Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

A case review of a patient experience of photopheresis using a peripherally inserted central catheter

Extracorporeal photopheresis (ECP) is a cell based immunomodulatory therapy in which the patient is attached intravenously to a cell separating machine. During ECP a patient's blood is collected via either a central venous access device (CVAD) or a peripherally inserted 16G arterial venous fistula needle in either one or both antecubital fossa. However, patients presenting for ECP with GVHD repeatedly present a challenge to the ECP team due to poor venous access resulting from previous therapies and skin changes. The use of peripherally inserted central venous catheters (PICCs) offers an alternative route of vascular access for this cohort of patients. Here we present a case report of a patient successfully treated with ECP following the insertion of a PICC line.     

Self-care activities,glycaemic control and health-related quality of life of patients with type 2 diabetes in a tertiary hospital in Nigeria

Background and aimsDiabetes is one of the global health emergencies of the 21st century. This study sought to assess self-care behaviours, glycaemic control and health-related quality of life (HRQoL) of type 2 diabetes patients at a Nigerian hospital, determine factors associated with HRQoL, and assess the inter-relationship among these outcomes.MethodsThe Summary of Diabetes Self-Care Activities (SDSCA) measure was used to assess self-care behaviours; HRQoL was assessed with the Appraisal of Diabetes Scale (ADS) and SF-12v2 Health Survey. Glycaemic control was assessed with fasting blood sugar (FBS). The questionnaires were distributed to 250 eligible patients attending Endocrinology clinic at the University of Uyo Teaching Hospital, Akwa Ibom State, Nigeria.ResultsMean scores (±SD) of self-care behaviours were 4.0 ± 1.3, 3.9 ± 1.0, 2.4 ± 1.2, 1.0 ± 1.1, and 2.5 ± 2.1 for general diet, specific diet, exercise, blood glucose monitoring, and foot care respectively. Mean FBS was 7.1 ± 2.1 mmol/L. Mean ADS score was 18.1 ± 4.2. The physical and mental component summary scores were 47.84 ± 8.21 and 45.66 ± 8.74 respectively. HRQoL was significantly associated with patient socio-demographic (except gender) and clinical variables (p < 0.05). Self-care activities, FBS and HRQoL were significantly inter-correlated (r_s ?0.31 to 0.68; p < 0.01, p < 0.001).ConclusionsPatients were more adherent to diet recommendations than to other aspects of self-care. Though most patients had adequate glucose control, the presence of diabetes had a negative impact on the mental component of health. HRQoL was affected by most of the patient-related variables. Interventions to improve adherence to self-care are recommended to achieve good glycaemic control and improve HRQoL.     

Interacting regional policies in containing a disease

Regional quarantine policies, in which a portion of a population surrounding infections is locked down, are an important tool to contain disease. However, jurisdictional governments—such as cities, counties, states, and countries—act with minimal coordination across borders. We show that a regional quarantine policy’s effectiveness depends on whether 1) the network of interactions satisfies a growth balance condition, 2) infections have a short delay in detection, and 3) the government has control over and knowledge of the necessary parts of the network (no leakage of behaviors). As these conditions generally fail to be satisfied, especially when interactions cross borders, we show that substantial improvements are possible if governments are outward looking and proactive: triggering quarantines in reaction to neighbors’ infection rates, in some cases even before infections are detected internally. We also show that even a few lax governments—those that wait for nontrivial internal infection rates before quarantining—impose substantial costs on the whole system. Our results illustrate the importance of understanding contagion across policy borders and offer a starting point in designing proactive policies for decentralized jurisdictions.

Global problems, from climate change to financial crises to disease control, are hard to address without policy coordination across borders. Carbon emissions in one region are everyone’s problem, as are financial collapses, as well as the spread of an infectious disease. Coordinating policies across jurisdictions in terms of both timing and scale is important whenever problems have spillovers. In this paper we shed light on this problem by examining how different types of decentralized policies fare compared to more centralized policies at containing the spread of an infectious disease.In particular, pandemics, like COVID-19, are challenging to contain if governments fail to coordinate efforts. Without vaccines or herd immunity, governments have responded to infections by limiting constituents’ interactions in areas where an outbreak exceeds a threshold of infections. Such regional quarantine policies are used by towns, cities, counties, states, and countries and trace to the days of the black plague. Over the past 150 y, regional quarantines have been used to combat cholera, diphtheria, typhoid, flus, polio, Ebola, and COVID-19 (1–4), but rarely with coordination across borders.Decentralized policies across jurisdictions have two major shortcomings. First, governments care primarily about their own citizens and do not account for how their infections impact other jurisdictions: The resulting lack of coordination can lead to worse overall outcomes than a global policy (5–7). Second, many governments are inward looking, paying attention only to internal situations, which leads them to underforecast their own infection rates.We examine three types of quarantine policies to understand the impact of noncoordination: 1) those controlled by one actor with control of the whole society—“single-regime policies”; 2) those controlled by separate jurisdictions that are inward looking and react only to internal infection rates, or “reactive” for short; and 3) those controlled by separate jurisdictions that are outward looking, tracking infections outside of their jurisdiction as well as within to forecast their infection rates when deciding when to quarantine, or “proactive” for short.We use a general model of contagion through a network to study these policies. We first consider single-regime policies. A government can quarantine everyone at once under a “global quarantine,” but those are very costly (e.g., lost days of work, school, etc.). Less costly (in the short run), and hence more common, alternatives are “regional quarantines” in which only people within some distance of observed infections are quarantined. Regional quarantines, however, face two challenges. First, many diseases are difficult to detect, because either some individuals are asymptomatically contagious (e.g., HIV, COVID-19) (8–10) or a government lacks resources to quickly identify infections (11, 12). Second, it may be infeasible to fully quarantine a part of the network, because of difficulties in identifying whom to quarantine (e.g., imperfect or inefficient contact tracing) or noncompliance by some people—by choice or necessity (13–18). Either way, tiny leakages can spread the disease.We show that regional quarantines curb the spread of a disease if and only if 1) there is limited delay in observing infections, 2) there is sufficient knowledge and control of the network to prevent leakage of infection, and 3) the network has a certain “growth balance” structure. The failure of any of these conditions substantially limits regional quarantine effectiveness.We then examine jurisdictional policies, which are regional quarantine policies conducted by multiple, uncoordinated regimes. The regions that need to be quarantined, however, often cross borders, leading to leakage that limits their effectiveness. As we show, jurisdictional policies that are reactive do much worse than proactive ones, as they do not forecast the impact of neighboring jurisdictions’ infection rates on their own population. Moreover, a few lax jurisdictions, which wait for higher infection rates before quarantining, worsen outcomes for all jurisdictions.