Stephen G. Ellis, MD

• Professor of Medicine
• Department of Cardiovascular Medicine
• Cleveland Clinic Lerner College of Medicine
• Case Western Reserve University
• Director, Cardiac Catheterization Laboratories
• Cleveland Clinic Foundation
• Cleveland, Ohio

Hyperglycemia increases neurological damage and behavioral deficits from post-traumatic secondary ischemic insults antibiotic while pregnant buy generic zyvox 600mg. Outcomes and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting infection signs zyvox 600mg amex. The prognostic value of blood glucose in diabetic patients with acute myocardial infarction infection after wisdom tooth extraction generic zyvox 600mg otc. Pathogenesis of substantia nigra lesions following hyperglycemic ischemia: changes in energy metabolites bacteria article purchase 600mg zyvox otc, cerebral blood flow, and morphology of pars reticulata in a rat model of ischemia. The neurologic implications of diabetic hyperglycemia during surgical procedures at increased risk for brain ischemia. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Short-term hyperglycemia depresses immunity through nonenzymatic glycosylation of circulating immunoglobulin. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. Usefulness of plasma lactate concentration in the diagnosis of acute abdominal disease. Blood lactate as a prognostic indicator of survival in patients with acute myocardial infarction. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity. Resuscitation of multiple trauma and head injury: role of crystalloid fluids and inotropes. The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations. Lactic acid as a predictor for erythrocyte transfusion in healthy preterm infants with anemia of prematurity. Changes in whole blood lactate levels during cardiopulmonary bypass surgery for congenital cardiac disease: an early indicator of morbidity and mortality. Changes in cerebrospinal fluid pressure and lactate concentrations during thoracoabdominal aortic aneurysm surgery. Interpretation of blood lactate measurements in paediatric open-heart surgery and in extracorporeal membrane oxygenation. Elevated serum lactate correlates with intracranial hemorrhage in neonates treated with extracorporeal life support. Serum lactates correlate with mortality after operations for complex congenital heart disease. High lactate predicts the failure of intraaortic balloon pumping after cardiac surgery. Serum lactate and base deficit suggest inadequate resuscitation of patients with burn injuries: application of a point-of-care laboratory instrument. Magnesium and cardiovascular biology: an important link between cardiovascular risk factors and atherogenesis. Neuropeptides, free radical stress and antioxidants in models of Mg-deficient cardiomyopathy. Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin. The use of magnesium in critical coronary care patients: management of cardiac arrhythmias. Advances in Magnesium Research: Magnesium in Cardiology: Fifth European Magnesium Congress, Viennnesa, 1995. Acute myocardial infarction without thrombolytic therapy: beneficial effects of magnesium sulfate. The effect of magnesium sulfate pretreatment and the significance of interleukin-6 levels in patients with acute myocardial infarction. Effects of magnesium infusion on thrombolytic and non-thrombolytic treated patients with acute myocardial infarction. Ventricular extrasystoles and intracellular electrolytes before and after potassium and magnesium infusions in patients on diuretic treatment. Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. Con: magnesium should not be administered to all coronary artery bypass graft surgery patients undergoing cardiopulmonary bypass. Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. Novel pharmacologic therapies in the treatment of experimental traumatic brain injury: a review. Predictive value of serum ionized but not total magnesium levels in head injuries. Magnesium attenuates persistent functional deficits following diffuse traumatic brain injury in rats. Decline in intracellular free Mg is associated with irreversible tissue injury after brain trauma. Pro: magnesium should be administered to all coronary artery bypass graft surgery patients undergoing cardiopulmonary bypass. Enhanced tumor necrosis factor- production following endotoxin challenge in rats is an early event during magnesium deficiency. Progressive magnesium deficiency increases mortality from endotoxin challenge: the protective effects of acute magnesium replacement therapy. Whole blood ionized magnesium: age-related differences in normal values and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital cardiac disease. Prophylaxis of atrial fibrillation with magnesium sulfate after coronary artery bypass grafting. Hypermagnesemia-induced cardiopulmonary arrest before induction of anesthesia for emergency cesarean section. Magnesium: Current Status and New Developments: Theoretical, Biological and Medical Aspects. Oxygen saturation as a predictor of prolonged, frequent bronchodilator therapy in children with acute asthma. Intrapartum management of nonreassuring fetal heart rate patterns: a randomized controlled trial of fetal pulse oximetry. Screening hospital admissions from the emergency department for occult carbon monoxide poisoning. Benzocaine-induced methemoglobinemia: report of a severe reaction and review of the literature. Effect of point of care testing on length of stay in an adult emergency department. Minimizing admission laboratory testing in trauma patients: use of a microanalyzer. Blood analysis at the point of care: issues in application for use in critically ill patients. Brain cell death following ischemia and reperfusion: a proposed biochemical sequence. Hypermagnesemia and hypocalcemia as predictors of high mortality in critically ill pediatric patients. Ar ch iv ed Chapter 6 Diagnosis and Management of Diabetes Mellitus Aasne Karine Aarsand, David Alter, Stephen J. It is a disease that is defined by the biochemical abnormalities associated with changes in glucose metabolism, but is also characterized by a more complex pathophysiology. The diagnosis of diabetes mellitus is based on an accurate assessment of the fasting blood glucose concentration, followed by a glucose tolerance test in the case of an equivocal result (1). The role of a range of biochemical tests in the management of diabetes was systematically reviewed by Sacks et al. It should be stressed at the outset that "absence of evidence of effect does not constitute evidence of absence of effect" (4). The following questions were searched in PubMed (682 different hits) and the Cochrane library (66 different hits) in December 2003. The abstracts were read by 2 reviewers to determine whether the articles should be retrieved or not.

Generally exposed children do antibiotics help for sinus infection order 600mg zyvox with amex, who have been vaccinated treatment for dogs eating onions discount zyvox 600 mg line, do not need to stay at home antibiotics for uti delay period discount 600 mg zyvox with visa. Usually the viral illness causes some combination of stuffy nose antibiotic ingredients discount zyvox 600mg on line, runny nose, sore throat, cough, runny eyes, ear fluid and fever. Occasionally, the common cold or influenza can be complicated by a bacterial infection such as an ear infection, sinus infections, or pneumonia. These complications can be treated with appropriate antibiotics after evaluation by their health care provider. While there is medication available, most health care providers suggest rest and plenty of fluids. To see if there is bacterial infection in addition to the viral infection, a healthcare provider should evaluate a child who has a high fever, persistent cough, or earache. Influenza vaccine is the primary method of preventing influenza and its severe complications. Two doses should be given the first year the child receives the influenza vaccine. As the number of persons in contact with a child increases, so does the likelihood of exposure to the common viruses that cause the cold and flu. The viruses can be transmitted from one person to another in respiratory secretions. Infected droplets may be scattered through sneezing or coughing or they may land on surfaces touched by other persons, who then touch their eyes, nose or mouth. The symptoms of influenza appear in 1-4 days after exposure, and typically last 2-3 days. Keep tissues available Toys that children put in their mouths and frequently used surfaces. Children should be excluded if they have a fever or are unable to participate in general activities. Influenza is not reportable, but please notify the Division of Public Health Services, Bureau of Infectious Disease Control at (603) 271-4496 of influenza outbreaks. It is most often caused by a virus (like those which cause the common cold), but can also be caused by bacteria, allergies or chemicals. Signs and symptoms of purulent conjunctivitis are white or colored discharge from the eye, eye redness, eyelid swelling, eye pain, and sometime fever. Occasionally the doctor will examine the discharge under the microscope or culture it. Often an antibiotic eye medicine will be given because treatment of bacterial conjunctivitis shortens the length of symptoms and decreases infectiousness. Signs and symptoms of nonpurulent conjunctivitis are clear watery discharge from the eye, without eye redness or pain or fever. Preschoolers and school-age children have it most often and can spread it to people taking care of them or to each other. Both viral and bacterial conjunctivitis spread by contact with discharge from the eye. It is recommended that children and staff with purulent conjunctivitis be excluded from childcare until examined by a healthcare provider and approved for re-admission, with or without treatment. Children with nonpurulent conjunctivitis do not need to be excluded from childcare. Conjunctivitis is not reportable by New Hampshire state law to the Division of Public Health Services, Bureau of Infectious Disease Control. However, Public Health Professionals are available for consultation at (603) 271-4496. Some of the causes of infectious diarrhea, such as Campylobacteriosis, shiga-toxin producing E. Although these other diseasecausing organisms are not discussed in detail, the general principles outlined in this section are applicable to prevent the spread of any of these germs. The germs can be diagnosed by stool cultures or by looking at stool under a microscope for eggs or parasites. Specific methods for preventing the spread of infectious diarrhea are discussed in each fact sheet. Any person with diarrhea shall be excluded from food handling, from childcare agencies and from direct care of hospitalized or institutionalized patients until 48 hours after resolution of symptoms. For diarrhea caused by a specific agent, see the related fact sheet to learn if exclusion is necessary. It can spread especially quickly among babies and young children who are not toilet-trained or who may not wash their hands well after going to the bathroom. It can also easily spread to the adults taking care of them and helping them with diapering and toileting. Clusters of diarrhea illness in a facility should be reported to the Division of Public Health Services, Bureau of Infectious Disease and Control at (603) 2714496. The bacteria are spread by direct contact with discharge from the nose, throat, skin, eyes, or from sores of infected persons. Patients and carriers of diphtheria should receive appropriate treatment and not return to childcare until two (2) cultures from both the nose and throat (and from skin sores in cutaneous diptheria), are negative for the bacteria. These cultures should be taken at least 24 hours apart and no sooner than 24 hours after finishing antibiotic treatment. Where culture is impractical, isolation may be ended after 14 days of appropriate treatment. Children and staff should be excluded until bacteriological examination proves them not to be carriers. Diphtheria causes a sore throat and swollen tonsils, with a grayish covering and swollen glands in the neck. The bacteria also produce a toxin (a type of poisonous substance) that can cause severe and permanent damage to the nervous system and heart. Yes, Diphtheria is reportable by New Hampshire law to the Division of Public Health Services, Bureau of Infectious Disease Control at (603) 271-4496. Individuals who have been in contact with an infected person and are not adequately vaccinated should receive a booster. Usually symptoms disappear in a few days but the bacteria can remain in the intestinal tract for several weeks. Drinking unpasteurized milk and swimming in or drinking sewagecontaminated water can also cause infection. An infected person having diarrhea can pass the bacteria from one person to another if hand-washing habits are not adequate. Young children usually continue to shed the bacteria in their stool a week or two following their illness. Avoid drinking from unknown water sources, raw milk, and unpasteurized apple juice. Children who are infected with this bacterium will be excluded from childcare while they are symptomatic. Infected adults should be excluded from childcare centers, food handling, and direct care healthcare, until their stool cultures are free of E. If antibiotics have been given, the initial cultures should be obtained at least 48-hours after the last dose. They vary from mild diarrhea to a bloody diarrhea with severe abdominal cramps and little or no fever. This is more likely to occur in children under five years of age and the elderly, and may lead to death. The virus has a complex life cycle involving birds and a specific type of mosquito, called Culiseta melanura. Sometimes though, the virus can escape from its marsh habitat by means of other mosquitoes that feed on both birds and mammals. Antibiotics are not effective against viruses, and no effective anti-viral drugs have yet been discovered. For people with infection of the central nervous system, a sudden high fever (103 to 106), severe headache, and stiff neck can be followed quickly by seizures and coma. Of those that survive, many suffer permanent brain damage and require lifetime institutional care. Prevention of the disease centers around controlling mosquitoes and on individual action to avoid mosquito bites. Although people may be asymptomatic with the illness, most children with it develop a facial rash.

Three of the four prospective studies were done in tertiary hospitals in the Philippines (Araneta 2001 bacteria que causa cancer de estomago zyvox 600mg without prescription, Aseron-Banaga 2003 bacteria history generic zyvox 600mg visa, Manuel 2005) treatment for dogs dry flaky skin discount 600mg zyvox fast delivery, one was done in Thailand (Chuansumrit 2010) bacteria in urine culture discount 600 mg zyvox, and another in French Guiana (Basurko 2012). Of the retrospective studies, one was done locally (Farol 2003), one was conducted in Thailand (Tantracheewathorn 2007), one was conducted in Brazil (Gibson 2013), and one in India (Gupta 2013). One study evaluated the value of a maculopapular rash in children hospitalized for Dengue (Basurko 2012) and another described clinical warning signs of severe dengue in children during an outbreak (Gibson 2013). One of the studies (Araneta 2001) 17 Clinical Practice Guidelines on Dengue in Children evaluated patients admitted from the outpatient and admitting section based on predefined criteria. None of the studies reviewed directly addressed the question - whether the presence of these clinical signs and symptoms warrant admission, but rather whether these signs and symptoms lead to severe dengue, defined as having dengue shock syndrome. Irritablity or drowsiness - There was one case control study that evaluated irritability and drowsiness on the 4th day and on the 5th day of illness (Gibson 2013). The quality of evidence was graded as very low because the patients were not sufficiently homogenous with respect to the prognostic factors, comparing those with hospitalized severe dengue cases with non-severe dengue in the community and because of indirectness. The study did not directly answer the question whether these clinical signs and symptoms warrant admission, but rather whether these signs and symptoms lead to severe dengue, defined as having dengue shock syndrome. One case control study (Gibson 2013) evaluated abdominal pain on the 3rd and 4th day of illness. The quality of evidence was graded as very low because patients included in the study were not sufficiently homogenous with respect to prognostic factors (groups that were compared were severe vs non-severe dengue) and because of indirectness because the study does not directly answer the question whether this clinical symptom warrants admission, but rather whether this symptom leads to severe dengue. The quality of evidence was graded as low because of indirectness and because of the risk of bias inherent to the study design and because participants recruited were already the ones hospitalized and thus results may be overestimated. Quality of evidence was low since patients were not homogenous in terms of prognostic factors and those evaluated were those hospitalized. Another study evaluated vomiting (Manuel 2005) but univariate analysis did not show this to be significant and this was not included in the analysis. The quality of evidence for two of the studies was low because of indirectness and increased risk of bias due to insufficient information on whether participants were representative or sufficiently homogenous with respect to prognostic factors (Chuansumrit 2010, Manuel 2005). The quality of evidence was very low in the two pooled studies (Araneta 2001, Gupta 2011) because of indirectness, significant heterogeneity of pooled results, and increased risk of bias due to insufficient information on whether participants were representative or sufficiently homogenous with respect to prognostic factors. The quality of evidence for another study was also very low due to indirectness, imprecision, and increased risk of bias due to insufficient information on whether participants were representative or sufficiently homogenous with respect to prognostic factors (Tantracheewathorn 2007). Four of the five studies showed that hemoconcentration was associated with developing dengue shock syndrome. The quality of evidence was very low in one study (Gupta 2011) because of indirectness, imprecision, and increased risk of bias due to insufficient information on whether participants were representative or sufficiently homogenous with respect to prognostic factors. Three of the five studies showed that thrombocytopenia was associated with developing dengue shock syndrome. Consideration for recommendation development during Stakeholders Panel meeting: There is insufficient evidence to recommend which clinical or laboratory finding could accurately predict development of severe disease and warrant admission. The studies evaluated different clinical and laboratory parameters and had different cut-off points for the laboratory parameters tested. There was a consensus among the stakeholders not to put absolute values but use "elevated hematocrit" and "decreased or decreasing platelet count" instead. In the absence of published normal values for age of hematocrit among Filipino children, no absolute value for the Hematocrit can be recommended as a cut-off for admission. It was also brought up during the stakeholders meeting that there is lack of data for hematocrit values for patients with iron deficiency anemia or hematologic disorders who subsequently develop dengue. However, there were no studies that evaluated this outcome 23 Clinical Practice Guidelines on Dengue in Children Question 2: Among patients with dengue, which risk factors are associated with mortality? Recommendation 1: Patients with dengue who present with any one of the following clinical findings may be at increased risk for mortality. Of the six studies, five looked at both clinical and laboratory parameters (Abiera 1996, Bunnag 2011, Moraes 2013, Mena Lora 2014, and Fajardo 1996) while the study by Chua, 1993 looked at laboratory parameters only. This study determined clinical manifestations and hematologic parameters as possible risk factors for mortality and bleeding. There was a serious risk of bias as participants were recruited from a tertiary hospital and there was not enough information on whether participants or subgroups of participants were sufficiently homogenous with respect to prognostic factors. There were two retrospective cohort studies, one done in a tertiary pediatric hospital in the Philippines (Fajardo 1996) and another in a tertiary hospital in Bangkok, Thailand (Bunnag 2011). These studies evaluated the association of both clinical presentation and hematologic parameters with mortality. The quality of evidence from Fajardo 1996 was graded as moderate because of serious risk of bias since the study was conducted in a tertiary hospital. Both studies had an increased risk for bias due to lack of information if subjects were sufficiently homogenous with respect to prognostic factors. Factors examined were demographic, clinical manifestations and hematologic parameters. The quality of evidence from this study was graded as very low due to a serious risk of bias since the study population was limited to cases of severe dengue, insufficiency of information on whether participants were homogeneous with respect to risk factors and because of indirectness since both adults and children were enrolled in the study. The last study was a cross sectional study (Mena Lora 2014) conducted in a referral general pediatric hospital in the Dominican Republic. Only admitted patients in a tertiary pediatric referral hospital were included, that may be a cause for a serious risk for bias. There was also lack of information on whether participants were homogeneous with respect to prognostic factors. Respiratory Failure: There was one study with low quality of evidence that evaluated this parameter (Bunnag 2011). Renal Failure: One study with low quality of evidence evaluated this parameter (Bunnag 2011). The wide confidence interval could be due to the small number of subjects with renal failure among the studied population. Bleeding: There were three studies that evaluated this parameter (Abiera 1996, Bunnag 2011, Moraes 2013). These latter two studies were done on patients with severe dengue which may produce bias. The quality of evidence was low for two studies (Abiera 1996: Bunnag 2011) and very low in one study (Moraes 2013) Effusion: There were two studies that evaluated this parameter (Abiera 1996, Moraes 2013). Abiera 1996 performed ultranosographic examination of the lungs to 27 Clinical Practice Guidelines on Dengue in Children confirm clinical evidence of pleural effusion. Moraes on the other hand, included different cavitary effusions: ascites, pleural effusion and pericardial effusion in his analysis. There was one study that evaluated this parameter (Moraes 2013), however with very low quality of evidence. Laboratory Parameters Decline in Hemoglobin: There was one moderate quality study that evaluated this parameter (Fajardo 1996). Increased Hematocrit: There were two studies that evaluated this parameter (Fajardo 1996, Moraes 2013). One study had moderate quality evidence (Fajardo 1996) and the other had very low quality evidence (Moraes 2013). Thrombocytopenia: There were three studies that evaluated this parameter (Mena Lora 2014, Chua 1993, Fajardo 1996). Different platelet levels were analyzed for risk of mortality in the studies but were consistent in reporting an increase in risk for mortality. Albumin Levels: There was one study with low quality evidence that evaluated this parameter (Bunnag 2011). The mean albumin levels among those who died were significantly lower than those who survived, with a median level of 1. Consideration for recommendation development during Stakeholders Panel meeting: There is insufficient evidence to recommend which clinical or laboratory finding could accurately determine mortality. Many findings were based on single studies or from studies that were inconsistent that could be a result of differences in study design and patient populations. The Stakeholders panel voted to remove this recommendation since it was based on a single study with low quality evidence. One retrospective cross sectional study evaluated only clinical parameters that could be used to predict bleeding (Abad 1998 unpublished). An additional two studies, one a prospective cohort study (Chua 1993) and the other a retrospective cross-sectional study (Rubio 2007) determined only laboratory parameters that may predict development of spontaneous bleeding in patients with dengue. The second prospective cohort study enrolled pediatric 30 Clinical Practice Guidelines on Dengue in Children patients aged 4 months to 17 years old admitted in a university tertiary hospital in Manila (Abiera 1996). The third prospective cohort study was conducted in 4 municipalities in a hyperendemic area in northeastern Colombia (Diaz-Quijano 2010).

Only a few studies in the literature explore the effect of intervention and participant characteristics on safety virus finder discount 600mg zyvox mastercard. Very few studies explored the effect of different treatment doses on the experienced adverse events antibiotics for sinus infection in india zyvox 600mg low cost. Definitions of high and low dose varied across the small number of studies that attempted to conduct dose comparisons bacteria water test kit order zyvox 600mg. This issue antibiotic resistance join the fight cheap zyvox 600 mg otc, together with other confounders, hindered systematic evaluation of a dose-response relationship. There were few descriptions of the time of onset of harms and the further clinical course of adverse events. In the few studies that reported on the time of onset of gastrointestinal effects, most effects were observed in the first three days of treatment. The onset of infections tended to occur one or several weeks later, however this information is primarily based on case studies. The route of administration is as much an intervention as it is a patient characteristic, and direct comparisons across routes of administrations are unlikely. In indirect comparisons, we found no evidence that the form of administration (oral, enteral, or other) of probiotic organisms pointed to an increased risk of participants in the probiotics group to experience an adverse event relative to a comparable control group from the same participant population. The included studies did not provide enough information to investigate whether safety results are associated with ethnic characteristics. With regard to the health status of participants, there was some indication that health status is associated with the experience of an adverse event when using probiotics. Case studies reporting serious adverse events described health-compromised patients, not generally healthy participants, contracting (most commonly) a serious infection potentially caused by probiotic organisms. The following describes the evidence related to hospitalizations as well as serious adverse events. Evidence for hospital admissions due to probiotics use came only from case studies. However, we also recorded all hospitalizations in included studies, regardless of perceived associations with the study products in question. Oh (1979) described a patient brought to the emergency room because of sudden disorientation, blurred vision, nausea, and vomiting. Rautio (1999) described a diabetic patient who was admitted to a hospital because of a 2-week history of mild abdominal discomfort and then fever. Tommasi (2008) described a patient admitted to a hospital for persistent fever and night sweating who was later diagnosed with bacteremia, associated with consumption of Lactobacillus casei- containing products. The case report by Zein (2008) described a hospital admission due to fever, headaches, nausea, and vomiting. The publication linked the Lactobacillus rhamnosus-associated septicemia to a probiotic product containing Lactobacillus rhamnosus, Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus casei, Bifidobacterium longum, and Streptococcus thermophilus. No study was identified that reported a new hospitalization other than the potentially Lactobacillus-associated case reported by Zein (2008), which involved use of a probiotics blend that included Bifidobacterium organisms. The condition was assumed to be food protein-induced enterocolitis syndrome caused by the probiotic intervention, according to the authors. No study was identified that reported a new hospitalization other than the potentially Lactobacillus-associated case studies described above that used blends. All other case reports were in patients who were already hospitalized, or an in-hospital treatment was not reported. Given that the specific diagnostic reason for hospitalization may be difficult to determine and hospitalizations may not have been associated with probiotic product use at all by other study investigators, we recorded all hospitalizations mentioned in included studies during or after receiving the study intervention. The outcome, hospitalization, was not an inclusion criterion per se for this review. Only hospitalizations recorded in publications addressing adverse events were considered, and studies using the number of hospitalizations as an efficacy or effectiveness measure were not sought. However, the studies did not report this outcome explicitly, and in order to provide a systematic evidence overview, only the exact reported outcome was considered for all treatment groups. A case series described by Huynh (2009) reported that one child with acute ulcerative colitis taking a product containing various Lactobacillus, Bifidobacterium and Streptococcus strains was hospitalized for vomiting and diarrhea, diagnosed as viral gastroenteritis. The authors reported further that three events in total were judged to be possibly related to the formula intervention (one gastrointestinal problem in each group and one respiratory problem in the control group). None of the identified studies indicated that the evaluated intervention led to a lengthened hospitalization. Serious Adverse Events We also investigated the quality of the adverse events, apart from exploring the quantity (Key Question 1) and the nature of the adverse events (Key Question 2). For all recorded adverse events reported in the individual studies, we assessed whether the experienced harm was a serious adverse event such as a hospitalization or recorded incidences of death. For a conservative analysis, we also included any sign of probiotics bacteria in blood samples as a serious adverse event. Several included studies reported on the presence or absence of serious adverse events, in particular the case studies. However, some controlled studies also reported on the presence or absence of serious adverse events and these studies allow a comparison of the risk experienced in a probiotic group compared to that of participants not using probiotics but from a similar population and with comparable underlying diseases, cointerventions, and other factors that may contribute to serious adverse events. Only the main treatment group was compared with the control group most similar to the treatment group minus the probiotics. The lack of Streptococcus, Enterococcus, and Bacillus interventions is highlighted in the following text. The risk of a serious 94 adverse event was low in both groups, and the difference between the probiotic and control groups was not detectable. The Evidence Table C4, Results shows all serious adverse events reported in all included studies. As documented in the Key Question 1 section, the serious adverse events associated with a Lactobacillus intervention where administered species or strains were matched with genetic fingerprinting approaches included two cases of an abscess, two cases of bacteremia, and one case of sepsis. In order to explore further whether the genus of the organism could be associated with reported serious adverse events, we undertook a metaregression adding the genus as a moderator to a meta-analysis of serious adverse events. This analysis compared studies that used Lactobacillus strains, alone or in combinations with other microorganisms, with interventions that did not. The relative risk ratio across studies did not indicate that the Lactobacillus genus was associated with a statistically significantly different risk of serious adverse events compared to other genera (relative risk ratio 1. As documented in the Key Question 1 section, the serious adverse events associated with a Bifidobacterium interventions where administered species or strains were matched with genetic fingerprinting approaches included one documented case of septicemia. A metaregression adding the presence of the genus Bifidobacterium in the intervention as a moderator to a meta-analysis of serious adverse events did not indicate that the Bifidobacterium genus was associated with a statistically significantly increased risk of serious adverse events (relative risk ratio 1. As documented in the Key Question 1 section, the serious adverse events associated with a Saccharomyces interventions where administered species were matched with genetic fingerprinting approaches included 20 cases of fungemia. A metaregression adding the presence of the genus Saccharomyces in the intervention as a moderator to a meta-analysis of serious adverse events did not indicate that the Saccharomyces genus was associated with a statistically significantly increased risk of serious adverse events (relative risk ratio 0. A metaregression adding the presence of the genus Streptococcus in the intervention as a moderator 95 to a meta-analysis of serious adverse events did not indicate that the Streptococcus genus was associated with a statistically significantly increased risk of serious adverse events (relative risk ratio 1. A metaregression adding the presence of the genus Enterococcus in the intervention as a moderator to a meta-analysis of serious adverse events did not indicate that the Enterococcus genus was associated with a statistically significantly increased risk of serious adverse events (relative risk ratio 0. As documented in the Key Question 1 section, the serious adverse events associated with a Bacillus intervention where administered species were matched with genetic fingerprinting approaches included 1 case of sepsis. We also explored pertinent subgroups that were identified in the review with regard to serious adverse events. The quality of adverse events can be very different, ranging from mild complaints to critical events, and analyses in prior chapters have shown that some investigated participants and some intervention characteristics warrant more exploration. We also explored whether critically ill participants taking probiotics were more likely to experience serious adverse events compared to control group participants. There was no indication that critically ill patients were more likely to experience serious adverse events when we stratified results for this subgroup. The relative risk in studies with participants of this health status to experience a serious adverse event was 1. The few published studies in the elderly did not report on the presence or absence of serious adverse events. Stratified analyses indicated that yogurt and dairy delivery vehicles may influence the ratio of risks for adverse events seen in intervention and control groups. Summary and Strength of Evidence Key Question 5 How often does harm associated with Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and Bacillus lead to hospital admission or lengthened hospitalization? A comparison of all reported hospitalizations regardless of the perceived association with the intervention treatment indicated no statistically significantly increased risk in probiotics interventions compared to the number of hospitalizations in control group participants. However, 97 the number of hospitalizations due to adverse events was explicitly reported on in only a few of the included studies, older publications may not have associated a hospitalization with probiotics intake, and several studies reported on participants who were already hospitalized. The same result was obtained for Lactobacillus and Saccharomyces interventions, but there were too few studies (Bifidobacterium) or no studies (Streptococcus, Enterococcus, Bacillus) to analyze serious adverse events as studies did not report on the presence or absence of serious adverse events.

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