The Judgment of 25 July 2018 of the Court of Justice of the European Union (CJEU) Confédération paysanne and Others, C-528/16, EU:C:2018:583 of the Court of Justice of the European Union (CJEU) (from now on “the Judgment” or “Confédération paysanne and Others”) deeply disappointed the scientific community  or similar materials, which record the legislators' intention and the purpose for which the provision was made.”As explained by After the Judgment, the idea of a revision of the EU legal framework on GMO as a reaction to interpretation of the CJEU rticles 2 and 3 of [sic.] and Annex I B to Directive [2001/18] on the deliberate release into the environment of [GMOs] constitute [ … ] a full harmonization measure prohibiting Member States from subjecting organisms obtained by mutagenesis to all or some of the obligations laid down in the directive or to any other obligation, or do the Member States, when transposing those provisions, have a discretion to define the regime to be applied to organisms obtained by mutagenesis” (para 25 of the Judgment). The Judgment concludes that “[a]rticle 3(1) of Directive 2001/18 [ … ] does not have the effect of denying Member States the option of subjecting such organisms [ … ] to the obligations laid down in that directive or to other obligations” (para 82).The Art 2(2) Directive 2001/18/EC: “(2) “genetically modified organism (GMO)” means an organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination;genetic modification occurs at least through the use of the techniques listed in Annex I A, part 1;the techniques listed in Annex I A, part 2, are not considered to result in genetic modification;”.Within the terms of this definition:Annex I B Directive 2001/18/EC:“TECHNIQUES REFERRED TO IN ARTICLE 3mutagenesis,cell fusion (including protoplast fusion) of plant cells of organisms which can exchange genetic material through traditional breeding methods.”Techniques/methods of genetic modification yielding organisms to be excluded from the Directive, on the condition that they do not involve the use of recombinant nucleic acid molecules or genetically modified organisms other than those produced by one or more of the techniques/methods listed below are:Pioneer Hi Bred Italia.Pioneer Hi Bred Italia the Court, even if bound by the same legal principles than in Confédération paysanne and Others, decides just in the opposite direction. The main reason motivating these diverging decisions seemingly derives from the fact that in Pioneer Hi Bred Italia the Court appreciates the “harmonized”  nature of the matter at issue, while in Confédération paysanne and Others it does not . Be that as it may, the interpretation of the Court in Confédération paysanne and Others was not the only possible reading of Directive 2001/18/EC in relation to mutagenesis.The Court justified its positioning by arguing that “to the extent to which the EU legislature has not regulated those organisms, Member States have the option of defining their legal regime” (para 79), with the only limitation of “compliance with EU law, in particular the rules on the free movement of goods set out in Articles 34 to 36 TFEU” (para 79). This conclusion apparently stems from art 5(3) of the Treaty of the European Union (TEU) and art 2(2) TFEU; i.e., from the principle of subsidiarity and the rules applying to shared competences see also . Such inArt 5(3) TEU: “Under the principle of subsidiarity, in areas which do not fall within its exclusive competence, the Union shall act only if and in so far as the objectives of the proposed action cannot be sufficiently achieved by the Member States, either at central level or at regional and local level, but can rather, by reason of the scale or effects of the proposed action, be better achieved at Union level.”Art 2(2) TFEU: “When the Treaties confer on the Union a competence shared with the Member States in a specific area, the Union and the Member States may legislate and adopt legally binding acts in that area. The Member States shall exercise their competence to the extent that the Union has not exercised its competence. The Member States shall again exercise their competence to the extent that the Union has decided to cease exercising its competence.”The Advocate General in its Opinion (see paras 115–117) frames two scenarios that in his view might explain the legislative positioning of the EU legislature in relation to mutagenesis: (a) “the EU legislature made a legislative choice. It carried out an evaluation, and on the basis of that evaluation came to the conclusion that all the mutagenesis techniques are to be excluded because they are safe” ; or, (b) “by inserting the mutagenesis exemption, the EU legislature did not make any statement about its safety” (para 117). The Advocate General compares the role of the EU legislature in the first scenario with that of “an architect that decided to have a room called ‘mutagenesis' in his house, but who also decided to keep that room empty” (para 116); while in the second scenario, according to the Advocate General, “the architect effectively decided to leave that space called ‘mutagenesis' outside his house” (para 117). The first scenario amounts to full harmonization (see para 116 of the Opinion), while the second scenario would represent a lack of harmonization (see para 117 of the Opinion). Such scheme stems from the legal reasoning formerly mentioned (deriving from arts 5(3) TEU and 2(2) TFEU) on the basis of the equilibrium on which the EU regime on GMO is built he protection of human health and the environment”  and the principles governing the internal market in the EU ]. HoweveConfédération paysanne and Others. In other words, if the possibility of traditional mutagenesis being regulated at a national level needed the pronunciation of the Court after so many years, then maybe the scenario of the EU legislature fully harmonizing those techniques should have been seriously considered by the Court as the most plausible option. However, this line of reasoning is somehow countered by the disharmonizing effect of Directive (EU) 2015/412 on the EU legal regime on GMO , in a renounce of the EU legislature to regulate GMO obtained by means of traditional techniques of random mutagenesis. This interpretation is supported by the very late appearance of a case like (1) non-GMO; (2) GMO mentioned in art 3(1) Directive 2001/18/EC obtained through traditional techniques of random mutagenesis; (3) GMO falling within art 2(2) Directive 2001/18/EC cceptable for organic breeding” and “[t]o be phased out” : 20; andIn The dynamic interpretation of law is an interpretative approach which maintains that “the real meaning of a legal norm can be best disclosed at the moment of its interpretation” : 35. It “TECHNIQUES REFERRED TO IN ARTICLE 2(2)PART 1recombinant nucleic acid techniques involving the formation of new combinations of genetic material by the insertion of nucleic acid molecules produced by whatever means outside an organism, into any virus, bacterial plasmid or other vector system and their incorporation into a host organism in which they do not naturally occur but in which they are capable of continued propagation;techniques involving the direct introduction into an organism of heritable material prepared outside the organism including microinjection, macroinjection, and microencapsulation;cell fusion (including protoplast fusion) or hybridization techniques where live cells with new combinations of heritable genetic material are formed through the fusion of two or more cells by means of methods that do not occur naturally.”Techniques of genetic modification referred to in Article 2(2)(a) are inter alia:“TECHNIQUES REFERRED TO IN ARTICLE 2(2)[…]PART 2in vitro fertilization,natural processes such as: conjugation, transduction, transformation,polyploidy induction.”Techniques referred to in Article 2(2)(b) which are not considered to result in genetic modification, on condition that they do not involve the use of recombinant nucleic acid molecules or genetically modified organisms made by techniques/methods other than those excluded by Annex I B:Several additional teachings deduced from the Judgment might be relevant to further clarify the situation of GMO and plant breeding in the EU, and to assess the possibility to operate out of the scope of Directive 2001/18/EC.First, although it is indisputable that a dynamic interpretation of Annex I B Directive 2001/18/EC to include additional techniques not listed in it is not possible  thus far [ … ]”), 48 (“[ … ] might prove [ … ]”), 51 , and 53 (“[ … ] might be [ … ]”)]. Furthermore, as remarked by Static legal interpretation may be defined as an interpretative approach based on the idea of the “sense […] that the norm had at the time of its adoption” as its true “sense” or meaning : 35.Regarding the requirements contained in Annex I B Directive 2001/18/EC, the Court only mentions them by quoting the content of the annex , and therefore no specific guidance is provided, but flexibility is neither preempted.Second, it is clear from the aforesaid as well as from other passages of the Judgment , that the critical motive founding the refusal of the Court to exclude NBT from the scope of Directive 2001/18/EC is the alleged lack of “certainty”  regarding the requirements comprised in recital 17 Directive 2001/18/EC . Therefore, if at some point those requirements imposed by recital 17 on “new techniques/methods” fitting within Annex I B Directive 2001/18/EC are proven with a reasonable degree of “certainty”, according to the teachings of the Judgment, those techniques might be excluded from the scope of Directive 2001/18/EC. However, in the light of the Judgment (see paras 50ff), even in the case of an NBT or a group of NBT eventually meeting all criteria [from recital 17 and the other applicable criteria from Directive 2001/18/EC see Table 1 “History of use in plant breeding”: approximate time when the technique has started to be used for plant breeding . It is not meant to substitute (nor it can substitute) the assessment to be done by the EU legislature on the fulfilment of the requirements contained in recital 17 Directive 2001/18/EC. Only proposed as a proxy of the requirements stemming from recital 17 Directive 2001/18/EC for indicative purposes in the strict framework of the theoretical exercise carried out in this section. Related to questions “7)” and “8)” from “Annex I A Part 1 Directive 2001/18/EC?”: “Does it fit in any of the techniques listed in Annex I A Part 1 Directive 2001/18/EC?” see Table 1:“Annex I A Part 2 Directive 2001/18/EC?”: “Does it fit in any of the techniques listed in Annex I A Part 2 Directive 2001/18/EC” see Table 1:“‘[M]utagenesis' or ‘cell fusion [ … ]'?”: “Does it fit in the notion of “mutagenesis” or “cell fusion (including protoplast fusion) of plant cells of organisms which can exchange genetic material through traditional breeding methods”?” see Table 1:species genome.  or allowing to consider as nonrecombinant sequences declared as “near-identical” (”‘[I]nvolve [ … ] recombinant nucleic acid molecules' (recNA)”: DNA or RNA sequences containing genetic elements whose sequence and/or combination were not originally present in the entical” : 387 basentical” ]: Yes, nlato sensu of recNA”: “use of recombinant nucleic acid molecules” (lato sensu), i.e., introduction in the plant of DNA or RNA sequences (but not insertion of heritable recombinant DNA sequences into the genome). Related to question “6)” from “‘[U]se’ stricto sensu of recNA”: “use of recombinant nucleic acid molecules” (stricto sensu), i.e., stable insertion of heritable DNA sequences into the genome. Related to question “6)” from “‘[U]se' “Classification according to Directive 2001/18/EC”: classification of the techniques in Directive 2001/18/EC interpreted according to the Judgment (see “Out of the scope of Directive 2001/18/EC?”: status of the techniques as regards the scope of Directive 2001/18/EC interpreted according to the Judgment: yes (non-GMO), yes (exempted GMO)  or to other obligations”], or no (nonexempted GMO).“Potentially exemptible?”: Possibility to exclude a technique if the requirements stemming from recital 17 Directive 2001/18/EC are ascertained by the EU legislature according to the legislative proposal outlined in the present paper  and the reasoning and justification of the limited legislative proposal (in the section Leeway to Operate Out of the Scope of Directive 2001/18/EC Post Judgment) shows that such proposal, launched as a transient solution until a reform arrives, is feasible from a legal perspective. The analysis carried out in the section Analysis of the Impact of the Judgment on the Breeding Techniques evinces that, although fairly limited, the proposal might be also meaningful for plant breeders, providing at least some leeway to the industry.In summary, the analysis of the Judgment . The analysis of the breeding techniques performed in this study shows that certain applications of ODM, SDN1, and SDN2 techniques potentially falling within the notion of mutagenesis and that “do not involve the use of recombinant nucleic acid molecules or GMOs [ … ]” could be exempted without amending the scheme of Directive 2001/18/EC. Approving a supplementary EU regulation or directive ascertaining that those techniques comply with the conditions stemming from recital 17 Directive 2001/18/EC would suffice. Certainly, even if the proposal here outlined is eventually approved, the minimum demands of the breeding sector would not be appeased by its implementation. Furthermore, it must not be forgotten that a narrow interpretation of the conditions laid down in Annex I B Directive 2001/18/EC , would make the proposal unfeasible. However, if it were successfully enforced, considering that years might pass until a reform of EU legal system on GMO succeeds , and thaAll datasets generated for this study are included in the article/supplementary material.JV-V designed the study, performed the analysis of the Judgment, participated in the analysis of the techniques, and wrote the paper. CC performed the analysis of the techniques and participated in the design and writing of the paper.The necessary means for the publication of this paper have been provided by the common institutional affiliation of the authors.The information and views set out in this paper are those of the authors only and do not necessarily reflect the official opinion of the CPVO or the EU. Nothing on this paper implies a policy position of the CPVO or the EU. Neither the CPVO nor the EU nor any person acting on their behalf may be held responsible for the use which may be made of the information contained therein.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Shigellosis is a major diarrheal disease in low- and middle-income countries. Although the incidence of such diseases in South and Southeast Asia has been associated with climate fluctuations linked to the El Niño–Southern Oscillation (ENSO), the impact of ENSO on shigellosis infections remains unknown. Data reported to being infected with shigellosis while traveling abroad from 2004 to 2017 were obtained from the Korea Centers for Disease Control and Prevention. We investigated the relationship between the Oceanic Niño Index (ONI) and Indian Ocean Dipole Mode Index and the relative risk of shigellosis in outbound travelers using distributed lag linear and non-linear models. From 2004 to 2017, 87.1% of imported shigellosis was infected in South and Southeast Asian countries. The relative risk of imported shigellosis infection in outbound travelers increased as the ONI decreased. In the association with the five-month cumulative ONI, the relative risk of infection continuously increased as the La Niña index gained strength. Climate fluctuations associated with the La Niña phenomenon in South and Southeast Asian countries can lead to issues in sanitation and water safety. Our findings suggest that the decreasing trend in the ONI is associated with an increased incidence of shigellosis in these countries. Shigellosis is a clinical syndrome with symptoms such as nausea, vomiting, diarrhea, and abdominal cramps caused by the Shigella species invading intestinal epithelial cells ,2. ShigeDiarrheal diseases, including shigellosis, are well known as climate-sensitive diseases; their incidence usually increases with the occurrence of drought or floods. This is related to poor hygiene, sanitation, and a lack of clean drinking water. Weather events such as droughts or floods in South and Southeast Asian countries are affected by the El Niño Southern Oscillation (ENSO) phenomenon, which refers to variations in climate conditions resulting from the interaction of sea surface temperatures and atmospheric pressure in the tropical Pacific ,8. El NiWe analyzed the relationship between the number of imported shigellosis cases from South and Southeast Asian countries and sea surface temperature indices as climate indices after adjusting for the number of outbound South Korean travelers, seasonality, and long-term time trends. In South Korea, shigellosis is designated as a notifiable infectious disease that must be reported to the national infectious disease reporting system within 24 h. Legal infectious diseases are reported by both the doctor who diagnosed them and the institutions that confirmed the pathogens of infectious diseases. Once a case of notifiable infectious disease is reported, a detailed epidemiological investigation is conducted by health authorities on the risk factors at the time of infection. The epidemiologic surveillance data of patients with shigellosis were obtained from the Korea Centers for Disease Control & Prevention (KCDC). Among outbound travelers, we included only those individuals with shigellosis infections acquired after traveling to South and Southeast Asian countries . The monthly statistical data of overseas South Korean tourists provided by the Korea Tourism Organization were used to determine the number of outbound travelers .For the tropical Pacific and Indian Oceans, there are modes of internal fluctuations leading to climate fluctuations, namely, the ENSO and the Indian Ocean Dipole (IOD), respectively. The ENSO is a climatic event in the Pacific that has a wide impact on the world’s climate and is particularly associated with droughts and floods. Meanwhile, IOD is associated with sea-level temperature fluctuations in the Indian Ocean as well as droughts and abnormal rainfall in Southeast Asia and the eastern African region. We included the dipole mode event in Indian Ocean as an independent variable because it is independent of the ENSO in the Pacific. The Oceanic Niño Index (ONI) is a major index used to monitor the ENSO. The ONI is calculated by a three-month time averaging of the sea surface temperature anomalies in an area of the east-central equatorial Pacific Ocean called the Nino 3.4 region . Just as ENSO-related climatic fluctuations are presented using ONI indicators, the Indian Ocean Dipole Mode Index (DMI) is used to present the IOD-related climatic fluctuations. DMI is an indicator of sustained changes in the difference between sea surface temperatures of the tropical western  and eastern  Indian Ocean. We used monthly data on the ONI and DMI provided by the Asia-Pacific Economic Cooperation (APEC) climate center [t is the month reported to the KCDC; tY is the monthly imported number of shigellosis cases for month t; α is the intercept; t,lONI is the matrix obtained by applying the DLNM to the ONI(DMI); l is the lag month; L is the maximum lag; tN is an offset to control for the number of outbound travelers; ns is the natural cubic spline smoothing function of the ‘season’ variable for the control of seasonal patterns; ns is the natural cubic spline smoothing function of the ‘time’ variable for the control of long-term time trends and fluctuations; β0, β1, β2, β3, and β4 are the coefficients for t,lONI, t,lDMI, ns, and log(tN), respectively. We used a natural cubic spline basis with three degrees of freedom (df) for the ONI and two df for the lag. A natural cubic spline with 3 df was used for both the DMI and the lag. To control seasonal patterns and long-term time trends, natural cubic splines with 3 df and 7 df were used, respectively. To choose the best model with optimal df, we adopted the smaller Akaike Information Criterion (AIC) value for the quasi-Poisson model and conducted a sensitivity analysis  and Poisson regression models were used to analyze non-linear exposure-response relationships while considering the lag-time effects of climate indices for imported shigellosis cases ,19. The analysis .This study was approved by the institutional review board of Dankook University (IRB No. DKUH 2018-09-011).The overall number of shigellosis cases reported in South Korea tended to decrease from 2004 to 2017 . The totThe number of outbound travelers in South Korea averaged about 750,000 per month in 2004 but continued to increase, exceeding an average of 1.1 million per month in 2007. In 2008–2009, the number of outbound travelers decreased due to the global economic crisis but has steadily increased since then, surpassing an average of 2 million per month in 2017. In the scatter plot between the ONI (DMI) and the number of imported shigellosis cases at lag 0 month from South and Southeast Asian countries, the number of cases tended to increase as the ONI decreased. However, we observed no distinct difference in the DMI values .As a result of analyzing the relative risk of the ONI and number of shigellosis cases by classifying from zero months to five months, the relative risk associated with shigellosis infection increased as the ONI decreased, until lagged two months . When 0 We reported that the risk of infection with shigellosis in South Korean travelers returning from South and Southeast Asian countries is influenced by the ONI, a large-scale oceanic index. The risk of this infection was non-linear and markedly increased in the La Niña situation, where the overall cumulative ONI level was less than −0.5 for a period of 5 months. El Niño (La Niña) is based on a three-month moving average of the deviation in sea surface temperatures in the monitoring area (Nino 3.4 region) for El Niño (La Niña). The first month of the period when the ONI of 0.5 °C or higher lasts more than five months is considered the starting point for El Niño. Additionally, the first month of the period when the ONI of 0.5 °C or lower lasts more than five months is considered the starting point for La Niña. Based on this definition, our study analyzed the overall cumulative association from the present to the last five months. The influence of meteorological factors on the incidence of shigellosis has a lagged effect, and it is known that a time lag of about 0–2 months considering the survival and incubation period of the pathogen. In our study, the time lag for ONI was classified from zero months to five months. At −0.5 (ONI), the relative risk associated with shigellosis infection was significant from lag zero months to lag two months. As the time lag was shortened, the relative risk increased. The relative risk is highest as 1.25 (1.12–1.40) at −0.5 (ONI) for lag 0 months. These results can be inferred by reflecting the temporal characteristics that the pathogen Shigella can survive in water for about four weeks, and the incubation period of shigellosis is within one week. Besides, the lagged effect on the increase in shigellosis cases increased by extreme weather events  did not exceed one week . ENSO and IOD are climate fluctuations in the Pacific and Atlantic Oceans but are known as important indicators of events that can affect climate globally through teleconnection of the atmosphere and oceans. While fluctuations in the ENSO are relatively influential in the context of global climate fluctuations, the IOD is known to account for approximately 12% of Indian Ocean sea surface temperature fluctuations, which mainly affect countries adjacent to the Indian Ocean ,21. VariAs overall water safety and hygiene levels improved in South Korea, the number of domestic cases with shigellosis decreased. However, with the increase in the number of overseas travelers, the proportion of imported cases among the total number of cases of shigellosis continued to increase. The absolute number of imported shigellosis cases changes every year due to fluctuating climate indices; the largest number of imported shigellosis cases reported in 2010–2011 was associated with the occurrence of the strongest La Niña at that time during the study period. Of the countries visited by South Korean travelers, Thailand was the most visited country among the Southeast Asian countries, followed by the Philippines, Vietnam, and Singapore . HoweverThis study has some limitations. In this study, data reported to the legal infectious disease surveillance system were used for cases of shigellosis infection among South Koreans who entered domestic after a short overseas trip. However, if a tourist infected with shigellosis improves before returning home and does not visit a medical institution in Korea, or if he/she continues to travel after receiving treatment at the local abroad after being infected with shigellosis, data may be omitted and under-reported. The incidence of diarrheal diseases in tropical countries can increase during drought and flood periods. However, there must be an ongoing surveillance system in tropical countries to evaluate the correlation between the incidence of shigellosis and our study’s findings in each country. We could not obtain reliable shigellosis surveillance data in each country, which is another limitation of our study. As this study was conducted on South Korean individuals diagnosed with shigellosis after visiting South and Southeast Asian countries, we adjusted the total number of overseas travelers. However, we did not consider regional meteorological factors according to the local area visited. Diarrheal disease is affected not only by meteorological factors, but also by personal hygiene and infrastructural socio-economic factors such as water safety and sanitation. If the spatial resolution is further narrowed to a local area or a single nation, the results may not be the same as those of our study. However, this study attempted to explain the relationship between climate indices in a tropical region and the occurrence of shigellosis. In this study, we aimed to assess the impact of the overall cumulative association of climate indices on the incidence of shigellosis in a widespread area such as South and Southeast Asian regions, rather than in a local region with specific meteorological changes.The incidence of shigellosis in travelers returning from trips to each Southeast Asian country represents the status of the shigellosis outbreak in each region. However, it is difficult to obtain the incidence data of shigellosis by tourist destinations. To solve these problems, we analyzed the relationship between the ONI and the DMI and the relative risk of shigellosis for overseas travelers. As a result, we have confirmed that the risk of imported shigellosis infection in outbound travelers increases as ONI decreases. Our results suggest that the decreasing trend of ONI, which increases the probability of La Niña occurring, is related to the increased incidence of shigellosis in these South and Southeast Asian countries. It is predicted that extreme rainfall frequency will increase in the future due to climate change. Still, it is difficult to project in advance how the amplitude and spatial pattern of climatic events such as El Niño and La Niña will occur in the distant future. However, the number of international tourist arrivals in South and Southeast Asian countries is increasing rapidly every year. Therefore, it can be expected that shigellosis cases will increase significantly among international tourists visiting this area during the La Niña period. It is recommended that guidance is required to pay attention to hand hygiene and food consumption to tourists visiting the South and Southeast Asian countries during the La Niña period.


The COVID-19 pandemic has drastically changed the physical activity (PA) landscape through the closures of gymnasiums, schools, and many outdoor spaces. Physical distancing guidelines have also reduced opportunity for PA. The popularity of free web-based home fitness videos on video hosting platforms  has spiked during the pandemic. Many web-based fitness videos offer a convenient, accessible, and cost-effective means of engaging in PA through regularly posted videos or discrete programs. Notably, traditional PA programs often suffer from poor adherence and high dropout rates, despite many advantages over web-based workout programs . Thus, notwithstanding clear advantages of these web-based fitness videos, their ability to maintain long-term engagement and adherence is unknown.We explored patterns of engagement  for channels posting daily or program-based web-based fitness videos since the declaration of COVID-19 as a pandemic, over 4 months. Our secondary objective was to examine potential moderators of engagement metrics.An environmental scan was used to identify eligible channels. Eligible channels were (1) freely available on YouTube or Instagram and (2) posted daily or weekday series workouts or offered quarantine-specific workout programs. Searches for eligible channels were conducted on June 1 and 4, 2020. Engagement metrics of views, likes, and comments were then collected from channels’ videos posted between March 11 and June 26 or 30, 2020, inclusive, on June 26 or July 8, 2020. A series of multilevel modeling analyses were conducted to examine longitudinal changes in each of the 3 outcome variables.P=.01) on average across all the channels. Channels with more subscribers declined in their views, likes, and comments at a significantly higher rate than those with fewer subscribers (P≤.04). The day of the week a video is posted, “virality,” and content of a video appear to influence engagement. Integrating behavior change techniques and posting new and varied videos often may help garner further engagement with these videos. Future research should examine common elements of videos, which drive engagement.Ten channels were deemed eligible and included in analyses; 6 posted regularly, while the other 4 posted discrete workout programs. Multilevel models revealed that both views and likes significantly decreased across days. Visually, channels display the sharpest drop in engagement within the first week. Linear change estimate indicates that the number of views initially declined by 24,700 per day (95% CI –44,400 to –11,300, Despite raw engagement metrics, each channel demonstrated peak engagement with the initial video followed by decreased engagement with subsequent videos. As many countries maintain restrictions on traditional PA facilities owing to the COVID-19 pandemic, determining methods to improve engagement and adherence with web-based fitness videos becomes increasingly important. The COVID-19 pandemic has scaled up to over 38 million cases and over 1 million deaths worldwide as of this writing , this leAs a result of these drastic shifts in opportunity for physical activity (PA), the population has altered daily PA behaviors . Fitbit’Despite general trends in physical inactivity, some people have reported increasing their PA or remaining stable ,15. For There are clear advantages of these web-based exercise programs in these unprecedented times; yet, there remain several unanswered questions about long-term effectiveness and engagement. These programs cannot emulate several elements of traditional exercise options, such as movements that require equipment , true in-person feedback, and individualization of training. It may be that dropout from these programs is high. Indeed, fast dropout of approximately 50% from traditional gymnasiums and recreation centers is a well-established phenomenon . More inThus, the purpose of this study was to explore the pattern of engagement levels of 10 web-based freely available exercise channels that posted either daily or program-based fitness videos since the beginning of the COVID-19 pandemic. We explored total engagement and changes in engagement through views, comments, and likes across a period of 4 months during the pandemic. We further explored potential moderators of engagement metrics, such as viewership across a week and engagement across specific video posting formats and video content. Given the exploratory nature of this study, no formal confirmatory hypothesis was proposed. However, based on prior exercise adherence research, we expected to see that engagement with these web-based videos—via higher engagement metrics—would occur for the initial videos posted by channels; however, a sharp drop-off in engagement was also hypothesized to follow in subsequent videos, paralleling retention and adherence patterns in existing PA efforts .Eligible media met the following criteria: (1) freely available on YouTube or Instagram and (2) posting daily or weekday series workouts or offering quarantine-specific workout programs, as these criteria were rationalized to parallel closest with regular gymnasium-going or exercise or PA guidelines . As suchThe following keywords were used (in combination) within search engines: “Daily,” “Online,” “Workout,” “Exercise,” “Program,” “Streaming,” “Fitness,” “At-Home,” “Of the day,” “Today’s date” , “Class,” “Session,” “quarantine,” “lockdown,” and “COVID-19.” For example, “Daily online workout program” was a permutation of search strategy used.Search term keywords and combinations therein were searched directly into a Google search engine, as well as YouTube and Instagram platform search engines. For Google searches specifically, webpages that contained lists of available web-based workouts  were paAn environmental scan was initially employed to determine the media sources  for longitudinal data extraction. According to Graham , environUpon selection of appropriate YouTube and Instagram channels, overall engagement metrics were collected for videos posted between March 11 and June 26 or 30, 2020, inclusive. Specifically, these overall engagement metrics were collected on June 26 or July 8, 2020. While this extraction method does infer that older videos have more time to accumulate engagement, the regular or programmed nature of the videos posted by the observed channels is likely still sensitive enough to reflect changes in engagement over time.Engagement metrics from videos of eligible channels were collected; specifically, number of views, number of likes (if available), and number of comments. Further, to explicate trends in video engagement, channels that posted a regular series of workout videos  were charted differently than channels that released a discrete workout program . Further, number of channel subscribers was collected as a potential moderator of channel engagement.P<.05.A series of multilevel modeling analyses were conducted to examine longitudinal changes in the engagement metrics. Separate models were carried out for each of the three outcome variables  and were predicted by a linear and quadratic time variable, coded as days since COVID-19 was declared as a global pandemic  [Overall, 10 channels were observed in this environmental scan: Fit Factory , One WorThe raw daily engagement metrics are displayed in The interaction between the number of channel subscribers and linear declines was significant for each of the 3 engagement metrics; that is, channels that had more subscribers experienced a decline in their views, likes, and comments at a significantly faster than those with fewer subscribers. Our study sought to explore the pattern of engagement levels of web-based freely available exercise channels that posted regular or program-based videos since the beginning of the COVID-19 pandemic. To this end, our environmental scan identified 10 channels that met inclusion criteria. While the study is the first of its kind and thus exploratory, we expected to see a large engagement presence for videos posted closer to the start of the pandemic, followed by a sharp drop-off in engagement in subsequent videos, which mirrored patterns among traditional PA opportunities . OverallSpecifically, earlier videos posted by a channel garnered more views, likes, or comments than subsequent videos, with a drop-off in engagement in subsequent videos, regardless of channel or posting format. The multilevel models also revealed the role of the video start date (in relation to the declaration of COVID-19 as a pandemic), in that channels that began posting videos closer to March 11, 2020, saw higher engagement than those that began posting later. These findings may be representative of the trend in popularity of web-based fitness videos throughout the course of the COVID-19 pandemic. Lockdowns and stay-at-home messaging in early March drastically increased the number of individuals who were staying at home , which cNotably, while our multilevel models revealed a significant negative linear relationship between the video posting date and engagement metrics, when examining our data descriptively, the sharpest decline in all engagement metrics was evident within a week of a channel posting its first video, regardless of the start date. This initial drop-off in channel engagement parallels the poor adherence rates to traditional PA programs, whereby 50% of adults drop out within a few months of beginning a PA program . HoweverDescriptively, several potential moderators for engagement were identified within the data. Specifically, while the larger trend of engagement demonstrated was a negative linear relationship, smaller patterns within the data were also observed through visual inspection. For example, some “regularly” posting channels appeared to demonstrate weekly patterns in video views; specifically, video views were higher at the beginning of the week  and tended to decline throughout the week. This weekly—or circaseptan—cycle has been previously documented for smoking cessation efforts  and otheIn general, patterns of engagement metrics were related to other engagement metrics. For example, views of a video were consistently several magnitudes higher than likes on a video; similarly, the number of likes was generally an order of magnitude higher than comments on a video. These findings are unsurprising given that these metrics likely represent an increasing level of engagement of a video, respectively. Views of a video represent a spectrum of viewers: from those who watch the full video (and presumably participate in the PA) to those who may only have a passing curiosity in the video and disengage after 30 seconds of watching the video . On theOf the channels observed, adults were the primary audience for these videos, followed by women, children and adolescents, and then older adults. Despite insufficient observations to statistically compare channels examining these groups, descriptively, channels demonstrate fairly consistent patterns of engagement. Perhaps a notable exception to this is the channel focused on older adults ; Gaby PiThis work holds several potential practical implications for both future digital exercise research and viewers or creators of digital exercise content. Our data suggest that COVID-19 has generated interest and engagement with web-based fitness and exercise videos. Furthermore, as reports of resurgences of COVID-19 cases emerge globally and many countries revert to lockdowns and stay-at-home orders—and consequently, limitations to traditional PA opportunities—interest in these web-based fitness and exercise videos is likely to rise again. Given the similar drop-off in adherence between the web-based exercise videos observed and traditional PA opportunities , research investigating means by which these videos can retain engagement with new viewers may be able to draw from existing exercise adherence research; for example, for content creators, posting videos often and regularly, encouraging habit formation , postingBy extension, research investigating how engagement with these types of videos is linked to actual exercise behavior is also crucial for understanding their effectiveness. Further, building on previous work examining engagement with YouTube videos , contentThere are limitations to our work and its interpretation. The primary limitation is that we cannot ascertain the extent to which any individual engagement metric, or combination thereof, translates to actual PA. YouTube only requires 30 seconds of video watch time to be considered a view ; similarIn summary, the declaration of COVID-19 as a global pandemic has coincided with a surge in engagement  with web-based fitness and exercise videos on YouTube and Instagram, with observed videos posted closer to the start of the pandemic garnering significantly more engagement than subsequent videos. However, compared to earlier posted videos, engagement metrics associated with subsequent videos decline significantly, regardless of posting type, with the sharpest decline in engagement occurring within a week of the initial video and greater decline for channels with higher subscriber counts. Investigating means by which these types of channels can improve and maintain engagement with viewers, elements of current popular videos that garner engagement, as well as how this engagement translates to actual exercise behavior, are all lucrative areas for future research, especially throughout the uncertainty associated with the COVID-19 pandemic.


Supplemental digital content is available in the text. With reported population differences in parameters of nonstrabismic binocular vision, the present study investigated and reports normative data among a sample of African children.This study aimed to determine expected binocular visual function data among schoolchildren in the Central Region of Ghana.The study used a prospective cross-sectional design and used a multistage cluster sampling approach. Eligible normal participants selected through the administration of Convergence Insufficiency Symptom Survey questionnaire (score <16) and preliminary vision screening underwent comprehensive binocular vision testing. Only data for participants who expressed no difficulty with the specific procedures were analyzed.A total of 1261 normal participants  were selected for comprehensive binocular vision testing in the normative data study. The means with ±1 standard deviation for normative data for the nonstrabismic binocular vision parameters include the following: accommodative target near point of convergence (NPC) break (6.10 ± 1.67 cm), NPC recovery (8.17 ± 1.67 cm), fixation light with red-green anaglyph (RG NPC) break (8.51 ± 2.43 cm), RG NPC recovery (10.95 ± 2.60 cm), cover test distance phoria (0.12 ± 0.79 exophoria), cover test near phoria (2.1 ± 2.3 exophoria), modified Thorington test near phoria (1.9 ± 2.5 exophoria), negative relative accommodation (+2.54 ± 0.75 D), positive relative accommodation (−2.58 ± 0.81 D), and the accommodative convergence over accommodation ratio (2.80 ± 1.07:1). Age (in years)-predicted normal linear regression equations for NPC break (5.13 + 0.07 × age), RG NPC break (10.00 − 0.10 × age), RG NPC recovery (12.83 − 0.13 × age), positive relative accommodation (2.05 + 0.04 × age), and the gradient accommodative convergence over accommodation ratio (3.97 − 0.08 × age) serve as a guide.The study provides expected data that optometrists may use with similar aged Black African populations. Notable among them are Morgan's table of expected findings,3 This is a pre-requisite to classifying patients as having normal or abnormal binocular vision status.9 Recently, studies have sought to define cutoff normative clinical values for specific tests and thus introduced different values among different populations.19 According to Hussaindeen et al.,9 “to optimize the sensitivity and specificity of diagnosis, ethnicity-specific cut-off values for binocular vision parameters are mandatory.”All known binocular vision case analysis techniques require clinic test results to be compared with established normative data.11 that reported normative data for visual function parameters for nonstrabismic binocular vision. If one considers the evidence of ethnic variability, these data are technically applicable to 14- to 17-year-old Black South African children only. In the absence of additional African studies to determine normative data, the applicability of the parameters found to other African children remains unknown. Access to education is growing in Africa, and children are exposed to an exponential increase in near-point devices with their associated demands on the binocular vision system. To ensure accurate and reliable diagnosis and management of nonstrabismic binocular vision disorders in African children, there is the need for standard population-specific normative data for the different parameters of nonstrabismic binocular vision disorders. This study was designed to sample normal junior high school children in the central region of Ghana to determine normative data for visual function parameters of nonstrabismic binocular vision. It will also provide an opportunity to compare not only with the White population studies but also with the nonstrabismic binocular vision findings of another African sample.In Africa, there is a single study among South African childrenThis population-based, prospective, cross-sectional study conformed to the tenets of the Declaration of Helsinki and was ethically approved by the Biomedical Research Ethics Committee of the University of KwaZulu Natal and Ghana Health Service Ethics Review Committee. Parents and guardians of participants gave written informed consent, and participants gave written assent after the authors explained the study to them. Each participant was educated that he/she could opt out of the study at any stage if he/she wished to do so.The study used a multistage, stratified, cluster sampling technique to select participants. The 20 districts within the central region of Ghana were clustered into five based on their proximity. The various localities within the districts in each cluster were stratified into two, namely, rural and urban areas based on the Ghana 2010 Population and Housing Census definition. Within each of the strata, one or two schools were randomly selected from each cluster. Children in the first selected school were randomly selected and examined, and in cases where their numbers were not up to that required for the study, children in the second selected school were recruited into the study.http://links.lww.com/OPX/A495) using the formula n = [Z1 − α/22SD2]/d2, where Z1 − α/2 represented standard normal variate at 95% confidence interval (P < .05) = 1.96; SD represented the standard deviation of current standards,3 and d represented the absolute allowable error in estimating values. As indicated , the minimum sample size of 984 was ideal to determine normative data for the parameter with the highest standard deviation to achieve acceptable precision. With an expected minimum sample size of 197 for each cluster, several (not less than 99) normal participants were expected to be randomly selected from each rural and each urban stratum in each cluster.Estimated normative minimum sample sizes were calculated for each of the nonstrabismic binocular vision parameters  was administered to all selected participants on the day of examination to exclude those with binocular vision anomaly–related symptoms. Asymptomatic participants (score <16)21 were selected for the preliminary vision examination.The revised Convergence Insufficiency Symptom Survey questionnaireThis involved distance and near visual acuity testing using Bailey-Lovie logMAR charts, external examination using handheld slit-lamp biomicroscope, pupillary assessment using a penlight, internal examination using a direct ophthalmoscope , ocular motility using the broad H test, stereoacuity using the TNO stereo test, the Worth four-dot test using a Worth four-dot flashlight, a unilateral cover test with prism neutralization, objective refraction using a static retinoscope (Riester CE ri-scope), and subjective refraction using a trial lens set.Asymptomatic schoolchildren with unaided visual acuity or maximum plus best-corrected visual acuity of 0.0 or better logMAR were enrolled in the comprehensive binocular vision assessment stage. Participants with ocular diseases, unilateral or bilateral blindness, constant or intermittent strabismus, reduced stereopsis (worse than 60 seconds of arc), suppression, and ocular motility problems were excluded from the comprehensive binocular vision assessment.The outcome parameters measured included near point of convergence using push-up techniques with an accommodative target and a fixation light with red-green anaglyphs, distance and near phoria using the alternate cover test with prism neutralization, near phoria using the modified Thorington test, fusional vergence amplitudes at distance and near using horizontal prism bars, positive relative accommodation, negative relative accommodation, and the gradient accommodative convergence over accommodation ratio. Participants performed each test using their best-corrected spectacle prescription in a trial frame or the phoropter. Only one examiner performed the tests for each of the parameters throughout the study. One examiner performed both near point of convergence techniques, and another examiner performed both phoria techniques. These procedures were followed to avoid interexaminer variability in results. The examiner who performed both near point of convergence test and the other who performed both phoria tests adopted the following masking technique. After the first technique had been performed, the examination form was submitted to an assigned member of the data collection team. This assigned member issued a different examination sheet to the participants and instructed them to join a “second-technique queue” to the same examiner who performed the first technique; the result for this second technique was recorded on the separate examination sheet. The order of testing was randomized to obtain reliable data for the different parameters from active participants.The target used was a vertical column of N6 letters on a near-point card. The card was brought from a distance of 50 cm along the facial midline in free space and moved approximately 2 cm/s toward the participants' nose bridge. The card was stopped when the participant reported that the letters were double; no eye turned out to suggest an objective breakpoint. The distance in centimeters from the lateral canthus to the point that the target became double was taken as the breakpoint and recorded. The examiner then pulled the target backward at a speed of approximately 2 cm/s until the participant reported that the letters had become single again. This distance in centimeters from the lateral canthus to this new point (recovery point) was recorded. Measurements were done with a centimeter rule. The procedure was performed twice, and averages were recorded as “break/recovery.”Participants wore red-green anaglyphs, with the red one in front of the right eye and the green one in front of the left eye. A pen torch was positioned at 50 cm along the midline of the participant's face and was brought forward 2 cm/s to the participant's nose bridge. Participants were instructed to report a point at which the red and green color lights were seen separately as two. The distance in centimeters between the lateral canthus and this new point was quickly measured and indicated as the breakpoint. The pen torch was then pulled away from the participant's nose bridge to a point where it became single. This new point (recovery point) was measured in centimeters. The procedure was performed twice, and the averages were recorded as the “break/recovery.”Testing was done only in the primary position of gaze as the room lights were kept on so that the participant's eye could be seen with no shadows. The procedure was explained to the participants, and they were instructed to fixate at a target, keeping it clear as they sat upright with their chin and head straight. For distance testing, the target used was a letter on the 6-m Bailey Lovie logMAR chart one line larger in size than the letters on the participant's visual acuity for the poorer eye. For near testing, the target used  was positioned at 33 cm and held in line with the participant's visual axis. The occluder was placed before one eye for approximately 2 to 3 seconds and quickly transferred to the other eye. The occluder was kept before the eye for another 2 to 3 seconds as the other eye took up fixation, and then the procedure was repeated. The participants were prevented from viewing the target binocularly at any time. The just-uncovered eye was observed for movements, and any deviation (refixation movements) observed was measured with the prism bar. The amount of prism that neutralized the movement or one prism value below that which reversed the movement was recorded.The push-button LED lighted Slant Modified Thorington card  was used. The red Maddox rod was slotted over the right eye for testing. The red Maddox rod was oriented horizontally and vertically, respectively, in the trial frame for near lateral and vertical phoria testing. The Slant Modified Thorington card was positioned at 40 cm, and participants were instructed to look at the light in the center of the card and to tell the examiner the location of the streak relative to the light. To determine the size of the phoria, the participant was asked to report the target closest to which the streak passed. If the vertical streak passed through the spot of light, orthophoria was recorded through a number (esophoria) and a letter (exophoria). In vertical phoria testing, a right hypophoria and a right hyperphoria were recorded with the corresponding magnitude if the horizontal streak passed through a number and a letter, respectively.The prism bar in the free-space (step vergence) method was used to measure fusional vergence amplitudes at distance and near. The target for distance and near measurements was letters one line better than the participant's distance and near visual acuities on 6-m and 40-cm Bailey-Lovie logMAR charts, respectively. The prism bar was oriented base-in and base-out in front of the right eye and increased in magnitude at a speed of approximately 2 seconds for each step to a point where the participants reported that the target became blurry and double (break) and when it became single again (recovery points). For vertical, the breakpoints and recovery points were noted for base-down and base-up at near and distance.Using the gradient method, the cover test heterophoria at near was measured again as +1.00 D lens was added to the participant's near prescription. The accommodative convergence over accommodation ratio was found as the change in heterophoria with +1.00 D lens.The target used for measuring relative accommodation was a line better than the participant's near visual acuity on a near-point card held at 40 cm on a near-point rod in front of the phoropter. The testing was done under bright light. The examiner instructed the participants to keep the target letters single and clear. Plus lenses and minus lenses were increased in 0.25-D intervals before both eyes for negative relative accommodation and positive relative accommodation, respectively, until the participants reported the target was blurred. The final minus lenses and plus lenses were noted for positive relative accommodation and negative relative accommodation, respectively.Participants who did not understand or give clear responses to instructions and/or were unable to report end points for a specific test during the comprehensive binocular vision assessment phase were excluded from the normative data analysis for that parameter. The specific test results for such participants were considered to be unreliable.t test was used to test for significant differences in normative data among demographic parameters. One-way ANOVA with Tukey post hoc test was used to test for significant difference of parameters  among different age groups. Welch ANOVA with Games-Howell post hoc test was used to test for significant difference of parameters  among different age groups. Pearson correlation coefficient tests were used to test for linear relationships between numerical variables. A one-sample t test was used to compare the differences between techniques of specific parameters. Simple linear regression equations were derived to predict specific nonstrabismic binocular vision parameters with age. P ≤ .05 was considered statistically significant.The IBM SPSS version 21 software was used to analyze the data . Normative data were described using means ±1 standard deviation with 95% confidence intervals, medians, and maximum and minimum values. An independent-sample t test revealed that the boys were significantly older (14.9 ± 1.6 years) than the girls ; rural children were significantly older (14.9 ± 1.4 years) than urban children . The number of participants who experienced difficulty with specific procedures for specific parameters is indicated . The final data reported were normally distributed.The Convergence Insufficiency Symptom Survey was administered to 1693 schoolchildren, of which 356 (26.6%) were symptomatic and were excluded from the study. A total of 1337 (73.4%) asymptomatic participants underwent a preliminary vision examination, of whom 76 (5.7%) were excluded because of ocular diseases (1.6%), amblyopia (1.1%), strabismus (0.7%), nystagmus (0.2%), reduced stereoacuity (0.5%), suppression (0.8%), ocular motility problems (0.1%), reading disability (0.1%), photophobia (0.2%), and uncooperative children (0.4%). The remaining 1261 (94.3%) asymptomatic participants  comprising 609 (48.3%) boys and 652 (51.7%) girls with ages ranging from 11 to 17 years , 605 (48.0%) of whom were from urban communities and 656 (52%) from rural communities, were chosen to undergo a comprehensive binocular vision assessment. An independent-sample The normative data for the nonstrabismic binocular vision parameters are indicated Table . AccommoParticipants were divided into three groups Table  as follor1146 = 0.059, P = .04), near point of convergence break using fixation light with red-green anaglyph , near point of convergence recovery using fixation light with red-green anaglyph , positive relative accommodation , and the gradient accommodative convergence over accommodation ratio . Predicted normal linear regression equations for these parameters were as follows: near point of convergence break using accommodative target = [5.13 + 0.07(age)], near point of convergence break using fixation light with red-green anaglyph = [10.00 − 0.10(age)], near point of convergence recovery using fixation light with red-green anaglyph = [12.83 − 0.13(age)], positive relative accommodation = [2.05 + 0.04(age)], and gradient accommodative convergence over accommodation ratio = [3.97 − 0.08(age)].There were significant correlations between age (in years) and near point of convergence break using accommodative target  and recovery (6.50 to 9.84 cm), fixation light with red-green anaglyph near point of convergence break (6.80 to 10.94 cm) and recovery (8.35 to 13.55 cm), cover test distance phoria (0.7 esophoria to 0.9 exophoria) and near phoria (0.2 esophoria to 4.4 exophoria), and modified Thorington test near phoria (0.6 esophoria to 4.4 exophoria). The ranges of normative data are +1.79 to +3.29 for negative relative accommodation, −1.77 to −3.39 for positive relative accommodation, and 1.73:1 to 3.87:1 for the accommodative convergence over accommodation ratio.In interpreting these normative data presented Table  to guide23 A moderate to high phoria may not be a problem in the presence of sufficient fusional vergence.Some participants who passed the preliminary vision screening recorded higher phoria measurements at near or distance, increasing the magnitude of the respective normative phoria ranges Table . However24 conducted among an older Iranian population. In both studies, accommodative target near point of convergence increased by 0.1 cm for each year of age.The new linear equations derived serve as a guide for predicting normative data for those nonstrabismic binocular vision parameters using the age of the participant within the study population. The results of data for the equations fall within the normative range presented previously for each specific parameter. The normal gradient accommodative convergence over accommodation ratio of a 14-year-old schoolchild in the central region of Ghana, for example, is predicted to be 3:1 using the equation 3.97 − 0.08(14). The linear relationship between age and accommodative target near point of convergence break is consistent with the findings of a study11 Asian,9 European,25 and American26 participants . The use of the temporal canthus in the present study is, in the opinion of the authors, justifiable because the near point of convergence lies in the plane of the center of rotation of the eyes,23 which are closer to the temporal canthi region.33 This distance is expected to be longer than measures taken from other reference points.33The technique used to measure the near point of convergence in the present study differed from that described in the previous studies,23As a normative data study, the focus was to identify participants with normal binocular vision status to investigate these parameters. It was, however, difficult to identify participants with asymptomatic binocular vision problems, as the use of other existing population-based normative values to diagnose anomalies (based on the signs) would have introduced a bias. It is possible that, with the administration of the Convergence Insufficiency Symptom Survey, asymptomatic subjects with binocular vision problems may have been included in the study. To help control this, however, it was ensured that all asymptomatic participants  were only included in the comprehensive binocular vision assessment if they had normal stereopsis, normal ocular motility, no ocular suppression, and no strabismus. These measures  are important determinants of a normal single binocular vision system.34 Notwithstanding, the normative data serve as a guide for evaluating and managing nonstrabismic binocular vision problems among junior high school children in Ghana. The data presented are delimited to the tests and techniques used and must be analyzed from the perspective of the limitations indicated.Because most of the techniques were done in free space, the authors acknowledge as a limitation the difficulty to maintain a steady target. Furthermore, it is acknowledged that, during the training session for examiners, the reliability and validity of specific test measurements were observational and not analyzed through statistical methods. Moreover, it is difficult to determine the extent to which these population-expected data may be applied to a single patient; this is seen to be the major limitation with normative data studies.


The COVID-19 pandemic resulted in a dramatic shift to video-based telehealth use in home-based primary care. We conducted an online 11-item survey exploring provider perceptions of patients’ experience with and barriers to telehealth in a large HBPC program in New York City. More than one-third (35%) of patients  engaged in first-time video-based telehealth encounters between April and June 2020. The majority (82%) required assistance from a family member and/or paid caregiver. Among patients who had not used telehealth, providers deemed 27% (n=153) “unable to interact over video” for reasons including cognitive or sensory ability. Fourteen percent lacked caregivers. Physicians were not knowledgeable about patients’ internet connectivity, ability to pay for cellular plans, and video-capable device access. These findings highlight the need for novel approaches to facilitating telehealth and systematic data collection before targeted interventions to increase video-based telehealth use.


Significant predictors of poor nutritional status were low concentrations of total cholesterol, haemoglobin, HbA1c, ferritin and vitamin D status, and high concentrations of C-reactive protein; except for HbA1c, these were also associated with established malnutrition indicators. Additional validation was provided by the significant association of established malnutrition indicators  with biochemically defined poor nutritional status. The prediction model  showed an AUC of 0.79 (95% CI: 0.76–0.81), sensitivity of 66.0% and specificity of 78.1%. Clinical routine biochemical diagnostic test data have the potential to facilitate early detection of malnutrition risk in free-living older populations. However, further validation in different settings and against established malnutrition screening tools is warranted.Malnutrition (undernutrition) in older adults is often not diagnosed before its adverse consequences have occurred, despite the existence of established screening tools. As a potential method of early detection, we examined whether readily available and routinely measured clinical biochemical diagnostic test data could predict poor nutritional status. We combined 2008–2017 data of 1518 free-living individuals ≥50 years from the United Kingdom National Diet and Nutrition Survey (NDNS) and used logistic regression to determine associations between routine biochemical diagnostic test data, micronutrient deficiency biomarkers, and established malnutrition indicators (components of screening tools) in a three-step validation process. A prediction model was created to determine how effectively routine biochemical diagnostic tests and established malnutrition indicators predicted poor nutritional status (defined by ≥1 micronutrient deficiency in blood of vitamins B Malnutrition (or “undernutrition”) is a major cause of poor health in older age and is associated with loss of body weight and skeletal muscle mass. As such, it is linked with sarcopenia , the losMalnutrition can be a consequence of inadequate intake of macro- or micronutrients, leading to undernutrition, protein-energy malnutrition (PEM) and/or micronutrient deficiency, resulting in recognisable physiological, metabolic and clinical symptoms. Micronutrient deficiencies alone are recognised as contributing to substantial health consequences in older adults, including frailty and sarcopenia ,20,21,22The detrimental health effects of malnutrition on individuals as well as its significant health and social care costs reinforce the need for early detection and intervention to address malnutrition. However, despite the use of “established malnutrition screening tools”  , SubjectIn order to provide a more readily available tool for early malnutrition screening and detection of at-risk free-living individuals in the community, we investigated the potential of blood measurement data from clinical “routine biochemical diagnostic tests” to predict poor nutritional status. Routine biochemical diagnostic tests are readily available from health checks in middle and older aged individuals in primary and secondary care in many healthcare systems in Europe and the United States (US). Since these biochemical tests are performed routinely, whereas malnutrition screening is not, these biochemicals may be useful to alert to the presence of under- or malnutrition. Routinely measured biochemical diagnostic tests include measurements of cholesterol, haemoglobin A1C (HbA1c), creatinine and Estimated Glomerular Filtration Rate (eGFR), which are typically used to determine risk and treatment for conditions, such as cardiovascular disease, diabetes or renal failure, and are predictive of morbidity and mortality ,28,29. COur analysis used data from the National Diet and Nutrition Survey (NDNS), which measures food consumption, nutrient intakes and nutritional status of a representative sample of people living in private households in the UK. The NDNS includes data on “established malnutrition indicators”, i.e., individual components included in established malnutrition screening tools and risk factors for malnutrition , but diThe current study therefore investigated whether routine biochemical diagnostic tests that are routinely measured in clinical practice  have the potential to detect and alert clinicians to the presence of an increased risk of malnutrition in free-living individuals of 50 years or older . We valiThe NDNS Rolling Programme is a cross-sectional annual survey designed to assess the diet, nutrient intake and nutritional status of a representative sample of people living in private households in the UK. The NDNS rolling programme started in 2008/09 and is currently in its eleventh year. A detailed description of the NDNS methodology is published elsewhere ,35,36,37For our study, NDNS data from years one to nine (2008/09 to 2016/17) were combined to generate a dataset spanning all years for analysis of individuals aged 50 years or older living in private households . A total2). During the nurse visit, a blood sample was collected and subjects were asked the number of medicines they used , age category , ethnicity , region , Scotland, Wales, Northern Ireland), qualification , marital status (single (never married), married or legally recognised civil partnership, divorced or widowed), self-assessed general health , presence of longstanding illness , any dietary supplement use in the past year , appetite  and whether subjects had any of their own teeth . Cigarette smoking status  was obtained through a self-completion questionnaire. Anthropometric measurements, height and weight, were measured by using a portable stadiometer and weighing scales. Body mass index (BMI) was calculated as weight (kg)/height squared (mpharmacy )). FurthDietary data collection and analyses used in the NDNS have been described in detail elsewhere ,40,41,42Blood samples were drawn after an overnight fast, except for people with diabetes not willing to fast, in which case a non-fasting blood sample was taken. Blood samples were collected by venepuncture and analysed for a wide range of biochemical markers, conducted at either the Medical Research Council Elsie Widdowson Laboratory (MRC EWL) or the Immunology and Biochemistry Laboratory at Addenbrooke’s Hospital in Cambridge. Full details of blood sample collection and analyses used in the NDNS are described elsewhere . In geneWe defined “routine biochemical diagnostic tests” as any biochemical or haematology test frequently measured in clinical practice to determine risk of particular diseases. The following routine biochemical diagnostic tests were selected for analyses: cardiovascular disease , low-density lipoproteins (LDL)), anaemia and iron status , diabetes (glycated haemoglobin HbA1c), inflammatory status or infection ), renal function  and risk of bone disease (plasma 25-hydroxy vitamin D (vitamin D status)). The selection of routinely measured diagnostic tests as potential predictors of poor nutritional status was mainly based on the availability in the dataset and additionally on measures used in the systematic review of Zhang et al. (2017) . MeasureA majority of the cut-off points we have used for inadequate status are those widely used by clinicians to assist in determining whether individuals are at risk of disease or poor health status. As most of these cut-off points are not developed to specifically identify malnutrition, a more extensive literature review was conducted on suggested cut-off points specifically for malnutrition. For the routine biochemical diagnostic tests, the lower cut-off points were mostly derived from established reference ranges used in clinical practice . Low chon = 3284) (vitamin B2 (erythrocyte glutathione reductase activation coefficient (EGRAC)), vitamin B6 PLP, selenium, vitamin B1 (erythrocyte transketolase activation coefficient (ETKAC)), zinc, red cell folate, vitamin B12, vitamin C, retinol and α-tocopherol), those found to be individually associated with low BMI, haemoglobin and/or total cholesterol in the study population with valid micronutrient measurements  (adjusted for age categories and sex) were selected. Retinol and α-tocopherol were already excluded because only a low proportion of the population was deficient in these micronutrients (~0.4%). In addition to the absence of associations of vitamin B2, vitamin B1 and red cell folate with our three chosen indicators, other reasons for exclusion were uncertainty about the clinical relevance of some cut-off points . Ideally, the selection of these micronutrients would have been based on full data of established malnutrition screening tools; however, these data were not available. Since a previous systematic review found associations between malnutrition and BMI, haemoglobin, and total cholesterol in a clinical setting , these ttamin B2 ,35), andCut-off points of deficiency are defined as concentrations below reference ranges which relate to being at risk of adverse health outcomes. These were obtained from reports of various public health institutes and organisations, including the European Food Safety Authority (EFSA), Norfolk and Norwich University Hospital (NNUH) and World Health Organization (WHO). For vitamin B12, vitamin C and selenium cut-off points defining deficiency were chosen. For vitamin B6 PLP and zinc it was less clear whether the chosen cut-off points defined deficient or suboptimal status, because of the lack of consensus about cut-off points for deficient and suboptimal micronutrient status.Individual components of established malnutrition screening tools and malnutrition risk factors were selected and defined as “established malnutrition indicators”. The selection of established malnutrition indicators as potential predictors of a poor nutritional status was based on previous research studying risk factors for malnutrition in older adults ,50,51,522 when age was <70 years and <22 kg/m2 when age was ≥70 years, using the Global Leadership Initiative on Malnutrition (GLIM) criteria [Cut-off points for various established malnutrition indicators are described above. Low BMI was defined as <20 kg/mcriteria . Low procriteria . Low enecriteria . The enecriteria , or <2 pcriteria . Additiop < 0.05. Continuous variables are expressed as mean ± standard deviation (SD) and categorical variables are expressed as frequencies and percentages (%). Descriptive statistics for characteristics of the study population were calculated, stratified by micronutrient deficiency biomarker status. Analyses to test differences between micronutrient deficiency biomarker status groups were performed by ANOVA for continuous variables and Pearson’s Chi-Square tests for categorical variables. Binary variables were created for each of the selected (micro)nutrients and routine biochemical diagnostic tests, with the categories “deficient” or “sufficient” (“inadequate” or “adequate”), according to the defined cut-off points. Where measurements for the routine biochemical diagnostic tests were invalid, subjects were assigned to a “missing data” category for that specific routine biochemical to prevent the loss of data of other variables in the model.Statistical analyses of the data were performed by using Stata  and IBM SPSS Statistics . Statistical significance was based on two-sided values of A binary outcome variable defined as “at least one micronutrient deficiency vs. no micronutrient deficiencies” was generated. There were no subjects deficient in more than two micronutrients. Prior to multivariable logistic regression analyses, multicollinearity between continuous blood concentrations of the routine biochemical diagnostic tests as well as between the established malnutrition indicators was explored by detecting Pearson Correlation Coefficients of greater than 0.7 in a correlation matrix as well as variance inflation factors (VIFs). Based on these criteria, haematocrit (haematocrit and haemoglobin: r > 0.9), LDL  and creatinine (creatinine and eGFR: r > 0.7) were excluded from multivariable analyses. Results from logistic regression analyses were expressed as crude and adjusted odds ratios (OR) with 95% confidence intervals. The analysis was conducted in four stages:Firstly, (Stage 1a) to examine associations between low concentrations of routine biochemical diagnostic tests and micronutrient deficiency (as defined by the binary outcome variable described above), separate logistic regression analyses were conducted for each biochemical. These analyses were then repeated, adjusted for relevant covariates . Thereafter, (Stage 1b) we tested a model that included all routine biochemical diagnostic tests together, adjusted for the covariates as before.Secondly, (Stage 2) as further validation the routine biochemical diagnostic tests associated with at least one micronutrient deficiency in Stage 1b were tested in logistic regression analyses against established malnutrition indicators, adjusted for the covariates.Thirdly, (Stage 3) to examine the associations between established malnutrition indicators and the presence of micronutrient deficiency, separate logistic regression analyses were tested for each established malnutrition indicator, adjusted for the covariates.p-values ≤ 0.05 for variable selection. Protein intake and energy intake were excluded before variable selection, because of the scarcity of dietary intake data collection in primary-care settings. In addition, based on the analysis of Stage 3, only a fruit and vegetable intake < 2 portions/day and fluid intake < 1600 mL/day (women) or <2000 mL/day (men) were included for variable selection, because these were significantly related to the presence of at least one micronutrient deficiency and had the greatest OR. In order to base the variable selection on adjusted odds ratio’s, the covariates  were locked into the multivariable logistic regression model.The next and last stage (Stage 4) was the creation of a model predicting a poor nutritional status (the presence of at least one micronutrient deficiency). The routine biochemical diagnostic tests, covariates, and established malnutrition indicators were entered in one multivariable logistic regression model. A manual stepwise backward elimination was then performed based on The predictive performance of the final model was evaluated: Overall performance was judged by the Brier score . The discriminative ability was judged by receiver-operating characteristic (ROC) curves and the corresponding area under the curve (AUC), also known as the “concordance” (C)-statistic. AUC values of 0.5 indicate a model that predicts no better than chance, while values of 1 indicate perfect discrimination. Accuracy  was judged by the Hosmer–Lemeshow goodness-of-fit test. The sensitivity and specificity of the final model were shown to describe the model’s screening ability for a poor nutritional status relative to the reference standard (micronutrient status measured in blood). Positive and negative predictive values were also calculated.Characteristics of the study population are presented in Most characteristics differed between the absence or presence of micronutrient deficiencies, except for sex, ethnicity, and energy intake below the EAR. Subjects with at least one micronutrient deficiency tended to be in the highest age category, had a lower qualification, and were more often divorced or widowed, and a smoker. In terms of health, this group had a higher mean BMI, as well as more subjects with a longstanding illness, polypharmacy, and a worse self-assessed general health, with fewer subjects taking any type of dietary supplements. In terms of nutritional intake, the prevalence of protein intake below the RNI, a low fruit and vegetable intake, and a fluid intake below 1600 mL/day for women and 2000 mL/day for men, were all higher in those with at least one micronutrient deficiency.n = 1518, 46.2%) and the total population  are shown in For comparison, the characteristics of subjects included for analysis , according to their blood concentrations of the selected routine biochemical diagnostic tests . EspeciaUnadjusted and adjusted associations between routine biochemical diagnostic tests and established malnutrition indicators are shown in Established malnutrition indicators predicting at least one micronutrient deficiency were polypharmacy as opposed to not using any medication, having a poor appetite, a bad self-assessed general health and less than 2 portions of fruit and vegetable intake per day. Subjects using any type of dietary supplement in the past year were less likely to have a micronutrient deficiency. Covariates predicting at least one micronutrient deficiency were a higher age category and living in Wales as opposed to living in Central England or the midlands. Furthermore, current smokers were three times more likely to have multiple micronutrient deficiencies than never smokers. The remaining routine biochemical diagnostic tests as well as BMI, fluid intake, sex, ethnic group, qualification, marital status, the presence of a longstanding illness and having any of your own teeth were not found to be predictors of at least one micronutrient deficiency.p ≤ 0.001) (p = 0.513) shows there is no evidence of poor fit of the final model and the Brier score (0.19) indicates good agreement of the obtained predictions on the outcomes. Sensitivity and specificity values of the model were 66.0% and 78.1% respectively, and positive and negative predictive values were 73.6% and 71.3%.The area under the ROC curves between five different models  differed significantly (≤ 0.001) . Model 1This study has demonstrated that biochemical diagnostic tests routinely used in clinical practice for determining risk of cardiovascular disease, anaemia, diabetes, renal failure, or vitamin D deficiency, could also potentially facilitate early screening of poor nutritional status in free-living older individuals. Our multiple validation of these diagnostic tests, firstly against micronutrient deficiency biomarkers in individuals with one or more independently measured deficiencies , and secondly against risk factors of malnutrition and established malnutrition indicators that comprise components of established malnutrition screening tools, supports further research into their use as screening tools to alert for poor nutritional status and malnutrition.The biochemical tests, total cholesterol, haemoglobin, ferritin, 25-hydroxy vitamin D, and CRP were predictors of poor nutritional status (defined by at least one micronutrient deficiency); apart from HbA1c, they were also associated with several of the established malnutrition indicators that comprise components of established screening tools. The third stage of our validation, showing associations between established malnutrition indicators and micronutrient deficiency, not only confirms the links between malnutrition and micronutrient deficiency, but also our findings of the associations between the biochemical diagnostic tests and micronutrient deficiency.Although malnutrition screening and treatment have proven value for health, there are logistical difficulties in performing regular malnutrition screening. The biochemical diagnostic tests we examined are widely used in primary and secondary care in many healthcare systems in Europe and the US to assist in diagnosis or treatment of clinical conditions. They provide the benefit of being readily and routinely available in clinical care to potentially highlight middle and older aged individuals at risk of poor nutritional status and malnutrition. Measures of vitamin D deficiency and anaemia are also measured frequently in clinical practice and, thus, may similarly be useful; therefore, they were included in our models. A strength of our study is the use of micronutrient deficiency biomarkers, not routinely measured in clinical practice, for validation of the biochemical diagnostic tests and established malnutrition indicators. Micronutrient deficiencies are highly relevant as they contribute to adverse health consequences in older adults ,20,21,22The high prevalence of older individuals with one or more deficiencies of vitamin C, selenium, zinc, or vitamins B6 or B12 (48%), despite excluding vitamin D deficiency and anaemia, indicates a high proportion of the population is at risk of substantial adverse health consequences, comparable to those of PEM, and should be given more attention.The lack of previous research in this area highlights the novelty of this study. Previous reviews have proposed low blood concentrations of haemoglobin and total cholesterol as biochemical indicators for malnutrition risk in older adults from various clinical settings ,45. Our 2 was not associated with low micronutrient status in an elderly UK population [Although low BMI is included as a key indicator for malnutrition in many nutritional assessment tools, in this study a low BMI was not associated with micronutrient deficiencies. Similarly, another study showed BMI < 23.9 kg/mpulation . As onlypulation .The lack of a direct comparison with complete established malnutrition screening tools  limits our conclusions, as does the unavailability of measurements of body fat or muscle mass  skinfold thickness and mid-upper arm circumference ). Blood Although we do not consider our proposed routine biochemical diagnostic tests as a replacement for established malnutrition screening tools, a range of these biochemical tests have potential for providing a simpler means for early detection of poor nutritional status risk and the associated adverse health outcomes, and to alert physicians to the potential need of further investigations into and treatment for malnutrition. Further testing of these biochemical tests and readily available malnutrition risk factors  in larger study populations in different settings, with further validation against established malnutrition screening tools and measures of muscle mass, is warranted. Furthermore, to improve sensitivity and specificity of (pre-)malnutrition identification with biochemical tests, cut-off points might need adaptation. As better predictive performance resulted from combining the most predictive biochemical tests with established malnutrition indicators, further testing of optimal combinations of routinely collected data is recommended.To our knowledge, this is the first study to have used a multiple-step validation process to examining direct biochemical measures of micronutrient deficiency and components of malnutrition screening tools, including protein intake, to investigate the use of routinely measured biochemical diagnostic test data in order to identify poor nutritional status and malnutrition. Although our results suggest that routine biochemical diagnostic tests have the potential to facilitate early malnutrition screening in free-living middle-aged and older-age populations, further assessment and refining in larger populations and comparison with established malnutrition screening tools are required.