Antimicrobial therapies for prevention of recurrent acute exacerbations of COPD (AECOPD): beyond the guidelines.

BACKGROUND: Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who 'failed' recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators. MAIN TEXT: There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa (Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies. CONCLUSION: Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.

High prevalence of stress urinary incontinence in adult patients with bronchiectasis.

Stress urinary incontinence (SUI) is frequently under-reported in patients with chronic lung disease and may have negative psychosocial consequences. We conducted a prospective study to determine the prevalence, severity and treatment outcomes of SUI in female bronchiectasis patients referred for airway clearance techniques. Nineteen out of 40 (48%) patients reported SUI symptoms. Of these, 14 (74%) reported a reduced quality of life secondary to SUI. Following personalised intervention, symptom improvement was observed in 13/19 (68%). Five out of 19 (26%) required specialist referral for further continence care. No associations with lung disease severity and SUI were noted. SUI is common in adult female bronchiectasis patients and should be routinely screened for to improve patients' overall quality of life.

The use of cough peak flow in the assessment of respiratory function in clinical practice- A narrative literature review.

Cough peak flow (CPF) is a useful clinical measurement to assess neuromuscular activity and effective coordination, yet it is rarely used in clinical practice outside of the management of patients with neuromuscular disorders. A CPF of above 160 L/min is required for an effective cough and less than 270 L/min is associated with increased secretion retention and risk of infection. Reduced CPF can be due to a number of mechanisms including reduced respiratory muscle strength, lack of co-ordination of glottic closure and opening, airway obstruction and, age and activity related changes. CPF has been shown to be correlated with other measures of pulmonary function in neuromuscular disorders and in predicting extubation failure. Patients with Parkinson's disease have a reduced CPF even at early stages and dedicated expiratory muscle strength training (EMST) has been shown to be beneficial. Sequential studies in patient with stroke-associated dysphagia reported CPF was correlated with risk of respiratory infection and results of formal swallow assessments. Age-related changes in expiratory muscle strength and lung physiology contribute to increased risk of aspiration and pneumonia. EMST may have a role in healthy adults to improve muscle strength and effective cough, potentially reducing risk of respiratory tract infections even in the absence of disease. CPF has potential to be extremely useful in clinical practice in a wide spectrum of diseases. In particular, studies in patients with frequent exacerbations of COPD and recurrent pneumonia are currently lacking and would be of benefit to explore the relationship between ineffective cough and recurrent infection.

A radioimmunoassay for the estimation of serum dehydroepiandrosterone sulphate in normal and pathological sera.

A radioimmunoassay is described for the measurement of dehydroepiandrosterone sulphate in serum. The method requires 0.1 ml of serum that needs no purification other than a single ether extraction. It is both rapid and economical, procedural losses are small and precision and accuracy are acceptable for both normal and pathological sera. Normal values have been established for children and adults which show a relationship to chronological age, values rising steadily as puberty intevenes, peak values occurring between 20 and 27 years, with a decline thereafter. An empirical curve was fitted to the data and approximate normal limits were obtained. The mean value for pregnanat women in the age range 20-40 years, was statistically significantly lower than in non-pregnant, premenopausal women. The levels of dehydroepiandrosterone sulphate in cord and newborn blood, were higher than at any other time during childhood until signs of puberty were demonstrable. Elevated levels are reported in six patients with untreated congenital adrenal hyperplasia and in one patient with a tumour of the adrenal cortex. It is suggested that this assay provides a useful and precise index of adrenal androgen secretion.

The assessment of the feto-placental circulation with continuous wave Doppler ultrasound.

Continuous wave Doppler ultrasound was used together with B-mode real time ultrasound to study feto-placental blood flow in utero. The results of 887 examinations on 221 patients are presented. The fetal heart rate acceleration slope and pulsatility index (P.I.) of the audiofrequency ultrasound display were analysed. There was a significant reduction in fetal heart rate (P less than 0.001) and P.I. (P less than 0.001) with advancing gestational age in normal pregnancy. In contrast, in retarded intrauterine growth a significant increase in P.I. values was observed in 77% of patients.

Evaluation of cerebral blood flow in the normal neonate by Doppler spectrum analysis.

Continuous wave Doppler ultrasound has seldom been applied to the evaluation of the cerebral circulation of the newborn infant. Twenty-five term infants were studied and records taken from the common carotid and anterior cerebral arteries during the first week of life using a bidirectional Doppler instrument. The best Doppler signals obtained were audiofrequency analysed and sonagrams recorded. Analysis of the carotid sonagrams revealed a mean Pulsatility Index (PI) on the first day of life of 0.98 compared to 0.88 on Day 2 (p less than 0.001). An unexpected finding was the absence of continuous carotid blood flow in the majority of infants in the first hours of life. The PI on subsequent days did not differ significantly from Day 2. The PI of the anterior cerebral arteries on Day 1 was significantly elevated (p less than 0.001) compared to Day 2 and subsequent days. The significance of these findings and their importance in the further evaluation of pathological cerebral states in the neonate, especially birth asphyxia and intracranial haemorrhage are discussed.

Polycystic ovarian disease.

Sex hormone binding globulin (SHBG) capacity was reduced in 9 of 31 patients with polycystic ovarian (PCO) disease and the mean level in PCO patients was significantly less (p less than 0.001) than normal. Serum testosterone levels were elevated in 21 of 32 PCO patients and the mean level was significantly elevated (p less than 0.001). Serum androstenedione values were raised in 17 of 31 patients and the mean value was also significantly raised (p less than 0.001). Serum dehydroepiandrosterone sulphate (DHAS) concentrations were elevated in only 2 of 14 patients. Urinary 17-oxo and 17-oxogenic steroids were normal in all patients studied. Basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were normal but LH release following injection of luteinizing hormone-releasing hormone (LH-RH) was enhanced. A highly significant negative correlation (r=--0.449; p less than 0.01) was found between the logarithm of testosterone and the logarithm of LH levels. Serum prolactin concentrations were elevated in 4 of 21 PCO patients. Thyroid-stimulating hormone (TSH) values were normal. Eighteen of 20 patients ovulated following treatment with clomiphene and nine became pregnant. Five of 12 of patients treated with oestrogen/progesterone preparations noticed an improvement in their hirsutism. It is suggested that the normal cyclical release of LH is inhibited in PCO disease by a negative feedback by androgens to the hypothalamus or the pituitary, and that wedge resection should be reserved for patients in whom other forms of treatment have failed.

Pharmacological studies with lincomycin in late pregnancy.

The placental transmission of lincomycin was studied in 60 patients in late pregnancy. A peak maternal blood level of 12.5 mug/ml was recorded 45 minutes after injection, and detectable levels were still present up to 42 hours after a single injection. A peak cord blood level of 2.7 mug/ml was recorded 55 minutes after injection; cord blood levels were about a quarter of the maternal blood levels, and in most cases no levels were detectable 24 hours after a single injection. The passage of lincomycin into and out of the liquor was slower and more variable, but some hours after injection the liquor levels were always higher than the maternal or cord blood levels, and detectable levels were still present in the liquor 52 hours after a single injection. Repeated injections did not lead to any significant accumulation of lincomycin. The only side effect was a possible case of neuromuscular block in a mother delivered by caesarean section. No infant was adversely affected.

Delivery after caesarean section: review of 2176 consecutive cases.

A total of 2176 consecutive patients who had had one previous caesarean section were studied retrospectively. A repeat elective caesarean section was performed in 395 (18.2%). Labour started spontaneously in 1363 patients, 301 of whom were given oxytocin to accelerate inert labour, and was induced by amniotomy and infusion of oxytocin in 418 women; 1618 of these 1781 patients (90.8%) delivered vaginally. Patients who had had a previous vaginal delivery were more likely to deliver vaginally again. Those women in whom the initial caesarean section had been performed during labour before the cervix was 4 cm dilated were less likely to deliver vaginally than those who had progressed further in labour or those who had had an elective caesarean section. Similarly, those who received oxytocin to stimulate inert labour were more likely to require a repeat caesarean section than those who did not. The uterine scar ruptured in only eight (0.45%) of the 1781 patients allowed into labour. The risk of rupture of the scar was not increased by the use of oxytocin alone either to induce or to accelerate labour. The combination of oxytocin to accelerate labour and epidural analgesia to provide pain relief, however, was associated with an increased incidence of scar rupture. Labour may be safely allowed in women who have had a previous caesarean section, most of whom will deliver vaginally. Induction of labour does not increase the risk of either a repeat caesarean section or rupture of a uterine scar.

Characteristics of normal labour in different racial groups.

The characteristics of normal labour in 1306 white, Asian and black parturients have been established following a prospective study of 3217 consecutive labours. Asian patients were found to be of significantly shorter stature than white or black women (p less than 0-001) and their infants significantly lighter than those of white (p less than 0-001) and of black (p less than 0-05) women, and a low positive correlation was found between maternal height and infant birth weight. The mean duration of the first stage of labour, taken from the time of admission to the labour ward, was 5-6 hours in primiparae and 3-7 hours in multiparae. The mean durations of the second stage of labour were 41-5 and 17-4 minutes respectively. The correlations between the duration of the first and second stages of labour were too low to be of value in patient management. Similar low correlations were found between the duration of the second stage of labour and both infant birth weight and the Apgar score at one minute. Cervical dilatation-time curves, constructed with reference to the cervical dilatation found on admission to the labour ward, revealed no significant differences in the progress of normal labour in the different racial groups.

Induction of labour, birthweight and perinatal mortality by day of the week.

There were 66,974 births at the three largest Dublin maternity hospitals in the years 1980-1982. Data on numbers of spontaneous and elective births, birthweight and perinatal mortality were analysed by day of the week. Perinatal mortality rates were highest on Wednesdays and Saturdays. The rate on Sunday was close to average. The largest number of perinatal deaths per day occurred on Wednesdays and the smallest on Sundays. Significant variations in mortality rates and percentage low birthweight were found among the 19% of infants who were born electively, but not among those born after a spontaneous onset of labour. High-risk pregnancies, including many with intra-uterine fetal death, were induced in large numbers from Tuesdays through Saturdays with a peak on Wednesdays. Low risk cases were induced mainly from Monday through Fridays with a peak on Fridays. The pattern of perinatal mortality through the week followed closely that of the risk status of pregnancies delivered electively. The results indicate that the pattern of perinatal mortality by day of the week of birth was determined by a highly organized weekly routine of selective elective delivery.

Delivery in an obstetric birth chair: a randomized controlled trial.

OBJECTIVE: To determine whether nulliparae whose second stage of labour is conducted in an obstetric birth chair have a lower incidence of instrumental delivery than those using a conventional delivery bed. DESIGN: Randomized controlled trial using sealed, opaque envelopes for allocation. SETTING: Delivery ward in a busy teaching hospital. PATIENTS: 1250 nulliparae with a singleton live fetus with cephalic presentation, without epidural anaesthesia, who had achieved full dilatation. INTERVENTION: Intention to conduct second and third stages of labour in either the Birth-EZ chair or the conventional delivery bed, as randomly allocated. MAIN OUTCOME MEASURES: Primary measure: vaginal operative delivery; principal secondary measures: duration of second stage, perineal trauma, blood loss, women's views, and neonatal status. RESULTS: Delivery in the birth chair did not result in a reduction in operative delivery, overall. However, there was a reduction in vaginal operative delivery for fetal heart rate abnormality. There was no beneficial effect on perineal trauma or puerperal perineal pain. Post-partum haemorrhage was more frequent in the birth chair group. CONCLUSIONS: Delivery in the birth chair does not offer any obvious advantage to women over delivery on a bed.