Read Ebook {PDF EPUB} Pseudo by dysonrules Pseudoreplication: choose your data wisely¶ Many studies strive to collect more data through replication: by repeating their measurements with additional patients or samples, they can be more certain of their numbers and discover subtle relationships that aren’t obvious at first glance. We’ve seen the value of additional data for improving statistical power and detecting small differences. But what exactly counts as a replication? Let’s return to a medical example. I have two groups of 100 patients taking different medications, and I seek to establish which medication lowers blood pressure more. I have each group take the medication for a month to allow it to take effect, and then I follow each group for ten days, each day testing their blood pressure. I now have ten data points per patient and 1,000 data points per group. Brilliant! 1,000 data points is quite a lot, and I can fairly easily establish whether one group has lower blood pressure than the other. When I do calculations for statistical significance I find significant results very easily. But wait: we expect that taking a patient’s blood pressure ten times will yield ten very similar results. If one patient is genetically predisposed to low blood pressure, I have counted his genetics ten times. Had I collected data from 1,000 independent patients instead of repeatedly testing 100, I would be more confident that differences between groups came from the medicines and not from genetics and luck. I claimed a large sample size, giving me statistically significant results and high statistical power, but my claim is unjustified. This problem is known as pseudoreplication, and it is quite common. 38 After testing cells from a culture, a biologist might “replicate” his results by testing more cells from the same culture. Neuroscientists will test multiple neurons from the same animal, incorrectly claiming they have a large sample size because they tested hundreds of neurons from just two rats. In statistical terms, pseudoreplication occurs when individual observations are heavily dependent on each other. Your measurement of a patient’s blood pressure will be highly related to his blood pressure yesterday, and your measurement of soil composition here will be highly correlated with your measurement five feet away. There are several ways to account for this dependence while performing your statistical analysis: Average the dependent data points. For example, average all the blood pressure measurements taken from a single person. This isn’t perfect, though; if you measured some patients more frequently than others, this won’t be reflected in the averaged number. You want a method that somehow counts measurements as more reliable as more are taken. Analyze each dependent data point separately. You could perform an analysis of every patient’s blood pressure on day 5, giving you only one data point per person. But be careful, because if you do this for every day, you’ll have problems with multiple comparisons , which we will discuss in the next chapter. Use a statistical model which accounts for the dependence, like a hierarchical model or random effects model. It’s important to consider each approach before analyzing your data, as each method is suited to different situations. Pseudoreplication makes it easy to achieve significance, even though it gives you little additional information on the test subjects. Researchers must be careful not to artificially inflate their sample sizes when they retest samples. Pseudomonas. Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful. Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below. Pseudomonas. In this article. Pseudomonas spp. are Gram-negative rod bacteria commonly found in soil, ground water, plants and animals. Pseudomonal infection causes a necrotising inflammation. Pseudomonads [1] Pseudomonads include a number of true Pseudomonas species as well as many species formerly classified in the genus. Pseudomonads are natural residents of soil and water. They rarely cause infections in healthy individuals. In immunocompromised patients, systemic infections can occur which may be severe and associated with a high mortality. The genus Pseudomonas once comprised over 100 species but over the period of a decade many of these have been reclassified into different genera. The main groups of pseudomonads of medical interest are: The fluorescent or 'true' Pseudomonas - P. aeruginosa , P. fluorescens and P. putida . Burkholderia spp. - within this genus, there are at least 30 species but the medically important species are B. cepacia , B. pseudomallei and B. mallei , which are are associated with human and animal infection: B. cepacia is an important pathogen of pulmonary infections in people with cystic fibrosis. B. pseudomallei is the causal agent of melioidosis, a life-threatening septic infection prevalent in Southeast Asia and Northern Australia. B. mallei causes glanders, a rare disease in horses and other species. Both B. pseudomallei and B. mallei must be handled in category 3 containment facilities and their exchange between laboratories is restricted. May be clinically significant in severely immunocompromised patients and is increasingly isolated from sputum of patients with cystic fibrosis. The overall incidence in 2017 for S. maltophilia bacteraemia was 0.8 cases/100,000 population in England, Wales and Northern Ireland. The rest of this article is specific for infections caused by P. aeruginosa . Pseudomonas aeruginosa. P. aeruginosa is an opportunistic pathogen that can cause a wide range of infections, especially in immunocompromised people and people with severe burns, diabetes mellitus or cystic fibrosis. P. aeruginosa is relatively resistant to many antibiotics, but effective antibiotics include imipenem, meropenem, ceftazidime, ciprofloxacin, amikacin, gentamicin, tobramycin, and piperacillin combined with tazobactam. Between 2015 and 2016, the resistance patterns for key antimicrobial agents remained broadly stable with small decreases in resistance for gentamicin (4% to 3%) and tobramycin (4% to 3%). Increases in resistance to imipenem (9% to 11%), amikacin (1% to 2%) and piperacillin\tazobactam (6% to 7%) were observed over the same time period [1] . Epidemiology [2] P. aeruginosa is found almost anywhere but rarely affects healthy people. Most community-acquired infections are associated with prolonged contact with contaminated water. In April 2017, the government extended the surveillance of bacteraemias caused by Gram-negative organisms to include P. aeruginosa . Between 2013 and 2017, there was a 26.6% increase in the number of Pseudomonas spp. bacteraemias reported to Public Health England (PHE) compared with a 6% decrease from 2008-2012. The overall incidence in 2017 for Pseudomonas spp. bacteraemias was 8.1 cases/100,000 population in England, Wales and Northern Ireland. P. aeruginosa is the most common cause of pseudomonal infection [1] . Studies suggest that P. aeruginosa may colonise up to one third of patients admitted to hospital. However, whether or not this causes clinical infection depends on the immune status of the host [3] . Pneumonia, urinary tract infections, surgical wound infections and bloodstream infections are the most common pathologies. In hospitals, P. aeruginosa particularly contaminates moist/wet reservoirs such as respiratory equipment and indwelling catheters. P. aeruginosa is also a frequent cause of chronic respiratory infection in patients with cystic fibrosis. As many as 80% of cystic fibrosis patients may be colonised in the lung with P. aeruginosa and, once established, it is very resistant to antibiotic treatment. Presentation [4] Respiratory tract. Pneumonia is seen in patients with immunosuppression and chronic lung disease. There is an increased risk in patients on mechanical ventilation, patients with neutropenia and in patients with HIV infection. Chronic infection of the lower respiratory tract with P. aeruginosa is common in patients with cystic fibrosis. Bacteraemia. There is an increased risk for people in hospitals and nursing homes. In 2017/18, 4,286 cases of P. aeruginosa bacteraemia were reported in England, of which 4,140 (97%) had known fatality outcomes. This equates to a case fatality rate of 27% [5] . Skin shows characteristic skin lesions (ecthyma gangrenosum), which are haemorrhagic and necrotic with surrounding erythema, and most often found in the axilla, groin or perianal area. Endocarditis. May infect heart valves in intravenous drug abusers and also prosthetic heart valves. Thromboembolism may cause widespread infection, including in the central nervous system. Central nervous system. May cause meningitis and intracranial abscesses. Most infections result from direct spread from local structures (eg, the ear, mastoid or sinuses) but blood-borne spread may also occur. Common cause of chronic otitis media. May also cause otitis externa (including malignant otitis externa). In adults: common cause of bacterial keratitis, scleral abscess and endophthalmitis; risk factors include trauma and contact lenses. May cause ophthalmia neonatorum in neonates. Infection may also cause orbital cellulitis. Bones and joints. The spine, pelvis and sternoclavicular joints are the most common sites affected. Risk factors include penetrating trauma, peripheral arterial disease, intravenous drug abuse and diabetes. Gastrointestinal. The clinical severity of infection is very variable. Severe pseudomonal diarrhoea may occur in neonates. Enteritis may present with prostration, headache, fever and diarrhoea (Shanghai fever). Pseudomonas spp. typhlitis most often occurs in patients with neutropenia and presents with a sudden onset of fever, abdominal distension and increasing abdominal pain. Urinary tract infections. Urinary tract infections are usually hospital-acquired and related to catheterisation or surgery. Severe infections may lead to renal abscess and bacteraemia. Green nail syndrome: may develop in people whose hands are frequently immersed in water. Secondary infections can occur in patients with eczema and tinea pedis; presents with a blue-green exudate with a fruity odour. Is also an important cause of secondary infection of burns. Common cause of whirlpool or swimming pool folliculitis: pruritic follicular, maculopapular, vesicular or pustular lesions occur where the body has been immersed in water. May lead to subcutaneous nodules, deep abscesses, cellulitis and fasciitis. Suppurative thrombophlebitis may originate from an intravenous cannula in situ. Investigations. Blood cultures. Local investigations, dependent on the site of infection - eg, CXR, sputum, stool, urine cultures. Investigation of underlying health problems - eg, FBC, diabetes control indicators. Management [6] Most infections are susceptible to third-generation cephalosporins (ceftazidime), carbapenems (imipenem and meropenem), aminoglycosides (gentamicin and tobramycin) and colistin. Serious infections are usually treated with ticarcillin or piperacillin, often in combination with an aminoglycoside. Novel antibiotics and antibiotic combinations are being developed to overcome anticipated growth in antibiotic resistance - eg: Ceftolozane-tazobactam Ceftazidime-avibactam Imipenem-cilastatin-relebactam. Surgery. Debridement of necrotic tissue. Removal of infected medical devices if possible. Malignant otitis requires debridement of granulation tissue and necrotic debris. Surgery may be required for bowel necrosis, perforation, obstruction or abscess drainage. Vitrectomy may be needed in cases of endophthalmitis. Complications [4] Thromboembolism from pseudomonal endocarditis may cause brain abscess, cerebritis, mycotic aneurysms. Local spread from ear infections can cause sinusitis, mastoiditis, osteomyelitis, cranial nerve palsy, venous thrombosis, meningitis and brain abscesses. Gastrointestinal infection can cause bowel perforation and peritonitis. Skin and soft tissue infections can cause gangrene. Prognosis. Prognosis depends on the site of infection and the underlying health of the individual patient. Acute fulminant infections (eg, bacteraemic pneumonia, septicaemia, burn sepsis and meningitis) are associated with significant mortality. Prevention. The following measures are important in all environments but especially in hospitals and nursing homes: Strict adherence to rules of general hygiene. Normal infection control measures should apply. Aseptic procedures - eg, Venflon® (peripheral (venous) cannula) and catheter insertion. Strict isolation is required for patients with severe burns. Proper cleaning, sterilisation and disinfection of reusable equipment. Prophylactic antibiotics are not recommended as they result in the emergence of resistant strains of bacteria. Vaccines against P. aeruginosa have been under development for several years but have yet to be marketed [13] . Studies using genomic sequencing show that some strains of Pseudomonas spp. rapidly colonise water supply systems in hospitals. Identification of these sources could enable appropriate preventative measures to be taken before clinical spread occurs [3] . Further reading and references. Ciofu O, Tolker-Nielsen T ; Tolerance and Resistance of Pseudomonas aeruginosa Biofilms to Antimicrobial Agents-How P. aeruginosa Can Escape Antibiotics. Front Microbiol. 2019 May 310:913. doi: 10.3389/fmicb.2019.00913. eCollection 2019. Wuerth K, Lee AHY, Falsafi R, et al ; Characterization of Host Responses during Pseudomonas aeruginosa Acute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002. Infect Immun. 2018 Dec 1987(1). pii: IAI.00661-18. doi: 10.1128/IAI.00661-18. Print 2019 Jan. Martin LW, Robson CL, Watts AM, et al ; Expression of Pseudomonas aeruginosa Antibiotic Resistance Genes Varies Greatly during Infections in Cystic Fibrosis Patients. Antimicrob Agents Chemother. 2018 Oct 2462(11). pii: AAC.01789-18. doi: 10.1128/AAC.01789-18. Print 2018 Nov. Quick J, Cumley N, Wearn CM, et al ; Seeking the source of Pseudomonas aeruginosa infections in a recently opened hospital: an observational study using whole-genome sequencing. BMJ Open. 2014 Nov 44(11):e006278. doi: 10.1136/bmjopen-2014-006278. Fujilani S et al ; Pseudomonas aeruginosa, Infectious Disease and Antimicrobial Agents, 2017. Bassetti M, Vena A, Croxatto A, et al ; How to manage Pseudomonas aeruginosa infections. Drugs Context. 2018 May 297:212527. doi: 10.7573/dic.212527. eCollection 2018. Smith S, Rowbotham NJ, Regan KH ; Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst Rev. 2018 Mar 303:CD001021. doi: 10.1002/14651858.CD001021.pub3. Remmington T, Jahnke N, Harkensee C ; Oral anti-pseudomonal antibiotics for cystic fibrosis. Cochrane Database Syst Rev. 2016 Jul 147:CD005405. doi: 10.1002/14651858.CD005405.pub4. Pai S, Bedford L, Ruramayi R, et al ; Pseudomonas aeruginosa meningitis/ventriculitis in a UK tertiary referral hospital. QJM. 2016 Feb109(2):85-9. doi: 10.1093/qjmed/hcv094. Epub 2015 May 18. Hobson CE, Moy JD, Byers KE, et al ; Malignant Otitis Externa: Evolving Pathogens and Implications for Diagnosis and Treatment. Otolaryngol Head Neck Surg. 2014 Mar 26. British National Formulary (BNF) ; NICE Evidence Services (UK access only) Tao H, Butler JP, Luttrell T ; The Role of Whirlpool in Wound Care. J Am Coll Clin Wound Spec. 2013 Jan 224(1):7-12. eCollection 2012 Mar. Priebe GP, Goldberg JB ; Vaccines for Pseudomonas aeruginosa: a long and winding road. Expert Rev Vaccines. 2014 Apr13(4):507-19. doi: 10.1586/14760584.2014.890053. Epub 2014 Feb 27. What Is Pseudomonas Aeruginosa? Symptoms, Causes, Diagnosis, Treatment, and Prevention. Pseudomonas is a group of bacteria that can cause various types of infections. Serious infections from P. aeruginosa primarily occur in healthcare settings, but people can also develop infections from hot tubs and swimming pools. Signs and Symptoms of Pseudomonas Aeruginosa. Symptoms of P. aeruginosa vary based on the type of infection. Infection of the lungs (pneumonia) may cause: Fever and chills Difficulty breathing Chest pain Tiredness , sometimes with yellow, green, or bloody mucus. Strong urge to urinate frequently Unpleasant odor in urine Cloudy or bloody urine Pain in the pelvic area. Wound infections can cause: Inflamed wound site Fluid leakage from wound. Ear infections (like swimmer’s ear) can cause: Causes and Risk Factors of Pseudomonas Aeruginosa. In healthcare settings, P. aeruginosa is spread through improper hygiene, such as from the unclean hands of healthcare workers, or via contaminated medical equipment that wasn't fully sterilized. Common hospital-associated P. aeruginosa infections include bloodstream infections, pneumonia, urinary tract infections, and surgical wound infections. These infections typically affect people who are ill in the hospital, particularly those with weakened immune systems from diseases or long-term treatments. When hospitalized, you have a higher risk for a serious, life-threatening P. aeruginosa infection if you have surgical wounds or burns, or are being treated with a breathing machine, such as a mechanical ventilator, or other medical devices, such as urinary or intravenous catheters. Exposure to contaminated water can also cause mild P. aeruginosa infections in healthy people. For instance, inadequately disinfected hot tubs and swimming pools can cause P. aeruginosa ear infections and skin rashes. They can also cause eye infections in users of contact lenses. How Is Pseudomonas Aeruginosa Diagnosed? To diagnose P. aeruginosa , your doctor will perform a physical examination and ask about your symptoms and medical history. Then they’ll send a sample of your blood or other bodily fluid to a lab to test for the bacteria. Prognosis of Pseudomonas Aeruginosa. Delays in treatment are associated with marked increases in mortality, according to a 2018 article in Drugs in Context . Pseudofusion Dilemma. A 53-year-old, nonsmoking woman came to the clinic with increasing back and right leg pain despite undergoing an L4-S1 Transforaminal Lumbar Interbody Fusion (TLIF) and lateral mass fusion with Bone Morphogenetic Protein (BMP) just 8 months prior. She initially had surgery for severe degenerative disc disease at L4-5 and a Grade I spondylolisthesis with stenosis at L5-S1. This procedure provided good relief of her pain. Her past surgical history also includes a retroperitoneal approach pelvic floor reconstruction for uterine and rectal prolapse and bladder neck suspension. Examination. The physical exam revealed dorsiflexion weakness in the ankle, as well as decreased sensation in the L5 dermatome bilaterally. The patient’s pain was reproduced with forward flexion. At this time, plain film imaging demonstrated pseudofusion at both levels as confirmed by CT scan. Prior Treatment. The patient’s treatment to-date was the TLIF and fusion with BMP 8 months prior and while she initially received relief from her pain, her back and right leg pain has returned and is worsening. Images. The images include a lateral plain film, demonstrating lack of bone growth at either disc space [Fig. 1] and a Sagittal CT scan confirming pseudofusion at both interspaces. Figure 1 Lateral plain film showing lack of bone growth at both disc spaces. Figure 2 Sagittal CT scan confirming pseudofusion at both interspaces Figure 3 Coronal CT showing lack of lateral mass fusion at either level. Discussion of Treatment Options and Recommendation. Imaging should be conducted to investigate whether there is there is any continued posterior compressive pathology causing the leg pain (MRI lumbar spine with contrast or a CT myelogram). Additionally, EMG and nerve conduction could be helpful in delineating the cause for leg pain. If it is determined that there is posterior continued stenosis, then a foraminal steroid injection could help as a diagnostic and therapeutic maneuver. However, if that fails, a redo minimally-invasive posterior foraminotomy could alleviate any continued stenosis. This patient also has pseudoarthrosis, for which I would suggest ALIF at L4-S1 with cages and BMP. I also would recommend a redo retroperitoneal approach or a transperitoneal approach, with the assistance of a vascular surgeon. Suggest Treatment. Selected Treatment. Editor’s note: In this particular case, you the readers brought to our attention that we may not have included all possible treatment options. Dr Reginald Knight of Kirkland, Washington, suggested that he would "perform no additional surgery." We appreciate the feedback and, based on readers' feedback, from now on we are including "Other" as a treatment option. Having failed conservative therapy and despite her previous abdominal surgeries we elected to undergo an anterior approach. With the help of a vascular surgeon we performed a transperitoneal exposure of L4-S1. This avoided the difficulty of scar tissue impeding a retroperitoneal approach. After performing an anterior discectomy, both cages were easily harvested and an aggressive preparation of the endplates was carried out. We then placed threaded interbody cages with BMP using an ALIF technique at each level. As there was no hallowing around the screws we elected to leave the posterior instrumentation. The patient tolerated the procedure well with minimal blood loss and no further complications. Outcome. One week postoperatively, the patient reported marked improvement in her leg pain with moderate improvement in her back pain (Figure 4) . She still required pain management for her back pain but reported it was improved by the surgery. At 6 months postoperatively, the patient demonstrated solid bony fusion at both levels as witnessed by CT imaging (Figure 5) . pseudouridine. pseu·do·u·ri·dine (Ψ, Q), pseu·do·u·ri·dine. Link to this page: ▲ Pseudouridylation ▼ ▲ Pseudouridylation ▼ All content on this website, including dictionary, thesaurus, literature, geography, and other reference data is for informational purposes only. This information should not be considered complete, up to date, and is not intended to be used in place of a visit, consultation, or advice of a legal, medical, or any other professional.