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The rapid uptake of mobile phones in low and middle-income countries over the past decade has provided public health programs unprecedented access to patients. While programs have used text messages to improve medication adherence, there have been no high-powered trials evaluating their impact on tuberculosis treatment outcomes. To measure the impact of Zindagi SMS, a two-way SMS reminder system, on treatment success of people with drug-sensitive tuberculosis. We conducted a two-arm, parallel design, effectiveness randomized controlled trial in Karachi, Pakistan. Individual participants were randomized to either Zindagi SMS or the control group. Zindagi SMS sent daily SMS reminders to participants and asked them to respond through SMS or missed (unbilled) calls after taking their medication. Non-respondents were sent up to three reminders a day. Public and private sector tuberculosis clinics in Karachi, Pakistan. Newly-diagnosed patients with smear or bacteriologically positive pulmonary tuberculosis who were on treatment for less than two weeks; 15 years of age or older; reported having access to a mobile phone; and intended to live in Karachi throughout treatment were eligible to participate. We enrolled 2,207 participants, with 1,110 randomized to Zindagi SMS and 1,097 to the control group. The primary outcome was clinically recorded treatment success based upon intention-to-treat. We found no significant difference between the Zindagi SMS or control groups for treatment success (719 or 83% vs. 903 or 83%, respectively, p = 0·782). There was no significant program effect on self-reported medication adherence reported during unannounced visits during treatment. In this large-scale randomized controlled effectiveness trial of SMS medication reminders for tuberculosis treatment, we found no significant impact. The trial was registered with ClinicalTrials.gov, NCT01690754.

Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy. In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013. Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04-1.71), being 35-59 years of age (OR: 1.54, 95% CI: 1.14-2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17-2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35-59 years of age (aOR: 1.49, 95% CI: 1.10-2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12-2.77) were associated with default. In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.

In many countries with a high burden of tuberculosis, most patients receive treatment in the private sector. We evaluated a multifaceted case-detection strategy in Karachi, Pakistan, targeting the private sector. A year-long communications campaign advised people with 2 weeks or more of productive cough to seek care at one of 54 private family medical clinics or a private hospital that was also a national tuberculosis programme (NTP) reporting centre. Community laypeople participated as screeners, using an interactive algorithm on mobile phones to assess patients and visitors in family-clinic waiting areas and the hospital's outpatient department. Screeners received cash incentives for case detection. Patients with suspected tuberculosis also came directly to the hospital's tuberculosis clinic (self-referrals) or were referred there (referrals). The primary outcome was the change (from 2010 to 2011) in tuberculosis notifications to the NTP in the intervention area compared with that in an adjacent control area. Screeners assessed 388 196 individuals at family clinics and 81 700 at Indus Hospital's outpatient department from January–December, 2011. A total of 2416 tuberculosis cases were detected and notified via the NTP reporting centre at Indus Hospital: 603 through family clinics, 273 through the outpatient department, 1020 from self-referrals, and 520 from referrals. In the intervention area overall, tuberculosis case notification to the NTP increased two times (from 1569 to 3140 cases) from 2010 to 2011—a 2·21 times increase (95% CI 1·93–2·53) relative to the change in number of case notifications in the control area. From 2010 to 2011, pulmonary tuberculosis notifications at Indus Hospital increased by 3·77 times for adults and 7·32 times for children. Novel approaches to tuberculosis case-finding involving the private sector and using laypeople, mobile phone software and incentives, and communication campaigns can substantially increase case notification in dense urban settings. TB REACH, Stop TB Partnership.

In Pakistan, despite publically available free testing and treatment throughout the country, there were an estimated 58,000 deaths due to tuberculosis in 2010. Understanding the experiences of people affected by TB is essential in addressing barriers to effective treatment. The Indus Hospital used Photovoice to understand the experiences of people affected by TB in Karachi. Two hundred and thirty photographs and stories were collected from 55 people affected by TB. Five major themes and 12 sub-themes emerged from the data: the physical aspects of TB (weakness and the side effects of the medication), the social aspects of TB (loneliness, stigma, and the fear/guilt of infecting family members), the socio-economic aspects of TB (financial difficulties/poverty and poor living conditions), supportive factors during treatment (support from family and friends, support from welfare organizations, prayer, visiting peaceful places), and recovery (happiness about getting better). The photographs, stories, and a Call for Action were shared at a Gallery event with patients, practitioners, and policy-makers. This study provides a look at the complexities surrounding TB and emphasizes the need for holistic interventions for TB that address all aspects of the disease, including its social determinants. It also highlights the potential of Photovoice as an effective means to bring much-needed attention to this disease.

Purpose Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy. Methods In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013. Results Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04-1.71), being 35-59 years of age (OR: 1.54, 95% CI: 1.14-2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17-2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35-59 years of age (aOR: 1.49, 95% CI: 1.10-2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12-2.77) were associated with default. Conclusions In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.

This article presents and investigates a modified version of the Weibull distribution that incorporates four parameters and can effectively represent a hazard rate function with a shape resembling a bathtub. Its significance in the fields of lifetime and reliability stems from its ability to model both increasing and decreasing failure rates. The proposed distribution encompasses several well-known models such as the Weibull, extreme value, exponentiated Weibull, generalized Rayleigh, and modified Weibull distributions. The paper derives key mathematical statistics of the proposed distribution, including the quantile function, moments, moment-generating function, and order statistics density. Various mathematical properties of the proposed model are established, and the unknown parameters of the distribution are estimated using different estimation techniques. Furthermore, the effectiveness of these estimators is assessed through numerical simulation studies. Finally, the paper applies the new model and compares it with various existing distributions by analyzing two real-life time data sets.

Hyperhidrosis is a disorder associated with detrimental effects on patients' quality of life, occupational activities, and social interactions. This study compares C-arm guided percutaneous radiofrequency (RF) ablation of the second and third thoracic sympathetic ganglions and local intradermal botulinum toxin type A (BTX-A) injection for the treatment of primary palmar hyperhidrosis. It focuses on clinical effectiveness, patient satisfaction, quality of life, safety, and the time at which repetition of the procedure is needed over one-year follow-up. This is a randomized single-blinded trial. This study took place in a single hospital. Eighty patients with primary palmar hyperhidrosis were randomly assigned to one of 2 interventions: local intradermal BTX-A injection (n = 40) or C-arm guided percutaneous RF ablation (n = 40). The Dermatology Life Quality Index (DLQI) questionnaire and the Hyperhidrosis Disease Severity Scale (HDSS) were used for assessment at one week, one month, and 2, 6, and 12 months after intervention. The number of patients who required repetition of the procedure later on and the time at which they needed it were recorded, and possible side effects were assessed. HDSS scores in the RF group were statistically significantly lower than in the BTX-A group at one week, one month, and 2, 6, and 12 months of follow-up. DLQI scores in the RF group were statistically significantly lower than in the BTX-A group at 6- and 12-month follow-up, whereas at one week, one month, and 2 months of follow-up, there was no statistically significant difference between both groups. The number of patients who required that the procedure be repeated was statistically significantly lower in the RF group than in the BTX-A group. The time at which patients needed repetition of the procedure in the BTX-A group was about 3 to 7 months after the first intervention. All patients in this group showed an increase in HDSS scores within this one-year follow-up. In the RF group, however, only one patient complained of increased HDSS scores after 8 months. There was no statistically significant difference in side effects between both groups. The first limitation of this study is that results were based on subjective scales. The second is the radiation exposure associated with the technique described. This study supports percutaneous C-arm guided RF ablation of the second and third thoracic sympathetic ganglions and local intradermal BTX-A injection as safe, effective options and rapid lines of treatment of primary palmar hyperhidrosis. However, percutaneous RF ablation proved to be more effective, with longer effectiveness time and better patient satisfaction, compared to local intradermal BTX-A injection. Botulinum toxin, hyperhidrosis, quality, radiofrequency ablation.

Background and Aims: Avoidance of general anaesthesia for short-duration surgeries is a prerequisite, especially for children. Spinal anaesthesia is established as an appropriate anaesthetic procedure for this target. Midazolam has been proven to be safe for children as premedication. This study aimed to evaluate the effects of adding midazolam to intrathecal bupivacaine on intraoperative quality, duration of spinal anaesthesia and postoperative (PO) analgesia for children undergoing lower abdominal surgeries. Methods: A prospective, comparative interventional study included 120 paediatric patients who were randomly divided into two groups that received intrathecal bupivacaine plus normal saline (B/S) or intrathecal bupivacaine plus midazolam (B/M). The efficacy of PO analgesia was assessed using the observational pain-discomfort scale (OPS). Duration of PO analgesia was measured, and recovery of motor block was assessed every 30 min till the Bromage scale reached 0. The level of PO sedation was assessed using the modified Wilson Sedation Score (WSS). Results were analysed using the one-way analysis of variance (ANOVA) test, Mann-Whitney test and Chi-square test. Results: Onset of sensory and motor blocks was significantly faster, and the frequency of patients having Bromage score of 3 within ≤10 min was significantly higher in group B/M than group B/S. Durations till sensory and motor recovery were significantly longer, the number of requests for PO analgesia was significantly lower and the mean of WSS was significantly higher at 30 and 120 min in group B/M than group B/S. Conclusion: Intrathecal bupivacaine-midazolam combination significantly prolonged the duration of spinal anaesthesia and provided prolonged PO analgesia.

The emergence of superbugs and resistant pathogens poses a challenge in scientific and medical research as they threaten public health worldwide. Many herbal natural products currently used in therapies have been suggested to exert antimicrobial, antiviral and even virucidal activities against a vast majority of impervious pathogens. Rhazya stricta, a folk medicinal desert plant from Saudi Arabia was recently revealed to exhibit bactericidal activity against multidrug-resistant (MDR) microorganisms. The pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a threat to public health worldwide. Hence, we examined the antiviral activity of R. stricta against the virus. The R. stricta water extract was prepared at the traditional dose. The antagonistic effects of this extract against pathogens have been proven in previous studies, and those against SARS-CoV-2 were shown in the present study. Therefore, we explored the effects of the plant extracts and fractions against the virus for future drug development. All plant extracts showed antiviral effects against SARS-CoV-2 in the Vero E6 cell lines. Non-alkaloids showed the strongest effect against the virus, followed by weak base alkaloids and finally strong base alkaloids. A cytotoxicity assay was performed to explore the safest dose with the strongest antiviral effects. The non-alkaloid extract derived from R. stricta leaves is a promising antiviral candidate for the development of potential drugs with appropriate activity against COVID-19 and other life-threatening diseases.

Respiratory syncytial virus (RSV) is an important viral pathogen of acute respiratory tract infection (ARI). Limited data are available on molecular epidemiology of RSV from Saudi Arabia. A total of 130 nasopharyngeal aspirates were collected from children less than 5 years of age with ARI symptoms attending the Emergency Department at King Khalid University Hospital and King Fahad Medical City, Riyadh, Saudi Arabia between October and December, 2014. RSV was identified in the 26% of the hospitalized children by reverse transcriptase PCR. Group A RSV (77%) predominated during the study as compared to group B RSV (23%). The phylogenetic analysis of 28 study strains clustered group A RSV in NA1 and ON1 genotypes and group B viruses in BA (BA9) genotype. Interestingly, 26% of the positive samples clustered in genotypes with duplication in the G protein gene (ON1 for group A and BA for group B). Both the genotypes showed enhanced O-linked glycosylation in the duplicated region, with 10 and 2 additional sites in ON1 and BA respectively. Selection pressure analysis revealed purifying selection in both the ON1 and BA genotypes. One codon each in the ON1 (position 274) and BA genotypes (position 219) were positively selected and had high entropy values indicating variations at these amino acid positions. This is the first report describing the presence of ON1 genotype and the first report on co-circulation of two different genotypes of RSV with duplication in the G protein gene from Saudi Arabia. The clinical implications of the simultaneous occurrence of genotypes with duplication in G protein gene in a given population especially in the concurrent infections should be investigated in future. Further, the ongoing surveillance of RSV in this region will reveal the evolutionary trajectory of these two genotypes with duplication in G protein gene from largest country in the Middle East.