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      Digital health for the End TB Strategy: developing priority products and making them work

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          In 2014, the World Health Organization (WHO) developed the End TB Strategy in response to a World Health Assembly Resolution requesting Member States to end the worldwide epidemic of tuberculosis (TB) by 2035. For the strategy's objectives to be realised, the next 20 years will need novel solutions to address the challenges posed by TB to health professionals, and to affected people and communities. Information and communication technology presents opportunities for innovative approaches to support TB efforts in patient care, surveillance, programme management and electronic learning. The effective application of digital health products at a large scale and their continued development need the engagement of TB patients and their caregivers, innovators, funders, policy-makers, advocacy groups, and affected communities.

          In April 2015, WHO established its Global Task Force on Digital Health for TB to advocate and support the development of digital health innovations in global efforts to improve TB care and prevention. We outline the group's approach to stewarding this process in alignment with the three pillars of the End TB Strategy. The supplementary material of this article includes target product profiles, as developed by early 2016, defining nine priority digital health concepts and products that are strategically positioned to enhance TB action at the country level.


          Priority digital health products will be profiled and developed to support the scale-up of WHO's End TB Strategy

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          Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research

          Introduction Tuberculosis (TB) is a global health concern, with an estimated 8.9 million new cases worldwide in 2004 and two million deaths each year [1]. It is a major contributor to the burden of disease, especially in low- and middle-income countries, where it is being fuelled by the HIV/AIDS epidemic [2]. DOTS (directly observed treatment, short course) is the internationally recommended control strategy for TB [3]. This strategy includes the delivery of a standard short course of drugs, lasting 6 mo for new patients and 8 mo for retreatment patients, to individuals diagnosed with TB. The delivery includes the direct observation of therapy (DOT), either by a health worker or by someone nominated by the health worker and the patient for this purpose (sometimes called a DOT supporter). The strategy has been promoted widely and implemented globally. Up to half of all of patients with TB do not complete treatment [4], which contributes to prolonged infectiousness, drug resistance, relapse, and death [5]. The difficulty experienced by patients following a particular treatment regimen has raised awareness of adherence as a complex behavioural issue, influenced by many factors [6], including gender and the impact of HIV/AIDS. WHO has attempted to classify factors that influence adherence to TB treatment based on a cursory review of key papers [6], but the impact of gender [7] and HIV status [8] on adherence are less well documented in the qualitative literature. Efforts to improve treatment outcomes require a better understanding of the particular barriers to and facilitators of adherence to TB treatment, and of patient experiences of taking treatment [9]. Qualitative research can contribute to this understanding and help interpret the findings of quantitative studies of the effectiveness of adherence-promoting interventions [10]. The volume of such qualitative research is growing and we believe that one way to draw useful lessons from this literature is by synthesising the findings of these studies. Systematic synthesis of relevant qualitative studies of TB treatment adherence can provide more complete knowledge than that derived from individual studies alone. It can assist in the interpretation of findings of single studies; help explain variation or conflicts in study findings; enable the development of new theories; and help inform the design of new interventions. In addition, it may allow the identification of gaps in existing adherence research. In this review we consider the perspectives of patients, caregivers, and health care providers regarding adherence to TB treatment. The findings of this review will have implications for a range of stakeholders including nongovernment organisations, national policy makers, and international bodies working towards reducing the global health burden of TB. Methods We followed a meta-ethnographic approach [11], the steps of which are outlined in Figure 1, to synthesise findings across included studies. This systematic approach translates ideas, concepts, and metaphors across different studies and is increasingly seen as a favourable approach to synthesising qualitative health research [11,12]. The research team included three social scientists (SM, SL, HS) and three clinical researchers (JV, AF, ME). The social scientists had different disciplinary backgrounds. Figure 1 Meta-ethnography Process Inclusion Criteria We included studies that examined adherence or nonadherence to preventive or curative TB treatments and described the perspectives of patients, care givers, or health care providers. We included studies from any discipline or theoretical tradition that used qualitative methods. We included papers that reported qualitative research only, as well as research using qualitative and quantitative methods (mixed method) that reported qualitative findings. Both published and unpublished studies reported in English were considered. Because of resource limitations, papers published in other languages were not considered. Search Strategy and Study Selection Figure 2 maps out the process by which articles were selected for our systematic review. We searched 19 databases, using the keywords: “TB AND (adherence OR concordance OR compliance)” from 1966, where available, until 16 February 2005 (see Table S1 for search results). This process was complemented by reviewing citations, searching in Google Scholar, and expert referrals. Additional articles were included as they became available. We used the search, assessment, and retrieval process outlined by Barroso et al. [13]. SM scanned more than 7,000 citations identified in the various databases and retrieved abstracts for potentially relevant studies (n = 2,162). Approximately 10% (n = 222) of these were also reviewed by JV to validate the selection of articles. Disagreements (n = 17 papers) were resolved by discussion and reference to the full article. Thereafter, SM screened the titles and abstracts of potentially relevant studies, excluding 1,536 papers and retrieving potentially eligible papers (n = 626). After scanning the full text, 560 of these articles were not considered eligible and 66 were considered potentially eligible, based on our inclusion criteria. The abstracts of these were assessed by SM and SL, and ineligible and duplicate papers were excluded, leaving 47 that were considered eligible. Two independent reviewers then read the full paper of each study, following which three more papers were excluded because they did not include qualitative data or because they had insufficient descriptions of data collection or analysis methods. The final synthesis therefore involved 44 papers. Figure 2 Search Process and Study Selection Quality Assessment We decided to assess the quality of individual studies using a checklist based on common elements from existing criteria for qualitative study quality assessment [10,14–17] (Table 1). These existing checklists are published and peer reviewed, but unlikely to be validated; only the Critical Appraisal Skills Programme criteria [17] have been used by other meta-ethnographers [18]. Evaluating study quality allowed us to describe the range of quality across included studies. Two reviewers independently assessed study quality using a pretested form and resolved differences by discussion. No studies were excluded on the basis of quality. This approach was taken for two reasons: first, both the original authors of the meta-ethnographic approach [11], and other users of the method [19], have found that poorer-quality studies tend to contribute less to the synthesis. The synthesis therefore becomes “weighted” towards the findings of the better-quality studies. Second, there is currently no consensus among qualitative researchers on the role of quality criteria and how they should be applied [10], and there is ongoing debate about how study quality should be assessed for the purposes of systematic reviews [20]. Table 1 Methodological Quality of Included Studies (n = 44) Synthesis Based on the meta-ethnography approach described by Noblit and Hare [11], we used reciprocal translation, analogous to constant comparison in primary qualitative research, to compare the themes identified in each study. We then conducted a “line-of-argument synthesis,” an approach similar to grounded theory in primary research, to determine a model of factors influencing treatment adherence. From this process we derived hypotheses relating to the reorganisation of treatment and care to improve adherence. The synthesis process is described below and illustrated in Figure 1. Identifying themes and concepts. We identified concepts, themes, and patterns by reading and rereading the included studies. In this process, we understood primary themes or first-order constructs as reflecting participants' understandings, as reported in the included studies (usually found in the results section of an article). Secondary themes or second-order constructs were understood as interpretations of participants' understandings made by authors of these studies (and usually found in the discussion and conclusion section of an article). However, we recognise that all reported data are the product of author interpretation [21]. One author (SM) extracted first- and second-order constructs from the articles, plus relevant data on study context, participants, treatment type, and methods using a standard form. The rest of the study team independently extracted data from half of the studies, but found no major differences. Although the foci of the studies were not all directly comparable, the study team identified a number of recurring first- and second-order constructs. Determining how the studies are related. We used thematic analysis to inductively develop categories from the first-order themes and concepts identified in the included studies. These categories represent related themes and concepts and initially included: family, community, and social support; professional practice and organisation of care; financial burden; personal characteristics as related to treatment adherence; access to services; disease progression; and knowledge, beliefs and attitudes towards treatment. We revised and merged these categories by discussing together as a team how they were related. We followed a similar process for second-order constructs identified from the included studies. Reciprocal translation of studies. Following the meta-ethnographic method closely, we compared the concepts and themes in one article with the concepts and themes in others. Translation involves the comparison of themes across papers and an attempt to “match” themes from one paper with themes from another, ensuring that a key theme captures similar themes from different papers (see Britten, et al. for further description [12]). We approached the reciprocal translation by arranging each paper chronologically, then comparing the themes and concepts from paper 1 with paper 2, and the synthesis of these two papers with paper 3, and so on. We began with the categories identified in the process described above, but incorporated others as they emerged. Two authors conducted the translation independently, returning to the full-text papers frequently throughout. In this review our aim was to explore adherence to TB treatment without confining this variable to a specific population or subgroup, but in doing so we were careful not to inappropriately synthesize the findings of heterogenous studies. In the process of comparing the studies against each other, we looked for explicit differences between the studies in relation to a range of factors including their geographic location, socioeconomic conditions, and the type of treatment programme. From the reciprocal translation we were able to construct tables showing each theme and related subthemes, and narratives to explain each theme. Synthesising translations. We chose to synthesise the results of the translation independently to account for different interpretations by disciplinary background. To develop an overarching framework (or third-order interpretation), we listed our translated themes and subthemes in a table, juxtaposed with secondary themes derived from author interpretations (see Table 2). Each member of the research team then independently developed an overarching framework by considering if and how the translations and authors' interpretations linked together. From this we produced a model (Figure 3) and generated hypotheses, in a “line-of-argument” synthesis. Line-of-argument syntheses create new models, theories, or understanding rather than a description of the synthesised papers [11]. Table 2 Primary and Secondary Themes Emerging from the Included Studies Figure 3 Model of Factors Affecting Adherence We attempted to explore systematically the influence of socioeconomic status and geographic location on the findings of our synthesis. However, it was difficult to determine many patterns except those highlighted specifically by authors of the primary research. We realised that synthesising studies from a variety of contexts would present challenges, but also felt that including these studies would provide an opportunity in the synthesis to explore the differences between the contexts, if these existed. Similarly, we chose to include studies examining adherence to latent TB treatment as well as adherence by injecting drug users (IDUs) and homeless people, with specific attention being paid to the ways that the issues raised in these studies differed from those focused on active TB in other populations. Again, few differences emerged. Results Description of Studies Forty-four studies published between 1969 and 2006 were included in the review. The studies were conducted in Africa (14), North America (9), South (8) and East Asia (8), Latin America (2), and Europe (2). It was difficult to discern the study setting from the published reports, but most were conducted within a clinic or health service setting (see Table 3). Most studies were concerned with curative TB treatment (33); others focused on preventive treatment (8) and some considered both (2). Most of the studies involved TB patients, often also including community members and health care workers. Three studies involved IDUs and homeless individuals. Approximately 3,213 individuals were involved in the included studies. We found few studies that justified their use of a qualitative approach (n = 13) or specified the underlying theoretical framework (n = 10), and few authors reported on their role as researcher (n = 12) (Table 1). In 12 papers the method of analysis was clearly described, but some derivation of thematic analysis appeared to be used in others. Although several studies seemed to have high face validity, they often scored poorly on our quality assessment instrument, possibly due to the instrument's ability to measure only the quality of reporting. Table 3 Characteristics of Primary Studies Included in this Review Table 3 Extended. Description of Themes Eight primary themes (identified from participants' understandings) and six secondary themes (derived from authors' interpretations) arose from the synthesis (Table 2). Each primary theme is described in Boxes 1–8 using direct quotes to illustrate meaning. Box 1: Organisation of Treatment and Care for TB Patients “The patients do not have the adequate means to go to the health centre to take their drugs. They just have camel, donkey or carts… And sometimes, the state of some patients prevents them from using these” (male family member of TB patient, Burkina Faso) [31]. “A dirty place can affect the psychology. It makes people lose heart and feel unenthusiastic about continuing treatment” (female participant with TB, Vietnam) [26]. “It just does not make sense as to why a grown up person should be given medicines by someone else. I felt very awkward, and tried to take my medicines myself” (male TB patient, Pakistan [22]. “…and I was afraid to go to the doctor, I thought he would scold me because I missed treatment for a day. For this reason, I didn't go back to get more pills. I was afraid…” (female participant, Bolivia) [32]. “The minute you tell them you're homeless they treat you real snobbish… They treat you like a dog down there once you get past the triage nurse…” (female TB patient, United States) [50]. ‘…It did help, cos I really needed assurance that it was definitely going to be [cured] and doctor spent a lot of time with me. And they were really, really um, they were outstanding there” (male TB patient, United Kingdom) [30]. Box 2: Interpretations of Illness and Wellness “…When I feel better, I don't take the tablets. Only when I feel pain” (completer, South Africa) [51]. “…She said ‘no no no I do not have TB any more' because she no longer has blood in her sputum” (provider, Indonesia) [46]. “Well, if you know a little bit about the disease and, like we say, if it's latent… you are not sick. It's only.. if it becomes active, then you are liable to be sick and probably very sick. So then you consider taking the medicine that is terribly bad: which is worse? That's when you weigh what is best for you” (provider, United States) [35]. “I think that I feel healthy, my lungs are good, but I have a bit of fear that the sickness will return… But as I told you, I don't want to take these pills, because they make me sick, they hurt me…. “ (female TB patient, Bolivia) [32]. Box 3: Financial Burden of TB Treatment “It's a bit difficult, because, as I told you, the radiography and the control smear cost more than 100B; the consult costs 15B…it will cost me almost 150B to start treatment again. At this moment, I don't even have the money for the trip to the hospital...” (male TB patient, Bolivia) [32]. “TB here is closely related to social and economic problems. People live in densely populated areas, their income is poor, and they don't understand about TB” (provider, Indonesia) [46]. “We cannot remain out of a job for long. As soon as we feel better we would like to go to work… If I cannot earn, my whole family will suffer” (male TB patient, South Africa) [51]. “Typically it [treatment] would be three months.. that's a long time for anyone to be available without any compensation… it's tremendously a matter of economics and economics only…” (male TB patient, Canada) [57]. Box 4: Knowledge, Attitudes, and Beliefs about TB Treatment “He believed that he should always use the expensive tablets and not the tablets from [the health care facility]. The … tablets were not correct with the problem inside, and the colour of the tablets doesn't look right” (participant, Indonesia) [33]. “No doctor is able to cure this” (patient, South Africa) [34]. “That's just like basic common sense, this is no test… if the doctor says to us take these tablets then that's common sense.” (male TB patient, UK) [30]. “…And when you take medications, these bugs will die, he told me. The medications kill the bugs. This is what I've been told, but I'm not sure. It seems uncertain to me. Because the pills didn't help me….” (female TB patient, Bolivia) [32]. “…a lot of people don't take the medicine because they feel that taking it doesn't do any good for their health” (female noncompliant patient on prophylaxis, US) [53]. Box 5: Law and Immigration “Because the nurse tells us that here they have a record of people who have TB, and when they go to apply for a job it shows up on the record that they have TB and it was untreated, they need [the completion record] for the job” (male Vietnamese refugee patient, US) [53]. Box 6. Personal Characteristics and Adherence Behavior “How would somone who starts drinking early in the morning visit the clinic? Some patients consume alcohol daily. They would rather decide to interrupt their treatment, than discarding their drinking habit” (male respondent, South Africa) [40]. “…When my husband went back home, he was angry with himself and he was upset about everything. He refused to eat and rejected his medicine. He threw his pills away. He did not take TB medicine at all” (female HIV+ TB patient, Thailand) [64]. “[interviewer: ‘Some people don't want to take their pills]’ Stupid people, sorry to say that” (male TB patient, UK) [30]. “I missed taking some pills because I was drunk or high on drugs” (female TB patient, US) [59]. Box 7: The Influence of Side Effects on Treatment Adherence “…Unpleasant metallic taste in his mouth… asked if a non-vegetarian diet would improve this problem. He was laughed at by the [provider] along with a number of others in the clinic and some personal remarks were made…he finally left treatment” (male TB patient, India) [24]. “I said no wonder they defaulted, many of them defaulted, you know, because it is [side effects] just too much, it is just too much …” (TB patient, UK) [30]. “These tablets let one's body itches for the whole day. I know someone who interrupted this treatment because of this problem.”(male TB patient, South Africa) [38]. “…I don't want to take these pills, because they make me sick, they hurt me…” (female TB patient, Bolivia) [32]. Box 8: Family, Community, and Household Influences “I arrive early in the morning so that people could not see me. I used to conceal my illness from people… People think that we are the filthiest people… it was really difficult to accept that I have TB” (male patient, South Africa) [40]. “We are two sisters and marriage arrangements have been made with men from one family. If my (future) family-in-law knows that I have TB they will be sure then to break the engagement...I'm worried for my sister. Her engagement also could break off because of my sickness” (female patient, Pakistan) [55]. “Just pick up the medication even if you don't use it” (patient advice to another patient on preventive treatment, US) [53]. “…I must have responsibility to take care of my child… If I die, who will take care of her? …. When I think of my child… I must be cured. This made me feel I must take the medicine” (female HIV-positive TB patient, Thailand) [64]. “…It was very important, I had my sister and my ex-girlfriend and it was really, really important to have someone, you know, to give you support especially when you don't know much about the disease” (male TB patient, UK) [30]. “…Since I have three children that I need to support… this worried me more” (male TB patient, Bolivia) [32]. We found no discernible patterns when we explored the influence of factors such as geographic location, socioeconomic status, latent or active TB, type of treatment programme, or special groups such as IDUs or the homeless. Although some studies differentiated between patients receiving treatment in urban and rural areas, no strong differences emerged between these settings, and we therefore judged it appropriate to synthesize findings across all studies. Any differences that emerged between studies with regard to specific factors are noted in the text below. Organisation of Treatment and Care for TB Patients For most patients, access to a health care facility depended on distance and available transport as well as their physical condition. One study indicated that, although the intention was for a DOT supporter to visit the patient's home, in practice the patient had to walk to the supporter's home [22]. This proved especially difficult for patients with severe symptoms [22–25]. One study noted that access to health care facilities was better in urban areas than rural areas [26], and both patients [27,28] and providers [29] noted that adherence was compromised if the distance from patients' homes to the nearest clinic was too great. If patients' homes were close to a clinic, however, the patients could attend regularly [30]. For patients on DOT, the time needed to present for direct observation of treatment-taking compromised their ability to attend to other daily tasks [25,31,32]. In one study, patients found private practitioners more accessible [26]. Problems manifesting specifically at health facilities included long waiting times, queues, lack of privacy, inconvenient appointment times [23,26–28,31–35], and the poor upkeep of clinics [26,27]. Many studies reported that patients experienced difficulty in accessing treatment at health care facilities because of inconvenient opening hours and provider absenteeism [22,23,31,37–38]. Poor TB medication availability at health care facilities was highlighted by patients [23,33,36,38] and providers [29]. For example, one study reported that a health care worker sold TB medication that should have been freely available [31]. A patient's relationship with the treatment provider also appeared to influence adherence. A large number of studies indicated that poor follow-up by providers [33,36,39], and maltreatment by providers [23,24,31,39–41], such as scolding a patient for missing appointments, resulted in nonadherence. In contrast, other studies noted the positive impact of increased provider–patient contact on adherence [26,39,42,43]. Some studies highlighted how treatment requirements could impact on patient attitudes towards treatment and thus on adherence behaviour. Patients could “become tired” of taking medications [26,30,40,44,45], discontinuing because of the length of treatment [38,40,45,46], the number of tablets [24], or fear of painful injections or drugs [29,47], as noted by both providers and patients. Some patients reported they found it difficult to meet the requirements of DOT [24,25,32,39,40]. In a number of studies conducted with patients being directly observed [22,24,34,42], adherence to treatment was facilitated by flexibility and patient choice. The continuity of the treatment process was important to patients [39,42], and irregular supervision by a family member sometimes compromised the treatment programme [22,23]. Some patients viewed direct observation negatively [22–25,40,45,48], interpreting it as distrust, and in one study describing the process as “doing time” [49]. In contrast, a study conducted with IDUs indicated that these patients appreciated the direct observation component of care because they received their treatment together with their methadone from a street nurse [50]. Interpretations of Illness and Wellness Studies in our synthesis reported that patients stopped treatment because they felt better and thought that they were cured [23,24,39,40,45,47,49,51] or because their symptoms abated [47,52,53]. Some studies noted that patients who felt worse than before treatment [23,24,32] or saw no improvement in their condition [22–24,46] might be more likely to interrupt treatment. A study conducted in The Gambia reported that migrants arrived in the country to receive TB treatment and returned home once they felt better [27]. This problem may be linked to patients' conceptions of recovery, and of the aetiology of TB. Treatment interruption was also reportedly related to perceptions about TB as a disease; some patients did not believe that they had TB, only wanted a cure for their symptoms and ceased treatment once these lessened [33,43,52]. Another study reported that patients were motivated to continue treatment as a consequence of symptom relief [30]. One study conducted in China noted that patients often continued to take medication after the necessary period of six months, and some patients would continue with treatment despite not having any symptoms, because they believed that the “roots” of the disease needed to be removed [54]. Some patients needed help in taking their medication when they were too weak [23], while others on preventive treatment and with no symptoms hesitated to even begin treatment, thinking that it could make them ill [35]. Three studies found that patients experiencing severe symptoms were more likely to adhere [39,43,54], possibly due to a fear of becoming more ill. Financial Burden of TB Treatment Several studies indicated that having TB had consequences for work [22–24, 26,27,29,32,34,42,52,54–56]. Studies suggested that patients hide their disease for fear that employers may discover that they have TB, with consequent effects on adherence. Additional work-related issues included difficulty in obtaining sick leave for treatment; fear of asking for money to purchase TB drugs; and fear of losing work or dismissal [26,29,36,55]. The reports showed how some patients prioritised work over taking treatment—and for many there appeared to be a “choice” between work and adherence [23,24,26,29,32,34,36,37,42,45,54]. More common in rural areas, this was not a real “choice” but rather a conflict between attending for clinic-based treatment and the need to earn a living. This was manifested in patients feeling “forced” to choose between work and attending treatment [26]; patients having “no choice” but to abandon treatment because it was too difficult to combine the two [29]; and patients not being able to afford treatment, but if they sought work, being unable to attend for treatment [32]. A study with inner-city homeless people on preventive treatment reported that treatment posed an economic barrier for them because they often worked out of town [57]. Patients also expressed guilt over the impact that the disease had on their family livelihoods [31]. Several studies found that patients had more pressing issues to attend to in everyday life [24,29,31,32,40,42,45,56], such as taking care of family. Economic constraints were especially noted in rural areas, especially for patients on preventive treatment [51]. Patients often explained treatment interruption by noting the costs of treatment [23,26,29,32,33]. In some settings, patients reported that drugs were expensive [29,36] and, where treatment itself was free, hidden costs such as hospital stays [29], reviews of X-ray results, and transport costs could be high. In some cases providers acknowledged patients' financial constraints [31]. However, there were examples of doctors not accepting that costs caused patients to stop taking treatment because, from the doctors' perspective, treatment was provided at no cost [32]. Failure to accept patients' reasons for nonadherence may contribute to the negative attitudes sometimes expressed by providers towards defaulting patients, resulting in difficulties in patients returning to treatment following missed appointments. Conflicts between treatment and work and the hidden costs of treatment, resulting in expenses exceeding resources [22,26–28,31,32,34,42,43,48,54,55], could push people into poverty. This possibility was cited both by health professionals and by patients as a reason for nonadherence [23,26,32,37,42,54–56]. Males (as head of households and often sole wage earners) tended to cite this reason more frequently than females [26,37,42,55]. In societies where female or adolescent patients depend on family for financial support (particularly India and Pakistan), poverty was reported as a major reason for nonadherence to treatment [22,23,36,51,55]. For patients living in poverty, the quality of food consumed while on TB treatment was reported to affect adherence [22,26,27,29,37,45,54]. Patients reported not being able to take medication on an empty stomach, or being unable to remain in hospital due to a lack of free food [26,29,37,45,54]. Knowledge, Attitudes, and Beliefs about TB Treatment Many studies centred on the influence of patients' understanding of treatment, including its duration and the consequences of defaulting, on adherence to treatment [23,24,26–28,33,34,36,38–40,42,44,46,52,57]. The long treatment period was poorly understood by patients [23,26,28,38–40,46,52]; and adherence appeared to be facilitated where patients understood the importance of completing treatment [24,26,32,36,39,44,55,58,59]. One study on adherence to prophylaxis reported that nonadherent patients had little information on TB as a disease, but were very aware of the potential adverse effects caused by treatment [44]. Patients' beliefs about the efficacy of treatment, both positive [39,41,52,59] and negative [22,23,26,28,32,34,36,39,44,52,54–56], may impact on adherence. Patients may question the efficacy of the pills or think that only injections are “medicine” [22], or even question the validity of diagnostic tests that are not considered sophisticated enough for such a dangerous disease [52]. Belief in treatment efficacy appeared to be related to patient confidence in the medical system [25,35,42]; in some cases community-based treatment programmes increased confidence among community members that TB could be cured [37,55]. Another study noted that patients preferred to consult traditional healers [34]. Fear and denial of diagnosis were common themes across the included studies. Some patients had difficulty accepting their diagnosis, often wanting to hide their disease [23,29,33,40,42,43,55,56]. In other studies, patients' desire to be cured was cited as a motivator for adherence in people presenting with TB symptoms [30,41,43,46,58,59], and patients' fear of the negative consequences of irregular treatment was associated with treatment adherence [30,32,39,54]. Patients could be nonadherent if they were taking other western [46] or traditional [51,52] medicines and perceived there to be negative consequences if these were taken concurrently with TB medication. Two studies mentioned a relationship between pregnancy and nonadherence [54,55], one of which noted that female patients believed that pregnancy would increase intolerance to drugs and make TB drugs ineffective. Law and Immigration In studies with IDUs and homeless people, mainly conducted in the US, legal and immigration requirements had an important influence on whether people adhered to prophylactic regimens. For refugees entering the US with inactive TB, obtaining certification of preventive treatment completion was a motivator for returning to the clinic [53]. Others also on preventive treatment were concerned that TB would affect their immigration status [60], that their illegal residence status would be discovered when accessing treatment [61], or that they would be incarcerated [62]. Some patients simply stated that they adhered because it was legally required [59]. In The Gambia, nonadherence was attributed by staff to Senegalese patients coming to the country for free treatment and returning home when feeling better [27]. Personal Characteristics and Adherence Behaviour Patients and providers thought that an individual's personal character determined whether they would adhere to treatment or not [24,25,28,36–38,49,57,63]. Substance abuse was noted frequently as a barrier [24,25,28,36–38,49,57,63]. Patients with mental illness [49,57]; particular ethnic groups, such as Hispanic patients in the US [49]; older and younger age groups [42,49]; and those who were residentially mobile [25,27,49,62] were considered to be at “high risk” for nonadherence by providers and patients. Religion [30,49] and personal motivation [22,27,37,39,46,54,57] were regarded as important influences on TB treatment adherence. Female patients were perceived as being more motivated [38,57], but in some countries they required permission from men or heads of household to attend treatment [27,51]. Two studies indicated that female patients who were, or wanted to be, pregnant were less likely to adhere to treatment as they perceived the medication to be harmful [54,57]. Some providers expressed the opinion that difficulties with adherence lay almost entirely with the patients [46], and used labels such as “difficult cases” for nonadherent patients [24,27,38,53]. Nonadherent patients were judged to lack interest [39], to be lazy and not care [53], or to want to remain sick to qualify for financial support [41]. Patients were criticised for not actively seeking treatment [26,29], and in one case patient characteristics were used to identify and exclude from treatment those considered at higher risk for nonadherence [25]. Wealthier, more educated people were deemed more likely to adhere [29], and illiterate patients more likely to default [22]. Two studies noted that a structured environment away from home could facilitate adherence [28,57]. Studies involving people living with HIV/AIDS noted the relationship between adherence and coping psychologically with their HIV diagnosis [64,65]. Personal agency was an important aspect of adherence behaviour; self-administering patients [22] and those who developed their own reminders adhered readily [54]. It appeared to be easier for male than female patients to be in control of the treatment process, but in one study patients felt the DOT system had transformed them from an adult to a minor, because it prevented them from managing their own treatment [42]. Treatment Side Effects and Adherence The influence of side effects—real, anticipated, or culturally interpreted—on adherence to treatment was mentioned in a number of studies [24,32,34,38,39,46,53,54,58]. Some patients reported stopping medication because of adverse effects [44,46] while others reported that they were not informed about side effects and what to do to counter them [25,34,58]. In some cases, patients had not communicated side effects to providers [38]; in others, the health care worker had not given attention to the side effects that patients reported [24,32,36], or had responded derisively to the patient's attempt to enquire about them [24]. Few patients acknowledged that side effects had influenced their decision to abandon treatment [51,54]. Cultural interpretations of side effects varied. For example, Vietnamese refugees with inactive TB interpreted treatment side effects as “hot” or “non-hot” and countered these effects differently [36]. Family, Community, and Household Influences A main theme across the included studies was the influence of community members or peers on treatment-taking behaviour [33,53,58], and the strong influence of stigma among family and friends [22,26–28,34,36,40,42,46,52,55,56,58,59,61,64]. TB patients may hide their diagnosis [26,27,29,34,37,38,40,42,56], and feel guilt and shame because of the disease [26,31,33,34,42,52]. Stigma may also make patients afraid to ask for support from their employer to purchase medication, thereby reducing adherence [29,65]. Sometimes a patient's role and responsibilities in the family could motivate them to adhere to treatment in order to recover and resume those duties [22,40,43,58,64,65]. But responsibilities in the home, such as providing income and caring for children, also reduced the likelihood of adherence for some [32]. Family support, including financial assistance, collecting medication, and emotional support, appeared to be a strong influence on patient adherence to treatment [22,26,27,29,34,36,38,40,42,52,55,56,58,59,61,64]. In some cases patients on treatment became increasingly demoralised and more likely to become nonadherent as family support weakened [23]. Providers in a study in Vietnam noted that support for the patients seemed to exist only in the family [29]. Having family members observe treatment taking was considered important for some patients, especially if the observer was a decision maker in the family [53], or a respected family member [48]. Husbands and other males' support was considered important for female patients [53]. Providers in one study noted that patients also could support each other through their treatment course [45]. Several studies reported that TB status could affect marriage [22,27,34,36,42,44,55,56]. In some cultures, females diagnosed with TB are at risk of divorce, of their husband taking a second wife, or of being sent to their natal homes [27,36,43,55]. In South Africa, red urine (a side effect of medication) was interpreted as harmful to the partner, causing abstinence from sex and thus familial disharmony and consequently potential nonadherence [34]. In Pakistan, parents' perceptions of marriage prospects influence treatment taking or avoidance among unmarried children [22,43,55]. Discussion The themes identified in this interpretive review were intricately linked and likely to have a combined effect on patient adherence to TB treatment. Secondary interpretations (by authors of included papers) allude to the complex, dynamic nature of adherence to TB treatment. One author suggested that patients experienced three layers of barriers to adherence: attending the health care facility initially, attending repeatedly, and experiences while there [31]. The layers were considered to be interlinked and exacerbated by geographic, economic, and gender inequalities; and patient decisions in relation to treatment taking were thought likely to shift for various reasons during the treatment course. Other authors considered adherence a chain of responsibilities including patients' behaviour, health care workers' conduct, and decision makers' and society's outlook [58]. These secondary (author) interpretations influenced our approach towards a higher-order interpretation (third-order interpretation), which distilled the translations into a whole, more complete interpretation. Based on the translated themes and secondary interpretations, we developed a model to depict our understanding of the main influences on adherence (Figure 3). Components of the model include structural, personal, and health service factors influencing adherence, as well as social context. We have presented structural factors and health service factors separately, instead of as a single “health systems” category, because we felt that some interventions could be directed towards wider society-level factors while others could intend to influence the person and the health care service. Structural Factors: Poverty, Gender, and Discrimination Structural factors are those factors present in society that influence treatment-taking behaviour, but over which a patient has little personal control. Structural factors have been defined as barriers or facilitators that relate to economic, social, policy, organisational, or other aspects of the environment [66]. Factors such as gender and poverty determine individual responses to treatment and subsequent behaviour; and they interact with a patient's social context, their personal characteristics, and the health care service. TB programme managers frequently assume that a willingness to adhere must be instilled in patients in order to improve adherence rates. Our synthesis has found that even where patients are willing to adhere, structural factors such as poverty and gender discrimination may prevent them from doing so. It is recognised that incorporating patients' views in medical practice often obscures the real constraints on agency that some patients experience [9]. In our synthesis, structural factors were discussed in various ways, with poverty remaining one of the most important of these for treatment taking, especially when linked to health care service factors, such as poorly accessible, poorly equipped, and distant clinics. Our findings support the assertion that interventions to increase adherence should focus not only on the patient but also on the wider context and the health care system [67]. There is a need for a shift in perspective to give greater attention to both the social and economic environment in relation to TB infection, of which the beginnings can already be seen in the international policy arena [68]. Patient Factors: Motivation, Knowledge, Beliefs, and Attitudes and Interpretations of Illness and Wellness Patient choice in taking treatment is framed by the physiological and psychological impacts of the disease and also by the social and cultural structures in which the person is immersed [68]. Patient motivation and willingness, and the effect of incentives on treatment taking, have received some attention [69]. However, it remains unclear whether the incentive, or the attention received by the patient, serves as the primary source of motivation [67]. Caution should therefore be exercised when attributing adherence solely to “personal motivation” [22,27,37,39,46,54,57], because not only can important influences be ignored, but this factor is difficult to modify or even operationalise. We found that personal and social factors, including poverty and social marginalisation, may be used by some providers to identify patients at risk of nonadherence to their medication regimen. However, it cannot be assumed that all individuals sharing a particular characteristic face the same barriers to adherence. Nonadherence can be a product of programme failures, such as an inadequate supply of drugs, rather than patient-related problems or failures [24]. Our synthesis also found that patient knowledge, attitudes, and beliefs about the disease TB, TB treatment, and patient interpretations of illness and wellness, can act as a “filter” for the information and treatment offered by the health services. The influence of patients' interpretation of various illnesses on their adherence behaviour is well documented, and it is recognised that patients may interpret the themes of illness, wellness, and disease differently from health professionals [70–73], highlighting the distinctions between lay and biomedical understandings of TB [10]. This is unlikely to be the only influence on treatment taking, however, and patient interpretations can interact with structural and health care service factors as well as with social context. Social Context The influence of social context on treatment adherence was apparent in all included studies. The community, household, and health care service helped in countering the shame and guilt that patients with TB experienced, and also offered support in maintaining treatment taking. Social support can help patients overcome structural and personal barriers, and may influence their knowledge, attitudes, and beliefs. Conversely, community and family members' attitudes may influence a patient's decision to stop taking TB treatment. In such circumstances, community-based TB treatment programmes and stronger involvement of local social networks to support TB patients may be justified [6]. Health Care Service Factors Factors related to the provision of health care services emerged strongly in the synthesis. Flexibility and choice in treatment, and options that maintain patient autonomy in treatment taking, appeared to run contrary to the traditional organisation of many TB services [6,10]. These problems were exacerbated by programme failures, such as inadequate supplies of drugs [23,33,36,38] and difficulties in consulting providers [22,23,31,36–38]. DOT at a health care facility often meant that a patient had to give up part of their working day to attend [22,23]. However, responsibilities in the home, including providing for their family, may be given priority over treatment adherence by patients. Other health care service factors, such as long waiting times and inconvenient opening times in clinics, add to economic discomfort and social disruption for patients [49], and negatively influence adherence. The studies suggest that patients often face a choice between employment and taking medication for TB; and there is evidence that patients consciously estimate the opportunity costs of taking treatment. Study Limitations The majority of studies included in this synthesis were conducted in developing countries; the findings are therefore most applicable to low- and middle-income countries that carry the greatest burden of TB disease and where interventions to improve treatment completion are needed urgently. The findings may also be applicable to countries with better resources; indeed, a meta-ethnography of treatment taking in high-income countries showed findings similar in many ways to those of our study [74]. The clustering of studies by region may have been due to the difficulties of locating primary studies, and may have produced some of the similarities between issues described by participants. Studies often included participants from several socioeconomic strata; did not always contain a detailed description of the treatment regimen; and did not explicitly consider gender in treatment adherence. Therefore it was not always possible to tease out similarities or differences in the identified themes based on these characteristics. We identified some patterns relating to the type of treatment intervention—for example, direct observation versus patient-administered treatment—but the majority of studies did not describe adequately interventions or treatment regimens. Our observations regarding gender differences in taking TB treatment are dependent largely on the information provided by original authors. Collecting author (secondary) interpretations proved difficult; most authors maintained a descriptive style in presenting their findings and so the distinction between findings and interpretation was often not clear. It is important to consider the effect on the review findings of combining studies from different theoretical traditions, and this is widely debated. We found that the level of interpretation in the included studies was fairly basic—most were descriptive studies that used thematic analysis to identify key themes and did not draw extensively on theory or on a particular theoretical tradition. While this made it more feasible to combine the study findings, it also meant we were unable to explore any differences in interpretation of factors affecting adherence in studies conducted within different theoretical frameworks. Implications for Policy and Practice Using the reconceptualised model of factors influencing adherence to TB treatment (Figure 3), we consider it important that policy makers, practitioners, and patient support groups acknowledge: patient autonomy in the treatment process; the importance of patient-centred interventions that encourage shared decision-making regarding treatment; the role of support systems tailored to patient needs; the role of informal, societal structures in reinforcing adherence through patient support; and the influence of poverty and gender on patients and their treatment adherence. New interventions to promote treatment adherence could be designed with these factors in mind. For example, when known barriers to adherence are mapped against the currently available interventions to promote adherence, it is interesting to note that very few interventions are designed to build on social and family support mechanisms. Most are targeted at overcoming barriers to health care delivery to the individual [75]. Based on our third-order interpretation, we identified a number of hypotheses that may guide policy makers and practitioners in developing and implementing specific measures to improve adherence, including influencing the behaviour of practitioners, the organisation of services, and the behaviour of individuals (Box 9). This review shows the usefulness of qualitative synthesis in informing policies for health interventions. Through bringing together data from multiple primary studies, and looking for commonalities across these studies, the approach provides fresh insights into the reasons for poor adherence and guidance on where the development of more patient-centred interventions to improve adherence could be useful. Such insights can be useful to both programme managers at local and national levels and also in facilitating the development of more appropriate international policies for the management of TB. Box 9. Factors Likely to Improve TB Treatment Adherence Increase the visibility of TB programmes in the community, which may increase knowledge and improve attitudes towards TB Provide more information about the disease and treatment to patients and communities Increase support from family, peers, and social networks Minimize costs and unpleasantness related to clinic visits and increase flexibility and patient autonomy Increase flexibility in terms of patient choice of treatment plan and type of support Increase the patient centredness of interactions between providers and clients Address “structural” and “personal” factors, for example through micro-financing and other empowerment initiatives Provide more information about the effects of medication to reduce the risk of patients becoming nonadherent when experiencing treatment side effects Implications for Research Based on the findings of this synthesis we believe that further research is needed both to understand people's experience of TB and its treatment and to develop more patient-centred approaches to improving treatment adherence among people with TB. By “patient-centred approaches” we mean interventions that focus on sharing decisions about interventions or the management of health problems with patients and that view the patient as a whole person who has individual preferences situated within a wider social context [76]. Key issues to be explored in this research include how gender shapes experiences of treatment taking and how differing gender roles may influence adherence. This aspect was reported less frequently than expected in the primary studies in this review and would benefit from further exploration. Patient experiences of side effects of treatment, and how these influence decisions to stop taking treatment, also warrant further research since the existing literature reports vary as to the influence of side effects on treatment adherence [77,78]. There is also little published evidence on the experiences of patients living with HIV/AIDS and taking treatment for TB or receiving concurrent treatment for both diseases; our review included only three reports of qualitative research in this area [51,63,64]. The small number of studies is surprising, given the high rates of TB–HIV coinfection, especially in sub-Saharan Africa [79]; the complex treatment regimens involved; and the need for high rates of treatment adherence for both diseases. There is also some evidence that where coinfection is common, a diagnosis of TB may be seen as a diagnosis of HIV and this “form” of TB may be seen as incurable, with consequent impacts on patient adherence to treatment [80]. Managing treatment for both HIV and TB is therefore likely to present unique challenges to patients, providers, and the health care system, and further research on the particular experiences of patients taking antiretroviral and anti-TB treatment would be very helpful. The process of data extraction and quality assessment identified a number of lacunae in the included study reports. Studies frequently failed to report the details of how treatment was delivered, for example whether direct observation of treatment was used; the treatment regimens used; and the sociodemographics of the included study populations. Greater attention to these areas would improve understanding of research findings and facilitate assessment of their transferability to other contexts. The reporting of a number of study quality issues also needs to be addressed in future reports, including the theoretical orientation of the research and sampling and analysis approaches (see Table 1). Finally, lay conceptualisations of illness and wellness, particularly of TB and its treatment, are not well understood. The TB treatment literature is almost entirely conceptualised from a biomedical perspective, and even studies of patient experiences are largely conducted with the aim of improving treatment adherence. Understanding lay conceptualisations will help in comprehending why people may stop taking treatment at particular times. This would involve acknowledging that patients have agency and are active [71] in shaping their own treatment decisions rather than seeing poor adherence simply as “irresponsible” behaviour. Research approaching TB adherence from a nonbiomedical perspective is required to further understand the impact of traditional beliefs [81] and perceptions of illness and wellness on adherence to treatment. Any further work on patient experiences of TB adherence should also acknowledge and explore the social, economic, and geographical contexts in which a patient is located. There are suggestions that the growing interest in the subjective experiences of health care consumers may result in these experiences being used as simply another tool with which to better promote treatment adherence. In addition, this focus, and its attendant notions of shared responsibility for treatment between consumers and providers, could be seen as acting to expand the surveillance of treatment taking from health care workers to consumers and the wider community [82,83]. We therefore believe it is important that this kind of evidence is used carefully by decision makers and practitioners. The extent to which new interventions come from biomedical rather than lay perspectives should be recognised to ensure that structural factors, as well as individual patient responsibilities in treatment taking, are considered. Conclusion This synthesis indicates that patients often take their TB medication under difficult circumstances and experience significant challenges, many of which are outside of their direct control. Taking a lengthy course of medication is not straightforward and frequently involves difficult decisions, sometimes at substantial personal and social cost to the patient. Adherence is a complex, dynamic phenomenon; a wide range of interacting factors impact on treatment-taking behaviour, and patient behaviour may change during the course of treatment. More patient-centred interventions, and far greater attention to structural barriers, are needed to improve treatment adherence and reduce the global disease burden attributable to TB. Supporting Information Alternative Language Abstract S1 Translation of the abstract into Norwegian by Atle Fretheim (48 KB PDF) Click here for additional data file. Table S1 Search Results (35 KB DOC) Click here for additional data file.
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            Mobile Phone Based Clinical Microscopy for Global Health Applications

            Light microscopy provides a simple, cost-effective, and vital method for the diagnosis and screening of hematologic and infectious diseases. In many regions of the world, however, the required equipment is either unavailable or insufficiently portable, and operators may not possess adequate training to make full use of the images obtained. Counterintuitively, these same regions are often well served by mobile phone networks, suggesting the possibility of leveraging portable, camera-enabled mobile phones for diagnostic imaging and telemedicine. Toward this end we have built a mobile phone-mounted light microscope and demonstrated its potential for clinical use by imaging P. falciparum-infected and sickle red blood cells in brightfield and M. tuberculosis-infected sputum samples in fluorescence with LED excitation. In all cases resolution exceeded that necessary to detect blood cell and microorganism morphology, and with the tuberculosis samples we took further advantage of the digitized images to demonstrate automated bacillus counting via image analysis software. We expect such a telemedicine system for global healthcare via mobile phone – offering inexpensive brightfield and fluorescence microscopy integrated with automated image analysis – to provide an important tool for disease diagnosis and screening, particularly in the developing world and rural areas where laboratory facilities are scarce but mobile phone infrastructure is extensive.
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              mHealth innovations as health system strengthening tools: 12 common applications and a visual framework

              The rapid proliferation of mHealth projects—albeit mainly pilot efforts—has generated considerable enthusiasm among governments, donors, and implementers of health programs. 1 In many instances, these pilot projects have demonstrated conceptually how mHealth can alleviate specific health system constraints that hinder effective coverage of health interventions. Large-scale implementation or integration of these mHealth innovations into health programs has been limited, however, by a shortage of empirical evidence supporting their value in terms of cost, performance, and health outcomes. 1 - 4 Governments in low- and middle-income countries face numerous challenges and competing priorities, impeding their ability to adopt innovations. 2 Thus, they need robust, credible evidence about mHealth projects in order to consider mHealth alongside essential health interventions, and guidance about which mHealth solutions they should consider to achieve broader health system goals. 2 Their tolerance for system instability or failure can be low, even when the status quo may be equally, or more, unreliable. Current larger-scale effectiveness and implementation research initiatives are working to address the evidence gaps and to demonstrate the impact of mHealth investments on health system targets. 1 Other efforts are underway to synthesize such findings. 5 MHEALTH AS A HEALTH SYSTEMS STRENGTHENING TOOL Recent mHealth reviews have proposed that innovators focus on the public health principles underlying mHealth initiatives, rather than on specific mHealth technologies. 6 International agencies and research organizations have also endeavored to frame mHealth interventions within the broader context of health system goals or health outcomes. 2 The term “health system” includes all activities in which the primary purpose is to promote, restore, or maintain health. 7 Some elements of a framework for evaluating health systems performance by relating the goals of the health system to its essential functions have been proposed previously, which we believe can serve as a model for articulating and justifying mHealth initiatives and investments. 7 Applying a health systems lens to the evaluation of mHealth initiatives requires different indicators and methodologies, shifting the assessment from whether the mHealth initiative “works” to process evaluation or proxy indicators of the health outcome(s) of interest. This new way of thinking would facilitate selection of mHealth tools that are appropriate for identified challenges. In other words, it would drive people to first identify the key obstacles, or constraints, to delivering proven health interventions effectively, and to then apply appropriate mHealth strategies that could overcome these health system constraints. 8 Presenting mHealth as a range of tools for overcoming known health system constraints, as a health systems “catalyst,” may also improve communication between mHealth innovators and health program implementers. Communicating mHealth technologies as tools that can enhance delivery of life-saving interventions through improvements in health systems performance, such as coverage, quality, equity, or efficiency, will resonate with health decision-makers. 7 Hence, rather than being perceived as siloed, stand-alone solutions, mHealth strategies should be viewed as integrable systems that should fit into existing health system functions and complement the health system goals of: health service provision; a well-performing health workforce; a functioning health information system; cost-effective use of medical products, vaccines, and technologies; and accountability and governance. 9 mHealth should be integrated into existing health system functions, rather than as stand-alone solutions. A SHARED FRAMEWORK TO EXPLAIN MHEALTH INNOVATIONS The absence of a shared language and approach to describe mHealth interventions will continue to hinder efforts to identify, catalog, and synthesize evidence across this complex landscape. The lack of a common framework also makes it hard to explain mHealth innovations to mainstream health-sector stakeholders. mHealth researchers and implementers at the World Health Organization (WHO), the Johns Hopkins University Global mHealth Initiative, the United Nations Children's Fund (UNICEF), and frog Design have jointly developed the “mHealth and ICT Framework” to describe mHealth innovations in the reproductive, maternal, newborn, and child health (RMNCH) field, in which mobile health technologies have been broadly implemented over the last decade across the developing world. The framework builds on prior efforts to describe types and uses of mHealth generally, such as in the WHO global survey on eHealth 2 and in the mHealth Alliance's typology for mHealth services in the maternal and newborn health field. 10 These previous efforts, however, have focused more explicitly on the type of actor (client, provider, or health system) and location of the mHealth activity (community, facility, or health information system). Some of these descriptions provide details about the use of specific mobile functions (such as toll-free help lines) to accomplish particular health goals, although other functions could have been used to accomplish the same goals and, over time, the functions described could be superseded by newer technologies. Furthermore, their classification approaches have not provided stakeholders with the tools to enable them to understand the diverse ways in which specific mobile functions could be employed for a particular health purpose. Our framework is constructed around standard health system goals and places intended users and beneficiaries in central focus, against the context of the proposed mHealth service package (Figure 1). By describing a specific mHealth strategy or approach, the framework visually depicts the when, for whom, what is being done to alleviate which constraints, and the how of the strategy. The framework comprises 2 key components: A place to depict the specifics of the mHealth intervention, described as one or more common mHealth or information and communications technology (ICT) applications used to target specific health system challenges or constraints within specific areas of the RMNCH continuum of care (Figure 1, upper section). A visual depiction of mHealth implementation through the concept of “touch points,” or points of contact, which describe the specific mHealth interactions across health system actors (for example, clients, providers), locations (such as clinics or hospitals), and timings of interactions and data exchange (Figure 1, lower section). Figure 1. The mHealth and ICT Framework for RMNCH Abbreviations: CHW, community health worker; ICT, information and communications technology; PMTCT, prevention of mother-to-child transmission of HIV; RMNCH, reproductive, maternal, newborn, and child health. 12 COMMON MHEALTH AND ICT APPLICATIONS The first part of the framework aims to address a previously identified challenge in mHealth: to systematically describe the constituent parts of an mHealth strategy or platform. 11 To do this, we define relationships between common applications of mHealth and ICT and the health systems constraints that they address. 2 , 12 - 13 Our list of 12 common mHealth applications has been vetted, through multiple iterations, by a wide group of mHealth stakeholders and thought leaders, ranging from academic researchers to program and policy implementers. Although a few mHealth projects deploy a single application, most comprise a package of 2 or more applications (Figure 2). In addition, mHealth projects employ 1 or more mobile phone functions—such as short message service (SMS), interactive voice response (IVR)—to accomplish the common applications (Table 1). Figure 2. Twelve Common mHealth and ICT Applications Table 1. Examples of Mobile Phone Functions Used in Common mHealth and ICT Applications Common mHealth and ICT Applications Examples of Mobile Phone Functions 1 Client education and behavior change communication (BCC) • Short Message Service (SMS) • Multimedia Messaging Service (MMS) • Interactive Voice Response (IVR) • Voice communication/Audio clips • Video clips • Images 2 Sensors and point-of-care diagnostics • Mobile phone camera • Tethered accessory sensors, devices • Built-in accelerometer 3 Registries and vital events tracking • Short Message Service (SMS) • Voice communication • Digital forms 4 Data collection and reporting • Short Message Service (SMS) • Digital forms • Voice communication 5 Electronic health records • Digital forms • Mobile web (WAP/GPRS) 6 Electronic decision support (information, protocols, algorithms, checklists) • Mobile web (WAP/GPRS) • Stored information “apps” • Interactive Voice Response (IVR) 7 Provider-to-provider communication (user groups, consultation) • Short Message Service (SMS) • Multimedia Messaging Service (MMS) • Mobile phone camera 8 Provider work planning and scheduling • Interactive electronic client lists • Short Message Service (SMS) alerts • Mobile phone calendar 9 Provider training and education • Short Message Service (SMS) • Multimedia Messaging Service (MMS) • Interactive Voice Response (IVR) • Voice communication • Audio or video clips, images 10 Human resource management • Web-based performance dashboards • Global Positioning Service (GPS) • Voice communication • Short Message Service (SMS) 11 Supply chain management • Web-based supply dashboards • Global Positioning Service (GPS) • Digital forms • Short Message Service (SMS) 12 Financial transactions and incentives • Mobile money transfers and banking services • Transfer of airtime minutes Abbreviations: GPRS, General Packet Radio Service; WAP, Wireless Application Protocol. 1. Client Education and Behavior Change Communication This series of mHealth strategies focuses largely on the client, offering a novel channel to deliver content intended to improve people's knowledge, modify their attitudes, and change their behavior. Targeted, timely health education and actionable health information—delivered through SMS, IVR, audio, and/or videos that engage 1 or more actors (such as a pregnant woman, a husband, family, community)—influences health behaviors, such as adherence to medication or use of health services. 3 , 14 The Mobile Alliance for Maternal Action (MAMA) is an example of an mHealth service package that provides gestational age-appropriate health information to pregnant women and new mothers on their family's mobile phone. 15 Most mHealth interventions in this category capitalize on people's ubiquitous access to mobile phones to increase their exposure to, and reinforce, health messages. In some instances, these types of interventions also enable clients to seek more information based on their interest in a particular message—for example, through a higher level of engagement with a call-center counselor. 4 Other mHealth interventions use mobile functions such as voice, video or audio clips, and images to enhance the effectiveness of in-person counseling, which is of particular value among low-literacy populations. Such examples include the BBC World Trust Mobile Kunji project 16 and Dimagi's CommCare Health Worker systems. 17 - 18 2. Sensors and Point-of-Care Diagnostics Harnessing the inherent computing power of mobile phones or linking mobile phones to a connected, but independent, external device can facilitate remote monitoring of clients, extending the reach of health facilities into the community and into clients' homes. Novel sensors and technologies are being developed to conduct, store, transmit, and evaluate diagnostic tests through mobile phones, from relatively simple tests, such as blood glucose measurements for diabetes management, to sophisticated assays, such as electrocardiograms (ECGs), in situations where the patient and provider are far removed from one another. These technologies also can store frequent longitudinal measures for later review during a patient-provider visit and monitor a patient's vital signs continuously and automatically, triggering a response when the device detects anomalous signals. Examples of such mHealth initiatives include the “ubiquitous health care” service in South Korea 19 that uses sensor technology to monitor patient health remotely and AliveCor, 20 a clinical grade, 2-lead ECG running on a mobile phone, recently approved by the U.S. Food and Drug Administration (FDA), that allows physicians to view and assess cardiac health at the point-of-care. These kinds of interventions are increasingly common in high-income settings but are less common in resource-limited contexts. New tests are being developed and evaluated to allow diagnostics to be conducted through mobile phones, from simple blood glucose tests to sophisticated electrocardiograms. 3. Registries and Vital Events Tracking Mobile phone-based registration systems facilitate the identification and enumeration of eligible clients for specific services, not only to increase accountability of programs for providing complete and timely care but also to understand and overcome disparities in health outcomes. 21 These are most often used for registering pregnancy and birth but also can be used for tracking individuals with specific health conditions, by age groups or other characteristics. Tracking vital events (births and deaths) supports the maintenance of population registries and determination of key development indicators, such as maternal and neonatal mortality. Such mobile registries issue and track unique identifiers and common indicators, link to electronic medical records, and enable longitudinal population information systems and health reporting. One such registry is the Mother and Child Tracking System (MCTS) in India 22 that registers pregnant women, using customized mobile phone-based applications, to help strengthen accountability for eligible clients to receive all scheduled health services (for example, 3–4 antenatal checkups, postnatal visits, and childhood vaccinations); both frontline health workers and their clients receive SMS reminders about scheduled services. Another example is UNICEF's birth registration system in Uganda, which uses RapidSMS to maintain a central electronic database of new births, updated using information transmitted via SMS, to overcome obstacles with the previously inefficient paper-based system. 23 - 24 4. Data Collection and Reporting Among the earliest global mHealth projects were those that allowed frontline workers and health systems to move from paper-based systems of ledgers, rosters, and aggregated reports to the near-instantaneous reporting of survey or patient data. Aggregation of information can occur at the server to analyze health system or disease statistics, by time, geographic area, or worker. In addition to optimizing the primary research or program monitoring and evaluation efforts of researchers, these types of mHealth initiatives reduce the turnaround time for reporting district-, local-, state-, or national-level data, which is useful for supervisors and policy makers. Countries such as Bangladesh, Rwanda, and Uganda are developing and enforcing national health information technology policies to improve the standardization and interoperability of public health data collection systems across government agencies and nongovernmental organizations (NGOs). Among the earliest mHealth projects were those that allowed collection of survey or patient data through mobile phones. Platforms commonly used to develop data collection systems include Open Data Kit (ODK) and FrontlineSMS. 25 - 26 The Formhub platform makes it easy for developers to use Microsoft Excel to create electronic forms, which can be deployed via Web forms or Android phones, with sophisticated server-side facilities for data aggregation, sharing, and visualization. 27 A large number of commercial systems exist for the range of mobile operating systems (iOS, Android, HTML5), and they often present user-friendly interfaces, such as Magpi, 28 that allow people to easily design mobile questionnaires. In Formhub and Magpi, forms can be shared with mobile data collectors and the data visualized in real time on a map, as the data are collected. National-level systems have also been developed for widespread use, such as the open-source District Health Information Software 2 (DHIS2) system, currently used in a number of countries for routine health collection and reporting. 29 In addition to being integrated into national health information systems, DHIS2 accepts data from authorized mobile devices and can allow management of data at the individual (such as district) or aggregate (national) levels. 29 5. Electronic Health Records Electronic health records (EHRs) used to be connected only to the facilities they served, allowing clinical staff to access patient records through fixed desktop computers. But the advent of mHealth has redefined the boundaries of the EHR; now, health workers can electronically register the services they provide and submit point-of-care test results through mHealth systems to update patient histories from the field. Rural health workers at the point-of-care (for example, in rural clinics or in the patient's home) can access and contribute to longitudinal health records, allowing continuity of care that was previously impossible in non-hospital-based settings. 30 Server-side algorithms to identify care gaps or trends in key indicators, such as weight loss or blood-glucose fluctuations, shift the onerous burden of identifying patterns and generating cues-to-action away from human reviewers. OpenMRS, a popular mHealth-enhanced EHR, allows frontline health workers to access information from a patient's health record using a mobile device and to contribute information into the health record—for example, about field-based tuberculosis (TB) treatment. 30 Other systems, such as RapidSMS or ChildCount+, might not be linked to a clinical file but still can maintain longitudinal client histories, such as antenatal care documentation, infant and child growth records, and digital vaccine records. 23 , 31 - 32 6. Electronic Decision Support: Information, Protocols, Algorithms, Checklists Ensuring providers' adherence to protocols is a paramount challenge to implementing complex care guidelines. In particular, shifting tasks, such as screening responsibilities, from clinicians to frontline health workers often entails adapting procedures designed for clinical workers to cadres with limited formal training. mHealth initiatives that incorporate point-of-care decision support tools with automated algorithm- or rule-based instructions help ensure quality of care in these task-shifting scenarios by prompting frontline health workers to follow defined guidelines. Point-of-care decision support tools through mobile phones can help ensure quality of care. Electronic decision support tools also can be used to identify and prioritize high-risk clients for health care, targeting interventions in resource-limited contexts. e-IMCI (electronic-Integrated Management of Childhood Illnesses), for example, provides community health workers with mobile phone-based, step-by-step support to triage and treat children according to WHO protocols for the diagnosis and treatment of common childhood diseases. 33 - 34 In addition, several groups are developing mobile phone-based checklists to help reduce clinical errors or to ensure quality of care at the point of service delivery. 35 7. Provider-to-Provider Communication: User Groups, Consultation Voice communication—one of the simplest technical functions of mobile phones—is among the most transformative applications in an mHealth service package, allowing providers to communicate with one another or across hierarchies of technical expertise. Once a key feature of telemedicine strategies, provider-to-provider communication by mobile phone can be used to coordinate care and provide expert assistance to health staff, when and where it is needed. Furthermore, communication is not limited to voice only; mobile phones allow the exchange of images or even sounds (for example, through digital auscultation, extending the reach of the traditional stethoscope) for immediate remote consultation. Providers can use simple voice communication through mobile phones to coordinate care and provide expert assistance. Current examples of provider-to-provider communication include the establishment of “Closed User Group” networks in Ghana, Liberia, and Tanzania by the NGO Switchboard, by which members of each mobile phone group can communicate with one another at heavily discounted rates, or for free. 36 - 37 In Nigeria, an mHealth feedback loop between rural clinics and diagnostic laboratories reduces the turnaround time between HIV testing and result reporting to facilitate prompt care and referral. 38 8. Provider Work Planning and Scheduling Work planning and scheduling tools help keep health care workers informed through active reminders of upcoming or due/overdue services, and they promote accountability by prioritizing provider follow-up. In low-resource settings, there often is a shortage of providers, making it a challenge to provide systematic population follow-up using traditional paper-based methods. mHealth systems can facilitate the scheduling of individuals listed in population registries (described in application number 3) for household-based outreach visits. Examples of this application include scheduling antenatal and postnatal care visits; alerting providers or supervisors about missed vaccinations or reduced adherence to medication regimens; and following up about medical procedures, such as circumcision or long-acting and permanent family planning methods. Provider work planning tools are common in many mHealth service packages, such as the scheduling functions of TxtAlert 39 and the MoTech “Mobile Midwife Service” that alerts nurses about clients who are due or overdue for care, to prevent missed appointments and delays in service provision. 40 9. Provider Training and Education Continuing medical education has been a mainstay of quality of care in high-income settings. Now, mobile devices are being used to provide continued training support to frontline and remote providers, through access to educational videos, informational messages, and interactive exercises that reinforce skills provided during in-person training. They also allow for continued clinical education and skills monitoring—for example, through quizzes and case-based learning. Applications for provider training include eMOCHA, 41 - 42 a platform that allows frontline health workers in rural Uganda to select streaming video content as part of continuing education. eMOCHA recently released “TB Detect,” a free application for Android devices in the Google Play Store, allowing providers to access continually updated educational content about tuberculosis prevention, detection, and care. 10. Human Resource Management Community health workers often work among rural populations, with only sporadic contact with supervisory staff. Web-based dashboards allow supervisors to track the performance of community health workers individually or at the district/regional/national level, either by noting the volume of digital productivity or by real-time GPS tracking of workers as they perform their field activities. This enables supportive supervision to those workers who may be lagging in their performance, while also enabling the recognition and reward of exceptional field staff. These approaches are embedded within a number of mHealth service packages, such as Rwanda's mUbuzima, which helps supervisors monitor community health worker performance and provide performance-based incentives, 43 - 44 and UNICEF's RapidSMS in Rwanda, which enables supervisors to monitor exchange of SMS messages between community health workers and a central server, thereby measuring service accountability and responsiveness of community health workers. 24 , 45 11. Supply Chain Management mHealth tools to track and manage stocks and supplies of essential commodities have received significant global attention. Relatively simple technologies that allow remote clinics or pharmacies to report daily stock levels of drugs and supplies, or to request additional materials electronically, have been implemented in a number of countries. Many countries use mHealth tools to track and manage stocks of health commodities. In Tanzania, at least 130 clinics are using the SMS for Life mHealth supply chain system to prevent stockouts of essential malaria drugs. 46 - 48 Pharmacists and other service providers are trained to send their district-level supervisors a structured text message at the end of each week to report stock levels of key commodities including anti-malarials. The supervisors can then take necessary actions to redistribute supplies, circumventing a potential crisis. In addition, a number of projects have developed mHealth strategies to reduce the risk of purchasing counterfeit drugs in countries where this is a major public health threat. 49 Companies such as Sproxil have partnered with drug manufacturers to provide mHealth authentication services to the purchasing public. 49 These strategies may help improve supply chain transparency and bolster a system's ability to be proactive and responsive to supply needs, with district or national-level visibility of performance. 12. Financial Transactions and Incentives mHealth and mFinance are converging rapidly in the domain of financial transactions to pay for health care, supplies, or drugs, or to make demand- or supply-side incentive schemes easier to deploy and scale. These strategies focus on decreasing financial barriers to care for clients, and they are testing novel ways of motivating providers to adhere to guidelines and/or provide higher quality care. Mobile financial transactions are becoming increasingly common. For example, a single African network operator, MTN, estimated having 7.3 million mobile money clients in mid-2012. 50 Thus, providing incentives to clients to use particular areas of health services will be increasingly attractive (for example, for institutional deliveries or vaccines, vouchers to subsidize health services, universal health insurance schemes, and mobile banking for access to resources for health services 51 ). Mobile-based cash vouchers have also been used where mobile money is not standard, as illustrated by the use of conditional cash transfers in Pakistan to provide families with an incentive to immunize their infants. 52 - 53 PLACING THE 12 APPLICATIONS WITHIN THE RMNCH FRAMEWORK One illustration of the application of component parts of our framework is the display of mHealth projects working within the RMNCH continuum to improve health systems functions. Specifically, the common mHealth applications capture the core uses of mobile technology and their contribution toward meeting health system needs. Health system challenges and constraints in the framework embrace and draw from concepts articulated in the WHO building blocks of health systems (service delivery, health workforce, health information systems, access to essential medicines, financing, and leadership/governance). 54 The framework's intended audience ranges from mHealth projects—to help locate their work within a broader context of mHealth in the RMNCH landscape—to stakeholders in government, implementation, or donor communities. In brief, the framework begins with the RMNCH continuum of care for women of reproductive age and their children to establish “when” during the reproductive life cycle the mHealth project will focus. 55 In other words, it identifies the beneficiary targets of the mHealth strategy, such as adolescents or pregnant women, as well as the intended users of the system, such as community health workers or district supervisors. Next, the framework identifies which RMNCH essential interventions (including preventive and curative care for improved maternal and child health outcomes) the mHealth approach will target, such as pregnancy registration or management of childhood illnesses. 56 - 57 This helps maintain focus on the needs of the health system and on the intervention that the mHealth approach is facilitating, 7 rather than on the technology being used. Rather than focus on technology, our new mHealth framework places emphasis on addressing health system needs. The common mHealth and ICT applications used by the project are indicated by horizontal, colored bars running across the RMNCH continuum of care, from adolescence to pregnancy and birth to childhood. The framework also incorporates space (to the right of the colored bars) to succinctly describe the specific health system constraints that the project is addressing (for example, “delayed reporting of events”). The framework includes categories of common health system challenges, such as information, availability, and cost. Finally, the “touch points” layer in the lower portion of the framework allows for mapping the mHealth-facilitated interactions among health system actors (for example, client, provider, manager, hospital, national health system). 58 See Figure 3 for an illustrative example of the fictional “Project Vaccinate.” Figure 3. Sample Application of the mHealth and ICT Framework for RMNCH Abbreviations: CHW, community health worker; ICT, information and communications technology; RMNCH, reproductive, maternal, newborn, and child health. The fictional “Project Vaccinate” is an mHealth system that integrates 5 of the 12 common mHealth applications to identify newborns and support families and community health workers in ensuring timely and complete vaccination. A detailed description of the components and use of the framework are beyond the scope of this commentary. In the near future, we will provide an updated framework and user guide as web-based, online tools that mHealth innovators and other stakeholders can use. Thus, the framework would serve to map and catalog mHealth service packages used across the RMNCH continuum, describing their work using a common language. As mHealth stakeholders begin to use this tool and employ this common language to describe their mHealth innovations, we expect to foster improved understanding between mHealth innovators and mainstream health system program and policy planners. This framework not only helps individual projects articulate their mHealth strategies through a shared tool but also facilitates identification of gaps in innovation, solutions, and implementation activity by overlaying multiple projects onto a single visualization. Any remaining blank spaces in the central area of the framework will signal areas of the continuum where future mHealth attention and investment may be warranted. This would also help identify common mHealth applications not yet utilized to target particular health system constraints. The new mHealth framework will help identify gaps in mHealth innovation. Ultimately, we hope these initial efforts at building consensus around a common taxonomy and framework will help overcome misgivings that mHealth innovations are the new “verticals” of this decade. Innovations in this space should be viewed not as independent, disconnected strategies but as vehicles to overcome persistent health system constraints. mHealth applications in this framework largely serve to catalyze the effective coverage of proven health interventions. Although shared frameworks are critical to communicating value, continued efforts to evaluate and generate evidence of mHealth impact are also necessary to sustain growth and mainstreaming of these solutions. These efforts should be complementary to improving the quality of deployments through end-user engagement, stakeholder inclusion, and designing for scale. 59

                Author and article information

                Eur Respir J
                Eur. Respir. J
                The European Respiratory Journal
                European Respiratory Society
                July 2016
                26 May 2016
                : 48
                : 1
                : 29-45
                [1 ]Global TB Programme, World Health Organization, Geneva, Switzerland
                [2 ]European Respiratory Society, Lausanne, Switzerland
                [3 ]WHO Collaborating Centre, Fondazione S. Maugeri, Tradate, Italy
                [4 ]FIND, Geneva, Switzerland
                [5 ]Find & Treat, University College London Hospitals, London, UK
                [6 ]University of California San Diego School of Medicine, La Jolla, CA, USA
                [7 ]Management Sciences for Health, Arlington, VA, USA
                [8 ]The Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland
                [9 ]WHO Country Office, Minsk, Belarus
                [10 ]Republican Scientific and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus
                [11 ]National TB Programme, Hanoi, Viet Nam
                [12 ]University College London, London, UK
                [13 ]Farr Institute of Health Informatics, University College London, London, UK
                [14 ]The Arcady Group, Richmond, VA, USA
                [15 ]Mayo Clinic, Rochester, MN, USA
                [16 ]ZMQ, New Delhi, India
                [17 ]TB Proof, Cape Town, South Africa
                Author notes
                Dennis Falzon, Global TB Programme, World Health Organization, 20, Avenue Appia, CH-1211, Geneva 27, Switzerland. E-mail: falzond@
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                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. This is one of a selection of articles published as ERJ Open papers, as part of an initiative agreed between the European Respiratory Society and the World Health Organization.

                Funded by: United States Agency for International Development
                Funded by: European Respiratory Society
                Award ID: ERS/WHO Global TB Programme Agreement 2014 (Phase
                Task Force Report

                Respiratory medicine


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