Proper understanding of recurrent stress urinary incontinence treatment in women (PURSUIT): a randomised controlled trial of endoscopic and surgical treatment.

BACKGROUND: Women with stress urinary incontinence (SUI) experience urine leakage with physical activity. Currently, the interventional treatments for SUI are surgical, or endoscopic bulking injection(s). However, these procedures are not always successful, and symptoms can persist or come back after treatment, categorised as recurrent SUI. There are longstanding symptoms and distress associated with a failed primary treatment, and currently, there is no consensus on how best to treat women with recurrent, or persistent, SUI. METHODS: A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the UK, randomising 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. The aim of the trial is to determine whether surgical treatment is superior to endoscopic bulking injections in terms of symptom severity at 1 year after randomisation. This primary outcome will be measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients' and clinicians' views and experiences of the interventions. DISCUSSION: There is a lack of high-quality, randomised, scientific evidence for which treatment is best for women presenting with recurrent SUI. The PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) registry ISRCTN12201059. Registered on 09 January 2020.

Chronic obstructive pulmonary disease in Welsh slate miners.

BACKGROUND: Exposure to respirable crystalline silica (RCS) causes emphysema, airflow limitation and chronic obstructive pulmonary disease (COPD). Slate miners are exposed to slate dust containing RCS but their COPD risk has not previously been studied. AIMS: To study the cumulative effect of mining on lung function and risk of COPD in a cohort of Welsh slate miners and whether these were independent of smoking and pneumoconiosis. METHODS: The study was based on a secondary analysis of Medical Research Council (MRC) survey data. COPD was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7. We created multivariable models to assess the association between mining and lung function after adjusting for age and smoking status. We used linear regression models for FEV1 and FVC and logistic regression for COPD. RESULTS: In the original MRC study, 1255 men participated (726 slate miners, 529 unexposed non-miners). COPD was significantly more common in miners (n = 213, 33%) than non-miners (n = 120, 26%), P < 0.05. There was no statistically significant difference in risk of COPD between miners and non-miners when analysis was limited to non-smokers or those without radiographic evidence of pneumoconiosis. After adjustment for smoking, slate mining was associated with a reduction in %predicted FEV1 [ß coefficient = -3.97, 95% confidence interval (CI) -6.65, -1.29] and FVC (ß coefficient = -2.32, 95% CI -4.31, -0.33) and increased risk of COPD (odds ratio: 1.38, 95% CI 1.06, 1.81). CONCLUSIONS: Slate mining may reduce lung function and increase the incidence of COPD independently of smoking and pneumoconiosis.

Asthma and allergies: is the farming environment (still) protective in Poland? The GABRIEL Advanced Studies.

BACKGROUND: Evidence exists that a farming environment in childhood may provide protection against atopic respiratory disease. In the GABRIEL project based in Poland and Alpine regions of Germany, Austria and Switzerland, we aimed to assess whether a farming environment in childhood is protective against allergic diseases in Poland and whether specific exposures explain any protective effect. METHODS: In rural Poland, 23 331 families of schoolchildren completed a questionnaire enquiring into farming practices and allergic diseases (Phase I). A subsample (n = 2586) participated in Phase II involving a more detailed questionnaire on specific farm exposures with objective measures of atopy. RESULTS: Farming differed between Poland and the Alpine centres; in the latter, cattle farming was prevalent, whereas in Poland 18% of village farms kept ≥1 cow and 34% kept ≥1 pig. Polish children in villages had lower prevalences of asthma and hay fever than children from towns, and in the Phase II population, farm children had a reduced risk of atopy measured by IgE (aOR = 0.72, 95% CI 0.57, 0.91) and skin prick test (aOR = 0.65, 95% CI 0.50, 0.86). Early-life contact with grain was inversely related to the risk of atopy measured by IgE (aOR = 0.66, 95% CI 0.47, 0.92) and appeared to explain part of the farming effect. CONCLUSION: While farming in Poland differed from that in the Alpine areas as did the exposure-response associations, we found in communities engaged in small-scale, mixed farming, there was a protective farming effect against objective measures of atopy potentially related to contact with grain or associated farm activities.

Impact of single-session motivational interviewing on clinical outcomes following periodontal maintenance therapy.

OBJECTIVES: Patient engagement in effective oral hygiene following periodontal therapy is essential to long-term success. Motivational interviewing (MI) is a behavioural counselling approach documented to positively influence behaviour change related to smoking, diabetes control and medication adherence. Emerging evidence suggests utility of MI to improve oral health. The objective of this study was to evaluate whether the use of brief motivational interviewing (BMI) is effective in improving internal motivation for oral hygiene behaviour. METHODS: A convenience sample of fifty-six previously treated periodontal patients who were in maintenance yet presented with signs of clinical inflammation were recruited to participate in this single blind, randomized controlled trial. Patients were randomly assigned to receive either BMI in conjunction with traditional oral health education (TOHE), (n = 29) or TOHE alone (n = 27). Bleeding on probing scores (BOP), plaque index (PI), pocket depths (PD), motivation (M), autonomous regulation (AR) controlled regulation (CR) and oral health knowledge (K) were assessed at baseline, 6 weeks and 12 weeks. RESULTS: Statistically significant decreases were found over time for BOP (P = 0.001), PI (P = 0.001) and PD 4-6 mm (P = 0.001) for both groups. Differences in clinical parameters between groups were not evident at either 6 or 12 weeks. CONCLUSION: Results show that a one-time MI session is insufficient for improving oral hygiene in long-standing maintenance patients.

Interproximal cervical lesions caused by incorrect flossing technique.

UNLABELLED: This case report describes an interproximal cervical lesion caused by the incorrect use of dental floss. A 58-year-old man who was asymptomatic, presented with unusual notch-like cervical lesions. After clinical and radiographical examinations, it was concluded that the aetiology of these lesions was an incorrect flossing technique. The treatment plan included extraction of maxillary 3rd molars and re-education of the patient in oral hygiene technique. CONCLUSION: These lesions are irreversible and often go undiagnosed; therefore, it is important for the clinician to be familiar with the clinical presentation and aetiology.

Cystic fibrosis and survival to 40 years: a case-control study.

The clinical course of patients with cystic fibrosis (CF) is variable and probably determined by many interacting factors. We aimed to examine the influence of early social and clinical factors on long-term survival. A case-control study of adult CF patients was used to compare long-term survivors (aged ≥ 40 yrs) with patients who died before reaching 30 yrs of age. Each case (n = 78) was matched by birth date with at least one control (n = 152), after exclusion of "late diagnosis" patients. Probability-weighted logistic regression models were used to identify influences on survival. Factors resulting in increased probabilities of survival included high body mass index (OR 1.76, 95% CI 1.40-2.22), forced expiratory volume in 1 s (OR per 5% increase 1.54, 95% CI 1.32-1.80), and forced vital capacity (OR per 5% increase 1.54, 95% CI 1.33-1.78) at transfer to the adult clinic and the exclusive use of oral antibiotics (OR 8.31, 95% CI 3.02-22.88). Factors resulting in decreased probabilities of survival were Pseudomonas aeruginosa acquisition (OR 0.18, 95% 0.05-0.65) or pneumothorax before transfer to the adult clinic (OR 0.02, 95% CI 0.004-0.08) and referral from a paediatric clinic in a deprived area (OR 0.13, 95% CI 0.04-0.38). Long-term survival is associated with the clinical features present by the time of referral to an adult clinic. Even "early-diagnosis" disease appears to have different phenotypes, possibly independent of CF gene function, that have different survival patterns.

Childhood peak flow and the Oxford Transport Strategy.

BACKGROUND: Studies of the health effects of traffic interventions are rare. The Oxford Transport Strategy (OTS), implemented in June 1999, involved a wide range of permanent changes designed to reduce congestion in the city centre of Oxford, UK. The impact of the OTS on peak expiratory flow (PEF) and respiratory symptoms among schoolchildren in the city is reported. METHODS: A dynamic cohort of 1389 children aged 6-10 years attending first schools in Oxford was studied. Schools were visited 2-3 times a year for 5-day periods between 1998 and 2000. On each day of each visit children had their PEF measured and were asked about their respiratory symptoms. RESULTS: Changes in traffic varied across the city. In the whole population, regression analysis of daily PEF adjusting for potential confounders showed statistically significant improvements post-OTS (beta = 5.52 l/min, 95% CI 3.08 to 7.97), but there was no consistent evidence that these improvements varied by changes in traffic exposure. In post-hoc analyses, children currently receiving treatment for asthma tended to experience a greater increase in PEF post-OTS as did children from less affluent homes, although these differences did not reach statistical significance. In each of these groups, greater benefits were observed among those living near roads where traffic levels fell post-OTS. CONCLUSIONS: These findings suggest that traffic management may lead to small localised improvements in childhood respiratory health and that such benefits are limited to children with pre-existing respiratory problems and those from less affluent backgrounds.

Atopy and asthma in rural Poland: a paradigm for the emergence of childhood respiratory allergies in Europe.

BACKGROUND: We hypothesized that, in south-west Poland, a 'rural' protective effect on atopy and respiratory allergies would be most pronounced among children but that at all ages would be stronger among those with a rural background. METHODS: A cross-sectional survey of the inhabitants (age >5 years, n = 1657) of Sobotka, a town of 4000 people in south-west Poland: and seven neighbouring villages. We measured and analysed responses to skin prick tests (atopy) and to a standard questionnaire (asthma and hayfever). RESULTS: Atopy was very uncommon (7%) among villagers at all ages but not among townspeople (20%, P < 0.001); the differences were most marked among those aged under 40 years. Asthma and hayfever were similarly distributed, both being very rare among villagers. The differences appear to be explained by the cohort effect of a communal move away from rural life. This interpretation is supported by an ecological correlation (rho = -0.59) between rural populations and childhood wheeze in 22 European countries. CONCLUSION: The very striking differences in the prevalence of allergy between these two neighbouring communities of central Europe reflect the pan-continental population movements that may have been responsible for the emergence of childhood allergies in Europe.

Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study.

BACKGROUND: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). METHODS: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. RESULTS: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. CONCLUSIONS: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.

Crete: does farming explain urban and rural differences in atopy?

BACKGROUND: Urban-rural differences in the prevalence of atopy and associated allergic diseases have been reported in several non-European countries. Within Europe, where such variations are less striking, a farm childhood has been postulated to be protective. OBJECTIVE: We aimed to compare the prevalence of atopy in urban and rural children living in Crete and to examine the role of early exposure to a farming environment in explaining any measured differences. METHODS: A cross-sectional survey of children attending secondary schools in Iraklion, the capital city, and five villages 100 km to the south. Atopy was determined by the responses to skin prick tests with seven common aeroallergens. RESULTS: Nine-hundred and ninety-seven children participated in the survey. 19.6% of those living in Iraklion, but only 9.6% of those from the villages, had a positive response to one or more skin prick tests. Among urban children there were significant gradients in the prevalence of atopy across several categories of animal contact and consumption of farm (unpasteurized) milk products--before the age of 5 years. These differences, however, were not apparent among the rural children.

The functional performance of elderly urban African-American women who return home to live alone after medical rehabilitation.

OBJECTIVE: Elderly women who live alone are at increased risk for loss of independence. Hospitalization, in particular, often marks the transition from independent living to institutional care. The purpose of this study was to examine the relationship of rehabilitation admission to the subsequent function of elderly women and their ability to return to live-alone status. METHOD: The women in the study (N = 138) were admitted to a geriatric rehabilitation unit at a large urban medical center between September 1997 and September 1998. The findings reported here pertain to the subset of African-American women (n = 122), the majority of the sample. Data were collected using several standardized assessments, including the Functional Independence Measure (FIM). RESULTS: The FIM motor scores improved significantly for the total sample between admission and discharge, and the mean FIM motor score for the group that subsequently attained live-alone status was significantly higher than the non-live-alone group at 3 months and 6 months postdischarge. The participants who returned to live alone also reported significantly greater independence than did their non-live-alone counterparts across a variety of activities of daily living and instrumental activities of daily living skills. CONCLUSION: These data suggest that rehabilitation is associated with improved functional outcomes, and higher functional performance is related to live-alone status.

DNA replication: partners in the Okazaki two-step.

The correct processing of Okazaki fragments during lagging-strand DNA replication has a vital role in maintaining genome integrity. Recent findings suggest that, in eukaryotes, the processing of Okazaki fragments occurs by a two-step mechanism governed by the single-stranded DNA binding factor RPA.

Effective screening for Alzheimer's disease among older African Americans.

Relatively little data exist concerning the utility of brief cognitive measures to detect dementia among African Americans. The current study evaluated the clinical utility of the Mini-Mental Status Exam (MMSE) and the Fuld Object Memory Evaluation (FOME) in detecting Alzheimer's disease (AD) among both African American and European American older adults. One hundred and forty geriatric patients from a large urban academic medical center were examined. Overall, the FOME appeared to be more effective in detecting AD than was the MMSE (93% sensitivity vs. 75% sensitivity, respectively), although both measures suffered from relatively low specificity (63.5) in the full sample. The FOME demonstrated exceptional clinical utility among African American patients (sensitivity 98.3%; specificity = 64.5; positive predictive power 83.8%; negative predictive power 95.2%). The results of this study support the use of the FOME among older African Americans to detect dementia.

Intrapocket anesthesia for scaling and root planing: results of a double-blind multicenter trial using lidocaine prilocaine dental gel.

BACKGROUND: The efficacy of a novel anesthetic gel (lidocaine 25 mg/g plus prilocaine 25 mg/g in thermosetting agents) for non-invasive periodontal pocket anesthesia was evaluated. METHODS: One hundred twenty-two (122) patients in 8 centers with moderate to severe periodontitis requiring scaling and root planing (SRP) were enrolled in this multicenter, randomized, double-blind, controlled clinical trial. The active dental gel or a matching placebo gel was applied into the periodontal pocket using a blunt applicator. Following a waiting period of 30 seconds to 2 minutes, scaling and root planing were performed. If the patient had any discomfort, a second application of the gel was applied. If the patient continued to experience discomfort, conventional anesthesia was offered. After all teeth in the test quadrant had received SRP, the overall pain was assessed by the patient using a 100 mm horizontal, ungraded visual analog scale in which the left side was marked "no pain" and the right side marked "worst pain imaginable." Patients also assessed pain by using a 5-point verbal rating scale, from "no pain" to "very severe pain." RESULTS: The visual analog scale showed significant reductions in reported pain, favoring the active gel over the placebo (mean reduction, 8 mm; P <0.0005). The verbal rating scale revealed that 90% of patients treated with active gel reported no pain or mild pain compared to 64% of placebo-treated patients (P<0.001). CONCLUSIONS: Intrapocket administration of lidocaine 25 mg/g plus prilocaine 25 mg/g and thermosetting agents may be effective for pain control for scaling and root planing and may offer an alternative to infiltration anesthesia.

Absence of germline and somatic p53 alterations in children with sporadic brain tumors.

Cancers of the central nervous system are the most common solid tumors of childhood. Although somatic alterations of the p53 tumor suppressor gene have been implicated in brain tumorigenesis, the role of germline p53 mutations in the development of childhood brain tumors has not been well defined. As a component of an ongoing extensive study of the epidemiology of childhood brain tumors, we prospectively examined the germline and tumor p53 gene status in 85 children without a family history of cancer who were diagnosed with a sporadic malignant central nervous system tumor. Using PCR/single-strand conformational polymorphism analysis and direct DNA sequencing, 85 children were screened for the presence of constitutional p53 sequence alterations in exons 2 and 4 through 11. No mutations were identified. Commonly reported sequence polymorphisms were observed at codon 72, as well as in 2 other previously described nucleotide residues. Forty-four brain tumor samples were available for analysis and of these 40 were paired with peripheral blood. Once again, no p53 mutations were found. Of the 5 germline samples with the 2 common polymorphisms, only one had a paired tumor sample for comparison and the tumor contained the same alteration as the germline. Of note, one tumor, a PNET of the cerebellum (medulloblastoma), showed loss of heterozygosity at codon 72. We can conclude that the frequency of germline and somatic p53 mutations in sporadic childhood brain tumors is very low, probably less than 1%, and there is no need to screen these patients routinely for their germline p53 status. However, the potential significance of LOH at codon 72 remains to be elucidated.

Tissue-specific expression of SV40 in tumors associated with the Li-Fraumeni syndrome.

Inactivation of wild-type p53 tumor suppressor function is the primary mechanism of tumor initiation in Li-Fraumeni syndrome (LFS) individuals with germline p53 mutations. Tumors derived from LFS patients frequently retain the normal p53 allele, suggesting that alternative mechanisms in addition to gene deletion must be involved in inactivating wild-type p53 protein. DNA tumor viruses, such as SV40, target p53 for inactivation through the action of viral oncoproteins. We studied the probands from two unrelated LFS families, each of whom presented with multiple malignant neoplasms. Patient 1 developed an embryonal rhabdomyosarcoma (RMS) and a choroid plexus carcinoma (CPC), while patient 2 developed a CPC and subsequently presented with both an osteosarcoma (OS) and renal cell carcinoma (RCC). We utilized DNA sequence analysis and immunohistochemistry to determine p53 gene status in the germline and tumors, as well as evidence for SV40 T-antigen oncoprotein expression. Each patient harbored a heterozygous germline p53 mutation at codons 175 and 273, respectively. In patient 1, the normal p53 gene was lost while the mutant p53 allele was reduced to homozygosity in the RMS. Both normal and mutant genes were maintained in the CPC. In patient 2, normal and mutant p53 alleles were retained in both the CPC and RCC. Both specific PCR and immunostaining detected SV40 T-antigen in both CPCs and the RCC. In addition to chromosomal alterations, epigenetic mechanisms may disrupt p53 function during tumorigenesis. In two LFS patients, we found SV40 DNA sequences and viral T-antigen expression that could account for inactivation of the normal p53 protein. Inactivation of p53 or other tumor suppressors by viral proteins may contribute to tumor formation in specific tissues of genetically susceptible individuals.

Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. A comparative multi-centre trial of 2 treatment approaches.

AIM: In the present 6-month multicentre trial, the outcome of 2 different approaches to non-surgical treatment of chronic periodontitis, both involving the use of a locally delivered controlled-release doxycycline, was evaluated. MATERIAL AND METHODS: 105 adult patients with moderately advanced chronic periodontitis from 3 centres participated in the trial. Each patient had to present with at least 8 periodontal sites in 2 jaw quadrants with a probing pocket depth (PPD) of > or =5 mm and bleeding following pocket probing (BoP), out of which at least 2 sites had to be > or =7 mm and a further 2 sites > or =6 mm. Following a baseline examination, including assessments of plaque, PPD, clinical attachment level (CAL) and BoP, careful instruction in oral hygiene was given. The patients were then randomly assigned to one of two treatment groups: scaling/root planing (SRP) with local analgesia or debridement (supra- and subgingival ultrasonic instrumentation without analgesia). The "SRP" group received a single episode of full-mouth supra-/subgingival scaling and root planing under local analgesia. In addition, at a 3-month recall visit, a full-mouth supra-/subgingival debridement using ultrasonic instrumentation was provided. This was followed by subgingival application of an 8.5% w/w doxycycline polymer at sites with a remaining PPD of > or =5 mm. The patients of the "debridement" group were initially subjected to a 45-minute full-mouth debridement with the use of an ultrasonic instrument and without administration of local analgesia, and followed by application of doxycycline in sites with a PPD of > or =5 mm. At month 3, sites with a remaining PPD of > or =5 mm were subjected to scaling and root planing. Clinical re-examinations were performed at 3 and 6 months. RESULTS: At 3 months, the proportion of sites showing PPD of < or =4 mm was significantly higher in the "debridement" group than in the "SRP" group (58% versus 50%; p<0.05). The CAL gain at 3 months amounted to 0.8 mm in the "debridement" group and 0.5 mm in the "SRP" group (p=0.064). The proportion of sites demonstrating a clinically significant CAL gain (> or =2 mm) was higher in the "debridement" group than in the "SRP" group (38% versus 30%; p<0.05). At the 6-month examination, no statistically significant differences in PPD or CAL were found between the two treatment groups. BoP was significantly lower for the "debridement" group than for the "SRP" group (p<0.001) both at 3- and 6 months. The mean total treatment time (baseline and 3-month) for the "SRP" patients was 3:11 h, compared to 2:00 h for the patients in the "debridement" group (p<0.001). CONCLUSION: The results indicate that simplified subgingival instrumentation combined with local application of doxycycline in deep periodontal sites can be considered as a justified approach for non-surgical treatment of chronic periodontitis.

Understanding the enzymology of archaeal DNA replication: progress in form and function.

The analysis of completed archaeal genome sequences led to the identification of a set of approximately 10-20 genes whose protein products were inferred to be involved in chromosomal DNA replication. Until recently, however, little was known of the biochemical properties of these proteins. Here, I review recent progress in this area brought about by biochemical and structural analysis. Aside from shedding considerable new light on the molecular machinery of DNA replication in the archaea, the results of these studies also present new opportunities for understanding the molecular events of chromosomal DNA replication in eukaryotic cells.

Rates and risk factors for recurrence of gestational diabetes.

OBJECTIVE: To determine the recurrence rate of gestational diabetes (GDM) during a subsequent pregnancy among women who had GDM during an index pregnancy and to identify factors associated with the probability of recurrence RESEARCH DESIGN AND METHODS: A retrospective longitudinal study was performed in Nova Scotia, Canada, of women who were diagnosed as having GDM during a pregnancy between the years of 1980 and 1996 and who had at least one subsequent pregnancy during this time period. When only the index and first subsequent pregnancy were analyzed, the cohort included 651 women. The recurrence rate of GDM in the pregnancy after the pregnancy with the initial diagnosis of GDM was determined. Multivariate regression models were constructed to model the recurrence of GDM in a subsequent pregnancy as functions of potential predictors to estimate RRs and CIs. RESULTS: The rate of recurrence of GDM in the pregnancy subsequent to the index pregnancy was found to the 35.6% (95% CI = 31.9-39.3%). Multivariate regression models showed that infant birth weight in the index pregnancy and maternal prepregnancy weight before the subsequent pregnancy were predictive of recurrent GDM. CONCLUSIONS: In this large cohort of women, slightly more than one-third of the subjects had diabetes in a subsequent pregnancy, which is consistent with recurrence rates in other predominately white populations. Strategies to reduce the occurrence of neonatal macrosomia and maternal prepregnancy obesity may help lower the rate of recurrence of GDM.