The treatment of HIV-1 infection and AIDS represents one of the greatest challenges in medicine. While there is no cure for HIV/AIDS, truly remarkable progress has been made for treatment of HIV/AIDS patients today. The advent of combination antiretroviral therapy (cART) in the mid-1990s dramatically improved HIV-1 related morbidity, greatly prolonged life expectancy, and delayed progression of AIDS. Due to current antiretroviral therapy, the mortality rate for HIV infected patients is closely approaching the mortality rate for the general population. The long-term success of HIV-AIDS treatment requires continued enhancement of cART with further development of novel drugs that would exhibit fewer side effects, higher genetic barrier to the development of resistance, and longer action with durable virologic suppression. This editorial article provides a quick review of four decades of intense drug development research efforts targeting various viral enzymes and cellular host factors leading to the evolution of today's treatment of patients with HIV-1 infection and AIDS. It also touches on challenges of future treatment options.
Hepatitis B virus (HBV) is a hepadnavirus, a small DNA virus that infects liver tissue, with some unusual replication steps that share similarities to retroviruses. HBV infection can lead to chronic hepatitis B (CHB), a life-long infection associated with significant risks of liver disease, especially if untreated. HBV is a significant global health problem, with hundreds of millions currently living with CHB. Currently approved strategies to prevent or inhibit HBV are highly effective, however, a cure for CHB has remained elusive. To achieve a cure, elimination of the functionally integrated HBV covalently closed chromosomal DNA (cccDNA) genome is required. The capsid core is an essential component of HBV replication, serving roles when establishing infection and in creating new virions. Over the last two and a half decades, significant efforts have been made to find and characterize antivirals that target the capsid, specifically the HBV core protein (Cp). The antivirals that interfere with the kinetics and morphology of the capsid, termed capsid assembly modulators (CAMs), are extremely potent, and clinical investigations indicate they are well tolerated and highly effective. Several CAMs offer the potential to cure CHB by decreasing the cccDNA pools. Here, we review the biology of the HBV capsid, focused on Cp, and the development of inhibitors that target it.
Cancer is currently a major public health issue faced by countries around the world. With the progress of medical science and technology, the survival rate of cancer patients has increased significantly and the survival time has been effectively prolonged. How to provide quality and efficient care for the increasingly large group of cancer survivors with limited medical resources will be a key concern in the field of global public health in the future. Compared to developed countries, China's theoretical research and practical experience in care for cancer survivors are relatively limited and cannot meet the multi-faceted and diverse care needs of cancer patients. Based on the existing models of care worldwide, the current work reviews care for cancer survivors in China, it proposes considerations and suggestions for the creation of models of cancer care with Chinese characteristics in terms of optimizing top-level system design, enhancing institutional mechanisms, accelerating human resource development, and enhancing self-management and social support for patients.
Emtricitabine (FTC) plus tenofovir alafenamide (TAF) has demonstrated efficacy and safety for pre-exposure prophylaxis (PrEP) to prevent HIV-1 infection. We measured the plasma PK of FTC, tenofovir (TFV), and TAF in a steady-state pharmacokinetic (PK) study of bictegravir/FTC/TAF in HIV-1-infected patients. Furthermore, validated liquid chromatography-tandem mass spectrometry was used to measure intracellular TFV-diphosphate (DP) and FTC-triphosphate (TP), the active metabolites of TFV and FTC, respectively. Plasma and dried blood spot samples were collected from 10 male patients aged ≥ 50 years at various time intervals: 0 (trough), 1, 2, 3, 4, 6, 8, 12, and 24 h after drug administration. The mean ± standard deviation of plasma PK parameters were as follows: The maximum concentrations of TAF, TFV, and FTC were 104.0 ± 72.5, 27.9 ± 5.2, and 3,976.0 ± 683.6 ng/mL, respectively. Additionally, their terminal elimination half-lives were 0.6 ± 0.5, 31.6 ± 10.4, and 6.9 ± 1.4 h, respectively. These results were consistent with previously reported data. The intracellular levels of TFV-DP and FTC-TP varied widely among individuals; however, they remained stable over 24 h in each individual at approximately 1,000–1,500 and 2,000–3,000 fmol/punch, respectively, indicating that plasma concentrations did not affect the intracellular concentrations of their active metabolites. These results demonstrated that measuring intracellular TFV-DP and FTC-TP could be useful for monitoring adherence to PrEP in clients on this regimen.
For patients suspected of sepsis, early recognition of the need for initial resuscitation is key in management. This study evaluated the ability of a modified shock index — the reverse shock index multiplied by the Glasgow Coma Scale score (rSIG) — to predict the need for initial resuscitation in patients with sepsis. This retrospective study involved adults with infection who were admitted to a Japanese tertiary care hospital from an emergency department between January and November 2020. The rSIG, modified Early Warning Score (MEWS), quick Sequential Organ Failure Assessment (qSOFA), and original shock index (SI) values were recorded using initial vital signs. The primary outcome was the area under the receiver-operating characteristic curve (AUROC) for the composite outcome consisting of vasopressor use, mechanical ventilation, and 72-h mortality. Secondary outcomes were the AUROCs for each component of the primary outcome and 28-day mortality. As a result, the primary outcome was met by 67 of the 724 patients (9%). The AUROC was significantly higher for the rSIG than for the other tools (rSIG 0.84 [0.78 – 0.88]; MEWS 0.78 [0.71 – 0.84]; qSOFA 0.72 [0.65 – 0.79]; SI 0.80 [0.74 – 0.85]). Compared with MEWS and qSOFA, the rSIG also had a higher AUROC for vasopressor use and mechanical ventilation, but not for 72-h mortality or in-hospital mortality. The rSIG could be a simple and reliable predictor of the need for initial resuscitation in patients suspected of sepsis.
In the present study, several research methods were adopted, including literature retrieval, theoretical analysis, and qualitative research, and then the draft of the prognostic factors for the chronic post-surgical pain (CPSP) index system after video-assisted thoracoscopic surgery (VATS) for lung resection was constructed. A Delphi survey was used for the study of 24 experts in the field of pain from three different grade-A tertiary hospitals in Guangzhou, China. In the two rounds of survey, the experts rated these indicators for the importance and feasibility of measurement (round 1, n = 21 participants; round 2, n = 20). Finally, we calculated Kendall's W index as a measure of consensus. A general consensus was reached on predicting CPSP after VATS, consisting of 10 first-level domains and 64 second-level indicators, involving biological, psychological and social perspectives. This study provides a comprehensive draft of risk factors developed and identified by experts to inform research-based evidence on chronic pain. Increased clinical awareness and a full understanding of how to screen and identify people with CPSP problems may lead to earlier recognition of chronic pain and greater facilitation of professional prevention.
Controlling avoidable causes of cancer may save cancer-related healthcare costs and indirect costs of premature deaths and productivity loss. This study aimed to estimate the economic burden of cancer attributable to major lifestyle and environmental risk factors in Japan in 2015. We evaluated the economic cost of cancer attributable to modifiable risk factors from a societal perspective. We obtained the direct medical costs for 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, and estimated the indirect costs of premature mortality and of morbidity due to cancer using the relevant national surveys in Japan. Finally, we estimated the economic cost of cancer associated with lifestyle and environmental risk factors. The estimated cost of cancer attributable to lifestyle and environmental factors was 1,024,006 million Japanese yen (\) (8,460 million US dollars [$]) for both sexes, and \673,780 million ($5,566 million) in men and \350,226 million ($2,893 million) in women, using the average exchange rate in 2015 ($1 = \121.044). A total of \285,150 million ($2,356 million) was lost due to premature death in Japan in 2015. Indirect morbidity costs that could have been prevented were estimated to be \200,602 million ($1,657 million). Productivity loss was highest for stomach cancer in men (\28,735 million/$237 million) and cervical cancer in women (\24,448 million/$202 million). Preventing and controlling cancers caused by infections including Helicobacter pylori, human papillomavirus and tobacco smoking will not only be life-saving but may also be cost-saving in the long run.
Sorafenib is a breakthrough in the medical treatment aiming to control hepatocellular carcinoma (HCC) progression, but there is some controversy in patients' selection. The introduction of Sorafenib has led to several positive effects. New more than promising antiangiogenic molecules have followed. Immunotherapy combined with antiangiogenic therapy has also strongly entered into the treatment of HCC. All of that has induced a significant guideline revision profiling Sorafenib as a second line systemic therapy in the event of advanced HCC. However, for those patients with advanced but resectable HCC, the selection of surgery or systemic therapy should be reviewed and reconsidered.
Strengthening nursing leadership in health systems has been identified as a priority for achieving Universal Health Coverage (UHC). We aimed to analyse the characteristics of Japanese technical assistance projects for nursing human resource development in Lao People's Democratic Republic (Lao PDR) and suggest directions for future assistance. An upgrading program, as part of human resource development, was initiated in the 1990s; it has contributed to the development of nursing leaders. Moreover, technical assistance from development partners has had synergistic effects by consistently promoting the involvement of nursing leaders in administration, education, and clinical practice to establish a functional regulatory system. In resource-limited settings, the application of both edge-pulling (leadership development) and bottom-up (quality improvement of the mass population) strategies are required. From a long-term perspective, development partners should continue to invest in increasing the number and quality of nursing leaders by upgrading the courses and leadership training programs, starting from the younger generation.
Cervical cancer is prevalent among women, with a reported 604,127 cases in 2020 worldwide. The incidence of cervical cancer has been mitigated in most high-income countries by promoting the human papilloma virus (HPV) vaccine. However, in Japan, cervical cancer is still a leading cause of mortality and the most prevalent cancer among women aged between 15 and 39. This can be attributed to the 7-year suspension of HPV vaccination recommendations by the Japanese government. A decline in vaccination coverage followed this suspension, caused by a small number of reported adverse events, resulting in a steep decline in vaccination coverage from over 70% to less than 1%. However, there have been indications of a change in trend in Japan. In 2020, a group of volunteer doctors initiated awareness-raising activities through social networking services and other platforms, and the target population that received at least one dose of the vaccine in 2020 increased to 15.9%. Additionally, in July 2020, the Japanese government approved the updated 9-valent HPV vaccine and resumed recommendations in November 2021. As a result, 30.1% of those eligible for routine HPV vaccination received at least one dose of the vaccine from April to September, 2022. However, the HPV vaccine coverage in Japan is still far from the 90% recommended by the World Health Organization, and continued communication and education on the vaccine’s benefits are necessary to achieve optimal coverage.