Severe pre-eclampsia as a rare cause of profound hyponatraemia.

Profound hyponatraemia, defined as sodium <125 mmol/L, is a very rare complication of pre-eclampsia (PET) with a relative paucity of cases reported. Pre-eclampsia is a multisystem disorder with a maternal mortality of up to 20%. Hyponatraemia is associated with disease severity, twin pregnancy, advanced maternal age, in vitro fertilisation and HELLP (haemolysis, elevated liver enzymes and low platelets). The authors present the case of a low-risk nulliparous woman presenting with frontal headache and normal BP at 31+2 weeks gestation. Laboratory investigations confirmed a sodium of 123 mmol/L. Her urine protein creatinine ratio was 322 mg/mmol. She developed PET (BP 171/100 mm Hg) refractory to pharmacological management. She underwent an emergency lower segment caesarean section and was delivered of a live neonate. The maternal serum sodium normalised within 24 hours. Hyponatraemia should be regarded as a marker of severity in the setting of pre-eclampsia and may be an indication for an expedited delivery. Prompt management is required to prevent convulsions, maternal mortality and adverse fetal outcomes.

Computational Analysis of the Morphological Aspects of Triadic Hybridized Magnetic Nanoparticles Suspended in Liquid Streamed in Coaxially Swirled Disks.

Currently, pagination clearly explains the increase in the thermophysical attributes of viscous hybrid nanofluid flow by varying morphological aspects of inducted triadic magnetic nanoparticles between two coaxially rotating disks. Copper metallic nanoparticles are inserted with three different types of metallic oxide nanoparticles: Al2O3, Ti2O, and Fe3O4. Single-phase simulation has been designed for the triadic hybrid nanofluids flow. The achieved expressions are transmuted by the obliging transformation technique because of dimensionless ordinary differential equations (ODEs). Runge-Kutta in collaboration with shooting procedure are implemented to achieve the solution of ODEs. The consequences of pertinent variables on associated distributions and related quantities of physical interest are elaborated in detail. It is inferred from the analysis that Cu-Al2O3 metallic type hybrid nanofluids flow shows significant results as compared with the other hybrid nanoparticles. The injection phenomenon on hybrid nanofluids gives remarkable results regarding shear stress and heat flux with the induction of hybridized metallic nanoparticles. Shape and size factors have also been applied to physical quantities. The morphology of any hybrid nanoparticles is directly proportional to the thermal conductance of nanofluids. Peclet number has a significant effect on the temperature profile.

Clinical Characteristics of COVID-19 Patients in a Regional Population With Diabetes Mellitus: The ACCREDIT Study.

Objective: To identify clinical and biochemical characteristics associated with 7- & 30-day mortality and intensive care admission amongst diabetes patients admitted with COVID-19. Research Design and Methods: We conducted a cohort study collecting data from medical notes of hospitalised people with diabetes and COVID-19 in 7 hospitals within the Mersey-Cheshire region from 1 January to 30 June 2020. We also explored the impact on inpatient diabetes team resources. Univariate and multivariate logistic regression analyses were performed and optimised by splitting the dataset into a training, test, and validation sets, developing a robust predictive model for the primary outcome. Results: We analyzed data from 1004 diabetes patients (mean age 74.1 (± 12.6) years, predominantly men 60.7%). 45% belonged to the most deprived population quintile in the UK. Median BMI was 27.6 (IQR 23.9-32.4) kg/m2. The primary outcome (7-day mortality) occurred in 24%, increasing to 33% by day 30. Approximately one in ten patients required insulin infusion (9.8%). In univariate analyses, patients with type 2 diabetes had a higher risk of 7-day mortality [p < 0.05, OR 2.52 (1.06, 5.98)]. Patients requiring insulin infusion had a lower risk of death [p = 0.02, OR 0.5 (0.28, 0.9)]. CKD in younger patients (<70 years) had a greater risk of death [OR 2.74 (1.31-5.76)]. BMI, microvascular and macrovascular complications, HbA1c, and random non-fasting blood glucose on admission were not associated with mortality. On multivariate analysis, CRP and age remained associated with the primary outcome [OR 3.44 (2.17, 5.44)] allowing for a validated predictive model for death by day 7. Conclusions: Higher CRP and advanced age were associated with and predictive of death by day 7. However, BMI, presence of diabetes complications, and glycaemic control were not. A high proportion of these patients required insulin infusion warranting increased input from the inpatient diabetes teams.

Emergence of a latent TSHoma pituitary macroadenoma on a background of primary autoimmune hypothyroidism

The coexistence of primary hypothyroidism and thyroid-stimulating hormone (TSH)-stimulating pituitary macroadenoma can be a rare occurrence and can make diagnosis very challenging. We describe a case of a 44-year-old female with a history of fatigue, poor concentration, weight gain and amenorrhoea together with biochemical evidence of primary autoimmune hypothyroidism. Her initial TSH levels were elevated with low normal free thyroxine (T4) levels. Levothyroxine treatment was initiated and the dose was gradually titrated to supraphysiologic doses. This led to the normalisation of her TSH levels but her free T4 and triiodothyronine (T3) levels remained persistently elevated. This prompted a serum prolactin check which returned elevated at 2495 µ/L, leading onto pituitary imaging. A MRI of the pituitary gland revealed a pituitary macroadenoma measuring 2.4 × 2 × 1.6 cm. Despite starting her on cabergoline therapy with a reduction in her prolactin levels, her TSH levels began to rise even further. Additional thyroid assays revealed that she had an abnormally elevated alpha subunit at 3.95 (age-related reference range <3.00). This corresponded to a thyroid-secreting hormone pituitary macroadenoma. She went on to have a transphenoidal hypophysectomy. Histology revealed tissues staining for TSH, confirming this to be a TSH-secreting pituitary macroadenoma. This case highlighted the importance of further investigations with thyroid assay interferences, heterophile antibodies, alpha subunit testing and anterior pituitary profile in cases of resistant and non-resolving primary hypothyroidism. Learning points: •• Levothyroxine treatment in primary hypothyroidism can potentially unmask the presence of a latent TSH-secreting pituitary macroadenoma, which can make diagnosis very challenging. •• A high index of suspicion should prompt clinicians to further investigate cases of primary hypothyroidism which despite increasing doses of levothyroxine treatment with normalisation of TSH, the free T4 and T3 levels remain persistently elevated. •• Clinicians should consider investigating for adherence to levothyroxine, thyroid assay interference, heterophile antibodies, TSH dilution studies, alpha subunit and anterior pituitary profile testing to further clarity the diagnosis in these patients. •• Although coexistent cases of TSHoma with primary hypothyroidism are rare, it should always be in the list of differential diagnoses in cases of unresolving primary hypothyroidism.

Colistin-resistant Acinetobacter baumannii: beyond carbapenem resistance.

BACKGROUND: With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging. METHODS: Patients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry. RESULTS: Twenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates. CONCLUSIONS: Colistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

Safety and efficacy of long-term outpatient ertapenem therapy.

Ertapenem is increasingly utilized in outpatient parenteral antimicrobial therapy (OPAT), but data regarding the efficacy and safety of long-term ertapenem therapy have been limited. We conducted a retrospective cohort study of adult patients who received outpatient ertapenem therapy at our center between 2010 and 2013. Among 306 unique patients who were discharged on ertapenem therapy, the most common indications were intra-abdominal infections (38%), followed by pneumonia (12%), bone and joint infections (11%), bloodstream infections (10%), urinary tract infections (10%), surgical site infections (5%), and skin and soft-tissue infections (4%). Of these 306 patients, 68 received regular outpatient follow-up visits at our infectious disease clinic, where the majority of patients (91%) were successfully treated with ertapenem by the end of therapy. Of the 6 patients who experienced clinical failure, 2 had adverse events leading to discontinuation of therapy and 4 required additional source control for clinical success. In addition, 2 patients had recurrent infection at 6 months.

Escherichia coli sequence type 131: epidemiology and challenges in treatment.

Escherichia coli ST131 has emerged as a global epidemic, multidrug-resistant clone of E. coli causing extra-intestinal infections. It is now highly prevalent among fluoroquinolone-resistant and CTX-M ESBL-producing E. coli isolates worldwide. Humans are likely the primary reservoir of ST131. Factors associated with its acquisition include residence in long-term care facilities and recent receipt of antimicrobial agents. E. coli ST131 causes a wide array of infections ranging from cystitis to life-threatening sepsis. Fluoroquinolones and trimethoprim-sulfamethoxazole are no longer adequate options for empiric therapy when E. coli ST131 is suspected from risk factors and local epidemiology. Expanded-spectrum cephalosporins, piperacillin-tazobactam and carbapenems are options to treat serious non-ESBL-producing E. coli ST131 infections, while carbapenems are indicated for ESBL-producing infections. There is a growing interest in reevaluating oral agents including fosfomycin and pivmecillinam for less serious infections such as uncomplicated cystitis.

Epidemiology and clinical outcomes of patients with carbapenem-resistant Klebsiella pneumoniae bacteriuria.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteriuria is a frequently encountered clinical condition, but its clinical impact is unknown. We conducted a retrospective cohort study to define the epidemiology and outcomes for patients with CRKP bacteriuria. Patients with positive urine cultures for CRKP were classified as having asymptomatic bacteriuria (ASB) or symptomatic urinary tract infection (UTI). Among 105 patients with CRKP bacteriuria, 80% (84/105 patients) and 20% (21/105 patients) had ASB and UTI, respectively. Older age (P = 0.002) and higher Charlson's comorbidity index scores (P = 0.001) were associated with ASB. The median duration of hospitalization prior to CRKP bacteriuria was significantly longer for patients with ASB versus UTI (8.5 versus 2 days; P = 0.05). In multivariate analysis, male sex (odds ratio [OR], 4.69 [95% confidence interval (CI), 1.44 to 15.26]; P = 0.01), solid-organ transplantation (OR, 4.50 [95% CI, 1.39 to 14.52]; P = 0.01), and neurogenic bladder (OR, 18.62 [95% CI, 1.75 to 197.52]; P = 0.01) were independently associated with UTI. Ten percent (8/84) of the patients with ASB received antimicrobial therapy. The treatment success rate for patients with UTIs was 90% (19/21 patients), including all patients who received doxycycline (n = 9). The overall 30-day mortality rate was 6% (6/105 patients); the deaths were unrelated to CRKP infections. Secondary CRKP infections, including UTIs, were notably absent among patients with ASB who were followed for 90 days. In conclusion, identification of CRKP in the urine was most commonly associated with ASB and did not lead to subsequent infections or death among asymptomatic patients. Factors associated with UTIs included male sex, solid-organ transplantation, and neurogenic bladder. Doxycycline may be an effective therapy for CRKP UTIs.

Role of ultraviolet (UV) disinfection in infection control and environmental cleaning.

Ultraviolet (UV) radiation is capable of disinfecting surfaces, water and air. The UV technology was used for many years. However, safer and more effective delivery systems of UV radiation, make it a very useful option for disinfection. Effective disinfection of environmental surfaces is a key step in the prevention of spread of infectious agents. The traditional manual cleaning is essential in assuring adequate elimination of contamination. However, terminal cleaning is frequently suboptimal or unpredictable in many circumstances. UV-C radiation is an adjunctive disinfectant new technology that could kill a wide array of microorganisms including both vegetative and spore forming pathogens. The technology is getting more affordable and has produced consistent reproducible significant reduction of bacterial contamination.

Features of infections due to Klebsiella pneumoniae carbapenemase-producing Escherichia coli: emergence of sequence type 131.

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has become endemic in many US hospitals. On the other hand, KPC-producing Escherichia coli remains rare. METHODS: We studied infection or colonization due to KPC-producing E. coli identified at our hospital between September 2008 and February 2011. A case-control study was conducted to document clinical features associated with this organism. Susceptibility testing, sequencing of ß-lactamase genes, pulsed-field gel electrophoresis, multilocus sequence typing, and plasmid analysis were performed for characterization of the isolates. RESULTS: Thirteen patients with KPC-producing E. coli were identified. The patients had multiple comorbid conditions and were in hospital for variable periods of time before KPC-producing E. coli was identified. The presence of liver diseases was independently associated with recovery of KPC-producing E. coli when compared with extended-spectrum ß-lactamase-producing E. coli. The isolates showed variable susceptibility to carbapenems. Seven isolates belonged to sequence type (ST) 131, which is the international epidemic, multidrug-resistant clone, but their plasmid profiles were diverse. KPC-producing organisms other than E. coli were isolated within 1 month from 5 of the patients. The KPC-encoding plasmids were highly related in 3 of them, suggesting the occurrence of their interspecies transfer. CONCLUSIONS: KPC-producing E. coli infections occur in severely ill patients who are admitted to the hospital. Acquisition of the KPC-encoding plasmids by the ST 131 clone, reported here for the first time to our knowledge in the United States, seems to represent multiple independent events. These plasmids are often shared between E. coli and other species.

Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens.

Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenemase (KPC) has been associated with serious infections and high mortality. The optimal antimicrobial therapy for infection due to KPC-producing K. pneumoniae is not well established. We conducted a retrospective cohort study to evaluate the clinical outcome of patients with bacteremia caused by KPC-producing K. pneumoniae. A total of 41 unique patients with blood cultures growing KPC-producing K. pneumoniae were identified at two medical centers in the United States. Most of the infections were hospital acquired (32; 78%), while the rest of the cases were health care associated (9; 22%). The overall 28-day crude mortality rate was 39.0% (16/41). In the multivariate analysis, definitive therapy with a combination regimen was independently associated with survival (odds ratio, 0.07 [95% confidence interval, 0.009 to 0.71], P = 0.02). The 28-day mortality was 13.3% in the combination therapy group compared with 57.8% in the monotherapy group (P = 0.01). The most commonly used combinations were colistin-polymyxin B or tigecycline combined with a carbapenem. The mortality in this group was 12.5% (1/8). Despite in vitro susceptibility, patients who received monotherapy with colistin-polymyxin B or tigecycline had a higher mortality of 66.7% (8/12). The use of combination therapy for definitive therapy appears to be associated with improved survival in bacteremia due to KPC-producing K. pneumoniae.

Ochroconis gallopava: a dematiaceous mold causing infections in transplant recipients.

The dematiaceous mold Ochroconis gallopava is increasingly recognized as a human pathogen. Infection is almost always associated with immunosuppression. We describe a case with a unique presentation in a kidney transplant recipient and retrospectively review all 10 cases of O. gallopava at our institution over 18 yr, all in organ transplant recipients. Sixty percent of infections at our institution occurred in the last five yr studied. Infection generally occurred late after transplantation, and pulmonary infection was the most common manifestation. Use of almetuzumab for induction was associated with infection in the first six months post-transplant (p = 0.03). Attributable mortality at six months was 20%. Ochroconis gallopava is a rare but important pathogen in immunosuppressed individuals and organ transplantation is the most common underlying condition. Pulmonary involvement is the most common manifestation among patients with organ transplant. Optimal therapy remains undefined. Prognosis in organ transplant recipients is good if infection is diagnosed prior to dissemination.

Clinical characteristics of bloodstream infections due to ampicillin-sulbactam-resistant, non-extended- spectrum-beta-lactamase-producing Escherichia coli and the role of TEM-1 hyperproduction.

Ampicillin-sulbactam is commonly used as an empirical therapy for invasive infections where Escherichia coli is a potential pathogen. We evaluated the clinical and microbiologic characteristics of bloodstream infection due to E. coli, with focus on cases that were nonsusceptible to ampicillin-sulbactam and not producing extended-spectrum ß-lactamase (ESBL). Of a total of 357 unique bacteremic cases identified between 2005 and 2008, 111 (31.1%) were intermediate or resistant to ampicillin-sulbactam by disk testing. In multivariate analysis, a history of liver disease, organ transplant, peptic ulcer disease, and prior use of ampicillin-sulbactam were independent risk factors for bloodstream infection with ampicillin-sulbactam-nonsusceptible E. coli. Among cases that received ampicillin-sulbactam as an empirical therapy, an early clinical response was observed in 65% (22/34) of susceptible cases but in only 20% (1/5) of nonsusceptible cases. Among 50 ampicillin-sulbactam-resistant isolates examined, there was no clonal relatedness and no evidence of production of inhibitor-resistant TEM (IRT). Instead, the resistance was attributed to hyperproduction of TEM-1 ß-lactamase in the majority of isolates. However, promoter sequences of bla(TEM-1) did not predict resistance to ampicillin-sulbactam. While the plasmid copy number did not differ between representative resistant and susceptible isolates, the relative expression of bla(TEM-1) was significantly higher in two of three resistant isolates than in three susceptible isolates. These results suggest high-level bla(TEM-1) expression as the predominant cause of ampicillin-sulbactam resistance and also the presence of yet-unidentified factors promoting overexpression of bla(TEM-1) in these isolates.

Risk factors and outcome of extended-spectrum ß-lactamase-producing Enterobacter cloacae bloodstream infections.

Enterobacter cloacae is a major nosocomial pathogen that causes serious infections, including bloodstream infections (BSIs). The clinical significance of extended-spectrum ß-lactamase (ESBL) production in E. cloacae is not well established. A multicentre, retrospective, cohort study was conducted to identify clinical characteristics of patients with E. cloacae BSI. ESBL production was confirmed by genotypic methods. A total of 159 patients with E. cloacae BSI were identified at three medical centres in north-eastern USA. Amongst them, 16 patients (10.1%) harboured ESBL-producing E. cloacae. Independent risk factors for ESBL production included admission from a nursing home, the presence of a gastrostomy tube and history of transplant. For the outcome analysis, 15 consecutive patients who had ESBL-producing E. cloacae BSI prior to the study were included. Amongst the 31 patients with ESBL-producing E. cloacae, 8, 9, 4 and 2 patients received a carbapenem, cefepime, piperacillin/tazobactam and ciprofloxacin, respectively, as initial therapy. All patients who received a carbapenem (n=8) were alive at 28 days, whereas 7 (38.9%) of 18 patients who received a non-carbapenem antibiotic did not survive (P=0.06). Clinical failure at 96 h was observed in 2 (25.0%) of 8 patients who received a carbapenem and in 14 (77.8%) of 18 patients who received a non-carbapenem antibiotic (P=0.03). Pulsed-field gel electrophoresis showed little clonality amongst the study isolates. The majority of isolates produced SHV-type ESBL, whereas two isolates produced CTX-M-type ESBL. Initial therapy with a carbapenem appears to be associated with improved clinical outcome in BSI due to ESBL-producing E. cloacae.

Clinical features and molecular epidemiology of CMY-type beta-lactamase-producing Escherichia coli.

BACKGROUND: Knowledge of the clinical features of infections caused by Escherichia coli strains that produce plasmid-mediated AmpC beta-lactamase is limited. Of the several groups of plasmid-mediated AmpC beta-lactamases, CMY-type beta-lactamase is the most common in the United States. METHODS: We prospectively identified patients infected or colonized with E. coli strains that produce CMY-type beta-lactamase, and we collected clinical data over a 7-month period. A retrospective cohort study was performed to identify features associated with these cases. Patients with extended-spectrum beta-lactamase-producing E. coli were used as a control group. Pulsed-field gel electrophoresis, plasmid analysis, and phylogenetic typing were performed. RESULTS: Twenty-two patients with infection or colonization due to CMY-type beta-lactamase-producing E. coli and 25 patients with infection or colonization due to extended-spectrum beta-lactamase-producing E. coli were identified. The demographic characteristics of the patients were similar in both cohorts. Patients with CMY-type beta-lactamase-producing E. coli were significantly more likely to have symptomatic infection than were patients with extended-spectrum beta-lactamase-producing E. coli (P = .028). The CMY-type beta-lactamase was identified as CMY-2 or its variants. Ninety-four percent of the CMY-type beta-lactamase-producing isolates belonged to E. coli phylogenetic groups B2 and D, which are associated with virulence. Many of the isolates shared similar plasmid profiles, whereas the pulsed-field gel electrophoresis profiles were diverse. Co-resistance to non-beta-lactam antimicrobials was common. CONCLUSION: In Pittsburgh, Pennsylvania, CMY-type beta-lactamase-producing E. coli strains are almost as common as extended-spectrum beta-lactamase-producing E. coli strains, and they cause symptomatic infection in the majority of cases.

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial.

BACKGROUND: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. METHODS AND DESIGN: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 x 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. DISCUSSION: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation.

Rebuilding the health care system in Afghanistan: an overview of primary care and emergency services.

Developing nations have many challenges to the growth of emergency medical systems. This development in Afghanistan is also complicated by many factors that plague post-conflict countries including an unstable political system, poor economy, poor baseline health indices, and ongoing violence. Progress has been made in Afghanistan with the implementation of the Basic Package of Health Service (BPHS) by the Ministry of Public Health in an effort to provide healthcare that would have the most cost-effective impact on common health problems. Trauma and trauma-related disability were both identified as priorities under the BPHS, and efforts have begun to address these problems. Most of the emergency care delivered in Afghanistan is provided by the military sector and non-governmental organizations. Security, lack of infrastructure, economic hardship, difficult access to healthcare facilities, poor healthcare facility conditions, and lack of trained healthcare providers, especially women, are all problems that need to be addressed. The long-term goal of quality healthcare for all Afghan citizens will only be met by a combination of specific goal-oriented projects, foreign aid, domestic responsibility, and time.

Risk factors, clinical characteristics, and outcome of Nocardia infection in organ transplant recipients: a matched case-control study.

BACKGROUND: Risk factors for Nocardia infection in organ transplant recipients have not been formally assessed in the current era of transplantation. METHODS: We performed a matched case-control study (1:2 ratio) between January 1995 and December 2005. Control subjects were matched for transplant type and timing. Univariate matched odds ratios were determined and conditional logistic regression was performed to identify independent risk factors. Clinical and microbiological characteristics of all case patients were reviewed. RESULTS: Among 5126 organ transplant recipients, 35 (0.6%) were identified as having cases of Nocardia infection. The highest frequency was among recipients of lung transplants (18 [3.5%] of 521 patients), followed by recipients of heart (10 [2.5%] of 392), intestinal (2 [1.3%] of 155), kidney (3 [0.2%] of 1717), and liver (2 [0.1%] of 1840) transplants. In a comparison of case patients with 70 matched control subjects, receipt of high-dose steroids (odds ratio, 27; 95% confidence interval, 3.2-235; P=.003) and cytomegalovirus disease (odds ratio, 6.9; 95% confidence interval, 1.02-46; P=.047) in the preceding 6 months and a high median calcineurin inhibitor level in the preceding 30 days (odds ratio, 5.8; 95% confidence interval, 1.5-22; P=.012) were found to be independent risk factors for Nocardia infection. The majority of case patients (27 [77%] of 35) had pulmonary disease only. Seven transplant recipients (20%) had disseminated disease. Nocardia nova was the most common species (found in 17 [49%] of the patients), followed by Nocardia farcinica (9 [28%]), Nocardia asteroides (8 [23%]), and Nocardia brasiliensis (1 [3%]). Of the 35 case patients, 24 (69%) were receiving trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis. Thirty-one case patients (89%) experienced cure of their Nocardia infection. CONCLUSIONS: Receipt of high-dose steroids, history of cytomegalovirus disease, and high levels of calcineurin inhibitors are independent risk factors for Nocardia infection in organ transplant recipients. Our study provides insights into the epidemiology of Nocardia infection in the current era, a period in which immunosuppressive and prophylactic regimens have greatly evolved.

GPs' attitudes to benzodiazepine and 'Z-drug' prescribing: a barrier to implementation of evidence and guidance on hypnotics.

Zaleplon, zolpidem, and zopiclone ('Z-drugs') prescribing is gradually rising in the UK, while that of benzodiazepine hypnotics is falling. This situation is contrary to current evidence and guidance on hypnotic prescribing. The aim of this study was to determine and compare primary care physicians' perceptions of benefits and risks of benzodiazepine and Z-drug use, and physicians' prescribing behaviour in relation to hypnotics using a cross-sectional survey. In 2005 a self-administered postal questionnaire was sent to all GPs in West Lincolnshire Primary Care Trust. The questionnaire investigated perceptions of benefits and disadvantages of benzodiazepines and Z-drugs. Of the 107 questionnaires sent to GPs, 84 (78.5%) analysable responses were received. Responders believed that Z-drugs were more effective than benzodiazepines in terms of patients feeling rested on waking (P<0.001), daytime functioning (P<0.001), and total sleep time (P = 0.03). Z-drugs were also thought to be safer in terms of tolerance (P<0.001), addiction (P<0.001), dependence (P<0.001), daytime sleepiness (P<0.001), and road traffic accidents (P = 0.018), and were thought to be safer for older people (P<0.001). There were significant differences between GPs' perceptions of the relative benefits and risk of Z-drugs compared with benzodiazepines. The majority of practitioners attributed greater efficacy and lower side effects to Z-drugs. GPs' beliefs about effectiveness and safety are not determined by current evidence or national (NICE) guidance which may explain the increase in Z-drug prescribing relative to benzodiazepine prescribing.