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Expression of concern regarding paper by Park et al, published on 25 June 2015: “Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015”, Euro Surveill.
It has been brought to our attention that some of the authors may not have been informed about the content of the above paper.
A prospective infection surveillance study was carried out among residents of seven nursing homes in and around Berlin, Germany, from October 2008 to August 2009. Clusters of infectious diseases can have major impact on healthcare facilities resulting in increased morbidity and mortality [1].
Up to 60% of residents can be affected during outbreaks in nursing homes [6,7], many of whom develop complications or suffer functional decline [8].
A wide range of viruses have been identified as aetiological agents of ARD in nursing homes [11], including influenza viruses, respiratory syncytial virus, rhinovirus and human metapneumovirus. Prospective surveillance for infections was carried out among residents of seven nursing homes in and around Berlin. In each of seven nursing homes in Germany, a prospective infection surveillance study was carried out over a period of six months between October 2008 and August 2009. At the beginning of the study, we collected for all participants demographic data, diagnosis of chronic diseases, score on the Braden scale (a multidimensional scoring system assessing a person's functional status in order to estimate the risk of developing pressure ulcers) and information on currently used medical devices such as urinary catheters.
Infections were identified either by the attending physician or by abstracting data from nursing files using previously described definitions for infection surveillance in long-term care patients  (McGeer criteria) [18].
A cluster was defined as infections of the same type according to the applied criteria for infection (McGeer criteria) affecting at least 10% of the study population within a time span of 21 days. One cluster of respiratory infections was characterised by a high attack rate and case fatality rate. Seven nursing homes participated in this prospective cohort study, all situated in or near Berlin.
Seven clusters could be identified in four of the seven observed nursing homes (Table 2), three ARD clusters, three GID clusters and one of infectious conjunctivitis. The first case of respiratory infection among the residents of nursing home B occurred on 11 January 2009. Seventeen of the 29 residents had received seasonal influenza immunisation in the autumn of 2008. Concomitantly with this respiratory cluster, a cluster of gastrointestinal disease occurred in nursing home B, which affected both staff and residents. Although clusters of infections in nursing homes have been widely described, the systematic recognition of increased rates of certain diseases is hampered by the lack of established infection surveillance systems. Only one cluster of gastrointestinal disease was investigated microbiologically and norovirus was detected in the stool of three symptomatic residents. Due to the high number of affected residents as well as the severity of the disease, one outbreak of ARD was investigated in more detail. Since any intervention including systematic microbiological analyses was beyond the scope of this study, aetiological diagnosis could only be based upon diagnostic steps taken by the attending physicians. Infection surveillance based on routine nursing files can detect clusters of infections, enabling staff to report them to infection control professionals quickly. Clinical features of infections are often unspecific and cannot usually be used to identify aetiology [2]. Control measures are most effective if initiated early during the course of an cluster [5,25] and early symptomatic treatment is crucial in the treatment of acute respiratory tract infection and severe gastrointestinal disease. Disclaimer: The opinions expressed by authors contributing to Eurosurveillance do not necessarily reflect the opinions of the European Centre for Disease Prevention and Control (ECDC) or the editorial team or the institutions with which the authors are affiliated. Oxaliplatin is an Antineoplastic agent and platinum coordination complex that is FDA approved for the treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor, advanced colorectal cancer. Prior to subsequent therapy cycles, patients should be evaluated for clinical toxicities and recommended laboratory test.
A final dilution must never be performed with a sodium chloride solution or other chloride-containing solutions.
The solution must be further diluted in an infusion solution of 250-500 mL of 5% Dextrose Injection, USP. Oxaliplatin is incompatible in solution with alkaline medications or media (such as basic solutions of 5-fluorouracil) and must not be mixed with these or administered simultaneously through the same infusion line. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration and discarded if present. Needles or intravenous administration sets containing aluminum parts that may come in contact with Oxaliplatin should not be used for the preparation or mixing of the drug. There is limited information regarding Off-Label Guideline-Supported Use of Oxaliplatin in adult patients. There is limited information regarding FDA-Labeled Use of Oxaliplatin in pediatric patients. There is limited information regarding Off-Label Guideline-Supported Use of Oxaliplatin in pediatric patients. There is limited information regarding Off-Label Non–Guideline-Supported Use of Oxaliplatin in pediatric patients. An acute, reversible, primarily peripheral, sensory neuropathy that is of early onset, occurring within hours or one to two days of dosing, that resolves within 14 days, and that frequently recurs with further dosing.The symptoms may be precipitated or exacerbated by exposure to cold temperature or cold objects and they usually present as transient paresthesia, dysesthesia and hypoesthesia in the hands, feet, perioral area, or throat. Peripheral sensory neuropathy was reported in adjuvant patients treated with the Oxaliplatin combination with a frequency of 92% (all grades) and 13% (grade 3). Oxaliplatin has been associated with pulmonary fibrosis (<1% of study patients), which may be fatal. Standard monitoring of the white blood cell count with differential, hemoglobin, platelet count, and blood chemistries (including ALT,AST, bilirubin and creatinine) is recommended before each Oxaliplatin cycle. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
More than 1100 patients with stage II or III colon cancer and more than 4,000 patients with advanced colorectal cancer have been treated in clinical studies with Oxaliplatin.
Although specific events can vary, the overall frequency of adverse reactions was similar in men and women and in patients <65 and ?65 years. Both 5-fluorouracil and Oxaliplatin are associated with gastrointestinal and hematologic adverse reactions.
Adverse reactions were similar in men and women and in patients <65 and ?65 years, but older patients may have been more susceptible to diarrhea, dehydration, hypokalemia, leukopenia, fatigue and syncope. Adverse reactions were similar in men and women and in patients <65 and ?65 years, but older patients may have been more susceptible to dehydration, diarrhea, hypokalemia and fatigue. The following tables list the hematologic changes occurring in ?5% of patients, based on laboratory values and NCI grade, with the exception of those events occurring in adjuvant patients and anemia in the patients previously untreated for advanced colorectal cancer, respectively, which are based on AE reporting and NCI grade alone.
The incidence of gastrointestinal adverse reactions in the previously untreated and previously treated patients appears to be similar across cycles. Hepatotoxicity (defined as elevation of liver enzymes) appears to be related to Oxaliplatin combination therapy. The following adverse reactions have been identified during post-approval use of Oxaliplatin. Based on direct interaction with DNA, Oxaliplatin may cause fetal harm when administered to a pregnant woman. Pregnant rats were administered oxaliplatin at less than one-tenth the recommended human dose based on body surface area during gestation days 1–5 (pre-implantation), 6–10, or 11–16 (during organogenesis). There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oxaliplatin in women who are pregnant.
The pharmacokinetic parameters of ultrafiltrable platinum have been evaluated in 105 pediatric patients during the first cycle. No significant effect of age on the clearance of ultrafilterable platinum has been observed. Patients ? 65 years of age receiving the Oxaliplatin combination therapy experienced more grade 3–4 granulocytopenia than patients < 65 years of age (45% versus 39%).
There is no FDA guidance on the use of Oxaliplatin with respect to specific gender populations.
There is no FDA guidance on the use of Oxaliplatin with respect to specific racial populations.
The exposure (AUC) of unbound platinum in plasma ultrafiltrate tends to increase in renally impaired patients. There is no FDA guidance on the use of Oxaliplatin in women of reproductive potentials and males.
Caution and close monitoring should be exercised when Oxaliplatin is administered to patients with renal impairment.
Patients suspected of receiving an overdose should be monitored, and supportive treatment should be administered. Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand.

The reactive oxaliplatin derivatives are present as a fraction of the unbound platinum in plasma ultrafiltrate. Interpatient and intrapatient variability in ultrafilterable platinum exposure (AUC0–48hr) assessed over 3 cycles was moderate to low (23% and 6%, respectively). Clusters of infectious diseases in German nursing homes – observations from a prospective infection surveillance study, October 2008 to August 2009.
Nursing homes pose unique challenges in early cluster identification and control as elderly people often present with atypical signs of disease.
The spectrum of bacteria causing outbreaks of pneumonia in nursing homes includes Bordatella pertussis, Streptococcus pneumoniae and Legionella pneumophila. As a considerable number of infections turned out to occur in clusters, these clusters are described here in more detail, and we estimate their impact on total infection rates.
Residents’ charts were reviewed for signs and symptoms of infection every second week by two external doctors. As the case definitions of influenza-like illness, bronchitis and pneumonia are similar these diagnoses were combined as ARD.
In a retrospective cohort study of that cluster, additional data for all residents living in the affected nursing home were collected using routine documentation.
Incidences of infection were calculated as the number of infections per 1,000 resident days (rd), (days that a resident is actually present in the home and not infected).
The mean age of residents was 85 years (median 86 years, range 31-104 years), and 410 (80%) were female. Clusters of other diseases such as skin infections or urinary tract infections could not be identified. Attack rates based on case finding using McGeer criteria varied between 11% and 60% (Table 2).
The population of the affected nursing home (B) consisted of 29 very old women (mean age 91 years). In total, 19 of 29 residents fulfilled the case definition, all within seven days after onset of disease in the index case. There was no significant difference in the number of cases or case fatality rate between the vaccinated and the unvaccinated group. Furthermore, systematic laboratory investigations of infections or clusters of infection in the context of prospective infection surveillance studies are rare in this setting.
In this nursing home (G), medical care was provided by a nursing home-based physician, for whom it may be easier to recognise higher rates of infection among the residents. Although no aetiological agent was identified, we assume that viral pulmonary disease was the most probable cause of the cluster, based on the rapid spread of disease, the high case fatality rate and the fact that both residents and staff members were affected.
In addition, the evaluation of infection control measures during a cluster was beyond the scope of this study. However, there is need to educate staff at the point of care in order to fully take advantage of this possibility [22,23]. Therefore nursing homes need to have plans in place in the event of a cluster including pre-established access to rapid laboratory testing for aetiological agents causing respiratory and gastrointestinal infections as well as structures enabling them to quickly initiate appropriate antimicrobial therapies and infection control measures [24]. Infectious disease outbreaks in nursing homes: an unappreciated hazard for frail elderly persons.
Rhinovirus outbreak in a long term care facility for elderly persons associated with unusually high mortality.
Outbreak of pneumonia in a long-term care facility: antecedent human parainfluenza virus 1 infection may predispose to bacterial pneumonia. Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. Etiological role of viruses in outbreaks of acute gastroenteritis in The Netherlands from 1994 through 2005. An efficient program for computing conditional maximum likelihood estimates and exact confidence limits for a common odds ratio. Control of influenza in the long-term-care facility: a review of established approaches and newer options.
Neither ECDC nor any person acting on behalf of ECDC is responsible for the use that might be made of the information in this journal.
It should not be used as a substitute for any medical professional opinion, advice or prescribed medication nor should it serve as diagnosis or treatment of health problems. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider.
For advanced disease, treatment is recommended until disease progression or unacceptable toxicity.
Premedication with antiemetics, including 5-HT3 blockers with or without dexamethasone, is recommended. Prolongation of infusion time for Oxaliplatin from 2 hours to 6 hours may mitigate acute toxicities. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. The infusion line should be flushed with 5% Dextrose Injection, USP prior to administration of any concomitant medication. These allergic reactions which can be fatal, can occur within minutes of administration and at any cycle, and were similar in nature and severity to those reported with other platinum-containing compounds, such as rash, urticaria, erythema, pruritus, and, rarely, bronchospasm and hypotension.
Jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and a feeling of chest pressure have also been observed. Ice (mucositis prophylaxis) should be avoided during the infusion of Oxaliplatin because cold temperature can exacerbate acute neurological symptoms.
At the 28-day follow-up after the last treatment cycle, 60% of all patients had any grade (Grade 1=40%, Grade 2=16%, Grade 3=5%) peripheral sensory neuropathy decreasing to 39% at 6 months follow-up (Grade 1=31%, Grade 2=7%, Grade 3=1%) and 21% at 18 months of follow-up (Grade 1=17%, Grade 2=3%, Grade 3=1%). Information regarding reversibility of neuropathy was not available from the trial for patients who had not been previously treated for colorectal cancer. Signs and symptoms of RPLS could be headache, altered mental functioning, seizures, abnormal vision from blurriness to blindness, associated or not with hypertension. The most common adverse reactions in patients with stage II or III colon cancer receiving adjuvant therapy were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue and stomatitis. The adverse reaction profile in this study was similar to that seen in other studies and the adverse reactions in this trial are shown in the tables below. When Oxaliplatin is administered in combination with 5-fluorouracil, the incidence of these events is increased.
This table does not include hematologic and blood chemistry abnormalities; these are shown separately below. The following tables list the clinical chemistry changes associated with hepatic toxicity occurring in ?5% of patients, based on adverse reactions reported and NCI CTC grade for adjuvant patients and patients previously untreated for advanced colorectal cancer, laboratory values and NCI CTC grade for previously treated patients.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Oxaliplatin caused developmental mortality (increased early resorptions) when administered on days 6–10 and 11–16 and adversely affected fetal growth (decreased fetal weight, delayed ossification) when administered on days 6–10.
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Oxaliplatin, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Oxaliplatin has been tested in 2 Phase 1 and 2 Phase 2 trials in 235 patients ages 7 months to 22 years with solid tumors (see below) and no significant activity observed.
The same efficacy improvements in response rate, time to tumor progression, and overall survival were observed in the ?65 year old patients as in the overall study population. In addition to thrombocytopenia, the anticipated complications of an Oxaliplatin overdose include hypersensitivity reaction, myelosuppression, nausea, vomiting, diarrhea and neurotoxicity. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. In combination with , oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models [HT29 (colon), GR (mammary), and L1210 (leukemia)]. Oxaliplatin is an organoplatinum complex in which the platinum atom is complexed with 1,2-diaminocyclohexane(DACH) and with an oxalate ligand as a leaving group.
Active surveillance was carried out using pre-established case definitions of infections in nursing homes (McGeer criteria). They are also likely to develop a more severe course of disease, often requiring hospitalisation [2-4]. Multiple routes of transmission have been identified in bacterial outbreaks such as staff-to-resident transmission and transmission via contaminated environment.
In infectious GID, viruses frequently are the causative agents, most notably norovirus, but also bacterial outbreaks of gastrointestinal disease have been reported [14-16].
The project was introduced during lectures for nursing home personnel responsible for hygienic matters. Antibiotic treatment and microbiological results that had been ordered by the attending physician were documented to further characterise infections.

The 95% confidence interval (CI) for infection rates was calculated using Mid-P exact test with Miettinen's modification as described elsewhere [19]. The contribution of infections occurring in clusters to the overall infection incidence rate was 19%. They were moderately impaired according to the Braden scale (n=21 at low risk), with few underlying diseases. When surveilling the population of seven nursing homes for the development of infections we identified seven clusters of infections including one with high attack rate and mortality.
It can be assumed that the very high age of the population (mean age 91 years) has contributed to the high mortality rate. As documentation was not standardised and the vigilance of nurses was not influenced in an active way infections with minor symptoms may have been underreported, which may explain the relative low incidence of common cold. Training should aim at standardising symptom documentation and at the correct evaluation of the documentation by designated staff members. Identifying pathogens for gastrointestinal disease is important as some pathogens may require modification of hygienic standards such as improved environmental cleaning in the case of C.
As clusters in nursing homes can occur throughout the year, continuous vigilance is needed, but it may be of additional benefit to intensify surveillance during the winter months.
The symptoms associated with hypersensitivity reactions reported in the previously untreated patients were urticaria, pruritus, flushing of the face, diarrhea associated with oxaliplatin infusion, shortness of breath, bronchospasm, diaphoresis, chest pains, hypotension, disorientation and syncope.
In this study, one patient died from eosinophilic pneumonia in the Oxaliplatin combination arm.
20%) was observed more commonly in the Oxaliplatin combination arm than in the control arm. The most common adverse reactions in previously untreated and treated patients were peripheral sensory neuropathies, fatigue, neutropenia, nausea, emesis, and diarrhea. Grade 3 and 4 events were reported in 35% and 18% of the patients previously untreated for advanced colorectal cancer, respectively.
Reproductive toxicity studies in rats demonstrated adverse effects on fertility and embryo-fetal development at maternal doses that were below the recommended human dose based on body surface area.
Administration of oxaliplatin to male and female rats prior to mating resulted in 97% post-implantation loss in animals that received approximately one-seventh the recommended human dose based on the body surface area. Patients had metastatic or unresectable solid tumors mainly neuroblastoma and ganglioneuroblastoma.
Viral outbreaks preceding outbreaks of bacterial pneumonia have been described [12], leading to prolonged illness.
Clostridium difficile seems to play an increasing role in diarrhoeal disease in nursing homes and outbreaks have been reported [17]. The study was observational only and no attempt was made to influence the routine documentation of physicians or nurses. Seventy-nine of the 506 participating residents died during the study and nine moved away from their nursing home. Some 134 residents (26%) had diabetes mellitus and 62 (12%) of them were insulin-dependant. Some 31 ARD infections (36%), 38 GID infections (31%) and five conjunctivitis infections (14%) occurred in clusters. Six of the affected residents died, all within 10 days after presentation of first signs of illness. The first three cases of ARD among staff members occurred before the first case among residents. The spectrum of clusters included acute respiratory disease, gastrointestinal disease and conjunctivitis. As resident-to-resident contact was limited within the institution, staff-to-resident transmission could have been an important mode of transmission [21].
During clusters staff awareness could be higher, resulting in increased reporting and documentation of symptoms. In our experience the weekly surveillance of nursing files takes a few hours and could be performed by a quality assurance representative or a nurse in charge of hygienic matters.
These reactions are usually managed with standard epinephrine, corticosteroid, antihistamine therapy, and require discontinuation of therapy.
The majority of the patients (80%) who developed grade 3 persistent neuropathy progressed from prior Grade 1 or 2 events.
Grade 3 and 4 events were reported in 27% and 17% of previously treated patients, respectively. Since cold temperature can exacerbate acute neurological symptoms, ice (mucositis prophylaxis) should be avoided during the infusion of Oxaliplatin.
If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. The rates of overall adverse reactions, including grade 3 and 4 events, were similar across and within arms in the different age groups in all studies.
Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). We focus here on clusters of acute respiratory disease (ARD) and gastrointestinal disease (GID) as these seem to predominate in this setting [1]. Other infectious diseases that have caused outbreaks in long-term care facilities include conjunctivitis, scabies and skin infections [1]. We systematically recorded the microbiological probes ordered by the attending physicians and to our knowledge, only one cluster (G-GID) was investigated further with microbiological methods.
Seven residents had to be hospitalised and another eight received systemic antibiotic treatment as prescribed by their general practitioner. This is in accordance with the patterns described in the published literature [1,2,7,11,13,14]. As exact information concerning start and duration of illness among staff members could not be obtained, we were not able to fully investigate this question. Thus the contribution of clustered infections to overall infection rates could have been overestimated. Furthermore, knowing the aetiological agent will direct the search for the source of an outbreak. Except where otherwise stated, all manuscripts published after 1 January 2016 will be published under the Creative Commons Attribution (CC BY) licence.
In case of unexplained respiratory symptoms such as non-productive cough, dyspnea, crackles, or radiological pulmonary infiltrates, Oxaliplatin should be discontinued until further pulmonary investigation excludes interstitial lung disease or pulmonary fibrosis. Changes noted on liver biopsies include: peliosis, nodular regenerative hyperplasia or sinusoidal alterations, perisinusoidal fibrosis, and veno-occlusive lesions. Women of childbearing potential should be advised to avoid becoming pregnant and use effective contraception while receiving treatment with Oxaliplatin. The incidence of diarrhea, dehydration, hypokalemia, leukopenia, fatigue and syncope were higher in patients ?65 years old.
Furthermore, inter-facility comparison of infection rates cannot be performed because documentation was not standardised and the periods of observation (seasonality) were different. You are free to share and adapt the material, but you must give appropriate credit, provide a link to the licence, and indicate if changes were made. Drug-related deaths associated with platinum compounds from anaphylaxis have been reported. In total 511 residents were observed during 74,626 resident days (rd), and 393 infections occurred in 243 participants, giving an overall incidence of infection of 5.3 per 1,000 rd. The study included only residents who were in a stable medical condition, did not need constant specialised care (e.g. In the remaining nursing homes medical care was provided by various community-based general practitioners. Seven clusters involving 74 infections in 57 residents were observed: three of acute respiratory disease, three of acute gastrointestinal disease and one of conjunctivitis. Residents newly admitted to the nursing home during the observation period were also asked to participate (open cohort study).
In total 282 (55%) could walk independently, 187 (37%) were dependant on a wheelchair and 40 (8%) were bedridden.
Clusters occurred frequently in the observed nursing homes and could be detected by infection surveillance based on routine documentation.

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