Benign Prostatic Hyperplasia

The UK prostate specimens in this study came from two sources. Cancer tissue came from men locally referred to St Mary's Hospital in West London with symptoms of voiding dysfunction and prostate specific antigen abnormality and requiring biopsy after appropriate counselling. In addition, some patients had participated in a voluntary screening study and these provided samples that were a mixture of benign and cancer pathologies. All biopsy tissue had been stored in formalin fixed, paraffin-embedded (FFPE) blocks over a period of 3-6 years. Slices were taken from the blocks and DNA extracted as described (see Additional File 1; Supplementary Methods). The FFPE samples from Thailand and Korea were excess tissue from histological samples taken from new cases of both benign prostate hyperplasia and prostate cancer. These were FFPE embedded and sent to London for analysis.
We investigated the prevalence of XMRV in the UK and in the Far East, aware that the close relationship (about 94% at the nucleotide level) to other murine exogenous and endogenous retroviruses posed a problem in distinguishing XMRV from contaminating mouse DNA sequences. We were further aware that in any retrovirology laboratory MLV sequence contamination is something of an occupational hazard [19 (link)]. For these reasons, we extracted the DNA from FFPE prostate cancers, along with benign hyperplasia tissue, and PBS without tissue. We used several sets of primers [12 (link)] to test for XMRV-specific sequences, derived from the XMRV gag leader [1 (link)] which encompasses the 24 bp deletion originally thought to distinguish XMRV as a new human virus. To control for low level contamination, we included multiple no-template controls (no less than 6 in every run) and included assays with primers that would amplify murine mitochondrial DNA (mtDNA) and intracisternal A particle (IAP) LTRs. IAPs are retrotransposons present at the level of about 1000 copies of varying length per mouse genome [20 (link)].

Medical history data was frequently redacted in the trial datasets to maintain patient confidentiality, and even when provided, different terminologies were used. In contrast, all the trials providing data on concomitant medication used the World Health Organization Anatomic Therapeutic Chemical (WHO-ATC) system, the de facto standard for drug coding in clinical trials [24 ]. We therefore used concomitant medication data to identify 21 comorbidities in both the trial and community datasets.
Trials either reported the ATC codes directly or reported preferred terms often along with the drug route. In the latter case, we used RxNorm (the US drug metathesaurus) [25 ], the UK British National Formulary [21 ] and manual review to assign ATC codes. Trial concomitant medications were defined as any drug started on or before the randomisation date.
For the community sample, we used the NHS Business Authority ATC to Read code lookup table (as processed by the OpenPrescribing project) [26 ]. For drugs not found in the lookup table, we manually mapped Read code-defined drugs to ATC codes. Any drug prescribed during 2011 was included.
The following comorbidities (detailed in Additional file 4) were identified based on medication use: cardiovascular disease, chronic pain, arthritis, affective disorders, acid-related disorders, asthma/chronic obstructive pulmonary disease, diabetes mellitus, osteoporosis, thyroid disease, thromboembolic disease, inflammatory conditions, benign prostatic hyperplasia, gout, glaucoma, urinary incontinence, erectile dysfunction, psychotic disorders, epilepsy, migraine, parkinsonism and dementia. These drug-based definitions were developed in consultation with a steering committee comprising clinicians, epidemiologists and statisticians and were finalised before the analysis of the primary care data.
For each patient/participant, and within each index condition, we summed the number of individual comorbidities, not including the index condition, to obtain a comorbidity count.

With the idea of an MFH technique limited only to small tumor sizes, a special instrument was needed to deliver the heat in a minimally invasive manner. One potential end use of the LIH is during a laparoscopic procedure, a minimal invasive surgery where the surgeon inserts multiple tube-like instruments (with different functions) through small incisions in the patient’s body [53 –56 (link)]. This instrument was designed with a tube-like structure, considering current laparoscopic instrument designs, and its performance is mainly limited by the magnetic generator parameters and the electrical current flowing through it. The TRIH was designed for prostate cancer malignancies. This instrument could be used to reach the prostate transrectally or to access the prostate by placing it in contact with the perineum. A normal prostate has a volume of approximately 25 cm³. Nevertheless, in cases of benign prostate hyperplasia (BPH) or prostate cancer, the prostate volume can increase to over 30 cm³. This was the rationale behind designing this coil larger than the one in the LIH.
The enclosures for each instrument were designed to have a medical device appearance, while also providing a means to maintain the internal temperature of the coil below 155 °C to avoid damage. Both embodiments were designed using NX software (Siemens, Plano, TX, USA) and were partially constructed by a Zortrax Inkspire 3D printer (Zortrax SA, Olsztyn, Poland) with epoxy-based resin from the same company. The constructs can regulate the coil temperature by circulating water (20 °C–25 °C) throughout the instrument similar as inside MFH coils [57 (link)]. The materials for the LIH design and its measurements were selected considering the dimensions of current laparoscopic instruments. A polycarbonate tubing (⌀_inner = 12.7 mm × ⌀_outer = 15.9 mm × 1.6 mm wall) (Small Parts Inc., Logansport, IN, USA) connected the 3D printed parts (handle and tip). The handle included the water inlet and outlets, as well as a nylon wet-location multi-cord grip (McMaster-Carr, Elmhurst, IL, USA) for the 6 AWG Type 2 Litz wires that connect directly to the circuit. The tip was where the coil was placed and served as a connection point for the Masterflex^® 25 L/S^® inner tubing (Cole-Palmer, Vernon Hills, IL, USA). This ensures that the water flows right into the coil before exiting the instrument. A cap at the tip ensured fast replacement of the coil if a problem was encountered. The overall length of the LIH was approximately 23 cm (see figure 3(a)).
The TRIH design was similar in the parts used, but different in shape. In this case, a tygon flexible tubing (⌀_inner = 25.4 mm × ⌀_outer = 31.8 mm × 3.2 mm wall) (McMaster-Carr, Elmhurst, IL, USA) connected the 3D printed parts (handle and tip). Similar to the LIH, the handle included the water inlet and outlets, as well as the nylon wet-location multi-cord grip for the 6 AWG Type 2 Litz wires that connect directly to the circuit. The tip in this case also enclosed the coil and served as a connection point for the 25 L/S^® inner tubing. This part had a 4-jet nozzle for improved heat removal of this larger coil. This design also had a cap for fast replacement of the coil if a problem was encountered. Because of the 3D printed enclosure, the instrument itself is slightly larger than what we aim to use in the future. However, this does not affect its performance, as the coil has the exact dimensions we designed for. The overall length of the TRIH was approximately 25 cm (see figure 3(b)).

The exclusion criteria were as follows: (1) pregnancy or planning to conceive in the next 6 months; (2) a history of allergy to solifenacin; (3) cardiac problems (e.g., heart failure); (4) a history of surgery to treat urinary incontinence or other surgeries of the urinary system; (5) stress urinary incontinence or prostatic hyperplasia; (6) diabetes; (7) Parkinson’s disease; (8) a history of anticholinergic drug therapy for OAB in the last month; (9) a history of electrotherapy of the lower limbs and the back; (10) performing the pelvic floor muscle exercise in the last month; and (11) having a heart pacemaker and/or leg prosthesis.