers had higher titers than smokers . Our finThe effect of cigarette smoking on immunity has been widely studied. It is usually associated with impaired function of immune cells, including B lymphocytes producing antibodies, often despite an increased number of B cells . HoweverSARS-CoV-2, similar to other RNA viruses, shows a high capacity to mutate ,74. NewlOur data provide important insights into the immune system’s dynamics of antibody production on the timeline in response to vaccination with the BNT162b2 vaccine. The SARS-CoV-2 virus-induced pandemic is still ongoing, and emerging subsequent virus variants pose a significant threat to public health. Therefore, elaboration of a strategy allowing the development and maintenance of high and long-lasting immunity after inoculation, especially in highly exposed groups, such as HCWs, should become an essential part of the COVID-19 management policy.Attention should be paid to some limitations of this study. First, our study group was strongly feminized, which might have affected our analysis results. In addition, data regarding undergoing COVID-19 before the study started, i.e., its severity and course (asymptomatic/low-symptomatic/symptomatic)—factors that could impact the titer of SARS-CoV-2 IgG antibodies level and hence a longitudinal humoral response—was collected through self-reports, and thus could be the subject of bias.Fully vaccinated convalescents are more likely to maintain an immune response than fully vaccinated volunteers without prior SARS-CoV-2 infection. Younger age and female gender are also associated with greater chances of developing long-lasting humoral responses after vaccination. Moreover, it is worth highlighting that increased muscle mass and decreased fat mass may positively affect long-term immunity following vaccination.To the best of our knowledge, this is the first study assessing the impact of body composition , not BMI solely, on the immune response following vaccination against COVID-19. We presented the influence of adipose and muscle tissue levels on the immunization process after vaccination with the BNT162b2 vaccine. Our results highlight the importance of not considering body mass index exclusively when analyzing the variables affecting response to the SARS-CoV-2 vaccine.A better understanding of factors affecting immune response after vaccination could result in introducing a more effective, tailored to particular groups’ conditions and immunological needs vaccination policy.


The objective of this study was to describe osteoporosis-related care patterns during the coronavirus disease 2019 (COVID-19) pandemic in Alberta, Canada, relative to the 3-year preceding.A repeated cross-sectional study design encompassing 3-month periods of continuous administrative health data between March 15, 2017, and September 14, 2020, described osteoporosis-related healthcare resource utilization (HCRU) and treatment patterns. Outcomes included patients with osteoporosis-related healthcare encounters, physician visits, diagnostic and laboratory test volumes, and treatment initiations and disruptions. The percent change between outcomes was calculated, averaged across the control periods (2017–2019), relative to the COVID-19 periods (2020).Relative to the average control March to June period, all HCRU declined during the corresponding COVID-19 period. There was a reduction of 14% in patients with osteoporosis healthcare encounters, 13% in general practitioner visits, 9% in specialist practitioner visits, 47% in bone mineral density tests, and 13% in vitamin D tests. Treatment initiations declined 43%, 26%, and 35% for oral bisphosphonates, intravenous bisphosphonates, and denosumab, respectively. Slight increases were observed in the proportion of patients with treatment disruptions. In the subsequent June to September period, HCRU either returned to or surpassed pre-pandemic levels, when including telehealth visits accounting for 33–45% of healthcare encounters during the COVID periods. Oral bisphosphonate treatment initiations remained lower than pre-pandemic levels.This study demonstrates the COVID-19 pandemic and corresponding public health lockdowns further heightened the “crisis” around the known gap in osteoporosis care and altered the provision of care .Osteoporosis has a known substantial care and management disparity, which has been classified as a crisis. The COVID-19 pandemic created additional burden on osteoporosis patient care with healthcare encounters, physician visits, diagnostic and laboratory tests, and treatment initiations all declining during the initial pandemic period, relative to previous years.The online version contains supplementary material available at 10.1007/s11657-022-01132-7. Osteoporosis is one of the most common chronic diseases, afflicting over 200 million people worldwide . AccordiAlthough osteoporosis is a prevalent disease, there has been a substantial care and management disparity, which has been classified as a crisis , 9. The Practitioners have been urged to focus on improving secondary fracture prevention, since these patients are at highest risk for a future fracture. In Canada, only the provinces of Alberta and Ontario have formal government-supported fracture prevention action plans and combined, contain 83% of Canada’s fracture liaison services despite only having 50% of the country’s population , 12. In With significant strains to the healthcare system in 2020 due to the COVID-19 pandemic, it was anticipated that osteoporosis care would be deprioritized, thus creating an even wider gap in care and management. A retrospective analysis of global google analytics data conducted between February and April 2020 found that compared to February 2020 numbers, the number of daily sessions on the FRAX® website for online fracture risk assessments fell 23.1% on March 2020 and 58.3% on April 2020 . FurtherThe objective of this study was to describe changes in osteoporosis-related care patterns including patients with an osteoporosis-related healthcare encounter, physician visits, diagnostic and laboratory test volumes, and treatment prescription dispense patterns during the COVID-19 pandemic in Alberta, Canada, relative to the three-years preceding.This study used a repeated cross-sectional study design, using three-month periods of population-level administrative health data from the entire province of Alberta, Canada, between March 15, 2017, and September 14, 2020  and treatment utilization during each cross-sectional period. Outcomes of interest included patients with osteoporosis-related healthcare encounters and resource utilization, including physician visits, hospital- and ambulatory care-based BMD diagnostic tests, vitamin D and red cell distribution width (RDW) laboratory tests, and osteoporosis-related medication dispensations. RDW tests, although not specific to osteoporosis care, were assessed as a more generic comparison to further validate the trends observed for other outcomes.Patients with an osteoporosis healthcare encounter were identified based on the presence of diagnostic codes for osteoporosis  or M80 or M81 from the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada (ICD-10-CA)), extracted from the Discharge Abstract Database (DAD), National Ambulatory Care Reporting System (NACRS), or Practitioner Claims datasets. Osteoporosis-related physician visits were identified based on the presence of the diagnostic code of osteoporosis from the Practitioner Claims dataset. Physician visits were stratified by general practitioner visits and specialist practitioner visits . In addition, outcomes were depicted visually to show increasing or decreasing trends over the study period. Treatment utilization was analyzed as the number of patients on each treatment per period based on the days supply. Treatment prescription dispenses were analyzed as treatment initiations and treatment disruptions. Treatment initiation was defined as any new osteoporosis-related prescription dispensed in each three-month period with no prior osteoporosis-related prescription dispensed in the prior 1.5 years. Treatment disruptions in each 3-month period were defined as a gap in treatment dispenses after the days’ supply plus 60 days. This definition was selected in order to measure systemic disruptions in treatment utilization. The days’ supply for oral bisphosphonates, romosozumab, teriparatide, and raloxifene was based on the days supply within the PIN dataset. For IV bisphosphonates and denosumab, the days’ supply data within PIN was not reflective of the duration of treatment effect; therefore, the days’ supply was set at 365 days for IV bisphosphonates and 182.5 days for denosumab, based on published literature . The JunResults with sample sizes < 10 were not reported to align with Alberta Health privacy standards. All analyses were conducted in SAS® version 9.4 and figures produced using Tableau online version 2021.3. Research ethics board approval was obtained from the Health Research Ethics Board of Alberta – Community Health Committee (HREBA-CHC).An overall slight increase in the number of osteoporosis-related healthcare encounters was observed over the study period with declines observed during the winter months, aligned with seasonal variations. However, during the initial 3-month period (March to June 2020) of the COVID-19 pandemic, large declines were also observed .Overall utilization of osteoporosis-related medication dispenses are presented in Fig. Reduced rates of treatment initiation  of oral bisphosphonates (− 43%), IV bisphosphates (− 26%), and denosumab (− 35%) were observed during the March to June 2020 COVID-19 period, relative to the weighted average of the March to June control period , and raloxifene prescription initiations and disruptions had sample sizes < 10 across the three-month periods and were therefore not reported.While patients with osteoporosis-related healthcare encounters have slightly increased in 3 years prior to the COVID-19 pandemic, this study observed notable reductions in the number of patients with osteoporosis-related healthcare encounters in the first 3-month period (March to June 2020) of the COVID-19 pandemic, when public health lockdowns were implemented. The COVID-19 pandemic also impacted the management of patients with osteoporosis as observed by reductions in HCRU including physician visits, hospital- and ambulatory care-based BMD tests, laboratory tests, and osteoporosis treatment initiations and disruptions.The current study revealed a slight increasing pattern in the number of osteoporosis-related healthcare encounters reported in each period throughout the control years. While a low number of patients with osteoporosis-related healthcare encounters was observed during the March to June 2020 period of the COVID-19 pandemic when lockdown measures were implemented, this appear to rebound once lockdown measures were removed in the June to September 2020 COVID-19 period, with the inclusion of telehealth visits, accounting for 33–36% of healthcare visits. Similar patterns were observed across the study periods in the number of patients with osteoporosis-related healthcare encounters when stratified by rural versus urban region. Interestingly, this study reveals a higher number of patients with osteoporosis treatments dispenses than patients with osteoporosis-related healthcare encounters in each period. This pattern supports the evidence suggesting a lack of application to assess patients for a diagnosis of osteoporosis, which may result in the general undermanagement of the disease as a whole.There was an overall trend observed during the study period of stable specialist visits and increasing general practitioner visits including telehealth visits, revealing a possible shift in the management of patients with osteoporosis in Alberta. As anticipated, large reductions were observed in the number of global physicians visits during the first COVID-19 pandemic period. This aligns with the changes in health care measures implemented in Alberta on March 2020 –20, 22. The reduction in HCRU measures observed in this study aligns with reports from other regions. A survey of health care providers from 53 countries revealed numerous institutions/clinics had closures during the pandemic, or changed services to focus on emergency care only and relied on other modes of visits to facilitate care . A greatJoint guidance was released by numerous societies and organizations on the management of patients with osteoporosis during the COVID-19 pandemic . These rWhile lockdown measures were implemented during the first three months of the COVID-19 pandemic in Alberta, the number of COVID-19 cases and hospitalizations during this time were low. Subsequent waves of the pandemic saw much higher cases within Alberta resulting in capacity issues within the health system, warranting further analyses. Additional analyses are underway with data extended up to March 2021 to explore how osteoporosis-related clinical outcomes are associated with treatment disruptions. Additionally, longer follow-up will enable greater exploration of the trends in telehealth for patint management. The impact of shifting to telehealth on patient management and outcomes will be an important area of research to guide policy and practice patterns. Future research could also explore other osteoporosis-related laboratory tests, including serum calcium and creatinine levels. Further research focusing on these laboratory test levels in patients with osteoporosis would be valuable to examine since practitioners request these test values before initiating treatment for osteoporosis to account for any contraindications for osteoporosis-related treatments. Lastly, other areas for future research could compare regional differences in care strategies for individuals with osteoporosis and their corresponding clinical outcomes to help assess the generalizability of these findings to other regions within Canada. Such research may help inform approaches to improve the care for patients with osteoporosis and osteoporosis-related outcomes, such as fractures.Along with future research directions, several strengths of this study should be noted. First, we used comprehensive population-based datasets, representative of the entire population of Alberta, Canada. Particularly, treatment patterns were obtained from community-based pharmacy dispensation records, which include dispensations from public, private, and out of pocket plans. Second, the repeated cross-sectional design utilized control periods three years before the COVID-19 pandemic to identify trends in the outcomes of interest. Third, examining osteoporosis-related healthcare encounters by urban and rural residence helps highlight the care gap in individuals, regardless of residency and account for variation in changes in care during the pandemic that may have occurred due to differences in COVID-19 case counts.Although this study provided a unique opportunity to examine osteoporosis care patterns before and during the COVID-19 pandemic, there are limitations to consider when interpreting these results. First, open year data was used; therefore, the administrative data for this study had not been cleaned and validated by Alberta Health prior to analysis. Some outcomes of interest demonstrated increasing trends over the control periods; therefore, the weighted average from the control period may underestimate the percent change during the COVID-19 periods. Due to this, outcomes were also presented per period in figure format to depict the trends over time and provide a more comprehensive perspective of the potential change during the COVID-19 period. On another note, BMD test volumes are likely underestimated since our study only included BMD captured in hospital, emergency department, and outpatient care facilities. Other community-based or specialized clinics that conduct BMD testing were not captured in the administrative data. While treatment disruptions were captured during the March to June 2020 COVID-19 3-month period, reasons for these treatment disruptions are not known and only based on the follow-up data available. Therefore, it is not possible to accurately determine if patients resumed treatments after a disruption or if a disruption occurred based on long dosing intervals for some treatments . Furthermore, for the treatment disruption analysis, patients in the last study period (June to September 2020) had insufficient follow-up available to meet the threshold of 60 days required to identify treatment disruptions; therefore, this data was not reported. Further analysis with extended data will help address this limitation. Lastly, the data from this study is from the province of Alberta; therefore, may not be generalizable to the rest of Canada. However, many regions within Canada imposed similar lockdown measures so these results are anticipated to provide relevant insights for such regions as to the impact on patients with osteoporosis.There was a known care gap in the management of osteoporosis prior to the COVID-19 pandemic and this evidence demonstrates the COVID-19 pandemic and corresponding public health lockdowns has further heightened this “crisis.” Understanding the impact of the COVID-19 pandemic on this patient population is fundamental to improve care and management of patients with osteoporosis moving forward. Further investigation regarding acute care, treatment patterns, and the use of telehealth throughout the course of the COVID-19 pandemic is warranted; however, this data from the initial 6 months may be beneficial for decision makers when implementing future public health measures.Supplementary file1 (DOCX 125 KB)Below is the link to the electronic supplementary material.


Background: Coronavirus disease 2019 (COVID-19) vaccine hesitancy has remained a significant concern among adults worldwide. However, not much is known about parental vaccine hesitancy for getting children vaccinated for COVID-19 in the U.S. Thus, the purpose of this study was to conduct a national assessment of parents’ preferences for COVID-19 vaccination of children using the evidence-based Multi-Theory Model (MTM) and explore the predictors of vaccine hesitancy. Methods: To participate in this study, a national random sample of parents (n=263) took a valid and reliable online questionnaire based on the MTM. Independent samples t test, chi-square test, multiple logistic regression was utilized to analyze data. Results: More than two-fifths (42%) of the participating parents were not willing to get their children vaccinated for COVID-19. Parental vaccination status, booster dose acceptance, education, and political affiliation were significant predictors of willingness to get children vaccinated for COVID-19. In the multiple logistic regression analyses, behavioral confidence and participatory dialogue  were statistically significant predictors of COVID-19 vaccination hesitancy for children among the participating parents.Conclusion: Given the multiple factors that were found influential in parental hesitancy for COVID-19 vaccination among children, multimodal and evidence-based interventions are needed to increase the uptake of COVID-19 vaccines among children by influencing the parents’ perceptions, increasing their confidence, dispelling misinformation, and reducing constraints for vaccination. Such interventions should emphasize communication and messaging that is truthful, interactive, scientifically correct, and to be delivered in a variety of community-based settings. These studies also highlight the reasons for widespread COVID-19 vaccination hesitancy.8 For example, a global review during the early phases of the vaccine rollout found that the rate of COVID-19 acceptance was 23.6% to 97% across 33 countries.6 In contrast, a review of data till February 2021 from 82 studies found that global vaccine hesitancy rates were 10–57.8% and vaccine refusal rates were in the range of 0–24%.4 Subsequently, a June 2021 study of 23 000 participants from 23 countries found that the average rate of vaccine acceptance was 75.2%.7 In the United States (U.S.), before the vaccine rollout in late 2020, more than a fifth of the adults did not want to take the COVID-19 vaccine. In alignment with these findings, the latest estimates from July 2022 suggest that almost a fourth of American adults remain either partially vaccinated or unvaccinated.8 The most common reasons found in global studies for not obtaining COVID-19 vaccination are fear of side effects, lack of trust in vaccines or authorities, misinformation and myths, low perceived risk of COVID-19 infections, and religious or cultural beliefs.7 Coronavirus disease 2019 (COVID-19) infections continue to disrupt lives and economies around the world. Vaccines for the prevention of COVID-19 have been available since late 2020 and early 2021. Despite the availability of COVID-19 vaccines and in many parts of the world now, a large proportion of the global population remains unvaccinated. In part, this is because of vaccine hesitancy and refusal.12 For example, the United States Food and Drug Administration (FDA) approved the use of COVID-19 vaccines for children 12-15 years of age by the summer of 2021.9 Around the same time or quickly in succession, the European Union and other countries ap-proved the use of vaccines for children of this age group.11 By late 2021, COVID-19 vaccination approvals were expanded to include children 5-11 years old.11 More recently, by the summer of 2022, these vaccines have also been approved for use among children 6 months to 5 years old.9 Similar to vaccine hesitancy among adults, a few studies have discussed COVID-19 vaccination hesitancy among parents to get their children vaccinated.16 Within a few months of the COVID-19 vaccine rollout for adults (in late 2020), many countries started administering the vaccines to children.12 Subsequent studies from various parts of the world found that half or more of the parents were either un-sure or not willing to get their children vaccinated for COVID-19.15 The major reasons discussed in these studies for COVID-19 vaccine hesitancy among parents (to get children vaccinated) were lower income/education or perceived risk of infection among children, parental vaccine hesitancy; concerns about vaccine safety and side effects, belief that vaccines can cause infection or transmit the infection to adults, dependence on social media for information, etc.16 Having children at risk of COVID-19 or with chronic conditions, knowing others who got vaccinated, a belief that vaccines have been tested extensively and are safe and effective, and recommend-dations from healthcare providers were associated with a higher willingness to get children vaccinated with the vaccines.17 One of the earliest studies on parental COVID-19 vaccine hesitancy in early 2021 found that higher education of parents was associated with greater willingness to obtain COVID-19 vaccines for themselves and their children.20 For example, most studies are from outside the U.S., have small sample sizes, use convenience/ snowball sampling, do not adequately quantify parental COVID-19 vaccine hesitancy, and assess a limited number of variables associated with vaccine hesitancy. Above all, in our review of studies on parental COVID-19 vaccination hesitancy, we could not find assessments that use evidence-based behavioral intention theories and behavior change models. Thus, the purpose of this investigation was to comprehensively assess the American parents’ COVID-19 vaccination hesitancy in getting their children vaccinated using the Multi-Theory Model (MTM) of health behavior change. The MTM was designed to address both initiation and sustenance of health behavior change but, in this study, only the initiation model was operationalized that entails the constructs of participatory dialogue (in which advantages of behavior change outweigh the disadvantages), behavioral confidence, and changes in the physical environment.5 This theory integrates cognitive, conative, and environmental factors that are intended to be utilized for designing health behavior change interventions.6 MTM constructs are adaptable across health behaviors and have been used to explain a variety of health behaviors (including an explanation of COVID-19 vaccination hesitancy in adults).5 The extant literature on parental COVID-19 vaccination hesitancy has certain limitations.20 Based on the aforementioned inputs, the minimum sample required was 243 (221 + 10% non-response = 243) after factoring in 10% non-response. This study received exempt status from the Institutional Review Board (or Ethics Committee) of the University of Nevada, Las Vegas (UNLV-2021-108). This cross-sectional analytical study was conducted in October 2021 and utilized a web-based survey to recruit a diverse sample of U.S. adults. Qualtrics Research Marketing Team was contracted to manage the data collection and for participant recruitment. Participants were provided incentives per terms and conditions set forth by Qualtrics and its data collection partners. Respondents were invited through emails, in-app notifications, and specialized campaigns for relatively inaccessible population subgroups. A non-probability sampling method was utilized for the data collection until the desired quota constraints are met. The sample requirement was pre-estimated using the formula: n = (z)2 p (1 − p)/d2 considering a 90% confidence interval, a margin of error d = 5%, and the proportion of parental hesitancy to get their children vaccinated was 28% based on the recent data reported by Yadete and colleagues.22 The MTM survey instrument has been validated by a previous study,5 which established construct validity of the MTM subscales through the confirmatory factor analysis with maximum likelihood estimation. The referenced study found a single-factor solution with all factor loadings over the threshold of 0.32. In addition, Eigenvalue criteria was satisfied in all the MTM subscales with value greater than one. Reliability diagnostics revealed appropriate Cronbach alpha value of at least 70% in all the MTM subscales. The survey instrument consisted of 52 items related to vaccine confidence, vaccine literacy, multilevel-theory-model-based initiation of vaccination behavior, and demographic questions.22 Vaccine literacy  includes knowledge and competence to deal with information concerning vaccines, and the vaccine confidence index measures the propensity toward vaccines (this measure has been developed for the influenza vaccine and was adapted in the present study for COVID-19 vaccination).22 The dependent variable used in this study was the parental willingness to get their children vaccinated, which was dichotomized into “yes” and “no” categories. Independent variables included demographic characteristics, primary series vaccination status, and booster-dose acceptability of the parents. Additionally, information related to the source of the COVID-19 vaccine information, and the level of trust in the informational sources were also measured. A set of questions related to the parents’ vaccination status were also asked, which allowed us to investigate the association between parental willingness to accept the vaccine and their hesitancy towards getting their children vaccinated.t test, and Pearson’s correlation) and multiple logistic regression tests were used to analyze the data. For the logistic regression, we used the maximum likelihood method to obtain Wald’s confidence intervals and adjusted odds ratio estimates. All variables were dummy coded to allow an appropriate estimation in the regression, and probability in the logistic regression was modeled on “willingness of parents” = “yes.” Statistical significance was assumed at P < 0.05. All data analyses were conducted using the Statistical Package for Social Sciences (SPSS) version 27 for Windows  and Statistical Analysis System (SAS), version 9.4 . Means and standard deviation were used to present continuous variables, where-as categorical variables were represented as counts and percentages. Bivariate , had greater acceptability towards booster dose , had a graduate degree , and had a democratic political affiliation (50.3% vs. 22.7%) as opposed to their hesitant counterparts  were willing to get their children vaccinated and the remaining  were hesitant . Among pterparts . No signP < 0.001) were statistically significantly higher among parents who were willing to get their children vaccinated as opposed to those who were not willing  and vac-cine confidence index  or ‘no trust at all’  in the informational source for vaccines ; “changes in the physical environment” and “behavioral confidence” , interactive vaccine literacy and critical literacy , and total vaccine literacy with interactive literacy . In a bivariate correlation test, a significant and positive correlation was noted between “perceived advantages” and “behavioral confidence” (P =0.01) and 1.22 times  respectively. Parents who were fully vaccinated has nearly 3.5 times greater odds in favor of their children getting the COVID-19 vaccine than parents who were not fully vaccinated (P =0.01). The results of logistic regression  indicate17 Furthermore, parents with higher education or Democratic political affiliation were more likely to have their children vaccinated. Education and Democrat political affiliation are strong predictors for adult COVID-19 vaccination preferences and also seem to hold an influence on the tendency to get children vaccinated.25 Interventions geared towards parents with lesser education are warranted to ensure robust uptake of COVID-19 vaccination among children.14 In this national study, we identified the correlates of parents’ willingness to have their children vaccinated with the COVID-19 vaccine based on the initiation con-structs of MTM, vaccine literacy, vaccine confidence index, sources of information, and trust of informational sources. The majority of the parents (58.2%) of the parents were willing to get their children vaccinated. Parents who were fully vaccinated or did not have hesitancy toward getting COVID-19 vaccine boosters had a higher willing-ness to have their children vaccinated. These findings have been confirmed in other studies outside of the U.S.19 Interventions to increase parents’ confidence, perceptions of vaccine advantage, and COVID-19 infection-related risks should be implemented in community-based settings and doctors’ office.25 In addition, trust building will play a vital role in improving the vaccine uptake. There are some historical concerns why people distrust healthcare systems in the U.S. and also among other countries.26 Asadi and Colleagues investigated general attitudes of people residing in African and Middle East countries towards the COVID-19 vaccine and cited “mistrust” as an important predictor of vaccine hesitancy.26 With regard to MTM constructs, scores of constructs  were significantly higher among those willing to have their children COVID-19 vaccinated. Furthermore, behavioral confidence and participatory dialogue along with parental self-status of getting vaccinated were significant predictors of parents’ willingness to get their children vaccinated with the COVID-19 vaccine. This model accounted for 66.6% of the variance in explaining the willingness of parents to get the COVID-19 vaccine for their children. These findings are consistent with other studies of adults examining this model in the context of COVID-19 vaccination.27 All dimensions of trust, including trust in the quality and safety of vaccines, institutional trust, and inter-personal trust in the professionals, who are involved in the communication and vaccines administration, will require a multipronged approach in the trust building process.27 Clear and effective messaging through community leaders, healthcare providers, public health professionals, and employers will be essential. For the trust building, a diverse, multisector set of partners and collaborators (collective responsibility) at global, national, and local levels will be instrumental.28 Similar to health literacy, vaccine literacy not only indicates the acquired knowledge of vaccines but also involves a person’s competence to locate credible in-formation and make responsible decisions about the vaccination. Increasing vaccine literacy should be a focus for future COVID-19 prevention efforts for children as well as adults.14 Likewise, we found that parents who were willing to have their children vaccinated had greater confidence in vaccines compared to hesitant parents. To increase COVID-19 vaccine confidence, parents’ concerns regarding vaccines should be addressed and communication with parents should emphasize conveying evidence-based information about vaccine safety, efficacy, and the development process.29 We also found that if the COVID-19 vaccine-related sources of information were public health organizations, the parents were more likely to get their children vaccinated. Interestingly, and in contrast, messaging from radio and news-papers led to more parents being reluctant toward getting their children vaccinated. Trust in the informational source also played a significant role for parents willing to get their children vaccinated. Public health organizations need to play a key role in disseminating evidence-based and truthful information to help increase COVID-19 vaccination among children.29 Finally, the construct of behavioral confidence can be built by helping people overcome the barriers to vaccination. This would also relate to the construct of changes in the physical environment wherein the issues of accessibility and affordability of COVID-19 vaccines especially for high-risk groups would need to be addressed.24 Vaccine literacy played a significant role in determining parents’ willingness to have their children vaccinated with the COVID-19 vaccine. Our findings showed that parents who were willing to have their children vaccinated performed significantly higher on total vaccine literacy than those who were not willing to have their children vaccinated. A recent study found that a substantial proportion of U.S. adults had very low coronavirus-related literacy scores; highlighting the need for greater health literacy. To authors’ best knowledge, this study is the first one to perform theory-based assessment of the parental hesitancy in getting their children vaccinated. However, this study is not without limitations. First, cross-sectional nature of this study limited our ability to establish causality. Second, certain type of biases  were inevitable. Also, some parents may have provided socially desirable responses, which might have introduced social desirability bias. Third, there could be individual characteristics and other influential factors that might have left unmeasured and could have influenced study participants’ willingness to get their children vaccinated . Next, as the sample is limited in nature and extent , external validity will be limited. Moreover, sample was not representative, which might limit the external validity of the results. Future studies can be planned with a nationally representative sample to investigate parental hesitancy. This study purported to examine the correlates of parents’ willingness to have their children vaccinated with the COVID-19 vaccine. Nearly two in five parents were not willing to get their children vaccinated and education, political affiliation, or pa-rental vaccination status were significant predictors of parents’ willingness to get children vaccinated for COVID-19. Also, the key constructs of MTM  were influential in predicting parents’ willingness to have their children receive COVID-19 vaccination. Given that multiple factors predict parental hesitancy for COVID-19 vaccination among children, multi-modal interventions need to be implemented in healthcare provider offices and community settings with a focus on communication, confidence building, constraint removal, calculation in favor of vaccines, and collective responsibility to prevent the spread of COVID-19 infections. Authors would like to thank their respective institutions for their kind support.Conceptualization: Kavita Batra and Manoj Sharma.Methodology: Manoj Sharma, and Kavita Batra.Software: Kavita Batra, Chia-Liang Dai.Validation: Manoj Sharma, Kavita Batra, Chia-Liang Dai, Ravi Batra and Jagdish Khubhchandani.Formal analysis: Kavita Batra, and Ravi Batra.Investigation: Manoj Sharma, Kavita Batra, Ravi Batra, Chia-Liang Dai, Jagdish Khubhchandani.Resources: Manoj Sharma.Data curation: Manoj Sharma, and Kavita Batra.Writing—original draft: Manoj Sharma, Kavita Batra, Chia-Liang Dai, Ravi Batra, Jagdish Khubhchandani.Writing—review and editing: Manoj Sharma, Kavita Batra, Chia-Liang Dai, Ravi Batra, Jagdish Khubhchandani.Visualization: Kavita Batra, and Ravi Batra.Supervision: Manoj Sharma and Kavita Batra.Project administration: Manoj Sharma and Kavita Batra.Funding acquisition: Manoj Sharma. All authors have read and agreed to the published version of the manuscript. This research study was funded by the School of Public Health, University of Nevada, Las Vegas, internal grant number PG03008. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of the University of Nevada, Las Vegas (UNLV-2021-108 dated 4 October 2021). All research activities were performed in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study. None.


Our data endorse MVD as a safe and effective surgical procedure also for elderly patients with TN.Microvascular decompression (MVD) is the only etiological technique for the treatment of trigeminal neuralgia (TN). Whilst there is a consensus MVD is likely effective regardless of age, the elderly population is thought to be more prone to have a higher rate of surgical complication, morbidity, and mortality. The main objective of our single-center, retrospective study was to analyze the surgical and clinical outcomes of MVD in TN elderly patients. From a surgical series of patients with TN who had undergone MVD from April 2018 to April 2022, 76 patients who matched the inclusion criteria were divided into two groups: twenty-five (32.9%) patients were older than 65 years and included in the elderly group, while the remaining fifty-one (61.1%) patients were below 65 years included in the non-elderly one. There were no differences between the groups in terms of acute pain relief (APR), Barrow Neurological Index (BNI) at follow-up, complications, and recurrence rate. In multivariate analysis  the presence of an offending artery with nerve root distortion/indentation emerged as the only independent prognostic factor for pain-free survival ( Trigeminal neuralgia (TN) is defined as recurrent paroxysms of unilateral facial pain restricted to trigeminal distribution, lasting from a fraction of a second to 2 min, severe in intensity with an electric shock-like shooting, stabbing or sharp quality, and precipitated by innocuous stimuli . The mosTherefore, the aim of the present study was to analyze clinical and surgical outcomes in elderly patients (≥65 years) undergoing MVD surgery for TN compared to younger ones (<65 years), in an effort toward implementing tailored clinical decision-making on the topic.Clinical data were collected from patients diagnosed with classical TN according to the criteria of the ICHD-3 (1), who underwent MVD surgery at the Neurosurgical Department of Fondazione Policlinico Universitario Agostino Gemelli IRCCS  between April 2018 and April 2022.All patients were operated on by the senior author (NM). Patients diagnosed with secondary trigeminal neuralgia  were a priori excluded.All patients (regardless the age) with TN and a suspected neurovascular conflict on magnetic resonance imaging (MRI) were recommended to undergo MVD if pharmacological treatment was insufficient to control pain or significant side effects were reported. Patients without visible neurovascular conflict on MRI or bearing relevant comorbidities were recommended for alternative treatment . The patients who matched our inclusion criteria and underwent MVD surgery were divided into elderly and non-elderly groups, above or below 65 years, respectively. -Clinical pre-operative data: age, sex, affected side, TN type, pain duration (years), Barrow Neurological Institute Pain Intensity (BNI) score , previou-Intraoperative data: craniotomy size; use of neuronavigation during surgery ; surgica-Post-operative/follow-up data: acute pain relief (APR) ; cerebrospinal fluid (CSF) leak after surgery and complication other than CSF leak; length of stay; pain-free survival determined at the most recent follow-up visit, need for re-operation and BNI at follow-up.For each patient, the following data were gathered: p < 0.05. Statistical analyses were conducted using Stat View version 5 software .Comparison of categorical variables was performed by means of the chi-squared statistic, using the Fisher exact test. Statistical comparison of continuous variables and ordinal variables was performed by the Student T-test and by the Wilcoxon signed-rank test, as appropriate. Long-term outcome was evaluated by Kaplan–Meier analysis with log-rank testing to compare the pain-free interval between groups. Cox logistic regression analysis was employed to analyze factors associated with recurrence. Differences were considered statistically significant at Ethical approval was waived by the local Ethics Committee in view of the retrospective nature of the study and all the procedures being performed were part of routine care. Informed consent was obtained from all individual participants included in the study.The sample studied consisted of 76 patients with a mean age of 59.6 ± 9.79 years. Twenty-five (32.9%) patients were included in the elderly group (≥65 years); the remaining fifty-one (61.1%) patients were included in the non-elderly group (<65 years). The two groups were not significantly different in terms of clinical pre-operative data . Intraoperative data were similar between non-elderly and elderly patients as well. In particular, this was true in terms of craniotomy size, use of neuronavigation, surgical duration, mastoid opening, and intraoperative conflict type see . p < 0.0001; 1.40 ± 0.96 and 4.13 ± 0.71, respectively), with no difference between the two groups. Within the follow-up period, no significant difference was found in terms of recurrence between the two age groups , post-operative complications occurrence (p = 0.507) and evidence of previous surgery (p = 0.573). The presence of a trigeminal nerve root distortion/indentation was associated with a statistically significant higher pain-free survival  no difference in pain-free survival was found when stratifying patients for age  including age, sex, evidence of previous surgery, post-operative complications occurrence, and intraoperative conflict type . The preTN is the most frequently reported type of facial pain, with an overall incidence ranging from 12.6/100.000/year to 27/100.000/year . ClassicThe herein presented data confirm what has already been reported in the literature. ,26,27. EAs is widely known, the key to MVD is to identify the offending vessel and to achieve effective decompression of the nerve. The offending vessel is most commonly an artery rather than a vein . We studThe relatively low number of patients in the elderly group and the retrospective nature of data are the main limitations of our study.Another critical issue could be the cut-off for the differentiation of the two groups. In the absence of universally recognized criteria for discriminating against elderly/non-elderly patients, we relied substantially on the most frequently reported cut-off in the literature ,33,34.Furthermore, some general clinical data potentially affecting the outcome and the complication occurrence (such as comorbidities and ASA status) were not recorded and evaluated.MVD surgery in elderly patients remains a controversial topic. In this single-center, retrospective study, we compared elderly and non-elderly patients treated with MVD in terms of clinical and surgical outcomes. We observed an excellent early and long-term pain outcome in both groups with no significant differences in terms of complications. The presence of a clear neurovascular conflict with nerve distortion/indentation was associated with a better long-term outcome. Our results endorse MVD as an effective and safe surgical procedure for elderly patients with TN.


As of March 2022, over 78 million cases of COVID-19 and 900,000 deaths have been reported in the United States. The consequences in the acute phase due to the SARS-COV-2 infection are well defined. Beyond the direct effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) involving the lung parenchyma, the post-viral complications within the central nervous system are still largely unknown, and a comprehensive evaluation regarding the long-term neuropsychological sequelae from this disease is not well characterized. An increasing number of patients previously diagnosed with COVID-19 have now presented with ongoing symptoms of inattention, executive function, and memory difficulties. These symptoms are collectively and commonly known by the public as ‘brain fog', with many expressing concerns over their inability to engage in the workplace due to these symptoms. Here, we describe three patients who were seen in the Memory Disorders Clinic at Duke University to characterize the long-term neuropsychological symptoms, neuropsychological test results and brain MRI findings after infection with SARS-CoV-2 in a cohort of patients under the age of 60. In December 2019, a novel coronavirus known as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, located in the Hubei Province of China. On January 31, 2020, the World Health Organization (WHO) issued a global health emergency, and the disease resulting from SARS-CoV-2, coronavirus disease 2019 (COVID-19), was declared a pandemic on March 11, 2020.via next-generation sequencing led to the identification of the angiotensin-converting enzyme 2 (ACE2) receptor as the receptor that is recognized by SARS-CoV-2 [via the ACE2 receptor to contribute to dyspnea and respiratory failure in patients, SARS-CoV-2 may act through similar mechanisms [SARS-CoV-2, a positive-sense single-stranded RNA virus that primarily manifests with respiratory complications, was isolated from airway epithelial cells in patients . The symRS-CoV-2 . In addiRS-CoV-2 . The ACERS-CoV-2 . Consistchanisms , 6.Those who recover from COVID-19 can manifest several extrapulmonary symptoms. Data from previous epidemics and outbreaks with coronaviruses, including SARS-CoV-1 (in 2003) and Middle East Respiratory Syndrome (MERS), have shown a diverse array of neuropsychiatric sequelae , 8, thouA 19-year-old Caucasian female with a history of multiple concussions, migraine headaches, autonomic dysregulation and unexplained fevers presented to the Memory Disorders Clinic five months after recovering from SARS-CoV-2 infection for evaluation of cognitive difficulties. In addition to endorsing dysgeusia and dysnomia, she reported a variety of psychiatric symptoms and behavioral changes, including persistent anxiety and depression, apathy, and irritability features that she did not experience pre-COVID-19. She also self-reported ‘brain fogginess' described as difficulty concentrating (including on her schoolwork) and delayed thought process during the entire course of her illness with COVID-19. During a follow-up visit nine months after initial infection, the patient continued to struggle with word-finding difficulties and engaging in planning tasks or multitasking. She reported fatigue and apathy but noted that some of her symptoms, including her depression, had improved. She denied any history of seizures, stroke, anoxia injuries, or surgical intervention to the brain for any reason. The patient also denied having motor symptoms, gait disturbance, lateralized sensory/motor weakness, vision difficulty, auditory or visual hallucinations, obstructive sleep apnea, or REM sleep disinhibition. In terms of sleep health, she indicated that she averages 10 hours of sleep per night. She denied any pain but reported that her migraine frequency is approximately two migraines per week. She also endorsed a history of four reported concussions, one of which included a loss of consciousness at the age of 12.A 56-year-old South Asian-American female with a history of hypertension, type 2 diabetes, hypothyroidism, mixed connective tissue disorder, and lupus on Plaquenil presented to the Memory Disorders Clinic with language and memory difficulties after developing COVID-19 syndrome with a positive SARS-CoV-2 RT-PCR result one month earlier. She reported progressively worsening memory loss since five years prior that was noted to worsen after recovering from her recent SARS-CoV-2 infection. The patient replaced common words with sound-alike words and endorsed difficulty searching for the correct terminology. Additionally, she reported difficulty in recalling conversations and losing her train of thought when discussing topics with other individuals. She often double checked that she closed the garage door or turned off the stove in the kitchen. Though she had not gotten lost while driving, she had incidents in which she was driving and did not know where she was or where she was headed. The patient works as a physician assistant in neurology; however, her language difficulties have not impaired her ability to function at work and interact with patients.A 50-year-old African-American female with a history of depression, hypertension, and migraines presented to the clinic with a chief complaint of inattention and difficulties in executive function after she tested positive for SARS-CoV-2 five months prior to her initial clinic visit. She described her memory difficulties as ‘drawing blanks', including entering a room and not recalling why she entered the room in the first place or recalling passwords at her workplace. Her family noted concerns that she was forgetting conversations and she self-reported misplacing various items and having to think about where those items might be located.th percentile. Given limited data for age-matched controls, the NeuroQuant Triage Brain Atrophy Report was not available for this patient.A Montreal Cognitive Assessment (MoCA) performed during the patient's initial visit to the Memory Disorders Clinic revealed a score of 28/30, with a score of 30/30 on a repeat testing four months later. Given mild executive dysfunction that did not impair her daily function, along with normal results on the MoCA, the patient was diagnosed with subjective cognitive impairment. Neuropsychological testing showed mild executive function difficulty with a low-average score on digit-symbol substitution, but other executive functions and overall neurocognitive function was considered normal. She endorsed mild depression and anxiety on self-report measures. Furthermore, examination of the brain MRI revealed normal findings without evidence of restriction diffusion, white matter or brain matter atrophy, and hyperintensity or hemorrhage. The patient's NeuroQuant Age-Related Atrophy Report showed a hippocampal occupancy in the 68th percentile and a hippocampal occupancy score in the 51st percentile. Further, atrophy was noted in the left lateral oribitofrontal as well as both left and right lateral occipital regions on the NeuroQuant Triage Brain Atrophy Report  in the U.K. has published guidelines to assess the clinical features of the long-term consequences of SARS-CoV-2 infection. NICE defines three stages reflecting symptomatic recovery, including the following: (1) acute COVID-19, which refers to symptoms up to 4 weeks or 28 days after the onset of infection with SARS-CoV-2; (2) ongoing symptomatic COVID-19, generally defined as symptoms ranging from four to 12 weeks after onset of infection; and (3) post-COVID-19, referring to symptoms associated with SARS-CoV-2 infection that continue for 12 weeks or greater . Symptomversus older patients, and is the timeline of these symptoms different between these two populations? Further, are there any significant changes on brain MRI that occur longitudinally after recovery from SARS-CoV-2 infection? (4) Given concerns over emerging COVID-19 variants, do the characteristics of cognitive symptoms depend on the specific variant? (5) Finally, what role does vaccination play in mitigating the effects in both who previously developed and recovered from COVID-19 illness and those who have not been infected with SARS-CoV-2 but are still at risk? While these questions are beyond the scope of our study, there is a dire need to elucidate the pathophysiology and identify the risk factors and treatment modalities for those suffering from persistent symptoms secondary to SARS-CoV-2.With an increase in the number of cases and hospitalization rates due to the surge in variants, there continues to be an increasing number of patients who develop persistent symptoms beyond the acute phase of infection. Several crucial questions such as follows remain: (1) Does the severity of cognitive dysfunction secondary to SARS-CoV-2 correlate with severity of disease in young cohorts? Younger patients generally tend to have fewer medical comorbidities and are at reduced risk for more severe infection compared to the older population. Certainly, PASC symptoms have been identified in both patients with mild disease requiring outpatient treatment as well as in those hospitalized with more severe illness, but risk has been noted to be greater in those with severe COVID-19 . (2) AreT score has a mean of 50 and a standard deviation of 10. It is to be noted that because this was a fixed flexible battery there are times in which certain subtests were not administered due to a patient's tolerance for testing or due to difficulties with psychometric properties of the test. If a test was not administered, it was indicated on the table with NA.Clinical neuropsychological evaluations of these individuals included a fixed flexible battery. Neuropsychological tests were administered in standard fashion according to test manuals. Publisher information and additional details about these tests can be found elsewhere . A masteTest measures included the following:The Test of Premorbid Functioning (TOPF) is an assessment tool to estimate premorbid cognitive ability that requires an examinee to read a list of phonetically irregular words. The TOPF provides multiple possible scores, including a predicted score and achieved score. Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) is a measure of intellectual function used to derive a full-scale IQ score and four indices based on verbal comprehension, perceptual reasoning, working memory, and processing speed.Trail Making Test (A&B) : Part A of this test assesses simple visual sequencing, psychomotor speed, and general processing speed by requiring the examinee to quickly draw lines sequentially in a numerical order from 1–25. Part B of the test is similar but requires alphanumeric sequencing . Part B is considered more complex and measures cognitive flexibility. These tests are sensitive to neurological impairment and are often categorized as measures of executive function. The raw score on Wisconsin Card Sorting Test (WCST) : This test assesses an individual's strategic planning and ability to utilize environmental feedback and problem solve. It is a common measure of executive function. It is sensitive to frontal lobe damage, particularly related to dorsolateral prefrontal regions. There are multiple subscores that can be derived from this test but the table presents the number of categories generated out of 6 possible categories.California Verbal Learning Test - Second Edition (CVLT-II) : As a test of verbal episodic memory, this test assesses for verbal learning and recall by requiring an examinee to repeat back a list of words over multiple trials and to recall as many words as possible after a delay.Brief Visuospatial Memory Test - Revised (BVMT-R) : As a visual memory test assessing episodic memory, this test requires an examinee to recall shapes and to draw them in the same location presented on a page. This test includes learning trials, a delayed recall trial, and a recognition memory trial.Boston Naming Test (BNT) : This is a common test of confrontational object naming in which an examinee is presented with simple line drawings and asked to name the item. Phonemic and semantic cues are often provided for individuals who cannot identify the object. Controlled Oral Word Associations Test (FAS) and Category Naming : Verbal fluency measures required individuals to rapidly name as many objects as they can that either begin with a certain letter or fall under a certain semantic category. These are one minute trials. Phonemic fluency is mediated by frontal regions, whereas semantic fluency is mediated by left temporal and inferior parietal regions.Beck Depression Inventory - Second Edition (BDI-II) and Beck Anxiety Inventory (BAI) : These self-report questionnaires assess for symptoms of depression occurring over the most recent 2 weeks and symptoms of anxiety occurring over the most recent week.