Well-being therapy and sleep hygiene in a non-clinical population of adults reporting poor sleep quality and distress: A remote pilot randomized controlled study.

OBJECTIVES: This pilot randomized controlled study evaluates the feasibility and preliminary efficacy of a 7-week remote intervention combining well-being therapy and sleep hygiene to improve sleep and psychological outcomes among adults reporting poor sleep and distress. METHODS: Thirty-one participants (81% women, 40.2 ± 13.0 y, 48% racial/ethnic minority) were recruited from the community during the COVID-19 pandemic through online and local advertisement, and randomized to well-being therapy+sleep hygiene or sleep hygiene-only. Study outcomes were evaluated by self-reported questionnaires administered at baseline and post-intervention and a daily sleep diary. RESULTS: Compared to sleep hygiene-only, well-being therapy+sleep hygiene led to greater improvements in wake after sleep onset (time-by-group interaction: 3.6 ± 1.5 min, p = .017), personal growth (ß -3.0, 95%CI -5.2, -0.8, p = .01), and purpose in life (ß -3.5, 95%CI -6.1, -0.9, p = .009). Anxiety, perceived stress, sleep quality, and insomnia symptoms improved similarly in both groups (between-group differences, p > .05). Improvements in sleep quality, insomnia, and sleep duration were associated with reductions in multiple measures of psychological distress (all p < .05). CONCLUSIONS: These findings suggest that, in a non-clinical setting of individuals suffering from combined poor sleep and psychological distress, the addition of well-being therapy to sleep hygiene may provide additional benefits for sleep by promoting sleep continuity and well-being.

Targeted Inhibition of Fibroblast Growth Factor Receptor 1-GLI Through AZD4547 and GANT61 Modulates Breast Cancer Progression.

The underlying mechanism of fibroblast growth factor receptor 1 (FGFR1) mediated carcinogenesis is still not fully understood. For instance, FGFR1 upregulation leads to endocrine therapy resistance in breast cancer patients. The current study aimed to identify FGFR1-linked genes to devise improved therapeutic strategies. RNA-seq and microarray expression data of 1,425 breast cancer patients from two independent cohorts were downloaded for the analysis. Gene Set Enrichment Analysis (GSEA) was performed to identify differentially expressed pathways associated with FGFR1 expression. Validation was done using 150 fresh tumor biopsy samples of breast cancer patients. The clinical relevance of mRNA and protein expression of FGFR1 and its associated genes were also evaluated in mouse embryonic fibroblasts (MEFs) and breast cancer cell line (MDA-MB-231). Furthermore, MDA-MB-231 cell line was treated with AZD4547 and GANT61 to identify the probable role of FGFR1 and its associated genes on cells motility and invasion. According to GSEA results, SHH pathway genes were significantly upregulated in FGFR1 patients in both discovery cohorts of breast cancer. Statistical analyses using both discovery cohorts and 150 fresh biopsy samples revealed strong association of FGFR1 and GLI1, a member of SHH pathway. The increase in the expression of these molecules was associated with poor prognosis, lymph node involvement, late stage, and metastasis. Combined exposures to AZD4547 (FGFR1 inhibitor) and GANT61 (GLI1 inhibitor) significantly reduced cell proliferation, cell motility, and invasion, suggesting molecular crosstalk in breast cancer progression and metastasis. A strong positive feedback mechanism between FGFR1-GLI1 axis was observed, which significantly increased cell proliferation and metastasis. Targeting FGFR1-GLI1 simultaneously will significantly improve the prognosis of breast cancer in patients.

Prophylactic potential of honey and Nigella sativa L. against hospital and community-based SARS-CoV-2 spread: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. TRIAL DESIGN: The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial. PARTICIPANTS: All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). INTERVENTION AND COMPARATOR: In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. RANDOMISATION: Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. BLINDING (MASKING): Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 1000 participants will be enrolled in the study with 1:1 allocation. TRIAL STATUS: The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. TRIAL REGISTRATION: Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Impact of environmental factors on COVID-19 cases and mortalities in major cities of Pakistan.

INTRODUCTION: Climate factors play an important role in the transmission of viruses, such as influenza viruses, MERS-CoV, and SARS-CoV-1. This study aimed to determine the relationship between changes in temperature, humidity, rainfall, and SARS-CoV-2 contagion. Five ecologically and climatically distinct regions were considered-Karachi, Lahore, Islamabad, Peshawar, and Gilgit-Baltistan. METHOD: Data on daily COVID-19 cases and deaths were retrieved from government officials, while meteorological information was collected from Pakistan Meteorological Department.. Statistical analysis was performed using SPSS version 20 and the Spearman rank correlation test was used to analyze the correlation between the meteorological factors and COVID-19 cases and deaths. RESULT: Positive correlation of COVID-19 incidence was observed with all the temperature ranges (maximum, minimum and average) and negative correlation was seen with humidity, DTR and rainfall. COVID-19 deaths were positively associated with temperature and were negatively associated only with humidity. Linear regression showed that for every unit increase in humidity, there was a -3.345 daily significant decrease in COVID-19 cases, while in Karachi for every unit increase in humidity, there remained a 10.104 daily significant increase in cases. In Gilgit-Baltistan, for every unit increase in average temperature and rainfall respectively, significant increases of 0.534 and 1.286 in daily cases were found. CONCLUSION: This study signifies the effect of climate factors on COVID-19 incidence and mortality rate, but climate factors are not the only variable and several other interlinked factors enhance the spread of COVID-19. Hence, effective mitigation policies, enhancing testing capacities, and developing public attitudes toward adopting precautionary measures are important to overcome this overwhelming pandemic.

A quadruple blinded placebo controlled randomised trial to evaluate the effectiveness of an Iodine complex for patients with mild to moderate COVID-19 in Pakistan (I-COVID-PK): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The objective of the study is to measure the efficacy of ionic-iodine polymer complex [1] for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients. TRIAL DESIGN: The trial will be closed label, randomized and placebo-controlled with a 1:1:1:1 allocation ratio and superiority framework. PARTICIPANTS: All PCR confirmed COVID-19 adult patients including non-pregnant females, with mild to moderate disease, will be enrolled from Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Patients with any pre-existing chronic illness will be excluded from the study. INTERVENTION AND COMPARATOR: In this multi-armed study ionic-iodine polymer complex with 200 mg of elemental iodine will be given using three formulations to evaluate efficacy. Patients will be receiving either encapsulated iodine complex of 200 mg (arm A), iodine complex syrup form 40 ml (arm B), iodine complex throat spray of 2 puffs (arm C) or empty capsule (arm D) as placebo; all three times a day. All the 4 arms will be receiving standard care as per version 3.0 of the clinical management guidelines for COVID-19 established by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcomes will be viral clearance with radiological and clinical improvement. SARS-CoV-2 RT-PCR and HRCT chest scans will be done on the admission day and then after every fourth day for 12 days or till the symptoms are resolved. RT-PCR will only be shown as positive or negative while HRCT chest scoring will be done depending on the area and severity of lung involvement [2]. Time taken for the alleviation of symptoms will be calculated by the number of days the patient remained symptomatic. 30-day mortality will be considered as a secondary outcome. RANDOMISATION: Stratification for initial COVID-19 status (or days from initial symptoms as a proxy), age groups, gender, baseline severity of symptoms and co-morbidities will be used to ensure that the study arms remain balanced in size for the 1:1:1:1 allocation ratio. Randomization will be done using the lottery method. As patients are being admitted at different times, they will be recruited after obtaining their voluntary written informed consent following all standard protocols of the infection, control and disinfection. BLINDING (MASKING): This is a quadruple (participants, care providers, investigators and outcomes assessors) blinded study where only the study's Primary Investigator will have information about the arms and their interventions. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 200 patients will be randomized into four groups with three experimental and one placebo arm. TRIAL STATUS: Protocol Version Number is 2.3 and it is approved from IRB Shaikh Zayed Hospital with ID SZMC/IRB/Internal0056/2020 on July 14th, 2020. The recruitment is in progress. It was started on July 30, 2020, and the estimated end date for the trial is August 15, 2021. TRIAL REGISTRATION: Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04473261 dated July 16, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.