Prenatal maternal stress and atopic diseases in the child: a systematic review of observational human studies.

BACKGROUND: A growing number of studies suggest that maternal stress during pregnancy promotes atopic disorders in the offspring. This is the first systematic review to address prenatal maternal stress (PNMS) and the subsequent risk of atopy-related outcomes in the child. METHODS: The review was performed in accordance to the PRISMA criteria. We searched and selected studies in PubMed, Scopus, Embase and PsychINFO until November 2014. RESULTS: Sixteen (with 25 analyses) of 426 identified articles met the review criteria. Five main PNMS exposures (negative life events, anxiety/depression, bereavement, distress and job strain) and five main atopic outcomes (asthma, wheeze, atopic dermatitis, allergic rhinitis and IgE) were assessed across the studies. Overall, 21 of the 25 analyses suggested a positive association between PNMS and atopic outcomes. Of the 11 exposure-response analyses reported, six found statistically significant trends. CONCLUSION: This systematic review suggests a relationship between maternal stress during pregnancy and atopic disorders in the child. However, the existing studies are of diverse quality. The wide definitions of often self-reported stress exposures imply a substantial risk for information bias and false-positive results. Research comparing objective and subjective measures of PNMS exposure as well as objective measures for atopic outcome is needed.

The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: a systematic review and meta-analysis.

Circadian- and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. The effect of melatonin on depression/depressive symptoms has been investigated previously. This systematic review assesses the current evidence of a therapeutic- and prophylactic effect of melatonin in adult patients against depression or depressive symptoms. A search was performed in The Cochrane Library, PubMed, EMBASE and PsycINFO for published trials on November 14th 2013. Inclusion criteria were English language, RCTs or crossover trials. Our outcome was measurement of depression/depressive symptoms with a validated clinician-administered or self-rating questionnaire. PRISMA recommendations were followed and the Cochrane risk-of-bias tool used. Ten studies in 486 patients were included in the final qualitative synthesis and four studies, 148 patients, were included in two meta-analyses. Melatonin doses varied from 0.5-6 mg daily and the length of follow-up varied from 2 weeks to 3.5 years. Three studies were done on patients without depression at inclusion, two studies in patients with depression and five studies included a mixture. Six studies showed an improvement in depression scores in both the melatonin and placebo groups but there was no significant difference. One study showed a significant prophylactic effect and another found a significant treatment effect on depression with melatonin compared to placebo. The two meta-analyses did not show any significant effect of melatonin. No serious adverse events were reported. Although some studies were positive, there was no clear evidence of a therapeutic- or prophylactic effect of melatonin against depression or depressive symptoms.

Sleep disturbances and changes in urinary 6-sulphatoxymelatonin levels in patients with breast cancer undergoing lumpectomy.

BACKGROUND: Sleep disturbances and changes in self-reported discomfort and melatonin secretion are common in the post-operative period. We aimed to study the distribution of sleep stages in the perioperative period and evaluate changes in secretion of the melatonin metabolite aMT6s and subjective parameters of sleepiness, pain, general well-being and fatigue in patients undergoing surgery for breast cancer. METHODS: Twelve patients, 30-70 years, undergoing lumpectomy were included. Polysomnography was performed the night before surgery (PREOP), the night after (PO1) and 14 days after (PO14). Recordings were scored as awake, light-sleep, slow-wave sleep and rapid-eye-movement (REM) sleep. Sleep stages were analysed as % of total sleep time (TST). Self-reported discomfort was assessed using questions about the level of fatigue, well-being, pain and sleepiness. Urinary aMT6s was measured by radioimmunoassay. RESULTS: There was significantly decreased REM sleep on PO1 (5.9% of TST) compared with PREOP (18.7% of TST) (P < 0.005). An increase in light sleep was observed on PO1 (68.4% of TST) compared with PREOP (55.0% of TST) (P < 0.05). No significant changes in TST, sleep latency, sleep period or total time awake were found. The observed sleep changes were normalised after 2 weeks. No significant changes were found in pain, well-being, fatigue or sleepiness. Night secretion of aMT6s showed a trend towards a decrease from PREOP to PO1 (P = 0.09) and normalisation on PO14 (P = 0.27 between PREOP and PO14). CONCLUSION: Patients with breast cancer undergoing lumpectomy had significantly disturbed sleep architecture the night after surgery, and these changes were normalised after 2 weeks.

Reproductive prognosis in daughters of women with and without endometriosis.

STUDY QUESTION: Do daughters of women with endometriosis exhibit an increased risk of endometriosis and impaired long-term reproductive prognosis when compared with daughters of women without endometriosis? SUMMARY ANSWER: Daughters of women with endometriosis have over a 2-fold higher risk of endometriosis but no difference in long-term reproductive prognosis compared with controls. WHAT IS KNOWN ALREADY: Several studies have found an increased prevalence of endometriosis in sisters and mothers of women with endometriosis, but none have examined the long-term reproductive prognosis in daughters of these patients. STUDY DESIGN, SIZE, DURATION: A controlled historical cohort study with a 33-year follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among women 15-49 years old during the period 1977-1982, 24 691 were diagnosed with endometriosis during the study period. These women were age matched to 98 764 women without endometriosis. Daughters of these two groups were followed until 31 December 2009 for an endometriosis diagnosis and reproductive outcomes. Women were excluded from the study at death or if they emigrated. MAIN RESULTS AND THE ROLE OF CHANCE: Except for 4-6% of emigrated women, the follow-up rate of the study was almost 100%. Daughters of women with endometriosis (n = 12 389) had a 2.12-fold (95% confidence interval 1.89-2.37, P < 0.0001) increased risk of being diagnosed with endometriosis, compared with daughters of women without endometriosis (n = 52 371). Delivery rate, risk of spontaneous abortions and ectopic pregnancies were similar for the two cohorts, whereas induced abortions were slightly more frequent in the exposed cohort. LIMITATIONS, REASONS FOR CAUTION: The most important limitation of the study was the lack of data concerning the attempt to become pregnant. Also, some women with endometriosis might never be diagnosed with the condition. This applies to both the control mothers and the control daughters, but also the daughters of mothers with endometriosis. Other limitations are lack of accounting for potential confounders and the lack of data on preterm birth. However, the influence of most confounding factors was expected to be minimal because of the close matching by age of controls. WIDER IMPLICATIONS OF THE FINDINGS: The external validity of the study is expected to be high owing to the unselected inclusion criteria. The encouraging finding was that despite the increased risk of being diagnosed with endometriosis, daughters of women with endometriosis have a reproductive prognosis comparable with that of daughters of women without endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The Department of Gynaecology at Rigshospitalet University Hospital, Copenhagen, covered all expenses of the study. Ø.L. has, within the last 3 years, received honoraria for speeches in pharmacoepidemiological issues and has been expert witness in a legal US case in 2011-2012. None of the other authors have any conflicts of interest.

Circadian aspects of post-operative morbidity and mortality.

It has been well established that there exists a circadian concentration of cardiovascular, cerebrovascular and cardiopulmonary events. The aim was to describe aspects of circadian variation in relation to cardiovascular, cerebrovascular and thromboembolic diseases and to describe the literature concerning post-operative circadian disturbances. We also present the literature concerning circadian variation in post-operative morbidity and mortality. PubMed and the Cochrane database were searched for papers using a combination of 'circadian,''surgery,''post-operative,''mortality' and 'morbidity.' Eleven relevant studies were found, and seven of these were excluded due to the use of time of surgery and not time of morbidity or mortality as the main variable. The results from the four articles showed a circadian distribution of morbidity and mortality that mimics the one seen without surgery. There is a peak incidence of myocardial ischemia, fatal thromboembolism and sudden unexpected death in the morning hours. A circadian variation exists in post-operative morbidity and mortality. The observed circadian variation in post-operative morbidity and mortality may warrant a chronopharmacological approach to patients in the perioperative period. The underlying pathophysiological mechanisms should be the focus for future studies.

Frequency and motives of blood glucose self-monitoring in type 1 diabetes.

AIMS: Recommendations for self-monitoring of blood glucose (SMBG) from the DCCT have not been implemented with the same rigour as recommendations for intensifying insulin therapy. We assessed the frequency of and motives for SMBG and compared SMBG behaviour with clinical, behavioural and demographic characteristics. METHODS: Cross-sectional Danish-British multicentre survey of 1076 consecutive patients with type 1 diabetes, who completed a detailed questionnaire on SMBG and related issues. The key variables were test frequency and motive. RESULTS: SMBG was performed daily by 39% of the patients and less than weekly by 24%. Sixty-seven percent reported to perform routine testing, while the remaining 33% only tested when hypo- or hyperglycaemia was suspected. Age, gender, and level of diabetes-related concern were associated with test pattern. Reported frequencies of mild and severe hypoglycaemia and awareness of hypoglycaemia were independently associated with testing behaviour, whereas the presence of late diabetic complications was not. Lower HbA1c was associated with more frequent testing. CONCLUSION: Patient compliance regarding SMBG is limited. Thus, almost two thirds of the patients do not perform daily SMBG and one third do not perform routine tests.

Randomised study of Lichtenstein compared with Shouldice inguinal hernia repair by surgeons in training.

OBJECTIVE: To compare the outcome following Lichtenstein open mesh technique or Shouldice repair for inguinal hernia operated on by surgeons in training. DESIGN: Prospective, randomised, trial. SETTING: District hospital, Sweden. SUBJECTS: 200 men with primary inguinal hernias. INTERVENTIONS: Lichtenstein mesh repair or Shouldice repair. MAIN OUTCOME MEASURES: Duration of operation, postoperative pain assessed by visual analogue scale (VAS), complications within 30 days, duration of sick leave, and recurrence within one year. RESULTS: 178 patients were available for evaluation (n = 89 in each group). There were no significant differences in duration of operation, pain score, or incidence of postoperative complications. Patients in the mesh group took significantly less sick leave (mean 18.2 days) than those in the Shouldice group (23.8 days, p<0.05). The number of recurrences differed significantly between the groups with 9 in the Shouldice group and none in the mesh group (p<0.01). CONCLUSION: For surgeons in training the Lichtenstein open mesh technique is a better method of inguinal hernia repair than the Shouldice technique. The outcome is better for the patients and it is more cost-effective.

Variations in the diagnostic process among urologists in one region recorded using an interactive computer program.

To analyse how male cases suffering from lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are handled within a well-defined health-care region in Scandinavia, an interactive computer program containing 20 cases suffering from LUTS due to BPH was used for recording the diagnostic process and the treatment decisions; 37 out of a total of 50 urologists practicing within a small health region participated. The diagnostic process varied considerably due to a varying choice of diagnostic tests and the large differences in interpreting the qualities described by the tests. The probability that a patient would be offered a treatment within the region was analysed. For many patients the probability that a treatment was chosen was in the vicinity of 50%. No treatment probability was correlated to the symptom score of the patients. While the probability that a transurethral prostatic resection would be offered to the patients within the region was correlated significantly to urodynamic variables, residual urine and to cystoscopy findings, the probability that transurethral microwave or finasteride therapy would be offered was not correlated to any of the described qualities. The costs of the diagnostic process in all the patients incurred by each of the urologists varied by up to 500%. It was estimated that approximately 40% of the costs involved diagnostic tests that did not influence the decision to offer or not to offer treatment. In conclusion, the enormous variations in the handling of the cases recorded in the study stress the need that a management formula should be used in the handling of patients with LUTS.

The agreement among urological experts on the diagnostic management of patients with common urological problems.

OBJECTIVE: To assess the level of agreement among randomly selected international urologists on the diagnostic management of patients with prostate cancer, bladder cancer, urinary stones or lower urinary tract symptoms (LUTS) arising from benign prostatic hyperplasia (BPH). METHODS: A computer program was used to provide an unbiased format of 53 simulated patients, comprising 13 with prostate cancer, 10 with bladder cancer, 10 with stones in the upper urinary tract and 20 with LUTS from BPH. For each case, the history was provided to the user while information from 60 diagnostic tests could be chosen interactively. Thirty-three university-based urologists participated in the study. The probability that a certain test was used by them in a certain patient [P(test)] and the related costs (Swedish 1995 prices) were recorded. The probability that two urologists would agree (relative measure of agreement, RMA) on whether or not to use one particular test in a certain case was RMA(test) = P(test)2 + [1-P(test)]2 and the mean of this RMA(test) for a certain patient [RMA(case)] was used as a measure of the inter-individual agreement among the urologists on the diagnostic management. The significance levels of the generalized kappa statistic, KG, were also calculated. The correlation between the RMA(case) and the diagnostic groups was analysed. RESULTS: The KG was statistically significant for all cases; the RMA(case) was significantly correlated with the diagnostic groups (rs = 0.86). The agreement in the diagnostic management was the strongest for stones, then for bladder cancer and prostate cancer, and the weakest for BPH. The mean cost for the diagnostic evaluation for one case varied from $455 to $1771 (mean 898) and varied in the diagnostic groups, i.e. $1718 for prostate cancer, $947 for bladder cancer, $400 for stones and $594 for BPH. CONCLUSION: The diagnostic management of urological patients varies greatly among urological experts from the industrial world. As a consequence, the related diagnostic costs might vary by about 400% if prices were similar everywhere. The agreement on the diagnostic management of cases is strongly correlated to the diagnosis. LUTS from BPH seems to be managed with the poorest agreement.

The urological management of men with lower urinary tract symptoms, recorded using an interactive computer program.

OBJECTIVE: To analyse the level of agreement among urologists from the industrialized world in the management of men with lower urinary tract symptoms (LUTS). METHODS: Thirty-three urological departments participated in the study. A computer program was used to provide an unbiased format of 18 simulated cases of men with LUTS which individual urologists then evaluated diagnostically and made therapeutic decisions about their management. The management of the patients was assessed for the probability that a diagnostic test was used, that a therapy was offered to a particular patient, the first-choice therapies selected, the mean cost and range for the diagnostic process per patient and the number of first-choice therapies offered by one urologist for all the patients. Various discriminators for these therapeutic decisions were evaluated, analysing the correlations between the information provided by the diagnostic tests and the probability of a particular therapy. RESULTS: For the 18 patients, the urologists, as a first choice, treated a mean (SD, range) of 8.3 (3.4, 3-16) patients with TURP, 3.9 (3.6, 0-11) with alpha-blockers, 2.3 (1.7, 0-6) with watchful waiting and 1.7 (2.4, 0-9) with finasteride. The other therapy options were only offered as a first choice by a few of the urologists in a few of the cases. The mean (SD, range) cost per patient of the diagnostic process was US$ 594 (209, 326-1350). CONCLUSION: There was considerable disagreement among the urologists about the management of men with LUTS, which included both the choice of diagnostic tests and the criteria for offering therapy to patients. If such disagreement prevails generally, it may be detrimental for the outcome of patients seeking medical attention for LUTS, and the cost of the medical care of these patients will be unnecessarily high.

The use of a simple home flow test as a quality indicator for male patients treated for lower urinary tract symptoms suggestive of bladder outlet obstruction.

OBJECTIVE: To evaluate the performance of a simple home flow test (HFT) in the examination and follow-up of patients suffering from lower urinary tract symptoms suggestive of bladder outlet obstruction. METHODS: One hundred seventy-two patients who were treated with either transurethral resection of the prostate or transurethral microwave therapy were included. Symptom evaluation, HFT and uroflowmetry were done before and 3 months following treatment. The patients' opinions about the need for further therapy and the effect of therapy were categorised at the follow-up. RESULTS: The HFT correlated strongly with the maximum flow rate (Qmax) both before and after therapy and it was better correlated to the symptoms of the patients and to the subjective effect of therapy compared to the Qmax. CONCLUSION: HFT is a cost-saving diagnostic technique for the classification of urinary flow and should be useful as a quality indicator in large-scale health care management programs.

Pre treatment decision making in prostatism--a stochastic analysis based on the most used diagnostic tests.

In order to estimate the probabilities that a patient would belong to subgroups created by the diagnostic tests most used by European urologists four hundred and twenty-one consecutively referred prostatism patients were studied. It was demonstrated that all the qualities described by these tests were distributed in such a way that the presumed accuracy of the tests might result in a 20 per cent variance in the number of treated patients. A simple self administered home flow test, which was significantly correlated to the maximum flow rate, was shown to be stronger correlated to the symptoms of the patients compared to any other quality. A stochastic table for prostatism was constructed, which may be used for estimations of the influence different decision making may have on the outcome of treatments in this kind of patients.

Attitudes of European urologists to early prostatic carcinoma. I. Diagnostic work-up on suspected prostatic cancer cases.

The diagnostic work-ups of 656 European urologists on theoretical cases of suspected early prostatic carcinoma were surveyed. The diagnostic work-ups varied considerably among the urologists. There was strong agreement that digital rectal examination (DRE) and prostate-specific antigen (PSA) should be used routinely in these cases, but there was a lack of agreement concerning the use of transrectal ultrasound examination (TRUS), prostate biopsies and bone scan. However, the use of TRUS, bone scan and biopsies was correlated positively to the PSA level and negatively to age (p < 0.0001), but was not correlated to whether the patient was asymptomatic or suffered from prostatism. Ninety-two percent of the urologists would perform biopsies if a palpable lesion were present. If the PSA was elevated, 22% would use biopsies if it was 7 ng/l, 62% if it was 15 ng/l and 83% if it was 35 ng/l. These results indicate that a majority of European urologists would attempt to diagnose prostatic cancer with biopsies only when results of DRE and PSA predict a high risk that the cancer is no longer organ-confined.

Attitudes of European urologists to early prostatic carcinoma, II. Attitude to therapy and to screening examinations.

The attitudes of 656 European urologists toward therapy of localized prostatic cancer (PC) and screening examinations of the male population for PC were surveyed. Eighty percent of the urologists would offer curative therapy to a 60-year-old patient with localized PC, while 20% would offer watchful waiting or hormonal therapy. The choice of curative therapy was not correlated to the grade of the cancer. Radical prostatectomies were offered 2.5 times as often as external beam radiotherapy. The number of radical prostatectomies performed was considered to be increasing by 56% of the urologists surveyed, decreasing by 10% and stable by 34%. Fifty-five percent thought that screening for prostate cancer should be undertaken in their country, but only 35% believed this would decrease mortality from prostate cancer. A majority would include digital rectal examination, prostate-specific antigen and symptom evaluation in a screening program. Agreement among urologists from different European countries regarding the handling of early prostatic cancer is poor. Large regional differences were observed with a more active attitude to therapy and screening in southern and central Europe. Attitudes to screening and to therapy, however, were only weakly correlated. In conclusion, it seems paradoxal that many urologists who would offer curative therapies to patients with localized PC would not take steps to diagnose this disease via screening of the male population.

Prostatism symptoms in a randomly selected population: introduction of a patient administered population based symptom evaluation score.

A questionnaire concerning micturition symptoms and bother was answered by 2559 (66%) randomly selected males. Voiding problems increased with age from about 4 to 40%. The symptoms were weakly but significantly correlated to each other (rs < 0.55). The ability of a particular symptom question to predict whether a subject actually would seek a doctor was generally low. A score system with a maximum score of 33 points was constructed. If prostatism was defined as a certain score or higher, a change in the definition in the score interval 4-10 would change the number of subjects with this syndrome with approximately 10%/score point. As a consequence of the results, the use of a symptom score as a criterion for the decision to treat patients suffering from prostatism is challenged. A patient administered symptom evaluation from is strongly recommended to obtain a more objective symptom registration.

A survey concerning the attitudes of urologists toward prostatism patients.

In a questionnaire all urological units in Norway were asked about: 1. The examinations they routinely used for prostatism patients before deciding upon treatment. 2. How they would score different objective and subjective information about these patients on a scale from 0 to 10. 3. How the physicians classified different prostatism symptoms into categories of weak, moderate and severe. The results were: Urinary retention occurring more than once or residual urine greater than 500 ml was considered an absolute indication for surgery. Agreement about indications for surgery was good for information which received a high median score, but was much poorer for information which received a lower median score. Agreement on how to classify different symptoms into categories according to severity was not good. Using the median classification of symptoms it was estimated that urologists believe that 0.1-5.8% of men over 60 years of age have severe symptoms, 2.1-36.4% have moderate symptoms and 57.8-97.8% weak or no symptoms.

Eosinophilic cystitis simulating invasive bladder carcinoma.

A case of eosinophilic cystitis simulating an invasive bladder carcinoma is reported. The disease had a subacute course and was associated with arthritis of the symphysis pubis and both sacroiliacal joints.

Examination of the descending pathway to the external anal sphincter and pelvic floor muscles by transcranial cortical stimulation.

In 26 neurologically normal patients and 9 healthy volunteers EMG responses after transcranial cortical stimulation (TCCS) were recorded from the external anal sphincter (EAS), the anterior tibial muscle (TA), the bulbocavernosus muscle (BC) and the rectus abdominis muscle (RA). Electrical TCCS was used in 29 subjects and magnetic TCCS in 6 subjects. Response patterns in the different muscles in relation to the strength of the stimulus were analyzed. It was found that the response patterns related to the strength of stimulation differed totally between the TA and the EAS. When the stimulus strength was increased stepwise, a response with a latency of 31.9 +/- 2.5 msec was first recorded in the TA, followed at higher strength by a secondary response with a latency of approximately 100 msec. In contrast, a response with a latency of 105.5 +/- 23.9 msec was first recorded in the EAS. The latency of this response gradually shortened with increasing stimulus strength until a response with a constant latency of 36.1 +/- 6.1 was obtained. In some subjects the response pattern in the BC was similar to that in the TA, and in others it was similar to that in the EAS. Responses in the TA, RA and EAS were all facilitated during voluntary contraction of the EAS. Both responses in the TA and in the EAS were facilitated by voluntary contraction of the TA. During voluntary contraction of the TA an inhibitory period was always recorded, while in the EAS no inhibitory periods were observed during either contraction or relaxation. The hypothesis that the fastest cortico-motoneuronal pathway to the EAS is polysynaptic is proposed.

Cerebral evoked potentials after stimulation of the posterior urethra in man.

Cerebral evoked potentials (EPs) were recorded in 25 neurologically normal subjects aged 22-73 years (mean 44.0) after stimulation of the posterior urethra (PU) and the pudendal nerve. After maximal PU stimulation 2 different configurations of the potential were found. In 12 cases a simple bi-triphasic wave form was recorded while in 12 cases there was a bifid form of the first negative wave. In 1 case identical EPs were recorded after PU and pudendal nerve stimulation. It was concluded that (1) PU stimulation excites fibres in the pudendal nerve at higher stimulation strength, resulting in a bifid wave form of the cerebral evoked potential in some individuals, (2) the most prominent negative peak, N1, with a latency of 102.1 +/- 13.2 msec, is the most reproducible part of the PU-evoked potential, (3) the N1 is probably transmitted through A delta fibres localized in the pelvic nerves, (4) there are differences between individuals concerning pudendal and pelvic nerve involvement in afferent innervation of the urethra.