The Ventilation-to-area Ratio and House Lighting Relate to the Incidence of Pulmonary Tuberculosis

Background: Indonesia is one of the heavy burden countries with high pulmonary tuberculosis incidence in the world. The physical condition of houses is one of the environmental factors on how the infection spreads. The objective of this study was to provide supporting facts between the physical environment of the houses and the incidence of pulmonary tuberculosis.Methods: This was an observational analytic study with a case-control design, using checklists among pulmonary tuberculosis patients (n 32) and their healthy controls (n 32). Study subjects were chosen by simple random sampling. The study was performed from March to August 2019 at the Public Health Center (Pusat Kesehatan Masyarakat, Puskesmas) in Sawahan district, Surabaya. The incidence of pulmonary tuberculosis was related to various factors, including window existence, window opening habit, ventilation-to-area ratio, humidity, temperature, lighting, and occupancy density. The collected data were analyzed using the chi-square test to assess statistical significance with a p-value <0.05 was considered significantly related.Results: The ventilation-to-area ratio (p<0.05) and house lighting (p<0.00) were related to pulmonary tuberculosis incidence, whereas other factors such as window existence, window opening habit, temperature, and occupancy density were not.Conclusions: The ventilation-to-area ratio and house lighting have been proven to be related to pulmonary tuberculosis incidence. Government regulation on building permit needs to be encouraged to reduce the spreading and the incidence of pulmonary tuberculosis

Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD. Here, we investigated the effect of PKLR in in vivo model and performed drug repositioning to identify a drug candidate for treatment of NAFLD. Methods: Tissue samples from liver, muscle, white adipose and heart were obtained from control and PKLR knockout mice fed with chow and high sucrose diets. Lipidomics as well as transcriptomics analyses were conducted using these tissue samples. In addition, a computational drug repositioning analysis was performed and drug candidates were identified. The drug candidates were both tested in in vitro and in vivo models to evaluate their toxicity and efficacy. Findings: The Pklr KO reversed the increased hepatic triglyceride level in mice fed with high sucrose diet and partly recovered the transcriptomic changes in the liver as well as in other three tissues. Both liver and white adipose tissues exhibited dysregulated circadian transcriptomic profiles, and these dysregulations were reversed by hepatic knockout of Pklr. In addition, 10 small molecule drug candidates were identified as potential inhibitor of PKLR using our drug repositioning pipeline, and two of them significantly inhibited both the PKLR expression and triglyceride level in in vitro model. Finally, the two selected small molecule drugs were evaluated in in vivo rat models and we found that these drugs attenuate the hepatic steatosis without side effect on other tissues. Interpretation: In conclusion, our study provided biological insights about the critical role of PKLR in NAFLD progression and proposed a treatment strategy for NAFLD patients, which has been validated in preclinical studies. Funding: ScandiEdge Therapeutics and Knut and Alice Wallenberg Foundation

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Hubungan Antara Kondisi Fisik Rumah Dengan Kejadian Tuberkulosis Paru Di Wilayah Kerja Puskesmas Sawahan Kota Surabaya

Latar Belakang: Pada tahun 2017, Indonesia menempati peringkat kedua dengan kejadian tuberkulosis paru terbanyak di dunia. Kota Surabaya menempati peringkat pertama dengan kejadian tuberkulosis paru terbanyak di Provinsi Jawa Timur. Wilayah kerja Puskesmas Sawahan menempati peringkat pertama dengan kejadian tuberkulosis paru baru terbanyak di Kecamatan Sawahan. Kondisi fisik rumah merupakan salah satu faktor lingkungan dari 3 faktor triase teori John Gordon tentang penyakit; inang, patogen, dan lingkungan. Tujuan: Penelitian ini bertujuan untuk menganalisis adanya hubungan antara kondisi fisik rumah (rasio ventilasi dengan luas tanah, kepadatan hunian, keberadaan jendela, suhu, kelembaban, dan pencahayaan) dengan banyaknya kejadian tuberkulosis paru. Metode: Penelitian ini dilakukan dengan metode kasus-kontrol yang membandingkan faktor risiko antara kontrol dengan kasus. Data diperoleh dari kuisioner yang diberikan ke rumah subjek penelitian yang berada di wilayah kerja Puskesmas Sawahan Kota Surabaya. Kasus adalah rumah penderita tuberkulosis paru pada bulan Januari 2018 hingga Juni 2019. Kontrol merupakan rumah yang berada di sekitar rumah penderita tuberkulosis paru di wilayah yang sama. Jumlah sampel adalah 64 rumah dengan menggunakan metode sampel acak sederhana. Waktu penelitian yaitu Maret-Agustus 2019 Hasil: Subjek penelitian berjumlah 64 rumah dengan 32 kasus dan 32 kontrol. Didapatkan hubungan yang signifikan antara rasio ventilasi dengan luas tanah dengan kejadian tuberkulosis paru dengan nilai P<0,05 dan antara pencahayaan dengan kejadian tuberkulosis dengan nilai P<0,00. Kepadatan hunian, keberadaan jendela, dan kelembaban tidak berhubungan signifikan dengan kejadian tuberkulosis paru dengan nilai P>0,05. Sementara suhu tidak berhubungan dengan kejadian tuberkulosis paru. Kesimpulan: Rasio ventilasi dengan luas tanah dan pencahayaan dalam rumah berhubungan dengan kejadian tuberkulosis paru. Kepadatan hunian, keberadaan jendela, dan kelembaban tidak berhubungan signifikan dengan tuberkulosis paru. Sementara suhu tidak berhubungan dengan kejadian tuberkulosis paru

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population