Non-steroidal anti-inflammatory agents and anastomotic leak rates across colorectal cancer operations and anastomotic sites: A systematic review and meta-analysis of anastomosis specific leak rate and confounding factors.

BACKGROUND: Surgical intervention presents a fundamental therapeutic choice in the management of colorectal malignancies. Complications, the most serious one being anastomotic leak (AL), still have detrimental effects upon patients' morbidity and mortality. We aimed to assess whether NSAIDs, and their sub-categories, increase AL in colonic anastomoses and to identify whether this affects specific anastomotic sites. MATERIALS AND METHODS: A systematic search of MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, Science Direct, Google Scholar was conducted between January 1, 1999 till the October 30, 2020. Cohort studies and randomized control trials examining AL events in NSAID-exposed, colorectal cancer patients were included. NSAIDs were grouped according to the 2019 NICE guidelines in non-specific (NS-NSAIDs) and specific COX-2 inhibitors. The primary outcome was AL events in NSAID-exposed patients undergoing operations with either ileocolic, colocolic or colorectal anastomoses. Secondary outcomes included NSAID category-specific AL events and demographic confounding factors increasing AL risk in this patient population. RESULTS: Fifteen studies involving 25,395 patients were included in the systematic review and meta-analysis. Of all anastomoses, colocolic anastomoses were found to be statistically more prone to AL events in the NS-NSAID-exposed population [OR 3.24 (95% CI 0.98-10.72), p = 0.054]. Male gender was an independent confounder increasing AL rate regardless of NSAID exposure. CONCLUSION: The association between NSAID exposure and AL in oncology patients remains undetermined. Whilst in present work, colocolic anastomoses appear to be more sensitive to AL events, the observed association may be anastomotic site and NSAID-category dependent.

Predictive value of bile duct dimensions measured by ultrasound in neonates presenting with cholestasis.

OBJECTIVES: : The significance of extrahepatic bile duct dilatation on ultrasound examination in jaundiced infants is often uncertain. We wished to clarify the diagnostic and prognostic significance of the present finding in neonatal conjugated hyperbilirubinaemia. PATIENTS AND METHODS: : We retrospectively enrolled all of the infants younger than 3 months with extrahepatic biliary dilatation > or =1.2 mm (nonfasting ultrasound) who presented during the study period. We reviewed clinical, radiological, and laboratory data to determine mode of presentation, diagnosis, interventions, and long-term outcome. RESULTS: Seventy-six infants (41 male) were identified, all of whom were referred with conjugated hyperbilirubinaemia. Median gestational age was 39 weeks (range 24-42 weeks). Inspissated bile was the most common diagnostic category, whereas congenital choledochal malformation was the diagnosis made in 13% infants. Dilatation was an incidental finding in 9% of the infants. Seventeen percent of infants had required either surgical or radiological intervention by the time of follow-up. Overall, 41% infants had spontaneous resolution of bile duct dilatation, including 8% who had "grown into" an unchanged duct size rather than involution of dilatation. The median size of bile duct at presentation for those who required intervention was 4.7 versus 2 mm for the remainder (P < 0.001). Of those who resolved spontaneously, the median size of duct at presentation was 1.8 mm. CONCLUSIONS: : Bile duct dilatation <3 mm (nonfasting ultrasound) with neonatal cholestasis is unlikely to be of significance whereas >4 mm is likely to be associated with choledochal malformation or need for intervention. The intermediate group is likely to be associated with inspissated bile syndrome following resolution of which innocent biliary dilatation may persist.

Interactive effects of genotype and social environment on alcohol consumption in female twins.

Information about drinking practices has been obtained by questionnaire from 1,984 monozygotic and dizygotic adult female twin pairs from the Australian twin register, including 1,690 pairs where both twins have used alcohol. Statistical analyses of these data show that marital status is an important modifier of genetic effects on drinking habits. In young twins, aged 30 years or less, genetic differences between individuals account for only 31% of the variance in alcohol consumption of married respondents, but for 60% of the variance of unmarried respondents. In twin pairs, aged 31 years or more, genetic differences account for 46-59% of the variance in married twins, but for 76% of the variance in unmarried twins. In our young sample (average age 35 years) there is no evidence that individuals genetically predisposed to heavy drinking are any less likely to be married than the rest of the population. Some alternative explanations of these findings are also rejected.

The inheritance of alcohol consumption patterns in a general population twin sample: II. Determinants of consumption frequency and quantity consumed.

Genetic models were fitted to self-report data on frequency of alcohol consumption and average quantity consumed when drinking, from 3,810 adult Australian twin pairs. Frequency of consumption is determined both by an abstinence dimension, which is strongly influenced by shared environmental effects but not by genetic effects, and by an independent frequency dimension, which is influenced by genetic effects in both sexes and possibly by shared environmental affects in men. Quantity of alcohol consumed is likewise determined by an environmental abstinence dimension and by an independent and partly heritable quantity dimension. The best-fitting model allowed for two routes to abstinence: those who were not abstainers by virtue of their position on the abstinence dimension could nonetheless become abstainers by their position on the second, frequency (or quantity) dimension. Heritability estimates were 66% in women and 42-75% in men, for frequency; and 57% in women and 24-61% in men, for quantity.

A survey on the treatment of atrial fibrillation in South Africa.

BACKGROUND: The burden of cardiovascular disease is expected to escalate in developing countries. However, studies and guidelines concerning atrial fibrillation (AF) are restricted to the developed world. OBJECTIVES: To assess the treatment modalities of AF in South Africa. METHODS: A cross-sectional, observational, multicentre, national registry of the treatment of 302 patients with AF was conducted from February 2010 to March 2011. Specific drug use for rate or rhythm control, as well as drug use for stroke prevention, was surveyed. Events during the 12 months prior to the survey were also characterised, including non-drug treatments, resource utilisation and complications. RESULTS: The single most prevalent clinical characteristic was hypertension (65.9%). Rhythm control was being pursued in 109 patients (36.1%) with class Ic and class III antiarrhythmic agents, while rate control, mainly with beta-blockers, was pursued in the remainder of the patients. Concomitant use of other cardiovascular drugs was high, and 75.2% of patients were on warfarin for stroke prevention. There was a high burden of AF-related morbidity during the preceding year, with 32.5% reporting a history of heart failure, 8.3% a stroke and 5.3% a transient ischaemic attack. Therapeutic success, as defined by either the presence of sinus rhythm or rate-controlled AF, was achieved in 86.8% as judged clinically by the treating physician, but in only 70.2% according to the electrocardiogram criterion of heart rate ≤80 bpm. CONCLUSION: There were no striking differences from previously reported registries worldwide. The lack of application of strict rate control criteria is highlighted.

Causes of variation in drinking habits in a large twin sample.

A genetic analysis of alcohol consumption in 3810 pairs of adult twins is reported. When no correction was made for age, individual environmental variance, including non-repeatable errors of reporting, accounted for approximately 44% of variation in both sexes. In females, there was no evidence of shared environmental effects and 56% of the variance was genetic in origin. In males, only 36% of the variance was genetic and common environmental effects accounted for the remaining 20% of individual differences. For females, the results for younger (30 years and under) and older (over 30) twins were similar. For males, however, the effect of age was striking. In younger male twins over 60% of the variance was genetic in origin, with the remaining variance due to environmental influences unique to the individual. In older twins genetic differences do not appear to be important, with approximately 50% of the total variance due to individual environmental differences and the remaining 50% due to the effect of the common family environment. Our results suggest that both age and sex need to be considered when analysing the causes of variation in alcohol consumption.

Flecainide acetate in the treatment of resistant supraventricular arrhythmias.

Thirty-one patients with a variety of supraventricular tachyarrhythmias resistant to conventional anti-arrhythmic therapy were treated with flecainide acetate, a new class Ic antiarrhythmic drug. The mean follow-up period was 7 months. Control was attained in 19 patients (62%) initially, and the long-term success rate was 39%. In 7 of the 19 controlled patients the drug was subsequently discontinued because of major side-effects, which included negative inotropism and pro-arrhythmia. The mechanisms and implications of these side-effects are reviewed.

Intravenous acebutolol raises serum potassium in acute myocardial infarction.

Hypokalaemia commonly occurs in acute myocardial infarction (AMI) and may be caused by elevated serum levels of adrenaline, allegedly by beta 2-adrenergic mediated influx of potassium (K) into cells. We investigated the effect on serum K of intravenous acebutolol (a relatively beta 1-selective agent) in 50 patients with AMI. Serum K was measured before and 1 hour after drug administration. The same measurements were made in a comparable control group of 30 patients who did not receive the drug. Mean serum K rose from 3.58 to 3.81 mEq/l (P less than 0.005) in the treated group. No significant change occurred in the control group. The rise in serum K could not be correlated with prior beta-blocker therapy, zone of infarction, prior diuretic therapy, or gender of the patient. We conclude that the administration of intravenous acebutolol after AMI raises serum K, despite the fact that this beta receptor blocking agent is relatively beta 1-selective. Since hypokalaemia is associated with an increased risk of ventricular fibrillation, it should no longer be assumed from acute intervention trials with beta-blockers in AMI which had mortality or arrhythmias as end-points, that beneficial effects were necessarily due to limitation of infarct size or to a direct anti-arrhythmic action of the drugs. Future trials should take the effect on serum K levels into consideration.

Evidence for directional non-additivity in the genetics of finger ridge counts.

A genetical analysis of variation in finger ridge counts of 221 pairs of twins and 80 pairs of opposite sex siblings has been carried out. Negative regression of DZ and sibling pair variances on pair means suggests the action of non-additive genes or unequal gene frequencies tending to increase finger ridge counts. Negative skewness of the distributions supports this view. While models including dominance or epistasis are not a significant improvement over purely additive genetic models, it is regarded as important that large and positive values of non-additive genetic variance are estimated. The evolutionary importance of dominance and epistasis for greater finger ridge counts is discussed.

Genetic covariation between neuroticism and the symptoms of anxiety and depression.

A genetic analysis of the trait of neuroticism and symptoms of anxiety and depression in 3,810 pairs of adult MZ and DZ twins is reported. Differences between people in these measures can be explained simply by differences in their genes and in their individual environmental experiences. There is no evidence that environmental experiences that are shared by cotwins, such as common family environment or social influences, are important. There are differences between the sexes in gene action affecting neuroticism, and genetic effects become more pronounced with age in females. The lack of evidence for dominance variance affecting neuroticism contrasts well with the detection of considerable genetical nonadditivity for extraversion in the same sample and reinforces the view that these two traits are not only statistically, but also genetically, quite independent. An analysis of the causes of covariation between anxiety, depression, and neuroticism shows that additive gene effects are more important causes of covariation than environmental factors. Genetic variation in symptoms of anxiety and depression is largely dependent on the same factors as effect the neuroticism trait. However, there is also evidence for genetic variation specific to depression.

Superlattice formation in mixtures of hard-sphere colloids

We report a detailed experimental study of the superlattice structures formed in dense binary mixtures of hard-sphere colloids. The phase diagrams observed depend sensitively on the ratio alpha=R(S)/R(L) of the radii of the small (S) and large (L) components. Mixtures of size ratio alpha=0.72, 0.52, 0.42, and 0.39 are studied. The structures of the colloidal phases formed were identified using a combination of light-scattering techniques and confocal fluorescent microscopy. At alpha=0.39, ordered binary crystals are formed in suspensions containing an equal number of large and small spheres which microscopy shows have a three-dimensional structure similar to either NaCl or NiAs. At the larger size ratio, alpha=0.52, we observe LS2 and LS13 superlattices, isostructural to the molecular compounds AlB2 and NaZn13, while at alpha=0.72 the two components are immiscible in the solid state and no superlattice structures are found. These experimental observations are compared with the predictions of Monte Carlo simulations and cell model theories.

Sex differences in the inheritance of some anthropometric characters in twins.

Biometrical genetical techniques have been applied to the analysis of certain anthropometric characters measured in 134 pairs of adult twins. After allowing for assortative mating it appears that there is a family environment (E2) component for variation in height larger than previously reported. "Fatness" traits - weight, ponderal index, and skinfold thickness - all show higher heritabilities in males and substantial E2 components in females, and reasons for this are discussed. The same is true for cephalic index and forearm length but the reason for these differences is not so obvious. Head length shows a much higher heritability than head breadth. A larger sample of DZ opposite-sex pairs would allow more powerful discrimination, but the variety of patterns of variation revealed by the model-fitting approach used here justify its use over more traditional techniques.

Anxiety disorders and neuroticism: are there genetic factors specific to panic?

Data from 2,903 adult same-sex twin pairs were analysed to investigate whether the genetic determinants of symptoms of panic are different from those underlying the neuroticism personality trait. Our results suggest that much of the genetic variation influencing the physical symptoms associated with panic is of the nonadditive type, perhaps due to dominance or epistasis. In both sexes these nonadditive genetic effects on physical symptoms influence the reporting of "feelings of panic". In males they also account for as much as half the genetic variance in neuroticism. The remainder is additive and also accounts for the balance of genetic variation in "feelings of panic". In females genetic variance in neuroticism is entirely additive but is not an important source of covariation with either panic symptom. Thus, symptoms of panic seem to be shaped in part by unique genetic influences which do not affect other anxiety symptoms. That a substantial part of the genetic variance in neuroticism in males may be due to the nonadditive effects on physical symptoms of panic may help to explain the rather low correlation between the genetic influences found to affect neuroticism in males and their counterparts in females.

Efficacy of oral sotalol in reentrant ventricular tachycardia.

Oral sotalol was given to 64 patients (78% postinfarction) with recurrent, reentrant ventricular tachycardia (VT) during an average follow-up period of 19.7 months. Fifty-nine (92%) patients had previously experienced recurrent ventricular tachycardia, in spite of having received an average of three conventional antiarrhythmic drugs (13 had previously failed on other Class III drugs). The nature and mechanism of the VT was proved with electrophysiologic testing (EPS), and the chronic sotalol dosage was determined by repeated EPS at 3- to 4-day intervals until the VT was no longer inducible. Sotalol failed in five patients and was discontinued in six patients because of severe side effects (three proarrhythmic effects, including two with torsades de pointes)--a total of 18%. Sotalol was successful alone in 42 patients (65%) and in combination with another antiarrhythmic drug in 11 patients (18%). The average dose of sotalol required for success was 589 mg; 658 mg was the mean daily dose when given alone and 486 mg when given in combination. Side effects were common and were due mainly to the beta-blocking effects of sotalol. Dual chamber pacing was required by 11 patients because of poorly tolerated bradycardia, and 14 patients remained symptomatic from worsening of the cardiac failure in spite of pacing, increased diuretics, or vasodilator therapy. The average drug dosage was the same for symptomatic (680 mg) and asymptomatic (627 mg) patients. Sotalol is a valuable antiarrhythmic drug for reentrant ventricular tachycardia. High doses are needed, and at these doses the beta-blocking activity is responsible for most of the side effects.

Late potentials, ventricular stimulation and ventricular tachycardia.

Late potentials are depolarizations which arise from areas of delayed ventricular activation and may indicate a propensity for ventricular tachycardia. Sixty-four subjects were assessed by non-invasive measurement. Late potentials were not present in 20 subjects with normal hearts nor in 6 patients with cardiac disease but with no evidence of ventricular tachycardia (VT). Seventeen of 20 patients with recurrent sustained ventricular tachycardia (RSVT) and 2 of 10 patients with unsustained VT had late potentials. None of the 6 patients with automatic VT or the 2 patients with torsades de pointe had late potentials. In a subgroup of 28 symptomatic patients in whom programmed ventricular stimulation was performed, late potentials correlated with inducibility of sustained VT (P less than 0.05). Late potentials may therefore serve as a useful marker of RSVT and confirm a re-entrant mechanism of VT.

Directional dominance for low IgM and IgA levels.

A biometrical genetical analysis of IgG, IgM, and IgA levels in 134 sets of twins is reported. High heritabilities, around .8, are found for all three immunoglobulin levels, and possible reasons for lower heritabilities found in family studies are discussed. There is evidence for genetical dominance tending to decrease IgM and IgA levels, but there is no evidence for the importance of family environment although the presence of dominance may make its detection difficult. The causes of covariation in the three measurements are unclear in males but in females appear to be mainly environmental in correlations with IgA and equally genetical and environmental in the IgG-IgM correlation.

A twin study of skin reflectance.

Skin colour has been measured by reflectance spectrophotometry on 134 pairs of twins at three sites, forehead, forearm and upper arm, each at three wavelengths, 425, 545 and 685 nm. Tanning is measured most reliably at 685 nm and at this wavelength the heritability is high at the least exposed upper arm site, intermediate on the forearm, while on the forehead variation is entirely environmentally determined. The same gradient is observed, through less strikingly at 545 nm, but at 425 nm, where haemoglobin is reflecting most of the light, the degree of genetic determination is the same at all sites.

Transmission of social attitudes.

Data gathered in Australia and England on the social attitudes of spouses and twins are largely consistent with a genetic model for family resemblance in social attitudes. There is substantial assortative mating and little evidence of vertical cultural inheritance.

Further experience with long-term captopril therapy in severe refractory congestive heart failure.

Fifty patients in severe congestive heart failure (CHF) were treated with captopril (Capoten; Squibb), an oral angiotensin-converting enzyme inhibitor, over a 2-year period (range 3-24 months, mean 8,6 +/- 7,7 months). At entry, all patients were in New York Heart Association (NYHA) functional class IV despite high-dose diuretic and conventional vasodilator therapy. The overall cumulative survival at 6 and 12 months was 64% and 53% respectively. There were 22 deaths (18 during captopril therapy) including 8 sudden deaths. At 2-year follow-up (mean 14,6 +/- 6,9 months), there were 25 survivors on captopril; 18 in NYHA class I or IIS and 7 in class IIM or III. Diuretic requirements were decreased considerably in all. Side-effects were common but transient and in no case did captopril have to be withdrawn. We confirm our earlier conclusion that captopril has long-term beneficial effects and is a highly effective drug in the treatment of patients with CHF refractory to currently accepted therapy. Sudden death despite satisfactory clinical improvement continues to cause concern. Precautions which may reduce or avoid these are briefly discussed.