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.

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.

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.

A pilot study of cervical screening in an inner city area--lessons for a national programme.

The objectives of this study were to examine aspects of organization of a proposed national screening programme based in general practice. The target population of women aged 25-59 years and their general practitioners (GPs), in a defined inner city area, was identified from a population register of persons eligible for free medical services; a computerized system was developed for invitations and record linkage of cytology results. Smears were examined in one laboratory and follow up of women with abnormal smears was undertaken by one gynaecologist. A random sample of non-responders was surveyed by questionnaire. Response following two invitations was only 20%. Practices with male doctors only had significantly lower response rates (P < 0.001) than those with a female doctor/nurse. A survey of non-responders showed that over 20% of addresses were incorrect and 16% of those interviewed were ineligible for smear tests. A preference for a female to undertake smears was expressed by 67%, and 77% believed that the purpose of the cervical smear was to detect cancer. An accurate population register, health promotion, support for GP practices, provision of alternative venues for smear tests, development of computer systems, accurate data entry and fail-safe follow up are aspects of a cervical screening service which must be addressed prior to setting up a national service.

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.

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.

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.

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.

Continuous wave Doppler ultrasound in evaluation of cerebral blood flow in neonates.

The cerebral circulation of 25 normal term infants was investigated using continuous wave Doppler ultrasound. Serial blood flow velocity signals were obtained from the common carotid and anterior cerebral arteries during the first week of life. The records were processed using a frequency spectrum analyser to provide cerebral blood velocity waveforms. The pulsatility index (PI), A/B ratio, and rise and fall slope of the waveforms were calculated. The results indicated that cerebrovascular resistance was raised appreciably on day 1 of life compared with later in the first week. In 18 of 25 infants (72%) there was no continuous carotid blood flow in the first hours of life. We suggest that the human cerebral circulation adapts to the process of birth in a similar fashion to that of animal models.

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.

Fetal blood velocity waveforms in uncomplicated labour.

A combination of pulsed echo and continuous wave Doppler ultrasound was used to obtain blood flow velocity signals from the umbilical arteries of 10 patients during uncomplicated spontaneous labour. Audio frequency analysis of these signals yielded fetal blood velocity waveforms. Analysis of these waveforms demonstrated that placental vascular resistance to feto-placental blood flow is not altered by uterine contractions, artificial rupture of the membranes, the infusion of oxytocin nor the administration of analgesia during uncomplicated labour.

The effect of lumbar epidural analgesia on the rate of cervical dilatation and the outcome of labour of spontaneous onset.

A study of 1055 spontaneous labours is presented relating progress and outcome to the presence of a lumbar epidural block in 282 of these patients and to the need for oxytocin augmentation in 427. Graphs for cervical dilatation starting at admission to hospital were constructed for normal and dysfunctional labours of spontaneous onset. Patients requiring augmentation of labour had a lesser cervical dilatation on admission to hospital, a longer first stage, more instrumental deliveries, more Caesarean sections and a greater number of babies with a low Apgar score. An epidural block had no effect on either the duration of first stage or the rate of cervical dilatation but was associated with a 20-fold increase in rotational forceps delivery and no increase in Caesarean section rate. With an epidural block there was no increase in the number of babies with cerebral irritation or low Apgar scores and there was a statistically significant improvement in the Apgar scores of babies of mothers in augmented dysfunctional labour who had an epidural block. The incidence of rotational forceps delivery in patients with an epidural block could be reduced with safety by allowing such patients to have a longer second stage before considering interference purely for delay.

Fetal blood velocity waveforms in normal pregnancy.

A combination of pulsed echo and continuous wave Doppler ultrasound was used to obtain blood flow velocity signals from the umbilical arteries of 18 normal patients from the 16th until the 40th week of pregnancy. Audio frequency analysis of these signals yielded fetal blood velocity waveforms. Analysis of these waveforms demonstrated that the placenta is an organ of low vascular resistance and that placental resistance to blood flow declines with advancing gestational age in normal pregnancy.

Sex hormone levels and gonadotrophin release in premature ovarian failure.

Premature ovarian failure was studied in ten women under the age of 30; eight had an ovarian biopsy and five of these showed primordial follicles. Plasma levels of oestradiol and progesterone were similar to the follicular phase of a normal menstrual cycle, but in eight patients cervical smears showed a cornification index of less than one per cent. Levels of both androgens and of sex hormone binding globulin capacity were generally normal. Administration of LH-RH caused a release of FSH which was similar to post menopausal women and higher than both. Two patients were treated with exogenous gonadotrophins without effect.