Varicella vaccination in Japan: necessity of implementing a routine vaccination program

Varicella-zoster virus (VZV) is the causative agent of varicella (chickenpox). It shows extremely high infectivity and is spread by airborne, droplet, and contact transmission. After a person is infected with VZV, the virus remains dormant in the dorsal root ganglia, but can be reactivated under circumstances where specific immunity declines, leading to the development of herpes zoster (shingles). Although varicella is a disease that usually resolves after about 1 week, it can cause various complications such as secondary bacterial skin infection, pneumonia, and encephalitis. In addition, varicella can become severe in immunocompromised persons, whereas VZV infection transmitted from an infected mother can cause the congenital varicella syndrome or serious neonatal varicella. In 1974, a live varicella vaccine (Oka strain) was developed in Japan for the prevention of varicella, and clinical trials performed during the development were mainly focused on high-risk children. In 1985, the Oka strain was recognized as the best varicella vaccine strain by the World Health Organization (WHO). Today, all the varicella vaccines used worldwide to immunize approximately 32 million people annually contain the Oka strain. In Japan, it has been commercially available since 1987 for the voluntary vaccination program, in which children over the age of 1 year with no history of previous varicella infection receive a single dose. In addition to healthy children, this vaccine can be used for immunocompromised children, and vaccination of elderly persons can also be done to enhance their immunity against VZV. Varicella vaccine is a highly safe vaccine with sufficient immunogenicity. The preventive effect of single-dose vaccination is believed to be approximately 80 % for all types of varicella, including mild cases; it is 95 % or greater for moderate to severe disease. Implementation of a two-dose vaccination schedule has proved to be effective against breakthrough varicella, which is observed in approximately 20–30 % of children vaccinated with a single dose. Because it is administered as part of the voluntary vaccination program, the varicella vaccination coverage rate in Japan has remained low until recently at around 20–30 %, with no sign of a decrease in the number of varicella patients. It is necessary to maintain a vaccination rate of 90 % or higher to prevent varicella epidemics. To achieve this goal, implementation of a routine vaccination program for varicella and introduction of a two-dose vaccination schedule, which is more effective than a single-dose schedule, would be highly desirable.     

Safety and Efficacy of Oral Transmucosal Fentanyl Citrate Compared to Morphine Sulphate Immediate Release Tablet in Management of Breakthrough Cancer Pain

Aim:

To compare the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) and oral morphine in Indian patients with breakthrough episodes of cancer pain.

Materials and Methods:

In this randomized, open label, active controlled, clinical study, total 186 patients who regularly experienced 1-4 episodes of breakthrough cancer pain (BTCP) daily, over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were randomized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days. Improvement in pain as determined by numerical rating scale (NRS) at 5, 15, 30, and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by >33% at 15 minutes were primary efficacy endpoints. Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient. Data of both treatment groups were analysed by appropriate statistical test using software, STATISTICA, version 11.

Results:

Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points (P < 0.0001). 56% of breakthrough pain episodes treated with OTFC showed a greater than 33% reduction in pain intensity from baseline at 15 minutes compared to 39% episodes treated with oral morphine (P < 0.0001). Patient''s and physician''s global assessment favoured OTFC than oral morphine (P < 0.0001). Requirement of rescue analgesia in both the study groups was similar (P > 0.05). Both study drugs were well tolerated.

Conclusions:

OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain.     

Tratamiento del dolor irruptivo con fentanilo sublingual en pacientes con úlceras cutáneas crónicas

ObjectiveThe aim of the study was to assess the efficacy and safety of opioids in the management of pain in those patients with chronic cutaneous ulcers and breakthrough/incidental pain.Material and methodAn open-label, multicentre, prospective, uncontrolled study was conducted in the pain and ulcer units of 5 hospitals across the Comunidad Valenciana. Eligibility criteria were baseline pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion criteria were cognitive impairment, opioid intolerance, or patient refusal to provide informed consent. The protocol scheduled 5 controls: baseline (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure of the study was the visual analogue scale score during rest, movement and procedures. Opioids were administered for release of the baseline pain, and sublingual fentanyl for breakthrough pain.ResultsA total of 32 patients (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6 visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD 2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain intensity improvement was statistically significant from the first control and at all controls thereafter (P < .001). Nausea was reported by 14 patients (43.8%), drowsiness and constipation by 7 (21.9%), itching by 5 (15.6%), and one (3.1%) reported vomiting.ConclusionsStructured assessment of pain is a key concept in the management of patient with chronic cutaneous ulcers. The results of this study suggest that opioid therapy provides clinically significant pain relief with few adverse effects.     

临床药师在不良反应监测中的实践与体会

目的浅析临床药师在临床实践中开展不良反应监测的工作模式及体会。方法通过对4例典型患者进行药学监护,从正确认识药品不良反应、特殊剂型药物的规范服用、重症患者的用药调整及输液管理等诸方面,阐述临床药师在不良反应监测工作中的切入点。结果临床药师判断出与突发不良反应相关的药物,并采取积极抢救措施,减少了药源性损害。结论临床药师应重点着眼于不良反应报告与监测工作,收集安全性信息,提出相应的药物警戒建议,保障公众用药安全。     

An Outbreak of Breakthrough Infections by the SARS-CoV-2 Delta Variant in a Psychiatric Closed Ward

BackgroundA rapid decline in immunity and low neutralizing activity against the delta variant in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees has been observed. This study describes an outbreak of coronavirus disease 2019 (COVID-19) breakthrough infections caused by the SARS-CoV-2 delta variant in a psychiatric closed ward.MethodsData from epidemic intelligence service officers were utilized to obtain information regarding demographic, vaccination history, and clinical data along with SARS-CoV-2 PCR test results for a COVID-19 outbreak that occurred in a closed psychiatric ward.ResultsAmong the 164 residents, 144 (87.8%) received two doses of vaccines and 137 (95.1%) of them received ChAdOx1 nCoV-19 vaccine. The mean interval between the second vaccination and COVID-19 diagnosis was 132.77 ± 40.68 days. At the time of detection of the index case, SARS-CoV-2 had spread throughout the ward, infecting 162 of 164 residents. The case-fatality ratio was lower than that in the previously reported outbreak before the vaccination (1.2%, 2/162 vs. 6.9%, P = 0.030). Prolonged hospitalization occurred in 17 patients (11.1%) and was less prevalent in the vaccinated group than in the unvaccinated group (8.5% vs. 25.0%, P = 0.040).ConclusionThe findings of this study highlight that while vaccination can reduce mortality and the duration of hospitalization, it is not sufficient to prevent an outbreak of the SARS-CoV-2 delta variant in the present psychiatric hospital setting.     

Clinico-Epidemiological Profile of Breakthrough COVID-19 Infection among Vaccinated Beneficiaries from a COVID-19 Vaccination Centre in Bihar,India

BackgroundWhen the whole world is fighting in an unprecedented pace against COVID-19 pandemic, the breakthrough COVID infections poise to dampen the rapid control of the same. We carried out this project with two objectives; first, to estimate the proportion of breakthrough COVID-19 infection among completely vaccinated individuals and second, to study the clinico-epidemiological profile of breakthrough COVID-19 infections among them.MethodsThis cross-sectional analytical study was conducted among 2703 fully vaccinated individuals from AIIMS, Patna COVID Vaccination Centre (CVC), Bihar, India. The participants were selected randomly using a systematic sampling technique from the list of beneficiaries maintained at the CVC. Telephonic interviews were made to collect the information by trained data collectors.ResultsA total of 274 fully vaccinated beneficiaries [10.1% (95% CI: 9.1%, 11.4%)] were diagnosed with breakthrough COVID-19 infection. The infections were more among males (10.4%) and the individuals aged ≤29 years (12.5%). The beneficiary categories, the healthcare-worker and the frontline-worker, were identified as predictors of the breakthrough COVID infections. Only one in three participants had adopted adequate COVID appropriate behaviour following the full vaccination. The majority of the breakthrough infections occurred during the second wave of COVID-19. The majority of the individuals with breakthrough infections were asymptomatic and no death was reported among them.ConclusionOne in every ten fully vaccinated individuals can get the breakthrough COVID infections. The healthcare-worker and the frontline-worker had independent risk of getting the breakthrough infections. Very few with breakthrough infections were serious and no death was reported among them.     

综合护理干预联合吗啡应用对晚期肿瘤患者爆发痛的效果观察

目的 观察护理干预联合吗啡对减轻晚期肿瘤患者爆发痛的效果.方法 将108例有爆发痛的晚期肿瘤患者随机分为对照组与实验组各54例.实验组在吗啡治疗疼痛的同时,进行综合护理干预;对照组只用吗啡治疗.用数字评分法(NRS)对两组患者爆发痛护理干预前后的疼痛强度进行评估,并记录评分值.结果 干预前两组患者NRS评分实验组和对照组分别为(8.2±1.05)和(8.15±0.8)分,组间差异无统计学意义(P＞0.05).干预后实验组和对照组NRS评分分别为(2.25±0.58)和(4.0±0.72)分,实验组患者爆发痛评分值低于对照组,差异有统计学意义(P＜0.05).结论 肿瘤患者在进行躯体治疗的同时,实施有效的综合护理干预能够更好地减轻晚期肿瘤患者的爆发痛.     

Inhibiting the nucleus tractus solitarii extends cerebrovascular autoregulation during hypertension

Autoregulation maintains cerebral blood flow near basal levels as blood pressure increases, but vasodilation, breakthrough, occurs when hypertension exceeds the autoregulatory range. Loss of breakthrough after transection of baroreceptor nerves suggests that breakthrough is neurally mediated. We hypothesize that central baroreflex interruption will likewise prevent breakthrough. In treated rats, injections of lidocaine into the nucleus tractus solitarii blocked breakthrough and the baroreflex. Therefore, central, like peripheral, baroreflex interruption extends autoregulation during hypertension.     

Effect of long-term progestin treatment on endometrial vasculature in normal cycling mice

The aim of this study was to develop a mouse model to investigate the effects of long-term progestin-only exposure on endometrial vascular structure. Normal cycling mice received Silastic implants containing either medroxyprogesterone acetate (MPA) or levonorgestrel (LNG) and were dissected after 1, 3 or 6 weeks. Endometrial vascular density increased significantly within 1 week of MPA (482 +/- 40.2 vessels/mm2) or LNG (440 +/- 26.5 vessels/mm2) treatment compared with normal cycling mice (293 +/- 10.5 vessels/mm2). MPA increased stromal cell density within 1 week of treatment (13813 +/- 1450 cells/mm2) compared with normal cycling mice (8256 +/- 928 cells/mm2). However, although LNG significantly increased stromal cell density overall, the increase did not reach significance within the individual weeks examined. There was no significant change in the ratio of vascular to stromal cell density among treated and normal cycling mice. Epithelial cell height significantly decreased within 1 week of LNG (17.6 +/- 1.3 microm) treatment compared with normal cycling mice (23.5 +/- 1.3 microm); epithelial cell height also decreased within 1 week of MPA treatment (16.6 +/- 2.1 microm), although this did not reach statistical significance. VEGF immunostaining increased significantly in luminal epithelium after MPA or LNG treatment, and in glandular epithelium after LNG treatment. These observations are similar to those reported in human endometrium, suggesting that this mouse model may facilitate further investigations into breakthrough bleeding due to long-term progestin use.