Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation

Introduction and hypothesis

This study evaluated the efficacy and safety of flexible-dose fesoterodine and factors associated with dose escalation in subjects with overactive bladder (OAB).

Methods

In this 12-week, open-label study, 331 adults with OAB symptoms for ≥3 months, ≥8 micturitions and ≥3 urgency episodes per 24?h and who reported at least “some moderate” bladder-related problems were treated with fesoterodine 4?mg once daily for 4?weeks, with the option to escalate to 8?mg for the remaining 8?weeks based on discussion of efficacy and tolerability with the investigator. Factors influencing dose escalation were identified using stepwise logistic regression. Efficacy was assessed via 3-day bladder diaries and patient-reported outcomes.

Results

Of the subjects, 59?% dose escalated at week 4; 93?% of escalators cited insufficient clinical response. The decision to escalate was most often made by the subject (alone or with the investigator). Improvements from baseline were observed in diary and patient-reported outcomes at weeks 4 and 12. Smaller improvements in micturition frequency and worse bladder-related problems at week 4 were significantly associated with increased likelihood of dose escalation; baseline micturition frequency, age, sex, body mass index, antimuscarinic-associated adverse events and OAB symptom duration were not. Non-escalators had greater improvement from baseline to week 4 than escalators; by week 12, improvement was similar among escalators and non-escalators. Fesoterodine was well tolerated.

Conclusions

Treatment with flexible-dose fesoterodine improved bladder diary and patient-reported outcomes. Lower clinical response was related to dose escalation; after escalation, response in escalators approached that of non-escalators.     

Cariogenic microbiome and microbiota of the early primary dentition: A contemporary overview

Recent advances in the field of molecular microbiology provide an unprecedented opportunity to decipher the vast diversity of the oral microbiome in health and disease. Here, we provide a contemporary overview of the oral microbiome and the microbiota of early childhood caries (ECC) with particular reference to newer analytical techniques. A MEDLINE search revealed a total of 20 metagenomic studies describing cariogenic microbiomes of ECC, 10 of which also detailed the healthy microbiomes. In addition, seven studies on site‐specific microbiomes, focusing on acidogenic and aciduric microbiota of deep‐dentinal lesions, were also reviewed. These studies evaluated plaque and saliva of children aged 1.5–11 years, in cohorts of 12–485 individuals. These studies reveal a very rich and diverse microbial communities, with hundreds of different phylotypes and microbial species, including novel species and phyla such as Scardovia wiggsiae, Slackia exigua, Granulicatella elegans, Firmicutes in the plaque biofilms of children with ECC. On the contrary, bacteria such as Streptococcus cristatus, S. gordonii, S. sanguinis, Corynebacterium matruchotii, and Neisseria flavescens were common in plaque biofilm of noncarious, healthy, tooth surfaces in subjects with caries. The review illustrates the immense complexity and the diversity of the human oral microbiota of the cariogenic plaque microbiome in ECC, and the daunting prospect of its demystification.     

Analysis of caudate lobe biliary anatomy and its implications in living donor liver transplantation – a single centre prospective study

Biliary complications are a significant cause of morbidity after living donor liver transplant (LDLT). Bile leak may occur from bile duct (anastomotic site in recipient and repaired bile duct stump in donor), cystic duct stump, cut surface pedicles or from divided caudate ducts. The first three sites are amenable to post‐operative endoscopic stenting as they are in continuation with biliary ductal system. However, leaks from divided isolated caudate ducts can be stubborn. To minimize caudate duct bile leaks, it is important to understand the anatomy of hilum with attention to the caudate lobe biliary drainage. This single‐centre prospective study of 500 consecutive LDLTs between December 2011 and December 2016 aims to define the biliary anatomy of the caudate lobe in liver donors based on intraoperative cholangiograms (IOCs) with special attention to crossover caudate ducts and to study their implications in LDLT. Caudate ducts were identified in 468 of the 500 IOCs. Incidence of left‐to‐right crossover drainage was 61.37% and right to left was 21.45%. Incidence of bile leak in donors was 0.8% and in recipients was 2.2%. Proper intraoperative identification and closure of divided isolated caudate ducts can prevent bile leak in donors as well as recipients.     

Antibacterial Efficacy of Silver Nanoparticles Synthesized by a Green Method Using Bark Extract of Melia azedarach L

Antibacterial efficacy of silver nanoparticles developed by a phyto-synthesis method has been investigated and presented in this work. Silver nanoparticles of mean size 30–45 nm having spherical shape and crystalline structure were synthesized at room temperature through bioreduction of silver nitrate solution treated with bark extract of Melia azedarach. Formation of nanoparticles was observed by the color change in the reaction medium which was further established with UV-vis spectroscopy. Structural and morphological characterizations on silver nanoparticles were made by X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infra-red spectroscopy (FTIR) analyses. FTIR spectroscopic analysis has revealed the presence of biomolecules enveloped around the silver nanoparticles. Antibacterial efficacy of these nanoparticles was analyzed against Escherichia coli and Klebsiella pneumonia by measuring the zones of inhibition on solid growth medium. These silver nanoparticles have shown efficient inhibitory activity against the tested bacterial strains. It is believed that the proposed biocompatible, eco-friendly, and green synthesis method would lead to development of novel biomedical products based on silver nanoparticles.     

Continuing Bonds in Bereaved Pakistani Muslims: Effects of Culture and Religion

This study explores the bereavement process and continuing bond in Pakistani Muslims with the focus on how culture and religion influence these processes. Ten participants were interviewed and their transcribed interviews were analyzed using a grounded theory approach. Three main domains were identified from the narratives expressed by the participants: death and the process of grieving, continuing the link with the deceased, and influencing agents. The findings indicated that Pakistani Muslims maintained their link with the deceased through cultural and religious rituals, such as performing prayers, reciting holy verses, talking and dreaming about the deceased, doing charity, visiting graves, and arranging communal gatherings. The prime purpose of many of these practices was the forgiveness of the deceased. Grief reactions seemed to be determined by the nature of death, prior relationships with the deceased, reaction of society and gender of the bereaved. Religion provided a strong basis for coping and adjustment of the bereaved, through rationalizing and accepting the death. This study has important implications for counselors and family therapists who can use religious affiliations to reduce the impact of loss and complicated bereavement.     

Intrabiliary rupture of hepatic hydatid cyst: multidetector-row CT demonstration

Rupture of a hydatid cyst into the biliary tract, also known as cystobiliary communication, is the most common complication of hepatic hydatid cyst. This may lead to obstructive jaundice, pancreatitis, cholangitis, and sepsis with high mortality. Imaging plays an important role in the preoperative diagnosis of this condition which facilitates its management. We studied six patients with rupture of hepatic hydatid cyst into a large bile duct in whom multidetector-row CT (MDCT) suggested the diagnosis. The imaging findings included a single hepatic cyst less than 10 cm in diameter in all the cases; interruption of the cyst wall adjacent to a bile duct signifying cyst-bile duct communication was seen in five patients. The common bile duct was dilated in all the patients, with linear membranes in four and diffuse irregular high dense intrabiliary material observed within the common bile duct in two of them. Intrahepatic ducts were dilated in all the six cases and two patients showed linear dense contents within distended gallbladder. Subcapsular and intrathoracic rupture was associated in one patient each. MDCT demonstration of hydatid cyst in the liver together with a dilated common bile duct and distended gallbladder containing high density hydatid material suggest rupture of the cyst into biliary tree. MDCT enhances demonstration of the dilated common bile duct with hydatid material inside. The diagnosis is reinforced by the demonstration of the cystobiliary communication itself.     

Primary idiopathic chylopericardium: a rare case with a synopsis of the literature

Primary idiopathic chylopericardium is a rare clinical entity characterised by the collection of chyle within the pericardial cavity without a definitive cause. This case report describes the history, physical examination, evaluation, diagnosis and treatment of a 19-year-old boy with primary idiopathic chylopericardium. Radiological findings and biochemical analysis of the pericardial fluid following pericardiocentesis sustained this diagnosis. Initial conservative management failed, and the patient was surgically treated subsequently. He recovered well postoperatively and remained asymptomatic thereafter. Primary idiopathic chylopericardium is a rare pathology with very few cases reported till date, and the symptoms are commonly due to cardiac compression. Computed tomography of the chest and bipedal lymphoscintigraphy are considered the standard methods for accurate diagnosis, and in cases of failed medical treatment, open and thoracoscopic thoracic duct ligation with pericardiectomy have been described as the best surgical options.