Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data

BackgroundThe ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction.MethodsThis is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression.ResultsThere were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5–13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3–23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0–91.8) and 34.8 (95% CI 23.7–44.4), respectively.ConclusionPCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE.     

Old Weapon for New Enemy: Drug Repurposing for Treatment of Newly Emerging Viral Diseases

正Emerging and re-emerging viral diseases are a public health concern for the whole world and pose a major threat to human health and life. In last decades, numerous major outbreaks of emerging and re-emerging viral diseases with gross public concern were recorded in different regions,including Ebola in western Africa, Zika in South America,     

Burden of pneumonia and meningitis caused by Streptococcus pneumoniae in China among children under 5 years of age: a systematic literature review

BACKGROUND AND METHODS: To understand the burden and epidemiology of Streptococcus pneumoniae disease among children between 1 and 59 months of age in China, we conducted a review of literature published between 1980 and 2008 applying standardized algorithms. Because of the absence of population-based surveillance for pneumococcal disease (PD), we identified all-cause pneumonia, bacteremia and meningitis burden, syndromes most commonly associated with S. pneumoniae, and applied the proportion of disease attributable to S. pneumoniae from studies that determined the etiology of these three syndromes to calculate PD burden. Because of the microbiologic difficulties in identifying S. pneumoniae-attributable pneumonia which likely underestimates the pneumonia burden, we also used the proportion obtained from vaccine efficacy trials. RESULTS: Between 1980 and 2008, there were 12,815 cases/100,000/year of all-cause pneumonia among children between 1 month and 59 months, with 526 deaths/100,000 annually. There were 14 meningitis cases/100,000/year. We estimate that as of 2000, there were 260,768 (113,000 to 582,382) and 902 (114-4,463) cases of pneumococcal pneumonia and meningitis, respectively with 10,703 (4,638-23,904) and 75 (9-370) pneumococcal pneumonia and meningitis deaths, respectively. Pneumococcal pneumonia cases and deaths were more than two-fold higher, 695,382 (173,845-1,216,918) and 28,542 (7,136-49,949), respectively, when parameters from efficacy trials were used. Serotypes 19F, 19A and 14 were the most common serotypes obtained from pneumonia/meningitis patients. Currently available vaccines are expected to cover 79.5% to 88.4% of the prevalent serotypes. With high antibiotic resistance, introducing pneumococcal vaccines to the routine immunization program should be considered in China. Population-based studies are warranted.     

Fulminant Mycoplasma pneumoniae pneumonia.

The frequency of fulminant pneumonia due to Mycoplasma pneumoniae is relatively rare despite the high prevalence of Mycoplasma species infection in the general population. We recently encountered such a case and have reviewed the English-language literature on cases of M pneumoniae pneumonia that have resulted in respiratory failure or death. Due to host factors or on epidemiologic grounds, fulminant cases seem to be more common in young healthy adults, in males, and possibly in smokers among the 46 patients we found. An enhanced host cellular immune response may be responsible for the development of severe cases. A spectrum of small airways disease is characteristic, including cellular bronchiolitis and bronchiolitis obliterans with and without organizing pneumonia. Based largely on anecdotal experience, corticosteroid use may be salutary in patients with respiratory failure. For reasons that are not well known, the incidence of pulmonary thromboembolism is increased in fatal cases.     

Comparison of Surgery and Prolonged Spironolactone Therapy in Patients with Hypertension,Aldosterone Excess,and Low Plasma Renin

The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin. In the series as a whole a highly significant reduction in both systolic and diastolic pressures was achieved, with no evidence of escape from control during therapy lasting several years in some cases. The drug was equally effective in controlling blood pressure in patients with and without adrenocortical adenomata. Occasional unresponsive patients were encountered in both groups; pretreatment blood urea levels in these were significantly higher than in the responsive patients. The hypotensive effect of spironolactone usually predicted the subsequent response to adrenal surgery.Spironolactone in all cases corrected plasma electrolyte abnormalities; significant increases in total exchangeable (or total body) potassium and significant reductions in total exchangeable sodium, total body water, extracellular fluid, and plasma volumes were seen. Plasma urea rose during treatment and there was a slight fall in mean body weight. Significant increases in peripheral venous plasma renin and angiotensin II concentrations occurred during treatment.In two patients no increase in aldosterone secretion rate was found during treatment, although plasma aldosterone rose in three of four subjects studied.Severe side effects were rare; in only two of the 67 patients did the drug have to be stopped.In addition to its routine preoperative use, spironolactone can now be advised as long-term therapy in selected patients.     

Hypothermia in the Treatment of Critical Head Injury

Because of the beneficial effect on the character and mortality of experimental brain injury, 21 patients with critical brain injury (thought to be incompatible with life using standard methods of treatment) were subjected to artificial hypothermia (28°-36° C.) for two to 10 days. Nine died and 12 survived, but six of the survivors are permanent invalids with dementia. The hazards are staphylococcal pneumonia, which occurred in eight cases and contributed to all the deaths, and gastrointestinal ulceration with bleeding and perforation, which was fatal in another. The results in patients with clots did not differ from those without. Youth was the only common factor in the successful cases. Prognosis was hopeless in the presence of large fixed pupils. About one in four of these critical cases will fare well, but it is evident that a large proportion have such gross or microscopic tearing of deep cerebral structures that in the event of survival there will be severe mental and physical handicaps.     

101例肺炎死亡病例分析

目的：探讨成年肺炎死亡病例的特征,以提高救治率。方法：利用医院住院病案管理系统软件及人工收集我院2008年1月1日-2011年4月26日的全部成年肺炎死亡病例临床资料,共计101例,对其进行回顾性分析。结果：101例观察病例中男性共计71例（占70_30％）,女性共计30例（占29．70％）,大于65岁者共计95例（占94．06％）,44-58岁者共计6例（占5．9％）,平均年龄80．30岁。单侧肺部病变22例（占21．78％）,双侧肺部病变79例（占78．22％）,观察病例均伴有多种基础病及并发症,并且多数病例存在多种致病茵感染及多重耐药茵感染。结论：成年肺炎死亡的发生与患者年龄（65岁以上）、性别（男性）、双侧肺部病变、基础病及并发症、多种致病茵感染及多重耐药茵感染等因素密切相关。     

Intrathoracic muscle flaps: a 10-year experience in the management of life-threatening infections

From 1977 to 1987, 87 consecutive patients underwent intrathoracic muscle transposition. Indications for the operation were bronchopleural fistula, postpneumonectomy empyema, perforation of the heart or great vessels, esophageal fistula, tracheal fistula, empyema, and prophylactic reinforcements of the airway. Of the 118 muscles transposed, the serratus anterior was used in 48 patients, the latissimus dorsi in 33, the pectoralis major in 26, and other muscles in 11. Depending on the wound status at the time of muscle transposition, the chest either was left open for dressing changes or was closed primarily. The number of operations per patient ranged from 1 to 16 (median 2). There were 13 operative deaths (14.9 percent). The follow-up period ranged from 3.9 to 130.9 months (median 28.3 months). Overall results were excellent in 65 patients (74.7 percent). There was no difference in results when considered according to treatment indication. We conclude that when there is an actual or potential leak of the tracheobronchial tree, heart and great vessels, or intrathoracic gastrointestinal tract, intrathoracic muscle transposition can be a lifesaving adjunct.     

Burden of Severe Pneumonia,Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates

The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results highlight the need to improve access to care and increase coverage and equity of pneumonia preventing vaccines in states with high pneumonia burden.     

mRNA Vaccines: Possible Tools to Combat SARS-CoV-2

正Coronaviruses are large, enveloped, positive-strand RNA viruses. Several coronaviruses are pathogenic in humans,including severe acute respiratory syndrome coronavirus(SARS-CoV), Middle East respiratory syndrome coronavirus(MERS-CoV) and this novel virus, SARS-CoV-2,     

Death from asthma.

The factors associated with the deaths of 31 asthma patients were examined. The subjects, whose deaths occurred in the period 1967 through 1979, had all received some care at the Hospital for Sick Children in Toronto, but only nine died there. The greatest single cause of death was the inappropriate use of beta-agonists, with or without the concurrent use of epinephrine. In seven patients an asthma attack that occurred outside hospital progressed so rapidly that there was insufficient time for them to obtain adequate therapy. In five cases the assessment of the patient''s condition or the therapy recommended by the attending physician appeared to have been inadequate. Two patients suffered an acute attack in hopital and did not respond to treatment that appeared to have been adequate. In six cases the available information was insufficient to indicate the cause of death. Over half (18) of the deaths occurred in teenagers. Various ways of preventing death from asthma are discussed, including better education of physicians and patients, adequate management of factors that provoke bronchospasm, sufficient follow-up -- especially in teenagers -- and the use of approaches with teenagers that encourage better compliance.     

Clinical and bronchoscopic diagnosis of suspected pneumonia related to AIDS.

In a series of 25 patients with suspected pneumonia related to the acquired immune deficiency syndrome (AIDS) the first 12 underwent routine fibreoptic bronchoscopy and bronchoalveolar lavage with or without transbronchial biopsy before treatment. Eight were found to have Pneumocystis carinii pneumonia and had typical clinical presentations with a prolonged history of symptoms, including a dry cough, and bilateral diffuse alveolar or interstitial shadowing in chest radiographs. Among the subsequent 13 cases, 11 had similar clinical presentations and were treated with high doses of intravenous co-trimoxazole without bronchoscopy first. Bronchoscopy was performed in those who deteriorated at any stage or failed to improve by the fifth day of treatment. Nine patients recovered and were discharged. In two patients who died P carinii pneumonia was confirmed in one but no diagnosis was made in the other. The early and late survival in both groups of patients was similar. In patients at high risk for AIDS who have clinical features suggestive of P carinii pneumonia starting treatment with intravenous co-trimoxazole is justified. The few patients who deteriorate or fail to respond should undergo bronchoscopy with bronchoalveolar lavage and transbronchial biopsy.     

SURGICAL TREATMENT OF INFANTILE HYDROCEPHALUS

The operation of endoscopic coagulation of the choroid plexuses for the relief of infantile hydrocephalus is now 18 years old. Nearly a hundred cases have been reported and the indications and procedure are well standardized. Several patients have grown up apparently normally from the earliest series of operations.In a recent series of 20 operations performed on ten patients in the past ten years, there have been no deaths attributable to the procedure. The operation has substantially decreased the pressure in all cases, and has brought it within normal limits in all cases in which it was performed before the head became grossly enlarged.The mentality has improved following relief of pressure in all cases. When the operation was performed before deterioration began, the results were uniformly excellent.     

SARS-CoV对幼年和成年布氏田鼠的感染研究

采用鼻腔喷雾法(CCID50=105.7)研究了SARS冠状病毒(SARS-CoV)对成年和幼年布氏田鼠的感染效果.成年动物攻毒后出现死亡,表现为口鼻有出血,肠道出血;肺组织呈出血性间质性肺炎改变,肝、脾、肾、胰腺组织均呈淤血性改变;存活动物肺组织呈间质性肺炎,局灶出血及肺气肿改变,其他脏器未见明显病变.幼年动物攻毒后未见死亡但行动较为迟缓,主要脏器未见明显异常;早期肺组织有局限性肺炎改变,且病毒分离为阳性;同居对照组的一只动物有肺组织局灶性肺炎.结果表明,SARS-CoV可以很强地感染布氏田鼠;成年布氏田鼠比幼年动物对SARS-CoV更敏感;布氏田鼠有望成为一种比较理想的小型SARS动物模型。     

Combined surgical approach to carotid and coronary artery disease

The aim of this study was to compare two different surgical approaches to patients with coexistent significant carotid and coronary artery obstruction. Patients were treated with combined operation of carotid endarterectomy and coronary artery bypass grafting (CEA/CABG). The first group of patients underwent the CABG procedure with the cardiopulmonary bypass (CPB) on arrested heart and the second group without the CPB on a beating heart--off pump. Between May 15 1998, and October 9 2003, thirty-five consecutive patients underwent the combined procedure. In both groups there were no cases of transient or permanent perioperative neurological events. Overall, early mortality was 5.6%. The incidence of a perioperative myocardial infarction was 5.5%. In the follow-up period there were no cases of late stroke. According to the presented results in this study, it was found that the combined CEA and CABG is an equally safe and effective procedure performed with or without cardiopulmonary bypass for patients with a severe coexistent carotid and coronary artery disease.     

Revascularization of the Entire Heart by Internal Mammary Artery Implantation,Epicardiectomy and Free Omental Graft

The indications for and the contraindications to total cardiac revascularization are described on the basis of the author''s experience. The combined operation of internal mammary artery implant, epicardiectomy and free omental graft was performed on 62 patients. Of 45 who did not have angina at rest without exciting cause (Grade I) 39 showed improvement; 32 returned to full-time work, 18 of whom had been unable to work before operation. There were two operative deaths. Among the 17 patients who were “bed-chair cripples” (angina at rest without cause-Grade II), there was a 24% operative mortality (four deaths), but 76% of the survivors had marked improvement. Only one of this group had been working full-time preoperatively; now nine are working full-time.     

Estimating pneumonia deaths of post-neonatal children in countries of low or no death certification in 2008

Background

Pneumonia is the leading cause of child deaths globally. The aims of this study were to: a) estimate the number and global distribution of pneumonia deaths for children 1–59 months for 2008 for countries with low (<85%) or no coverage of death certification using single-cause regression models and b) compare these country estimates with recently published ones based on multi-cause regression models.

Methods and Findings

For 35 low child-mortality countries with <85% coverage of death certification, a regression model based on vital registration data of low child-mortality and >85% coverage of death certification countries was used. For 87 high child-mortality countries pneumonia death estimates were obtained by applying a regression model developed from published and unpublished verbal autopsy data from high child-mortality settings. The total number of 1–59 months pneumonia deaths for the year 2008 for these 122 countries was estimated to be 1.18 M (95% CI 0.77 M–1.80 M), which represented 23.27% (95% CI 17.15%–32.75%) of all 1–59 month child deaths. The country level estimation correlation coefficient between these two methods was 0.40.

Interpretation

Although the overall number of post-neonatal pneumonia deaths was similar irrespective to the method of estimation used, the country estimate correlation coefficient was low, and therefore country-specific estimates should be interpreted with caution. Pneumonia remains the leading cause of child deaths and is greatest in regions of poverty and high child-mortality. Despite the concerns about gender inequity linked with childhood mortality we could not estimate sex-specific pneumonia mortality rates due to the inadequate data. Life-saving interventions effective in preventing and treating pneumonia mortality exist but few children in high pneumonia disease burden regions are able to access them. To achieve the United Nations Millennium Development Goal 4 target to reduce child deaths by two-thirds in year 2015 will require the scale-up of access to these effective pneumonia interventions.     

Retrospective study of 1000 deaths from injury in England and Wales

One thousand consecutive deaths from injury in 11 coroner''s districts in England and Wales were reviewed by four independent assessors, who studied necropsy reports to identify deaths in hospital that might have been preventable. Of 514 patients admitted to hospital alive, 102 deaths (20%) were judged by all four assessors to have been potentially preventable. When those cases in which three out of four assessors considered that the death was preventable were added the total rose to 170 (33%). Nearly two thirds of all non-central nervous system deaths were judged to have been preventable. The median age of the 170 patients whose deaths were preventable was 41, and the mean Injury Severity Score was 29. Further analysis suggested that the preventable deaths were principally the result of failure to stop bleeding and prevent hypoxia and the absence of, or delay in, surgical treatment.The results closely parallel those from similar studies from the United States and suggest that there are serious deficiencies in the services for managing severe injury in England and Wales. Debate is needed now on how to correct these deficiencies. In particular, the place of trauma centres must be considered.     

Long-term survival of patients with breast cancer: a study of the curability of the disease.

A retrospective analysis was made of 3878 cases of breast carcinoma first seen in Edinburgh from 1954 to 1964. During this time there was a policy to treat breast cancer by simple mastectomy and x-ray therapy, and over 90% of cases classified as international stages I and II were so treated. The mortality in these women was compared with that in an equivalent normal population using Scottish national age-specific death rates. For every year of follow-up within 20 years of initial treatment there was an excess mortality from all causes. There was an overall excess mortality of 58% among patients with breast cancer 15-20 years after initial treatment, and 20 times more deaths occurred in this period from breast cancer than in a normal population. For patients disease-free after 15 years there was still a 28% excess mortality from all causes. Factors known to be of major prognostic significance for five-year survivorship had less influence than might have been expected when the ratio of observed to expected deaths was considered for longer periods of follow-up. The effect of clinical staging (I, II, or III), though initially marked, largely disappeared by the 10th year of follow-up, and after allowing for age there was no evidence beyond 10 years of an effect on survival of the original stage of the disease. Similarly, the effect of tumour size on survival disappeared after 10 years. Women who were premenopausal at presentation still had a significant excess of deaths in the fourth quinquennium of follow-up. In the menopausal and postmenopausal groups combined there was still a small non-significant excess of deaths from all causes after 15 years but this almost disappeared when patients who had already relapsed were excluded. In terms of overall mortality only patients who have undergone the menopause before presentation and who are disease-free 15 years after primary treatment may prove to be cured by conventional techniques such as simple mastectomy and postoperative radiotherapy.     

Clinical and X-ray features of pneumonia in drug addicts

The authors observed 68 drug addict in-patients, who received treatment for the pneumonia at the Primorski Regional Clinical Hospital and Vladivostok Municipal Clinical Hospital No. 1. The article details the specific features of the pneumonia of these in-patients. It was distinguished the 3 groups of hospital patients with the following characteristic features: patients with the respiratory distress syndrome of the adults; patients with the primary infective endocarditis mainly with the damage of respiratory (right) heart; patients with non-specific pneumonia. The peculiarities of the clinical process with the X-Ray pictures of the disease were also presented. The article identifies the acute beginning of the disease; the strongly pronounced intoxication syndrome; the usual cases of the late going to hospital of those patients; the extensiveness of the damage; the occurrence of the following complications at the early stage: pulmonary destruction, exudative pleurisy, empyema; the long period of the disease process; the development of the extensive pulmonary fibrosis. It was identified the 33.7% lethality for these groups of in-patients, while the average lethality of the in patients treated for pneumonia was 3.3% for the same period of time. The complicated pneumonia process of young patients with the infective endocarditis with damages of respiratory (right) hearts let us suppose their drug addiction.