Barnet Hospital

BACKGROUND: In recent years, a growing number of methods for synthesising qualitative research have emerged, particularly in relation to health-related research. There is a need for both researchers and commissioners to be able to distinguish between these methods and to select which method is the most appropriate to their situation. DISCUSSION: A number of methodological and conceptual links between these methods were identified and explored, while contrasting epistemological positions explained differences in approaches to issues such as quality assessment and extent of iteration. Methods broadly fall into 'realist' or 'idealist' epistemologies, which partly accounts for these differences. SUMMARY: Methods for qualitative synthesis vary across a range of dimensions. Commissioners of qualitative syntheses might wish to consider the kind of product they want and select their method - or type of method - accordingly.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Autologous chondrocyte implantation (ACI) and mosaicplasty are methods of treating symptomatic articular cartilage defects in the knee. This study represents the first long-term randomised comparison of the two techniques in 100 patients at a minimum follow-up of ten years. The mean age of the patients at the time of surgery was 31.3 years (16 to 49); the mean duration of symptoms pre-operatively was 7.2 years (9 months to 20 years). The lesions were large with the mean size for the ACI group being 440.9 mm(2) (100 to 1050) and the mosaicplasty group being 399.6 mm(2) (100 to 2000). Patients had a mean of 1.5 previous operations (0 to 4) to the articular cartilage defect. Patients were assessed using the modified Cincinnati knee score and the Stanmore-Bentley Functional Rating system. The number of patients whose repair had failed at ten years was ten of 58 (17%) in the ACI group and 23 of 42 (55%) in the mosaicplasty group (p < 0.001). The functional outcome of those patients with a surviving graft was significantly better in patients who underwent ACI compared with mosaicplasty (p = 0.02).

The 2003-2005 Confidential Enquiry into Maternal and Child Health report recommended the introduction of the modified early obstetric warning system (MEOWS) in all obstetric inpatients to track maternal physiological parameters, and to aid early recognition and treatment of the acutely unwell parturient. We prospectively reviewed 676 consecutive obstetric admissions, looking at their completed MEOWS charts for triggers and their notes for evidence of morbidity. Two hundred patients (30%) triggered and 86 patients (13%) had morbidity according to our criteria, including haemorrhage (43%), hypertensive disease of pregnancy (31%) and suspected infection (20%). The MEOWS was 89% sensitive (95% CI 81-95%), 79% specific (95% CI 76-82%), with a positive predictive value 39% (95% CI 32-46%) and a negative predictive value of 98% (95% CI 96-99%). There were no admissions to the intensive care unit, cardio respiratory arrests or deaths during the study period. This study suggests that MEOWS is a useful bedside tool for predicting morbidity. Adjustment of the trigger parameters may improve positive predictive value.

1. In this paper several historical and contemporary aspects of Newcastle disease (ND) are reviewed, with particular reference to the greater understanding which modern techniques have allowed. 2. Virulent ND viruses were generally thought to have emerged in 1926 as a result of transfer from a wild bird host reservoir but there is evidence that the virulent virus may have existed in poultry before 1926. Recent findings suggest that the virulent virus may emerge in poultry as a result of mutations in viruses of low virulence. 3. The history of ND in Great Britain reflects the four known panzootics that have occurred and serves as a model for the impact this disease may have on poultry populations. 4. Attempts to control and eradicate ND are not as straightforward as it may appear; in particular vaccination, while preventing deaths and disease, on challenge may not prevent virus replication and could therefore lead to the virulent virus becoming endemic. 5. Village chickens are extremely important assets in most developing countries, representing a significant source of protein in the form of eggs and meat but endemic ND can cause mortality of up to 60% in village chickens.

OBJECTIVES/HYPOTHESIS: To assess the feasibility of balloon dilatation eustachian tuboplasty (BET) as an option for treatment of patients with eustachian tube (ET) dysfunction. STUDY DESIGN: Ethics approved case controlled interventional study. METHODS: Eight patients were identified with poor ET function using a ET score and were assigned to the study. The endoscopic procedure involved the dilatation of the cartilaginous and bony portion of 13 ETs with a balloon catheter. Pre- and postinterventional computed tomography was performed. All patients were reassessed 1, 2, and 8 weeks after BET. RESULTS: BET was technically easy to perform. No damage to essential structures, particularly the carotid canal, was found in the human study. Patients revealed a significant improvement of the ET score comparing pre- and the 2-month post-treatment results. Improvement was found to be time dependent. CONCLUSIONS: This newly introduced method of BET was found to be a feasible and safe procedure to inflate the ET. It significantly helped to improve ET function in our study group. However, larger long-term studies are necessary to fully evaluate the clinical value of BET.

PURPOSE: There are few randomized controlled trial data to confirm that improved homogeneity with simple intensity-modulated radiotherapy (IMRT) decreases late breast tissue toxicity. The Cambridge Breast IMRT trial investigated this hypothesis, and the 5-year results are reported. PATIENTS AND METHODS: Standard tangential plans of 1,145 trial patients were analyzed; 815 patients had inhomogeneous plans (≥ 2 cm(3) receiving 107% of prescribed dose: 40 Gy in 15 fractions over 3 weeks) and were randomly assigned to standard radiotherapy (RT) or replanned with simple IMRT; 330 patients with satisfactory dose homogeneity were treated with standard RT and underwent the same follow-up as the randomly assigned patients. Breast tissue toxicities were assessed at 5 years using validated methods: photographic assessment (overall cosmesis and breast shrinkage compared with baseline pre-RT photographs) and clinical assessment (telangiectasia, induration, edema, and pigmentation). Comparisons between different groups were analyzed using polychotomous logistic regression. RESULTS: On univariate analysis, compared with standard RT, fewer patients in the simple IMRT group developed suboptimal overall cosmesis (odds ratio [OR], 0.68; 95% CI, 0.48 to 0.96; P = .027) and skin telangiectasia (OR, 0.58; 95% CI, 0.36 to 0.92; P = .021). No evidence of difference was seen for breast shrinkage, breast edema, tumor bed induration, or pigmentation. The benefit of IMRT was maintained on multivariate analysis for both overall cosmesis (P = .038) and skin telangiectasia (P = .031). CONCLUSION: Improved dose homogeneity with simple IMRT translates into superior overall cosmesis and reduces the risk of skin telangiectasia. These results are practice changing and should encourage centers still using two-dimensional RT to implement simple breast IMRT.

OBJECTIVE: To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery. DESIGN: Cross sectional observational study of registered and published trials. SETTING: Randomised controlled trials of interventions in patients undergoing a surgical procedure. DATA SOURCES: The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword "surgery". Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed. MAIN OUTCOME MEASURES: Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size. RESULTS: Of 818 registered trials found using the keyword "surgery", 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators' email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished. CONCLUSIONS: One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns.

Abstract Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).

Adults with an acquired flatfoot deformity may present not with foot deformity but almost uniformly with medial foot pain and decreased function of the affected foot (for a list of causes of an acquired flatfoot deformity in adults, see box 1).1 Patients whose acquired flatfoot is associated with a more generalised medical problem tend to receive their diagnosis and are referred appropriately. However, in patients whose “adult acquired flatfoot deformity” is a result of damage to the structures supporting the medial longitudinal arch, the diagnosis is often not made early.2 These patients are often otherwise healthier and tend to be relatively more affected by the loss of function resulting from an acquired flatfoot deformity. The most common cause of an acquired flatfoot deformity in an otherwise healthy adult is dysfunction of the tibialis posterior tendon, and this review provides an outline to its diagnosis and treatment. We seached PubMed for publications by using the keywords “flatfoot” and “tibialis posterior dysfunction”. ### Tibialis posterior dysfunction: a common condition Tibialis posterior dysfunction is well recognised by orthopaedic surgeons specialising in foot and ankle surgery and by podiatrists. However, greater general awareness of this condition is required,2 as most patients presenting to a general practitioner receive a diagnosis of ankle sprain or arthritis. By the time most patients present to a specialist foot and ankle clinic they have had the condition for several years and have consulted numerous doctors.3 Even general orthopaedic surgeons and physiotherapists often miss the diagnosis.3 However, tibialis posterior dysfunction need not remain a “specialist diagnosis” as it is usually diagnosed without any investigations, from a history and physical examination.2 Many patients benefit from relatively simple treatment, such as orthotic devices.4 Population based studies to identify the prevalence of tibialis posterior dysfunction are under way. In elderly people the condition …

Cerebral oxidative metabolism was studied using phosphorus magnetic resonance spectroscopy during the first week of life and neurodevelopmental outcome was assessed at 4 years in 62 infants who had clinical and/or biochemical evidence consistent with birth asphyxia (critically impaired intrapartum gas exchange). Twenty-one died and the neurodevelopmental status of the 41 who survived was assessed by a range of tests at age 4 years. The minimum recorded values for the cerebral phosphocreatine:inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed significant relations between the extent of derangement of neonatal oxidative metabolism and a range of adverse outcomes, including death, and at 4 years reduced head growth and the presence and severity of neuromotor impairments, overall neurodevelopmental impairments, and cognitive functioning. Strong correlations between the extent of derangement of neonatal oxidative metabolism and outcome at 1 and 4 years were also shown. We conclude that the severities of adverse outcomes at 1 and 4 years of age were closely related to the extent of cerebral energy derangement in the first week of life, and we also conclude that primary intrapartum hypoxic-ischaemic cerebral injury was generally responsible for the events that led to death, microcephaly, and impaired

BackgroundValidated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD).Study DesignProspective cohort study with validation in a separate cohort.Setting & ParticipantsCox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort).Factors44 baseline characteristics (including 30 blood and urine assays).OutcomesESRD and all-cause mortality.ResultsIn the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death.LimitationsOther important factors may have been missed because of limited study power.ConclusionsSimple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results. Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD). Prospective cohort study with validation in a separate cohort. Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort). 44 baseline characteristics (including 30 blood and urine assays). ESRD and all-cause mortality. In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death. Other important factors may have been missed because of limited study power. Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results.

OBJECTIVE: The choice of analgesia in the management of post-thoracotomy pain remains controversial. Although several alternative forms of post-thoracotomy analgesia exist, all have their disadvantages. Cryoanalgesia, localized freezing of intercostal nerves, has been reported to have variable effectiveness and an incidence of long-term cutaneous sensory changes. We carried out an animal study to assess the reversibility of histological changes induced by cryoanalgesia and a prospective randomized trial to compare the effectiveness of cryoanalgesia with conventional analgesia (parenteral opiates). METHODS: In six anaesthetized dogs, intercostal nerves were exposed to a varying duration of cryo-application (30, 60, 90 and 120 s). The nerves were biopsied and examined histologically at regular intervals over the following 6 months. In the clinical study, 200 consecutive patients undergoing thoracotomy were randomized to cryoanalgesia and conventional (parenteral opiates) analgesia groups. Postoperative pain scores, respiratory function tests and use of opiate analgesia were measured for the two groups. RESULTS: Following application of the cryoprobe, degeneration and fragmentation of the axons was evident with associated inflammatory changes. As the endoneurium remained intact, axonal regeneration took place after the resolution of axonal swelling. Over the course of weeks, recovery of the intercostal nerve occurred and was complete after 1 month for the 30 and 60 s groups. For nerves exposed to longer durations of cryoanalgesia, the time taken for complete recovery was proportionally increased. Clinically, there was a statistically significant (P<0.05) improvement in postoperative pain scores and use of opiate analgesia and an improvement (P>0.05) in respiratory function tests for patients in the cryoanalgesia group. The previously suggested cutaneous sensory changes resolved within 6 months with complete restoration of function. CONCLUSIONS: We suggest that cryoanalgesia be considered as a simple, inexpensive, long-term form of post-thoracotomy pain relief, which does not cause any long-term histological damage to intercostal nerves.

A series of 10 pectoralis minor vascularized muscle transfers to reanimate the face in unilateral facial palsy are presented. The procedure is carried out in two stages. The first stage constitutes a nerve graft from the functional contralateral facial nerve to the preauricular region of the paralyzed side. Six months later, the pectoralis minor is transferred to the denervated side of the face with restoration of its neurovascular pedicle. The muscle is well suited to its new position with respect to length and bulk, as well as its fanlike shape. The diameter of its vascular pedicle is comparable with the facial vessels. The results demonstrate function in 8 of the 10 grafts, the two failures relating to early vascular thrombosis rather than an inability to reinnervate the muscle grafts.

OBJECTIVE: To test the hypothesis that metformin therapy, given as an adjunct to insulin therapy, improves metabolic control in insulin-treated NIDDM patients with suboptimal glycemic control. RESEARCH DESIGN AND METHODS: A total of 33 subjects with insulin-treated NIDDM were investigated; all had commenced insulin after secondary failure of antihyperglycemic agents. Two randomized double-blind placebo-controlled crossover studies were run. In study 1 (n = 19), insulin-treated subjects with suboptimal glycemic control received 12 weeks of metformin 1 g b.i.d. and 12 weeks of placebo. In study 2 (n = 14), subjects already established on adjunctive metformin/insulin therapy stopped the metformin component and received 12 weeks of metformin at their baseline dosage (range 1-2.5 g) and 12 weeks of equivalent placebo. Fasting plasma glucose, HbA1c, and serum lipids were measured at baseline and midway through and at the end of each treatment phase. The effect of 12 weeks of metformin treatment was compared with the effect of 12 weeks of placebo in each study and in both studies combined. RESULTS: In study 1, metformin treatment was associated with significant improvements in fasting plasma glucose (mean 12-week difference from placebo [95% CI]: 5.8 mmol/l [3.5-8.1], P < 0.001) and HbA1c (1.6% [0.9-2.4], P < 0.001). In study 2, metformin treatment was associated with significantly lower fasting plasma glucose (5.3 mmol/l [0.6-9.9], P = 0.029) and lower HbA1c (2.4% [1.0-3.8], P = 0.003) compared with those for placebo. Study 2 also showed metformin treatment to be associated with significantly lower total cholesterol than that for placebo (1.0 mmol/l [0.1-1.9], P = 0.032) and lower LDL cholesterol (1.0 mmol/l [0.1-1.9], P = 0.028). This significant difference in serum lipids seen in study 2 was not seen in study 1, but was present when both sets of data were combined (n = 33, mean total cholesterol difference at 12 weeks [95% CI]: 0.6 mmol/l [0.1-1.1], P = 0.015). Metformin had no significant effect on triglyceride, HDL cholesterol, weight, or blood pressure. Two subjects on metformin withdrew because of side effects. CONCLUSIONS: Metformin, when given as adjunctive therapy, was well tolerated and improved glycemic control and lipid concentrations in patients with insulin-treated NIDDM whose diabetes was poorly controlled. These improvements could be maintained over the long term.

CONTEXT: Readmission to hospital for heart failure is common after recent discharge. Remote monitoring (RM) strategies have the potential to deliver specialised care and management and may be one way to meet the growing needs of the heart failure population. OBJECTIVE: To determine whether RM strategies improve outcomes for adults who have been recently discharged (<28 days) following an unplanned admission due to heart failure. STUDY DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Fourteen electronic databases (including MEDLINE, EMBASE and PsycINFO) were searched to January 2012, and supplemented by hand-searching relevant articles. STUDY SELECTION: All randomised-controlled trials (RCTs) or observational cohort studies with a contemporaneous control group were included. RM interventions included home telemonitoring (TM) (including implanted monitoring devices) with medical support provided during office hours or 24/7 and structured telephone support (STS) programmes delivered via human-to-human contact (HH) or human-to-machine interface (HM). DATA EXTRACTION: Data were extracted and validity was assessed independently by two reviewers. RESULTS: Twenty-one RCTs that enrolled 6317 patients were identified (11 studies evaluated STS (10 of which were HH, while 1 was HM), 9 studies assessed TM, and 1 study assessed both STS and TM). No trial of implanted monitoring devices met the inclusion criteria. Compared with usual care, although not reaching statitistical significance, RM trended to reduce all-cause mortality for STS HH (HR: 0.77, 95% credible interval (CrI): 0.55, 1.08), TM during office hours (HR: 0.76, 95% CrI: 0.49, 1.18) and TM24/7 (HR: 0.49, 95% CrI: 0.20, 1.18). Exclusion of one trial that provided better-than-usual support to the control group rendered each of the above comparisons statistically significant. No beneficial effect on mortality was observed with STS HM. Reductions were also observed in all-cause hospitalisations for TM interventions but not for STS interventions. Care packages generally improved health-related quality-of-life and were acceptable to patients. CONCLUSIONS: STS HH and TM with medical support provided during office hours showed beneficial trends, particularly in reducing all-cause mortality for recently discharged patients with heart failure. Where 'usual' care is less good, the impact of RM is likely to be greater.

Hematoma remains the most common complication of rhytidectomy and can lead to prolonged facial edema and skin necrosis. A number of ancillary procedures have been suggested to reduce hematoma, including dressings, drains, fibrin glue, tumescence, and adrenaline. The aim of this study was to investigate the statistical effect of these parameters on hematoma incidence in a large series of face lifts. Over an initial 6-year period, 678 consecutive face lifts were performed and included in the first part of the study. The effect of dressings, drains, fibrin glue, and tumescence on hematoma rate was investigated retrospectively. In the second part of the study, the specific effect of adrenaline was analyzed while all other parameters were kept constant. The 229 patients with adrenaline-containing infiltrations were compared with the 232 patients whose infiltration had no adrenaline. Retrospective analysis of both groups was performed using Fisher's exact test. In the first part of the study investigating 678 consecutive face lifts, no difference in hematoma rate (4.4 percent overall) was observed with the use of dressings (p > 0.5), drains (p > 0.4), fibrin glue (p > 0.6), or tumescence (p > 0.5). In the second part of the study, the specific effect of withdrawing adrenaline in a comparative group of 461 face lifts significantly reduced the incidence of hematoma requiring surgical evacuation (p < 0.0001). There was also a significant reduction in the incidence of minor hematoma requiring only aspiration (p = 0.02). There was no change in the incidence of any other face lift complications observed during this part of the study. This study found a significant reduction in the incidence of hematoma following face lifting. Although many of the suggested ancillary methods used to reduce hematoma did not produce any statistical reduction in the incidence of this complication, the exclusion of adrenaline had a profound effect. The technique and implications with respect to safety and outcome are described.