Mobile Screening Units for the Early Detection of Breast Cancer and Cardiovascular Disease: A Pilot Telemedicine Study in Southern Italy

Abstract

Introduction:

Telemedicine is the use of Information and Communication Technologies (ICT) to improve patient outcomes by increasing access to care, medical information and services. The aim of this pilot study was to evaluate and support the implementation of screening and early detection programs in the prevention of breast cancer and cardiovascular diseases with the establishment of a remote diagnosis through the use of ICT in mobile units.

Materials and Methods:

A total of 430 individuals were recruited in an area of Southern Italy. Particularly, 321 women were recruited to undergo breast cancer screening in accordance with Italian guidelines. Likewise, cardiovascular screening interested 109 subjects. A self-contained mobile unit with connectivity was provided to offer breast and cardiovascular screenings. To maximize the benefit, we have evaluated the return of investment.

Results:

The telemedicine screening program allowed the detection of early pathologies. In breast cancer screening, 40.8% of cases were negative to lesions, 34.9% were positive to benign lesions, and 3.1% presented suspicious malignant lesions; these lesions were further checked by histological analyses, which showed a positive response in 70% of cases. The cardiovascular screening concerned 109 participants based on age and other risk factors. We observed a significant difference among risk factors in patients with cardiac disease (p < 0.001); particularly, hypertension was significantly the most present risk factor (51.4%, p < 0.05), followed by smoking (28.4%, p < 0.05). A cardiovascular pathology was detected in 40.4% of enrolled subjects. A 3.3:1 return on investment was calculated.

Conclusion:

Our findings demonstrate that telemedicine may represent a promising approach to deliver several health services, such as screening programs, with users who cannot utilize services in their locations. The use of telemedicine on diagnostic campers greatly reduces the costs of screening for breast cancer and major cardiovascular diseases within the Southern Italian Health Service. We believe that public investment can have a further significant return on investment by implementing the principles of precision medicine.

Introduction

Telemedicine is the use of Information and Communication Technologies (ICT) to improve patient outcomes by increasing access to care, medical information and services. Telemedicine application removes time barriers and remote locations, creating new connections among treatment providers, patients and their family members.¹

ICT provides great potential for reducing the variability of diagnoses as well as improving clinical management and delivery of health care services by enhancing access, quality, efficiency, and cost-effectiveness, restricting disparities between rural and urban areas that persist.^2
–4 In particular, telemedicine can assist communities that are not under care—those in remote or rural areas with few health services and staff—because it can overcome distance and time barriers between health care providers and patients.^3,5 Different evidences are reported on important socioeconomic benefits to patients, families, health practitioners, and the health system, including enhanced patient–provider communication.⁶

Health care is the sector where the adoption of technology has been neglected, even though nowadays the available technologies should make a substantial contribution in the development and organization of the health system toward the well-being of citizens.⁷ However, inequities in coverage and provided treatment still persist due to geographical barriers, trained personnel capacity, technological capacity, and organization among local health care systems.^1,8

In Italy, although there are different studies, the introduction of conventional health telemedicine still seems very slow and its use should be further encouraged.^9

–12 Typical difficulties, which continue to challenge widespread telemedicine adoption by health care organizations, comprise technology, financial, legal/standards, business strategy, and human resources issues.^13,14 By increasing accessibility of medical care with telemedicine, patients may look for treatment earlier and adhere better to their prescribed treatments improving the life quality, as already used in patients with chronic conditions.^1,8 The burden and morbidity of chronic illness and aging in our community continues to place demands on all aspects of the health system in Italy and worldwide.^14
–16 Managing these chronic conditions, along with the level of patient disability, will increase the financial demands on our health care system. Development of new technology innovations and their different telemedicine applications in integrated care programs, such as teleassessments, have positive effects on the quality of care in chronic patients.^14,15,17,18

Although telemedicine has been shown to be useful for screening, diagnosis, and management in different studies,^19
–21 there are still serious difficulties including deficiency of provider availability, community access to screening, and community demand for screening.^22,23 Challenges related to health care providers can involve scarcity in screening delivery or policies requiring a consultation from a family physician to access screening. Community access can be limited by prohibitive costs or inaccessibility of screening clinics due to distance, hours of operation, or a lack of knowledge about places. Finally, individuals are not always aware of the benefits of screening; they do not perceive themselves at risk, or fear screening results. Mobile units are an innovative alternative to screening exams in clinics or hospitals and may include vans or other travelling clinics that are staffed by health workers and outfitted with equipment for early detection.²⁴ Mobile units allow care providers to increase their capacity for service delivery outside of fixed clinics, which is particularly important in areas without an infrastructure for screening services.²⁵ These ones increase community access by offering screening services in convenient locations, thus decreasing the distance and travel time needed.²⁶

The object of this pilot study was to support the implementation of screening and early detection programs in cancer and cardiovascular diseases with the establishment of a remote diagnosis through the use of ICT in mobile units. Here, we evaluated the use of telemedicine in the prevention of breast cancer and some cardiovascular diseases in terms of feasibility, care team/task, and areas of major interventions. To maximize the benefit, we have evaluated the return of investment (ROI) for our pilot study.^27,28

Materials and Methods

Study Population

A total of 430 subjects (387 women and 43 men) were recruited between January and December 2014 in the Campania Region, in southern Italy. All subjects were enrolled in 13 different locations of Caserta Province (Fig. 1).

Fig. 1.

Caserta areas interested by the TM program are represented. TM, telemedicine.

The study protocol matched the Declaration of Helsinki ethical guidelines for clinical studies and it was approved by the Technical Scientific Committee of “Sant'Anna and San Sebastiano” hospital in collaboration with the local Committee of Italian Red Cross. All patients signed their informed consent.

A total of 321 individuals from 14 sites of Caserta Province were recruited to undergo breast cancer screening in accordance with the age, as suggested by Italian guidelines. Only women, within the 19–82 range, mean age of 51.1 years old ±12.3 years old participated in the study (Table 1). Women aged at least 18 years were eligible to participate and were excluded if they were pregnant or lactating. Study participants included women who were asymptomatic and represented their first access to breast cancer screening or women with a family risk history (i.e., type of affected relative, age at which the relative developed breast cancer, and number of affected relatives).

Table 1.

Characteristics of 321 Participants to the Breast Screening

PARAMETERS	MEAN ± SD/PERCENTAGES
Gender
Male	0% (0/321)
Female	100% (321/321)
Age	51.1 ± 12.3
Diagnosis
Negative	62.0% (199/321)
Positive/benign	34.9% (112/321)
Suspicious	3.1% (10/321)
Mammography response	263
Negative	70.7% (186/263)
Positive/benign	25.5% (67/263)
Suspicious	3.8% (10/263) [7]
Ultrasound response	264
Negative	62.1% (164/264)
Positive/benign	35.6% (94/264)
Suspicious	2.3% (6/264) [4]
Histological response
Positive	70.0% (7/10)
Negative	30.0% (3/10)

In squared brackets, the histologically confirmed cases are indicated.

SD, standard deviation.

The cardiovascular screening interested 7 cities and 109 subjects (66 women and 43 men), with an age range of 23–93, mean age of 53.7 years old ±15.3 years old Participant enrolment was based on the risk factors resulting from an appropriate medical and behavioral history. Risk factors included age, gender, family history of the diseases, smoking, high blood cholesterol, high blood pressure, obesity, and diabetes.^29,30

Telemedicine program

The telemedicine program was developed in a telehealth service consisting of two prevention screenings for breast cancer and cardiovascular disease. The mobile unit was provided with connectivity (digital subscriber line) and a self-contained mobile site to offer breast and cardiovascular screenings. All participants received telehealth services from different health care professionals (4 medical specialists, 3 radiology technicians, 1 nurse, 2 computer engineers, 1 Informatic expert, and 15 social workers) previously trained in telemedicine. The study design used different methodologies to evaluate the patient's clinical condition, depending on the aspect to be assessed. Thus, the participants underwent mammograms, mammographic ultrasounds, cardiovascular screening, and remote control of pacemakers and defibrillators.

In the breast cancer screening program, mammography and ultrasound approaches were used in agreement with guidelines. Mammograms analysis is usually used in asymptomatic woman and in a screening program it has the ability to detect breast cancer at an early stage. The diagnostic accuracy of mammography screening largely depends on the radiographic density of the breasts; in fact, in radiographically dense breasts, non-calcified breast cancers are more likely to be missed than in fatty breasts. As a consequence, some cancers are not detected by mammography screening. The adding of ultrasound to the screening for breast cancer is an approach to reduce the false negative rates of the screening process, especially in the presence of young women.^31,32 Digital mammograms and ultrasound obtained were sent in real time to the operative center in the “Sant'Anna and San Sebastiano” hospital, where specialists analyzed images and referred in real time to mobile units.

The telemedicine system

The telemedicine procedure used in this pilot study included three highly specialized mobile health units (named operative unit 1, operative unit 2, and operative unit 3) equipped with radiological, ultrasound, cardiovascular, and videoconferencing diagnostics for multi-specialized teleconsulting. Each operative unit was connected via the internet to the operative center of telemedicine in Sant'Anna and San Sebastiano hospital. Through a mobile phone, complex medical DICOM images >20 MB and sensitive data were transmitted safely, printed in the operative center, and finally reported by specialists in real time. Each operative unit included a Web-based platform, an access point, and a wireless system, which were specifically designed to supply telemedicine health services. In particular, all the vehicles were equipped with a patient waiting area, an operator area, and a diagnostic equipment area, including female and male toilets. Considering the different application modules, each operative unit showed different equipment: X-ray table with tube stand, ultrasound equipment available in operative unit 1; digital mammography machine and radiological scanner transforming the mammograms originated analogically into digital format in operative unit 2; and electrocardiograph machine in operative unit 3. All the mobile units were deployed in each community at the same time. Within each diagnostic camper there is an admission and a receiving area where, with full respect of privacy, the patient's medical history is obtained together with a separate specialized diagnostic area, which is fundamental in case of radiation emission (mammography). This choice of setup has made screening more efficient as it allows different patients to be examined or preparing to be examined all at the same time, thus improving the time required for analysis and significantly reducing any interruptions caused by the transmission of data to or from the operations center.

E-government platform

E-government platform was used to support telemedicine services. It consists of image acquisition hardware (computers, cameras, and other peripherals), systems for image transmission, storage, and retrieval such as Picture Archiving and Communication Systems, wired and wireless networks, software applications for image analysis and clinical workflow management (scheduling follow-up examinations, clinical communication management, and decision support tools), audio-videoconferencing sessions with patients or with other specialists, and an electronic medical record system containing the medical and treatment history of the patients in one practice.

Statistical Analysis

The statistical analysis was performed by MATLAB toolbox version 2008 (MathWorks, Natick, MA) for Windows. Data are presented as number and percentage for categorical variables, and continuous data are expressed as the mean ± standard deviation unless otherwise specified. Quartiles were used to define age ranges. The McNemar test was performed to evaluate the significant difference between paired data. The multiple-comparison chi-square test was used to compare the differences among percentages for unpaired data. When the multiple chi-square test was positive (p-value less than 0.05), the residual analysis with the Z-test was performed to individualize the most and less frequent response. In the case of paired data, the multiple-comparison Cochran's Q test was used to compare the differences among percentages under the consideration of the null hypothesis with no differences between the variables.³³ When the Cochran's Q test was positive (p < 0.05), a minimum required difference for a significant difference between two proportions was calculated by using the Minimum Required Differences method with Bonferroni p-value corrected for multiple comparisons according to a previous work.³⁴ Finally, sensitivity, specificity, positive predictive value, and negative predictive value with confidence intervals at 95% were computed to evaluate the performance of the ultrasound tool in breast screening. We considered significant all statistical tests with a p-value less than 0.05.

Results

In this pilot study, participants included only women who were asymptomatic and at their first access to breast cancer screening. The employed telemedicine breast cancer screening services were based on the criteria reported in Table 1. Particularly, 54 cases underwent mammography only, 55 cases executed ultrasound, and 209 cases received both services for a total of 318 subjects. In three further cases, diagnosis was achieved without a diagnostic tool. These three women showed perfect breast status and no regression of breast pathologies.

In our cohort, 40.8% (131/321) of cases were negative to lesions, 34.9% (112/321) were positive to benign lesions, such as fibrocystic formations or fibroadenoma, and 3.1% (10/321) presented suspicious malignant lesions that were checked by subsequent histological analyses. The histological response was positive in 70% (7/10) and negative in 30% (3/10) of cases (Table 1). Moreover, we compared the diagnostic tools considering only 209 patients in whom both mammography and ultrasound were performed. In our cohort, we found that 131 cases were negative and 55 cases were positive by both mammography and ultrasound whereas in 23 cases discordant responses were obtained; particularly, 20 cases were ultrasound positive and mammography negative, whereas 3 cases were ultrasound negative and mammography positive. Statistical analysis showed a significant difference between mammography and ultrasound (27.8% <35.9%, p = 0.0005), confirming that ultrasound is more accurate than mammography, as already reported.^35
–37

The cardiovascular screening concerned 109 participants (66 women and 43 men) based on age and other risk factors (Table 2). We observed a significant difference among risk factors in patients with cardiac disease (p < 0.001); particularly, hypertension was significantly the most present risk factor (51.4%, p < 0.05), followed by smoking (28.4%, p < 0.05); pharmacological treatment for other pathologies, obesity, and dyslipidemia were also frequently registered (Table 2). A percentage of 40.4 (44/109) showed a cardiovascular pathology (Table 2).

Table 2.

Characteristics of Cardiovascular Screening Participants

PARAMETERS	MEAN ± SD/PERCENTAGES
Gender
Male	39.4% (43/109)
Female	60.5% (66/109)
Age	53.7 ± 15.3
Cardiac pathologies
Yes	40.4% (44/109)
No	59.6% (65/109)
Risk factors
Hypertension	51.4% (56/109)
Smoking	28.4% (31/109)
Pharmacological treatment	27.5% (30/109)
Being overweight/obesity	21.1% (23/109)
Dyslipidemia	16.5% (18/109)
Diabetes	11.9% (13/109)
Ischemic heart disease	11.0% (12/109)
Dysthyroidism	8.3% (9/109)
Pacemaker	5.5% (6/109)
Chronic atrial fibrillation	4.6% (5/109)
Defibrillator	2.8% (3/109)

Among cardiovascular screening, we observed no significant difference among cities about the presence of patients with cardiovascular pathologies and we found a significant association between age and gender (p = 0.0073). Particularly, the chi-squared test revealed a significant trend in cardiovascular screening frequency connected to gender and age (p = 0.0037). Besides, when compared with men, women exhibited a decreasing attention to the prevention of cardiovascular diseases with the age increase; vice versa, men showed a growing attention to the prevention with the age advancement.

To maximize the benefit, we have evaluated the ROI for our pilot study.^27,28 The evaluation of the ROI was performed by using the formula:

$R O I = \frac{G a i n f r o m i n v e s t e m e n t - C o s t o f i n v e s t e m e n t}{C o s t o f i n v e s t e m e n t}$

For the evaluation of the total cost, all the items related to the costs incurred for each intervention were used, as shown in Table 1. Similarly, the gain was calculated considering the savings deriving from the activity carried out compared with the tariff value usually used in the Italian National health system. The value for all the interventions is shown in Table 3.

Table 3.

Total Cost of an Intervention

FACTOR	TOTAL COST (ε) PER SINGLE INTERVENTION
Staff employed for single intervention	495.48
Cost of maintenance and management	180
Total	675.48

The value of a single intervention, therefore, is 2897.56 ε. From this value, it was possible to derive the net gain for each output, which turned out to be 2222.1 ε. Compared with a total cost (assessed for each single issue) equal to 675.48 ε, we have reached an ROI (ratio) equal to 3.3:1 (Table 4).

Table 4.

Return on Investment Measures and Results

DIAGNOSTIC SERVICE	RATE VALUE+TICKET (ε)	TOTAL NUMBER OF TAKEN EXAMS	OVERALL ENHANCEMENT (ε)
Bilateral mammography	54.86	263	14428.18
Ultrasound of the bilateral breast	55.89	264	14754.96
Cardiologic examination	40.66	109	4431.94
Electrocardiogram	31.62	109	3446.58
Other revenue	43.24	6	259.44
Mammary needle biopsy	34.72	10	347.20
Total			37668.3

The return on investment ratio was 3.3:1.

Discussion

Telemedicine opens the possibility to increase the range of medical services available, thus increasing the chances for saving in terms of cost of health care organizations. Telemedicine facilitates a patient's direct contact with a distant specialist, without requiring the displacement of any of the participants, allowing access to several services of medical care that otherwise would not be accessible because of geographical distance or absent health infrastructures.^37

–40 Thus, telemedicine can create a new collaboration between hospitals and locations, either extending the hospital into a patient's house and/or allowing the patient to be virtually in the hospital and easily accessible to early diagnosis screenings, which greatly increase the chances for successful disease treatment.²⁴ This care approach involves new rules and management models with the acquisition of more advanced technologies.⁴¹

Despite different benefits, telemedicine is still far from being widely used in Italy as well as in Europe.⁴² In Italy, telemedicine services show different development levels and they are widespread in few regions.^32,43

–46

This study is the first telemedicine pilot screening developed in Southern Italy. The use of mobile units is the first approach that reaches any area of the Caserta Province, with particular attention to the rural areas bringing assistance and diagnostic equipment. Particularly, we have demonstrated the potential of telemedicine application to transmit diagnostic images and relative reports, virtually connecting patients and medical specialists in a screening program. Our telemedicine screening program allowed detecting early pathologies. We observed 10 suspicious cases, with 7 malignant confirmed by histological exam and 112 benignant cases in breast screening; 44 pathological patients were registered in cardiovascular screening.

Heart disease is the leading cause of death in Italy and a major cause of disability.^7,47,48 Here, cardiovascular screening showed hypertension and smoking as the highest impact risk factors (51.4% and 28.4% respectively). In patients identified at high risk of cardiovascular events, suitable pharmacological therapy and lifestyle changes (avoid smoking, exercise, heart-healthy diet) were recommended to reduce the risk of heart disease.

Cardiac implantable electronic devices are increasing.^47,48 Postimplant follow-up is important for monitoring both the function of the device and the patient's condition. A further challenge would be the ability to promptly identify problems, manage unplanned meetings, and manage data downloaded from increasingly complex devices. Our idea is that it is necessary to create a standard system, which allows liberalizing the remote reading of devices, allowing the care of the chronic patient, to enhance the timeliness of intervention.

Our opinion is that telemedicine is the solution of a complex extra-hospital assistance activity, with continuity and competence over time. At the moment of intense fragility, people are pleased at the center of an integrated and organized socio-health network, where the patient is connected directly with telemedicine operators, operative centers, and hospitals.^1,3 In this application, telemedicine represents an important tool for health systems to solve the socioeconomic challenges. Its role in the optimization of health resources, improved management of demand, reduction of hospital stays, and reduction in the number of trips increases the importance of this technology to improve the efficiency and sustainability of health systems.^28,29 Future perspectives will be the enrolment of more patients and the expansion of the area of interest, to promote people health everywhere with the association of prevention, monitoring, and home care.

Our findings demonstrate that telemedicine may represent a promising approach to deliver several health services with users who cannot access services in their locations. Especially, in the screening program, this method has the potential to decrease some of the barriers to access and use of evidence-based health assistance for populations in need of health services.

Our pilot study consists of a screening based on age, within the Southern Italian Health Service program. We have, therefore, made reference to the regional tariff quota in effect at the time of this study regarding the break-even analysis of objectives. On the basis of these tariffs, services and surveys have reached a total of 37668.3 Euro.

The capital equipment used (i.e., campers and operations center) were offered on loan for free use by government administrations exclusively for the completion of our study. The only expenses incurred were related to the cost of remote staff (6441.24 Euro), since the personnel at the operations center worked during normal working hours; thus, the total operating cost of the campers was 2340 Euro. The ROI totaled to 3.3.

Pashayan et al., in an article that appeared in JAMA Oncology in 2018, subsequent to our study, stated that the risk–benefit ratio and cost effectiveness of screening programs, in the specific case for breast cancer, can be improved by adopting a screening strategy, based on risk stratification.⁴⁹

Our experience shows that the use of telemedicine in diagnostic campers greatly reduces the costs of screening for breast cancer and major cardiovascular diseases within the Southern Italian Health Service. We believe that public investment can have a further significant return on investment by implementing the principles of precision medicine.

Footnotes

Acknowledgments

The authors wish to thank Pasquale Izzo and Philomena Cusano. The authors disclosed receipt of the following financial support for the Telemedicine Program, from the European Community, Campania POR 2000–2006 (Measure 4.11) and 2007–2013 for the valorization of disadvantaged rural areas, identified by the Regional Department of Agriculture, for the project “Integrated Telemedicine Services” in the Province of Caserta.

Disclosure Statement

No competing financial interests exist.

References

Kvedar

, Coye

, Everett

. Connected health: A review of technologies and strategies to improve patient care with telemedicine and telehealth. Health Aff, 2014; 33:194–199.

Greenwald

, El-Zein

, Bouten

, et al. Mobile screening units for the early detection of cancer: A systematic review. Cancer Epidemiol Biomarkers Prev, 2017; 26:1679–1694.

Craig

, Patterson

. Introduction to the practice of telemedicine. J Telemed Telecare, 2005; 11:3–9.

Heinzelmann

, Lugn

, Kvedar

. Telemedicine in the future. J Telemed Telecare, 2005; 11:384–390.

Mehrotra

, et al. Utilization of telemedicine among rural Medicare beneficiaries. JAMA, 2016; 315:2015–2016.

Jennett

, Affleck Hall

, Hailey

, Ohinmaa

, et al. The socio-economic impact of telehealth: A systematic review. J Telemed Telecare, 2003; 9:311–320.

Wilson

, Maeder

. Recent directions in telemedicine: Review of trends in research and practice. Healthc Inform Res, 2015; 21:213–222.

Chanussot-Deprez

, Contreras-Ruiz

. Telemedicine in wound care. Int Wound J, 2008; 5:651–654.

Vitacca

, Paneroni

, Trainini

, Bianchi

, et al. At home and on demand mechanical cough assistance program for patients with amyotrophic lateral sclerosis. Am J Phys Med Rehabil, 2010; 89:401–406.

10.

Vitacca

, Comini

, Tabaglio

, et al. Tele-assisted palliative homecare for advanced chronic obstructive pulmonary disease: A feasibility study. J Palliat Med, 2019; 22:173–178.

11.

Chirra

, Marsili

, Wattley

, et al. Telemedicine in neurological disorders: Opportunities and challenges. Telemed J E Health, 2018; 25:541–550.

12.

Faccio

, Renzi

, Crico

, Kazantzaki

, et al. Development of an eHealth tool for cancer patients: Monitoring psycho-emotional aspects with the Family Resilience (FaRe) Questionnaire. Ecancermedicalscience, 2018; 12:852.

13.

Ippolito

, et al. A cost study of prenatal telemedicine. J Telemed Telecare, 2003; 9:288–291.

14.

Lattanzio

, Abbatecola

, Bevilacqua

, et al. Advanced technology care innovation for older people in Italy: Necessity and opportunity to promote health and wellbeing. J Am Med Dir Assoc, 2014; 15:457–466.

15.

Kvedar

, Heinzelmann

, Jacques

. Cancer diagnosis and telemedicine: A case study from Cambodia. Ann Oncol, 2006; 17:viii37–viii42.

16.

Orozco-Beltran

, Sánchez-Molla

, Sanchez

, et al. Telemedicine in primary care for patients with chronic conditions: The ValCrònic Quasi-Experimental Study. J Med Internet Res, 2017; 19:e400.

17.

Bohingamu Mudiyanselage

, Stevens

, Watts

, et al. Personalised telehealth intervention for chronic disease management: A pilot randomised controlled trial. J Telemed Telecare, 2018;1357633 × 18775850.

18.

Bernetti

, et al. Stroke networks and telemedicine: An Italian national survey. Neurol Int, 2018; 10:7599.

19.

Vujosevic

, Pucci

, Casciano

, et al. A decade-long telemedicine screening program for diabetic retinopathy in the north-east of Italy. J Diabetes Complications, 2017; 31:1348–1353.

20.

Bert

, Gualano

, Clemente

, et al. Technology and prevention in the era of mobile health: Applications for cancer screening programs. Ig Sanita Pubbl, 2017; 73:13–27.

21.

Van Velsen

, Frazer

, N'dja

, Ammour

, Del Signore

, Zia

, Hermens

. The reliability of using tablet technology for screening the health of older adults. Stud Health Technol Inform, 2018; 247:651–655.

22.

Baron

, Rimer

, Coates

, et al. Client-directed interventions to increase community access to breast, cervical, and colorectal cancer screening: A systematic review. Am J Prev Med, 2008; 35:S56–S66.

23.

Sirintrapun

, Lopez

. Telemedicine in cancer care. Am Soc Clin Oncol Educ Book, 2018; 38:540–545.

24.

Uldal

, Amerkhanov

, Manankova Bye

, et al. A mobile telemedicine unit for emergency and screening purposes: Experience from north-west Russia. J Telemed Telecare, 2004; 10:11–15.

25.

Brown

, Fintor L

U.S

. screening mammography services with mobile units: Results from the National Survey of Mammography Facilities. Radiology, 1995; 195:529–532.

26.

Sabatino

, Lawrence

, Elder

, et al. Effectiveness of interventions to increase screening for breast, cervical, and colorectal cancers: Nine updated systematic reviews for the guide to community preventive services. Am J Prev Med, 2012; 43:97–118.

27.

Brown-Connolly

, Concha

, English

. Mobile health is worth it! Economic benefit and impact on health of a population-based mobile screening program in New Mexico. Telemed J E Health, 2014; 20:18–23.

28.

Oriol

, Cote

, Vavasis

, Bennet

, DeLorenzo

, Blanc

, Kohane

. Calculating the return on investment of mobile healthcare. BMC Med, 2009; 7:27.

29.

Padwal

, Straus

, McAlister

. Cardiovascular risk factors and their effects on the decision to treat hypertension: Evidence based review. BMJ, 2001; 322:977–980.

30.

Hong

, Lin

, Gu

. Risk factors and therapies in vascular diseases: An umbrella review of updated systematic reviews and meta-analyses. J Cell Physiol, 2019; 234:8221–8232.

31.

Ohuchi

, Suzuki

, Sobue

, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-Cancer Randomized Trial (J-START): A randomised controlled trial. Lancet, 2016; 387:341–348.

32.

Thigpen

, Kappler

, Brem

. The role of ultrasound in screening dense breasts—A review of the literature and practical solutions for implementation. Diagnostics (Basel), 2018; 8:20.

33.

Cochran

WG.

Some methods for strengthening the common chi-squared tests. Biometrics, 1954; 10:417–451.

34.

Sheskin

. Handbook of parametric and nonparametric statistical procedures. Third Edition. Boca Raton, FL: Chapman and Hall/CRC Press, 2003:867–877.

35.

Berg

, et al. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA, 2008; 299:2151–2163.

36.

Devolli-Disha

, Manxhuka-Kërliu

, Ymeri

, et al. Comparative accuracy of mammography and ultrasound in women with breast symptoms according to age and breast density. Bosn J Basic Med Sci, 2009; 9:131–136.

37.

Reboli

, Assi

, Brentnall

, Parmar

, Duffy

. Addition of ultrasound to mammography in the case of dense breast tissue: Systematic review and meta-analysis. Br J Cancer, 2018; 118:1559–1570.

38.

Brandling-Bennett

, et al. Delivering health care in rural Cambodia via store-and-forward telemedicine: A pilot study. Telemed J E Health, 2005; 11:56–62.

39.

Smith

, Bensink

, Armfield

, et al. Telemedicine and rural health care applications. J Postgrad Med, 2005; 51:286–293.

40.

Kamsu-Foguem

, Foguem

. Could telemedicine enhance traditional medicine practices?. Eur Res Telemed, 2014; 3:117–123.

41.

Mohan

, Deepa

, Pradeepa

, Prathiba

, et al. Prevention of diabetes in rural India with a telemedicine intervention. J Diabetes Sci Technol, 2012; 6:1355–1364.

42.

Wagner

SE.

Age grading in sociolinguistic theory. Lang Linguist Compass, 2012; 6:371–382.

43.

Raposo

VL.

Telemedicine: The legal framework (or the lack of it) in Europe. GMS Health Technol Assess, 2016; 12:Doc03.

44.

Nardetto

, Dario

, Tonello

, et al. A one-to-one telestroke network: The first Italian study of a web-based telemedicine system for thrombolysis delivery and patient monitoring. Neurol Sci, 2016; 37:725–730.

45.

Bisignani

, De Bonis

, Bisignani, et al. Telecardiology: Clinical, technical and social aspects. The project of the ASP of Cosenza, Italy. G Ital Cardiol (Rome), 2016; 17:959–965.

46.

Brunetti

, Scalvini

, Molinari

. Innovations in telemedicine for cardiovascular care. Expert Rev Cardiovasc Ther, 2016; 14:267–280.

47.

De Lazzari

, Genuini

, Gatto

, et al. Screening high school students in Italy for sudden cardiac death prevention by using a telecardiology device: A retrospective observational study. Cardiol Young, 2017; 27:74–81.

48.

Wiles

, Roberts

. Lead or be led: An update on leadless cardiac devices for general physicians. Clin Med, 2017; 17:33–36.

49.

Pashayan

, Morris

, Gilbert

, Pharoah

. Cost-effectiveness and benefit-to-harm ratio of risk-stratified screening for breast cancer: A life-table model. JAMA Oncol, 2018; 4:1504–1510.