Hepatocellular carcinoma: Where there is unmet need.
Ontology highlight
ABSTRACT:
SUBMITTER: Bupathi M
PROVIDER: S-EPMC5528787 | biostudies-other | 2015 Oct
REPOSITORIES: biostudies-other
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Project description:Background/aimAn effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD).MethodsFrom March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score.ResultsMedian time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p < 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p < 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p < 0.001), and continuing LEN beyond PD (HR 0.297, p < 0.001).ConclusionWhen ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.
| S-EPMC8077500 | biostudies-literature
Project description:Cough is among the most common complaints for which patients worldwide seek medical attention. Thus, the evaluation and treatment of cough result in tremendous financial expenditure and consumption of health care resources. Yet, despite the clinical significance of cough, research efforts aimed at improving diagnostic capabilities and developing more effective therapeutic agents have been, to date, disappointing in their limited scope and outcomes. Acute cough due to the common cold represents the most common type of cough. Currently, available medications for the symptomatic management of acute cough are inadequate due to lack of proven efficacy and/or their association with undesirable or intolerable side effects at anti-tussive doses. Subacute cough, often representing a prolonged post-viral response, is typically refractory to standard anti-tussive therapy. Few clinical trials have evaluated therapeutic options for subacute cough. Diagnostic challenges facing the clinician in the management of chronic cough include the determination of whether symptoms of upper airway cough syndrome (formerly, postnasal drip syndrome) or gastro-oesophageal reflux disease are indeed the underlying cause of cough. Chronic, refractory unexplained (formerly, idiopathic) cough must be distinguished from cough that has not been fully evaluated and treated according to current guideline recommendations. Eagerly awaited are new safe and effective anti-tussive agents for use when cough suppression is desired, regardless of underlying aetiology of cough, as well as practical, validated ambulatory cough counters to aid clinical assessment and future research in the field of cough.
| S-EPMC3085873 | biostudies-other
Project description:BACKGROUND:Admission criteria and standardized management strategies for bronchiolitis are addressed in several guidelines and have shown to be beneficial; however, guidance regarding discharge criteria is limited and widely variable. We assessed the impact on clinical outcomes of a discharge protocol for children <2 years of age hospitalized with bronchiolitis in a tertiary care pediatric hospital. METHODS:In October 2013, a protocol to standardize the discharge of children with bronchiolitis was implemented in the infectious diseases (ID) ward but not in other pediatric units caring for these children (non-ID). The protocol included objective clinical criteria and a standardized oxygen weaning pathway. Patients were identified via International Classification of Diseases-9 codes and data manually reviewed. We compared length of stay (LOS) and readmission rates within 2 weeks of discharge according to protocol implementation (ID versus non-ID), adjusted for demographic factors, comorbidities, viral etiology and stratified by pediatric intensive care unit admission. RESULTS:From October 2013 to May 2015, 1118 children were hospitalized in ID and 695 in non-ID units. Median age was 4.5 months, 55% were males and 28% had comorbidities. LOS was 36% longer in non-ID units (risk ratio: 1.36 [1.27-1.45]; P < 0.001) adjusted for age, gender, comorbidities and viral etiology. Difference in LOS remained significant after excluding children with comorbidities and stratifying by pediatric intensive care unit admission. Readmission rates were comparable between units (ID, 2.9% versus non-ID, 2.6%). CONCLUSIONS:A standardized discharge protocol for bronchiolitis reduced LOS without increasing readmission rates. Unifying bronchiolitis discharge criteria and oxygen weaning pathways could positively impact hospital-based patient care for this condition.
| S-EPMC5953775 | biostudies-literature
Project description:PURPOSE:Choroideremia is an incurable, X-linked, recessive retinal dystrophy caused by loss of function mutations in the CHM gene. It is estimated to affect approximately 1 in 50,000 male patients. It is characterized by progressive degeneration of the retinal pigment epithelium, choroid, and photoreceptors, resulting in visual impairment and blindness. There is an unmet need in choroideremia, because currently, there are no approved treatments available for patients with the disease. METHODS:We review the patient journey, societal impact, and emerging treatments for patients with choroideremia. RESULTS:Its relative rarity and similarities with other retinal diseases in early years mean that diagnosis of choroideremia can often be delayed. Furthermore, its impact on affected individuals, and wider society, is also likely underestimated. AAV2-mediated gene therapy is an investigational treatment that aims to replace the faulty CHM gene. Early-phase studies reported potentially important visual acuity gains and maintenance of vision in some patients, and a large Phase 3 program is now underway. CONCLUSION:Choroideremia is a disease with a significant unmet need. Interventions that can treat progression of the disease and improve visual and functional outcomes have the potential to reduce health care costs and enhance patient quality of life.
| S-EPMC7347087 | biostudies-literature
Project description:X-linked adrenoleukodystrophy (ALD) is an inherited progressive neurometabolic disease caused by mutations in the ABCD1 gene and the accumulation of very long-chain fatty acids in plasma and tissues. Patients present with heterogeneous clinical manifestations which can include adrenal insufficiency, myelopathy, and/or cerebral demyelination. In the absence of a genotype-phenotype correlation, the clinical outcome of an individual cannot be predicted and currently there are no molecular markers available to quantify disease severity. Therefore, there is an unmet clinical need for sensitive biomarkers to monitor and/or predict disease progression and evaluate therapy efficacy. The increasing amount of biological sample repositories ('biobanking') as well as the introduction of newborn screening creates a unique opportunity for identification and evaluation of new or existing biomarkers. Here we summarize and review the many studies that have been performed to identify and improve knowledge surrounding candidate molecular biomarkers for ALD. We also highlight several shortcomings of ALD biomarker studies, which often include a limited sample size, no collection of longitudinal data, and no validation of findings in an external cohort. Nonetheless, these studies have generated a list of interesting biomarker candidates and this review aspires to direct future biomarker research.
| S-EPMC8699919 | biostudies-literature
Project description:The management of mitral regurgitation (MR) is challenging - patients may be asymptomatic, oligosymptomatic, older with comorbidities, or clinically symptomatic and not appropriate for surgery. The current review assesses morbidity, mortality, and risk factors associated with functional and organic MR, with a focus on severe MR.A structured literature review was conducted in MEDLINE, Embase, the Cochrane Library, and via hand-searching of conference proceedings. Prospective randomised controlled trials and observational studies including adult patients with MR reporting on treatment response rates, survival, time-to-treatment failure, quality of life, and adverse events were eligible for inclusion.In total, 32 publications met the inclusion criteria (9 in functional, 18 in organic, and 5 in functional/organic). Despite study heterogeneity, an increased risk of mortality and morbidity was observed which increased with MR severity. Risk factors associated with mortality and morbidity included advancing age, presence of atrial fibrillation, increasing effective regurgitant orifice, ejection fraction, left ventricle end systolic diameter, diabetes, and increasing New York Heart Association class.The current review represents one of the most comprehensive conducted in the medical/conservative management of MR. An increased risk of mortality and morbidity, which appeared to rise with greater severity, was associated with MR (versus no MR). An unmet need exists in the management of patients with severe symptomatic MR and a high surgical risk as they have a poor prognosis and limited treatment options. Further research into alternative medical strategies and patient management is needed to improve prognoses and reduce mortality and morbidity.
| S-EPMC5497153 | biostudies-other
Project description:Access to care for headache sufferers is not always simple. A survey conducted in a large number of members of lay associations point to the existence of multiple barriers to care for headache in several European countries. Patients usually discover the existence of specialized structures with a delay of several years after the onset of their headache. Furthermore, a relevant portion of them are not satisfied with the management of their disease, partly because of the poor efficacy of treatments and partly because of the difficulty to get in touch with the specialist. Headache disorders, and primary headaches in particular, represent an important issue in public health, because they are common, disabling and treatable. A joint effort is required from the relevant stakeholders (scientists, lay organizations, decision-makers, healthcare policymakers, and others) to improve the access to care for headache sufferers.
| S-EPMC4021552 | biostudies-literature
Project description:Robust thrombus imaging is an unresolved clinical unmet need dating back to the mid 1970s. While early molecular imaging approaches began with nuclear SPECT imaging, contrast agents for virtually all biomedical imaging modalities have been demonstrated in vivo with unique strengths and common weaknesses. Two primary molecular imaging targets have been pursued for thrombus imaging: platelets and fibrin. Some common issues noted over 40 years ago persist today. Acute thrombus is readily imaged with all probes and modalities, but aged thrombus remains a challenge. Similarly, anti-coagulation continues to interfere with and often negate thrombus imaging efficacy, but heparin is clinically required in patients suspected of pulmonary embolism, deep venous thrombosis or coronary ruptured plaque prior to confirmatory diagnostic studies have been executed and interpreted. These fundamental issues can be overcome, but an innovative departure from the prior approaches will be needed.
| S-EPMC5741521 | biostudies-literature
Project description:BackgroundIn the central nervous system (CNS) myelin sheaths stabilize, protect, and electrically insulate axons. However, in demyelinating autoimmune CNS diseases such as multiple sclerosis (MS) these sheaths are destroyed which ultimately leads to neurodegeneration. The currently available immunomodulatory drugs for MS effectively control the (auto)inflammatory facets of the disease but are unable to regenerate myelin by stimulating remyelination via oligodendroglial precursor cells (OPCs). Accordingly, there is broad consensus that the implementation of new regenerative approaches constitutes the prime goal for future MS pharmacotherapy.Main textOf note, recent years have seen several promising clinical studies investigating the potential of substances and monoclonal antibodies such as, for instance, clemastine, opicinumab, biotin, simvastatin, quetiapin and anti-GNbAC1. However, beyond these agents which have often been re-purposed from other medical indications there is a multitude of further molecules influencing OPC homeostasis. Here, we therefore discuss these possibly beneficial regulators of OPC differentiation and assess their potential as new pharmacological targets for myelin repair in MS.ConclusionRemyelination remains the most important therapeutic treatment goal in MS in order to improve clinical deficits and to avert neurodegeneration. The promising molecules presented in this review have the potential to promote remyelination and therefore warrant further translational and clinical research.
| S-EPMC7650135 | biostudies-literature
Project description:ObjectiveThe coronavirus disease (COVID-19) pandemic is a disaster of unprecedented proportions with global repercussions. Psychological preparedness, the primed cognitive awareness and anticipation of dealing with emotional responses in an adverse situation, has assumed a compelling relevance during a health disaster of this magnitude.MethodsAn anonymized eSurvey was conducted in India to assess psychological preparedness toward the ongoing pandemic with a focus on knowledge, management of own and others' emotional response, and anticipatory coping mechanisms among the survey population. An adapted version of the qualitative Psychological Preparedness for Natural Disaster Scale validated by the World Health Organization was widely circulated over the Internet and various social media platforms for assessment. Results are expressed as median ± standard deviation. Descriptive statistics were used and figures downloaded from surveymonkey.com.ResultsOf the 1120 respondents (M:F 1.7:1, age 35 years ±14.1), most expressed a high level of perceived knowledge and confidence of managing COVID-19, such as awareness of the symptoms of the illness (95.1%), actions needed (94.4%), hospital to report to (88.9%), and emergency contact number (89.1%). A majority (95%) monitored regularly the news bulletins and scientific journals regarding COVID-19. However, nearly one-third (29.2%) could not assess their likelihood of developing COVID-19, and 17.5% were unaware of the difference between a mild and severe infection. Twenty-three percent (23.3%) were unfamiliar with the materials needed in an acute illness situation.ConclusionPsychological disaster preparedness is reasonable, although lacking in specific domains. Timely but focused interventions can be a cost-efficient administrative exercise, which federal agencies may prioritize working on.
| S-EPMC7385318 | biostudies-literature