BACKGROUND: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic.
METHODS: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis.
RESULTS: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis.
CONCLUSIONS: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO\'s 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB.
METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters.
RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients\' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses.
CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.

BACKGROUND: In tuberculosis (TB) control, nonadherence to treatment persists as a barrier. The traditional method of ensuring adherence, that is, directly observed therapy, faces significant challenges that hinder its widespread adoption. Digital adherence technologies such as video directly observed therapy (VDOT) are emerging as promising solutions. However, as these novel technologies gain momentum, a critical gap is the lack of comprehensive studies evaluating their efficacy and the unique experiences of patients in Africa.
OBJECTIVE: The aim of this study was to assess patients\' experiences that affected acceptability, usefulness, and ease of use with an enhanced VDOT system during monitoring of TB treatment.
METHODS: We conducted individual open-ended interviews in a cross-sectional exit qualitative study in Kampala, Uganda. Thirty participants aged 18-65 years who had completed the VDOT randomized trial were purposively selected to represent variability in sex, adherence level, and HIV status. We used a hybrid process of deductive and inductive coding to identify content related to the experience of study participation with VDOT. Codes were organized into themes and subthemes, which were used to develop overarching categories guided by constructs adapted from the modified Technology Acceptance Model for Resource-Limited Settings. We explored participants\' experiences regarding the ease of use and usefulness of VDOT, thereby identifying the facilitators and barriers to its acceptability. Perceived usefulness refers to the benefits users expect from the technology, while perceived ease of use refers to how easily users navigate its various features. We adapted by shifting from assessing perceived to experienced constructs.
RESULTS: The participants\' mean age was 35.3 (SD 12) years. Of the 30 participants, 15 (50%) were females, 13 (43%) had low education levels, and 22 (73%) owned cellphones, of which 10 (45%) had smartphones. Nine (28%) were TB/HIV-coinfected, receiving antiretroviral therapy. Emergent subthemes for facilitators of experienced usefulness and ease of VDOT use were SMS text message reminders, technology training support to patients by health care providers, timely patient-provider communication, family social support, and financial incentives. TB/HIV-coinfected patients reported the added benefit of adherence support for their antiretroviral medication. The external barriers to VDOT\'s usefulness and ease of use were unstable electricity, technological malfunctions in the app, and lack of cellular network coverage in rural areas. Concerns about stigma, disease disclosure, and fear of breach in privacy and confidentiality affected the ease of VDOT use.
CONCLUSIONS: Overall, participants had positive experiences with the enhanced VDOT. They found the enhanced VDOT system user-friendly, beneficial, and acceptable, particularly due to the supportive features such as SMS text message reminders, incentives, technology training by health care providers, and family support. However, it is crucial to address the barriers related to technological infrastructure as well as the privacy, confidentiality, and stigma concerns related to VDOT.

WHO recommended multidrug-resistant tuberculosis (MDR-TB) should be treated mainly under ambulatory model, but outcome of ambulatory treatment of MDR-TB in China was little known.
The clinical data of 261 MDR-TB patients treated as outpatients in Shenzhen, China during 2010-2015 were collected and analyzed retrospectively.
Of 261 MDR-TB patients receiving ambulatory treatment, 71.1% (186/261) achieved treatment success (cured or completed treatment), 0.4% (1/261) died during treatment, 11.5% (30/261) had treatment failure or relapse, 8.0% (21/261) were lost to follow-up, and 8.8% (23/261) were transferred out. The culture conversion rate at 6 months was 85.0%. Although 91.6% (239/261) of patients experienced at least one adverse event (AE), only 2% of AEs caused permanent discontinuation of one or more drugs. Multivariate analysis showed that previous TB treatment, regimens containing capreomycin and resistance to FQs were associated with poor outcomes, while experiencing three or more AEs was associated with good outcomes.
Good treatment success rates and early culture conversions were achieved with entirely ambulatory treatment of MDR-TB patients in Shenzhen, supporting WHO recommendations. Advantageous aspects of the local TB control program, including accessible and affordable second-line drugs, patient support, active monitoring and proper management of AEs and well-implemented DOT likely contributed to treatment success rates.

BACKGROUND: Drug resistant tuberculosis (DR-TB) infringes substantial burden in terms of longer treatment duration, morbidity and mortality. Timely identification of patients at risks of DR-TB will aid individualized treatment. Current study was aimed to ascertain several factors associated with DR-TB among patients attending a tertiary care hospital.
METHODS: This retrospective study was conducted among patients with confirmed diagnosis of DR-TB and drug susceptible TB (DS-TB) seeking medical care from a tertiary care hospital during 2014-2019. The types of DR-TB included were rifampicin resistant tuberculosis (RR-TB), Multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Appropriate statistical methods were implied to evaluate the factors associated with DR-TB.
RESULTS: Out of 580 patients, DS-TB was diagnosed in 198 (34.1%) patients while DR-TB was present in 382 patients. Of resistance cases, RR-TB, MDR-TB and XDR-TB were diagnosed in 176 (30.3%), 195 (33.6%) and 11 (1.9%) patients, respectively. Significant differences (P < 0.05) in demographics and clinico-laboratory characteristics were observed between patients with DS-TB and DR-TB. Logistic regression analysis revealed age ≤38 years (OR: 2.5), single marital status (OR: 11.1), tobacco use (OR: 2.9), previous treatment (OR: 19.2), treatment failure (OR: 9.2) and cavity on chest X-ray (OR: 30.1) as independent risk factors for MDR-TB. However, XDR-TB was independently associated with age group of ≤38 years (OR: 13.6), students (OR: 13.0), previous treatment (OR: 12.5), cavity on chest X-ray (OR: 59.6). The independent risk factors associated with RR-TB are age ≤38 years (OR: 2.8), females (OR: 5.7), unemployed (OR: 41.5), treatment failure (OR: 4.9), previous treatment (OR: 38.2) and cavity on chest X-ray (OR: 4.3). ROC curve analysis accentuate the excellent predictive accuracy of all logistic regression models as shown by AUC (0.968, P < 0.001) for MDR-TB, AUC (0.941, P < 0.001) for XDR-TB and AUC (0.962, P < 0.001) for RR-TB.
CONCLUSIONS: Current study demonstrates a sizeable extent of resistant cases among pulmonary TB patients. This study presaged significant risk of DR-TB among females, young adults, unemployed, smokers, patients with previous treatment failure and cavitation on chest X-ray. Timely identification of high risk patients will give pronounced advantages regarding appropriate choices of prevention, treatment and disease control.

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed.

OBJECTIVE: Dynamic Optimal Timing (Dot) is a smartphone application (app) that estimates the menstrual cycle fertile window based on the user\'s menstrual period start dates. Dot uses machine learning to adapt to cycles over time and informs users of \'low\' and \'high\' fertility days. We investigated Dot\'s effectiveness, calculating perfect- and typical-use failure rates.
METHODS: This prospective, 13 cycle observational study (ClinicalTrials.gov NCT02833922) followed 718 women who were using Dot to prevent pregnancy. Participants contributed 6616 cycles between February 2017 and October 2018, providing data on menstrual period start dates, daily sexual activity and prospective intent to prevent pregnancy. We determined pregnancy through participant-administered urine pregnancy tests and/or written or verbal confirmation. We calculated perfect- and typical-use failure rates using multi-censoring, single-decrement life-table analysis, and conducted sensitivity, attrition and survival analyses.
RESULTS: The perfect-use failure rate was calculated to be 1.0% (95% confidence interval [CI]: 0.9%, 2.9%) and the typical-use failure rate was 5.0% (95% CI: 3.4%, 6.6%) for women aged 18-39 (n = 718). Survival analyses identified no significant differences among age or racial/ethnic groups or women in different types of relationships. Attrition analyses revealed no significant sociodemographic differences, except in age, between women completing 13 cycles and those exiting the study earlier.
CONCLUSIONS: Dot\'s effectiveness is within the range of other user-initiated contraceptive methods.

BACKGROUND: Smartphone apps that provide women with information about their daily fertility status during their menstrual cycles can contribute to the contraceptive method mix. However, if these apps claim to help a user prevent pregnancy, they must undergo similar rigorous research required for other contraceptive methods. Georgetown University\'s Institute for Reproductive Health is conducting a prospective longitudinal efficacy trial on Dot (Dynamic Optimal Timing), an algorithm-based fertility app designed to help women prevent pregnancy.
OBJECTIVE: The aim of this paper was to highlight decision points during the recruitment-enrollment process and the effect of modifications on enrollment numbers and demographics. Recruiting eligible research participants for a contraceptive efficacy study and enrolling an adequate number to statistically assess the effectiveness of Dot is critical. Recruiting and enrolling participants for the Dot study involved making decisions based on research and analytic data, constant process modification, and close monitoring and evaluation of the effect of these modifications.
METHODS: Originally, the only option for women to enroll in the study was to do so over the phone with a study representative. On noticing low enrollment numbers, we examined the 7 steps from the time a woman received the recruitment message until she completed enrollment and made modifications accordingly. In modification 1, we added call-back and voicemail procedures to increase the number of completed calls. Modification 2 involved using a chat and instant message (IM) features to facilitate study enrollment. In modification 3, the process was fully automated to allow participants to enroll in the study without the aid of study representatives.
RESULTS: After these modifications were implemented, 719 women were enrolled in the study over a 6-month period. The majority of participants (494/719, 68.7%) were enrolled during modification 3, in which they had the option to enroll via phone, chat, or the fully automated process. Overall, 29.2% (210/719) of the participants were enrolled via a phone call, 19.9% (143/719) via chat/IM, and 50.9% (366/719) directly through the fully automated process. With respect to the demographic profile of our study sample, we found a significant statistical difference in education level across all modifications (P<.05) but not in age or race or ethnicity (P>.05).
CONCLUSIONS: Our findings show that agile and consistent modifications to the recruitment and enrollment process were necessary to yield an appropriate sample size. An automated process resulted in significantly higher enrollment rates than one that required phone interaction with study representatives. Although there were some differences in demographic characteristics of enrollees as the process was modified, in general, our study population is diverse and reflects the overall United States population in terms of race/ethnicity, age, and education. Additional research is proposed to identify how differences in mode of enrollment and demographic characteristics may affect participants\' performance in the study.
BACKGROUND: ClinicalTrials.gov NCT02833922; http://clinicaltrials.gov/ct2/show/NCT02833922 (Archived by WebCite at http://www.webcitation.org/6yj5FHrBh).

BACKGROUND: The Direct Observation of Treatment (DOT) is an important component of the country\'s TB Control strategy. Standards of TB care in India and the End TB strategy emphasised the importance of a patient-centered approach to foster adherence. A qualitative study was conducted to explore the perception of people with Tuberculosis in Kerala regarding DOT, mechanisms to make the treatment of TB more patients centered and to identify the preferable mechanisms to ensure adherence.
METHODS: Six focus group discussions were conducted - two among people with TB from rural area, two among people with TB in urban area, one among multipurpose health workers of rural area and one among key field staff of TB control in urban area.
RESULTS: Patients who were on a strict DOT were unhappy about the issues of confidentiality, patient inconvenience and provider centered approach. A flexible, patient centered approach were a family member can act as the DOT provider with guidance from a trained health worker was evolved as the most acceptable and comfortable mode of treatment to majority of the TB patients. They felt that a strict external monitor as a DOT provider was not a necessity in majority of the cases. Only practical way to effectively incorporate ICT in monitoring patient compliance in current scenario was identified as daily phone call reminders. Patients also expressed their concerns in keeping the medicines for entire duration at home.
CONCLUSIONS: A flexible patient wise individualized system based on patient\'s behavior, literacy and awareness along with attitude of family members is needed to ensure adherence to anti TB drugs.

Safer and shorter antituberculosis treatment (ATT) regimens represent the unmet medical need.
The patients were randomly assigned into two arms: the first (n = 137) received once-daily sublingual honey lozenge formulated with botanical immunomodulator Immunoxel and the second (n = 132) received placebo lozenges along with conventional ATT. Immunoxel and placebo arms were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus 20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR-TB); and 22 versus 20 TB-HIV. The primary end point was sputum smear conversion.
After 1 month 87 out 132 (65.9%) of Immunoxel recipients became sputum smear negative, whereas 32 out of 127 (25.2%) in placebo group had converted (p < 0.0001). Sputum clearance produced by Immunoxel was equally effective across all forms of TB. In the immunotherapy arm the average weight gain was 2 kg, but placebo recipients gained only 0.6 kg. Immunoxel reduced TB-associated inflammation as evidenced by defervescence and normalization of elevated leukocyte counts and erythrocyte sedimentation rate. No adverse effects were seen at any time. The liver function tests indicate that ATT-caused hepatotoxicity was counteracted by Immunoxel. These results are in agreement with prior 20 trials of Immunoxel conducted over the past 17 years.
Immunoxel is affordable, safe, effective, fast-acting, commercially available immunotherapeutic intervention to supplement conventional TB chemotherapy. Clinicaltrials.gov ID: NCT01061593.