Peyronie’s disease is an acquired connective tissue disease of the tunica albuginea of the penis which usually presents with penile curvature/deformity and a palpable penile plaque. It is more common in Caucasian men over the fifth decade of life, but it is an under-reported disease. Conservative and non-surgical options are supported by limited evidence except for intralesional injection of collagenase clostridium histolyticum and have limited success. The improved outcome of surgical treatment is accompanied by the risk of erectile dysfunction. This is a brief overview of Peyronie's disease, its impact on the patient, and the available treatment options. Peyronie's disease (PD) is an acquired connective tissue disorder of the tunica albuginea of the corpus cavernosum, characterized by islands of fibrosis and plaque formation. These may impede the uniform expansion of the cylindrical tunica albuginea during penile erection, leading to penile curvature and deformity. The cause is unknown, but the prevailing theory is one of repeated micro-trauma to the tunica during sexual intercourse followed by aberrant wound healing in susceptible individuals ,2. PrevaRisk factorsPD has been strongly linked with Dupuytren’s disease (DD). A study on men with DD reported the prevalence of PD-like symptoms as 26% . An inheClinical presentationPatients are usually Caucasian and between 40 and 60 years of age ,13. The PD is divided into acute and chronic phases. The acute phase is characterised by penile pain during erection, a soft plaque and penile curvature the severity of which may increase (21-48%), not change (36-67%) or improve (3-13%). It may last up to 12 months and is followed by the chronic phase characterized by stability in penile curvature, resolution of penile pain and a hard, calcified plaque -17.Psychological impactThere is an underappreciated, significant negative impact of PD on body image, mood, sexual relationships and quality of life. Men have described themselves as “disgusting,” “ugly” and “half a man.” The imposed restrictions on sexual intercourse are linked with feelings of shame, stigmatization and social isolation, and these reinforce each other. In studies, about 80% of men with PD admit to “emotional difficulties” with up to 50% experiencing moderate (26%) to severe (21%) clinical depression as a direct result of PD ,19. The Treatment optionsThe goals of treatment are correction of the penile curvature or deformity, preservation of penile length and restoration of erectile function. The heterogenicity in the phase of presentation, severity and characteristics of penile deformity, quality of erectile function and patients' characteristics demand that these goals be tailored to the patient’s disease and expectations. This very variability, however, makes a comparison of data across treatment studies difficult.Medical therapyThere is currently no high-quality evidence to support medical therapy as an effective avenue for remodelling or resorption of the penile plaque underpinning the penile deformity seen in PD -27.Conservative managementThe role of non-surgical management of PD, based on the current evidence, is mostly limited to the acute phase and the aims are the resolution of penile pain, inhibition of further curvature, improvement in erectile function and restoration of penile length. The current options include extracorporeal shockwave treatment (ESWT), penile traction therapy (PTT), vacuum pump devices (VP) and intralesional Collagenase Clostridium histolyticum (CCH). The evidence for these interventions derives from small studies of mixed qualities except for intra-lesional CCH which is supported by high-quality evidence.ESWT has been shown to relieve pain but has no effect on curvature or plaque size. There is conflicting evidence for and against improvement in erectile function as assessed by International Index of Erectile Function (IIEF) scores ,29. WhenPTT has been deployed in both the acute and chronic phases of the disease and has been shown to safely reduce penile curvature by mean values of 20-30⁰. The effect on the restoration of penile length and girth is minimal ,32.The role of VP devices as monotherapy is unclear. One small study showed a moderate reduction in pain score and penile curvature by 5-25⁰ with the most benefit seen in patients with non-calcified plaques . It doesIntralesional TherapyIntralesional therapy using CCH is both minimally invasive and supported by the highest quality of evidence from two large, double-blind, randomised placebo-controlled studies. The principle is based on enzymatic cleavage of the plaque in conjunction with mechanical remodelling. The studies included men with stable curvatures, but no complex deformities. CCH was injected into the penile plaque 24-72 hours apart followed by penile plaque remodelling 24-72 hours later. This was done in four cycles spanning a total of 24 weeks. There was a statistically significant 17% reduction in penile curvature compared with the placebo ,35. A vaSurgical managementSurgical correction is still the most effective and durable treatment modality for PD. It should not be performed in the acute phase and ideally only be considered once the penile curvature has been stable and painless for more than three months. The indications for surgery are deformity causing significant interference with sexual intercourse and/or inadequate penile rigidity; and patients’ desire for a more predictable outcome ,25-27. STunical ShorteningPlication sutures are placed into the convex surface of the tunica albuginea sometimes with incision or excision of the tunica. It was originally described by Nesbit in 1965 for the correction of congenital penile curvature . It was Tunical LengtheningThis is plaque incision (+/- limited plaque excision) and graft (PIG). The plaque on the concave surface is incised to release the tunica and the defect is covered by a graft. Plaque excision by itself has largely been abandoned. There is more pronounced mobilisation of the neurovascular bundle (NVB) and the veno-occlusive mechanism for an erection is at increased risk. The main premise for these techniques is the conservation of penile length and better correction of waist deformities. The trade-off is significantly increased risk with the rate of de novo ED up to 50% and penile hypoesthesia up to 52% .Insertion of Penile Prosthesis (IPP)This is the surgery of choice for men with PD and unresponsive ED. Insertion of an inflatable or semi-rigid, malleable penile prosthesis may be sufficient to correct the deformity but penile modelling or even PIG may be necessary as an adjunct.The critical factors governing the type of surgery are stretched penile length, the severity of penile curvature, the presence of complex deformity, erectile function and patient preference. The choice of surgery is easier at both ends of the spectrum - Plication (+/- corporoplasty) for men with a good penile length and no complex deformities and good erectile function. IPP for men with short penile length and complex deformities and poor erectile function. In between these poles, difficult choices must be made by the patient and the surgeon with regard to the risks of post-operative penile shortening, erectile function and residual curvature.DiscussionThe 60⁰ GuideIt was canon that men with curvatures greater than 60⁰ were best served by PIG with or without IPP ,44,46-48Penile ShorteningAs a rule, patient perception of penile shortening after corporal plication (CP) is often more than objective measurements and on average, the loss of length is between 1 and 1.5cm. Data from non-comparable series estimates “significant” penile shortening occurs in 3.2-8.9% of patients who undergo CP ,45. The Penile StraighteningThe definition of a straight penis following reconstructive surgery has been inconsistent ranging from <10⁰ to < 20⁰ and some studies not supplying an objective measurement . The 201Penile ProsthesisThe two types of penile prostheses are inflatable and malleable. There appears to be no significant difference in satisfaction rates between them ,52,53 anPatients with PD are often disappointed with the dearth of medical and conservative options and those who opt for surgical correction may have unattainable expectations compounded by the enforced wait until the chronic phase of the disease. The patient satisfaction rate is high for all the surgical options but there is a drop off in 5-10 years in those who undergo PIG. A comprehensive conversation covering penile length, de novo ED, residual curvature and in the case of IPP, the risk of device failure or infection should be the norm. How much risk is acceptable in the pursuit of a cosmetically straight, but functionally unnecessary penis is a decision for the patient and surgeon to negotiate.


Optimal frequency and duration of pneumatic compression device (PCD) therapy for lymphedema is undetermined. This prospective, randomized preliminary study evaluated the impact of different PCD dosing protocols on physiological and patient-reported outcomes (PROs) to estimate treatment effects, assess the responsiveness of various measurement techniques, and identify endpoints for a definitive PCD dosing trial.p = 0.003) on day 1 and of 97 (86) mL (p = 0.024) on day 5. Group A also showed possible single-treatment decreases in extracellular fluid volume by bioimpedance spectroscopy (BIS) on day 5. There were no consistent changes in groups B and C. Long-term assessment of LV and BIS showed no clear change. Tonometry, ultrasound, local tissue water, and PROs showed wide variation among participants.Twenty-one patients with lower extremity lymphedema were randomized into three groups for treatment with the Flexitouch advanced PCD: (A) once per day for 1 hour, 12 consecutive days; (B) twice per day in 1-hour treatments, 5 consecutive days; or (C) twice per day in 2-hour treatments, 5 consecutive days. Outcomes measured were changes in limb volume (LV), tissue fluid, tissue tone, and PROs. Those in group A experienced mean (standard deviation) LV reductions of 109 (58) mL (LV measurements showed potential benefit for 1-hour daily PCD treatment. A definitive dosing trial should include LV, BIS, and PROs in a comparison of 1- and 2-hour daily treatment protocols conducted over a study period of 4 weeks. These data may inform appropriate outcome measures for other intervention studies in lymphedema. Pneumatic compression devices (PCDs) assist with limb volume (LV) control in the management of lymphedema and have been used for many years as an adjunct to home care. The Flexitouch system  simulates the low pressure, more frequent cycles of manual lymphatic drainage, a component of complete decongestive therapy (CDT).1 and no formal dosing study has been carried out. There has been a trend toward shorter treatment duration, from 8 or more hours for hospital inpatient care to 1 hour or less for current home-based care.1 However, it remains unclear whether 1-hour dosing is therapeutically optimal or a concession to patient convenience. The aim of this preliminary study was to evaluate the impact of various PCD dosing protocols on multiple physiological and patient-reported outcomes (PROs) to assess treatment effects and determine suitable sample size and endpoints for a definitive dosing trial.Although several studies have reported on PCD use for treatment of lower extremity lymphedema, there is little consensus on optimal frequency and duration of treatmentThis three-arm, prospective, randomized, preliminary study assessed the comparative efficacy of different treatment frequency and duration in achieving a measurable effect on lower extremity lymphedema using the FT device . Many paThe outcomes were measured within day, that is, before and after treatment and before and after 5 days of treatment to determine possible long-term differences. The group which had 1 hour of treatment daily continued treatment for 12 days to explore whether this resulted in better outcomes than after 5 days. It was felt that doing this for the other groups would pose too heavy a burden and deter patients from participating in the study.The protocol was approved by the National Research Ethics Service Committee East Midlands, Derby, United Kingdom (revised May 2014). Written informed consent was obtained from all study participants. Recruitment was conducted among patients who presented to the Derby Lymphedema Service between December 2013 and March 2019.2 Participants were required to be using adequate compression garment(s) as determined by the physician  and attend all in-clinic treatments.Patients who had undergone treatment for clinically confirmed primary or secondary lower extremity lymphedema were eligible for enrollment. Participants had to be ≥18 years old and present with pitting unilateral or bilateral leg edema .Exclusion criteria included body mass index (BMI) >40; active or recently treated cancer; active infection or inflammation, recent venous thromboembolic disease, chronic venous insufficiency, heart failure, chronic kidney disease, poorly controlled asthma, peripheral artery disease; presence of an open wound, and pregnancy. At the screening visit, duplex ultrasound (US) tests were used to rule out significant venous insufficiency (defined by reflux >2 seconds).It should be noted that under an earlier version of the protocol (July 2013), 468 patients were screened, leading to only one recruitment. Due to this slow recruitment, the following exclusion criteria were revised to the above: primary lymphedema, compression garment <30 mm Hg and BMI >35.Enrolled participants were allocated randomly and in equal numbers into one of three treatment groups by a sealed envelope method . A treatGroup A received one treatment per day for 12 consecutive days. The first five treatments were administered in clinic followed by two patient-administered treatments at home (Saturday and Sunday) for participant convenience, concluding with an additional five in-clinic treatments .AM and PM with at least 2 hours between treatments) for 5 consecutive days .Group B received two in-clinic 1-hour treatments per day (AM and PM with at least 2 hours between treatment sessions) for 5 consecutive days .Group C received two consecutive 1-hour in-clinic treatments two times per day  to ensure uniform application of the device across all participants before inflation (7–10 mm Hg).The study evaluated changes in tissue fluid, tissue tone, and PROs. Measurements of the treated and untreated limb were taken before and after each treatment, while PROs were assessed at baseline and after final treatments. A clinician assessed participants for any signs or symptoms that required medical intervention or study discontinuation.4Limb volume measurements, especially in the short term, provide a proxy measure of fluid changes. These were taken with an optoelectronic system .5 measured as changes in electrical resistance at zero frequency (R0) using an SFB7 impedance spectrometer  according to the protocol as described by Steele et al.6 Increases in R0 values correspond proportionally to decreases in ECF.7Extracellular fluid (ECF) changes in the whole limb were assessed by bioimpedance spectroscopy (BIS) of the individual lower limbs,8Local tissue water (LTW) was assessed by measuring tissue dielectric constant (TDC) with a Moisture Meter D , at specific anatomical sites  using two probes that measure LTW to depths of 2.5 and 5 mm, respectively.9Ultrasound with a 5–16 MHz probe , was used to measure skin thickness at the same anatomical sites as TDC. Skin thickness (epidermis and dermis) has previously been shown to be increased uniformly around the arm in breast cancer-related lymphedema and correlates strongly with the degree of swelling.10A tissue tonometer  was used at the same defined locations as TDC to estimate the extent of pitting and fibrotic induration.11 A lower score represents a better QoL. LYMQOL is a validated lymphedema QoL assessment tool that covers symptoms, body image/appearance, function, and mood, as well an overall QoL score.12 A lower score in the four domains represents a better QoL but for the “overall QoL” section, a higher score represents a better QoL.PROs assessed symptoms and quality of life (QoL). Symptom assessment was obtained using the Measure Yourself Medical Outcome Profile (MYMOP) and QoL using a lymphedema-specific QoL questionnaire (LYMQOL). The MYMOP questionnaire was designed to be not only a patient-generated outcomes questionnaire, problem-specific, but also focused on general wellbeing.This preliminary study was not powered for statistical analysis of differences in outcomes between the three groups. Physiological responses to both individual daily treatments and changes at the completion of the course of treatment  were studied to assess short- and long-term effects.To evaluate the potential future use of the various methods used in this study, the dispersion of measurements and their responsiveness to change were assessed. The coefficient of variation (CV) is used as a standardized measure of data dispersion, that is, the larger the CV (%), the less consistent the data. In this study, the CV is a measure of both biological variation and the inherent error of each measurement technique. The day 1 CVs of all measurements used in this study were calculated to assess which measurements exhibited the greatest consistency and thus may be of greatest utility in a future study.The responsiveness to change was examined a posteriori by comparing the change in each measure at the end of day 5 from baseline on day 1 with the change in LV measured by perometry in group A as the gold standard (as this demonstrated a significant reduction over this time).Sample size estimates for a future study were derived from a variety of scenarios assuming normally distributed data using the z-score method for independent (unmatched) samples.To assess the feasibility for recruiting to a future definitive study, a screening log was maintained to record the number of patients eligible for this study and the numbers recruited.A total of 2576 patients were screened leading to 20 recruitments (July 2014 to November 2018), with one participant having been recruited under the first version of the protocol. The original plan was to recruit 10 participants in each group but even with the amendments, recruitment was slow. Therefore, it was decided to carry out the interim analysis reported here when each intervention arm included seven completed participants.In total, 21 participants  with chronic lower limb swelling were included in the study with 7 in each group. Individuals with primary lymphedema accounted for 81% of study participants, with 76% of participants experiencing bilateral swelling. All participants had pitting edema. None had used a PCD in the last year. All participants completed the study protocol with no adverse events.Although there was wide variation in some of the baseline characteristics, especially lymphedema duration and age, there was no statistically significant difference in any of these between the groups .p = 0.0026 and p = 0.024, respectively). However, there were no consistent changes in groups B and C, with some participants experiencing LV increases. Interestingly, a reduction in LV was seen in most untreated limbs especially on day 5 (on day 5 .0) after the final treatment on day 1, with no consistent pattern evident (There were wide variations in the change in ECF as measured by BIS (R evident . This ap evident .0) on day 5 were compared with those on day 1  showed no consistent pattern with wide variations in within-day changes in response to treatment, long-term effects to end of day 5, baseline CVs, and responsiveness to change .Therefore, for the physical assessment methods, perometry and BIS showed the greatest consistency and responsiveness to change and, hence, utility for future studies. LYMQOL is the better PRO, based on its lower CVs (23.7%–35.5%) than those of MYMOP  and S8.p-value of 0.05 would require a sample size of 14 participants in each group.Sample size calculations for a future definitive study, based on the effect sizes of LV changes from baseline day 1 to after the final treatment on day 5 in each group in this preliminary study, are provided in 1; however, it remains unclear whether this 1-hour dosing standard is physiologically based. This preliminary study was designed to obtain data to inform a definitive study of whether a longer duration of treatment would be more effective. While great caution must be exercised in interpreting the results, the finding that 1 hour of daily treatment appeared to produce better within-day LV results compared with 2- and 4-hour daily treatments challenges this hypothesis  recommended by international guidelines15To examine whether these potential improvements immediately following a 1-hour treatment have a long-term benefit, pretreatment LV and BIS values on day 5 were compared with those on day 1  and 3. T16 It is suggested that the truncal component of the FT device may have facilitated contralateral limb drainage. In addition, particularly for those in groups B and C, there could have been an effect from lying supine for several hours.The apparent effect of unilateral treatment on contralateral limbs –5 deservIn developing a future definitive study design, we considered the following several factors.The recruitment logs demonstrated that this was a difficult study to recruit to, largely because of its intensity and the time commitment required. The initial inclusion criteria were limited to secondary nonvenous lymphedema. After screening hundreds of patients without success, the inclusion criteria were broadened. Despite this, it took an additional 4 years to recruit a modest sample size of 21 participants. Allowing participants to conduct their own PCD treatments at home with fewer clinic visits for measurements should facilitate recruitment in a future trial.17 and it is now recognized that all chronic edema stems from lymphatic dysfunction and should be considered lymphedema.19With the benefit of hindsight, the decision to exclude patients with venous insufficiency seems unnecessarily limiting, as lymphedema related to venous insufficiency is common,This study suggests that longer daily dosage may not necessarily be more effective. The sample size calculations  suggest To reduce the burden of the study, most daily treatments could be carried out at home with attendance for pre- and posttreatment assessments weekly. To examine potential long-term effects, it is suggested that participants are followed up for a longer period , although the data from this study do not inform the optimum follow-up period.20 US (of subcutaneous tissues),21 and TDC22 have contributed valuable information on edema and tissue changes/fibrosis in long-term lymphedema studies, these measures provided little added perspective on treatment effects over the 5-day study period. For a future dosing trial, it is recommended that physical measurements are limited to LV and BIS, although it is recognized that TDC can be particularly helpful in identifying local fluid changes in different regions of the limb.This study assessed the CV and responsiveness to change of a wide range of measurements used in previous lymphedema studies. Perometry and BIS measured both single-treatment effects and those over the 5 days of the study. While tonometry,PROs are also recommended but given the CVs found here, it is suggested that they are limited to LYMQOL, to reduce the burden on participants for completing questionnaires.1This preliminary study succeeded in defining a feasible framework for a future definitive trial of PCD dosing. Strengths of this study include the broad set of measurements assessed and the comparison of short- and medium-term effects. Limitations include the difficulty in recruiting participants which led to a failure to recruit the planned number; a study population unrepresentative of real-world clinical practice; and the lack of a control group of “no treatment” (as the use of PCDs was considered an established treatment).In this preliminary study, perometry and BIS were shown to be the better measurements to determine the response to PCD treatment, while tonometry, US, and TDC were of lesser utility. The findings indicate a potential benefit for 1 hour of daily treatment compared with twice-daily treatments of 1 or 2 hours. A future definitive randomized controlled trial design is proposed. These data are also of wider value in informing the design of other studies examining the outcome of interventions for the treatment of lower limb lymphedema.


Anthropogenic emissions of ammonia to the atmosphere, particularly those from agricultural sources, can be damaging to the environment and human health and can drive a need for sensor technologies that can be used to detect and quantify the emissions. Mobile sensing approaches that can be deployed on ground-based or aerial vehicles can provide scalable solutions for high throughput measurements but require relatively compact and low-power sensor systems. This contribution presents an ammonia sensor based on wavelength modulation spectroscopy (WMS) integrated with a Herriott multi-pass cell and a quantum cascade laser (QCL) at 10.33 µm oriented to mobile use. An open-path configuration is used to mitigate sticky-gas effects and achieve high time-response. The final sensor package is relatively small (~20 L), lightweight (~3.5 kg), battery-powered (<30 W) and operates autonomously. Details of the WMS setup and analysis method are presented along with laboratory tests showing sensor accuracy (<~2%) and precision (~4 ppb in 1 s). Initial field deployments on both ground vehicles and a fixed-wing unmanned aerial vehicle (UAV) are also presented. Ammonia thus represents a major nitrogen emission species from agricultural sites with contributions from both synthetic fertilizer and animal waste  = 100 ppb, [H2O] = 0.013 (50% relative humidity), and [CO2] = 390 ppm.The modulation of injection current leads to simultaneous variation of laser wavelength and intensity. These functions were determined in separate experiments using an ammonia reference cell and etalon for establishing the frequency axis . In partndwidth) . A givenf amplitude normalized by 1f, i.e., Rf2/Rf1) for the case of NH3 concentration of 150 ppb . The figure illustrates the scan range used in actual experimental measurements and shows an example of the data quality. One can see that there is excellent agreement in the peak amplitude and overall spectral shape, showing the validity of the assumed methods.We first illustrate the workings of our WMS implementation by showing an example of a specific measurement simulation and result with gas delivered from a reference cylinder through a closed-cell cavity. 2 = 0.9997). The right of t−0.44 dependence, close to what one expects in a shot-noise limited case (t−0.5).A closed-path configuration at atmospheric pressure was used to examine the precision and accuracy of the sensor. Zero-air  and ammonia gas  from two reference cylinders were mixed and passed through the optical cavity. The left of The preliminary outdoor tests were conducted via vehicle (truck) deployment at ground level using the sensor and vehicle mounting described above. We found this configuration to allow successful data recording including for sensor operation in the presence of vibrations associated with driving on a rugged road with vehicle movement. We have also shown the ability to deploy the sensor on a UAV to record aerial ammonia data. Again, the sensor and mounting are as described above, though in this case with the UAV mounting configuration. The aircraft used was a fixed-wing Senior Telemaster piloted by a team of CSU flight personnel. The runway used was hardpacked ground on farmland, which illustrates the versatility of the approach . The flights were performed at a site which was ~1.5 km away from a big feedlot. Flight times for the Telemaster are relatively short (depending on payload and flight-speed) with the flight shown in 3 WMS sensor for sensitivity and accuracy. We have also presented results of initial mobile deployments using both a truck and UAV including detection of multiple outdoor plumes from a range of source types. Future work will include more extensive deployments in a range of ambient conditions to further characterize (and optimize) sensor usage in real, outdoor conditions.We have presented the design and performance of a sensitive and compact ammonia sensor based on WMS using a QCL source operating at the favorable spectral region of 10.3 μm. There is a rather complex trade-space among possible ammonia sensors as was summarized in the introduction. In comparison to our past work on CRDS detection in the similar spectral region (and with the same laser), the WMS sensor has slightly poorer detection limit ; the WMS package is far smaller and less power-hungry (~3.5 kg and 30 W for WMS as compared to >10 kg and ~600 W for CRDS). The smaller mass and power-draw are very enabling for practical applications, particularly mobile deployment, whereas the CRDS system was too bulky and power-hungry for most realistic UAV deployments. We have presented laboratory testing of the NH3:CH4 readings can be interpreted as being due to loss to the ground from which deposition velocity and related parameters of ammonia transport can be inferred [Mobile, particularly aerial, deployment of the ammonia sensor can open the door to multiple measurement possibilities. One example is to make multiple passes (transects) of an emitting source and to use the concentration data, along with wind data, to infer the location and mass-flux of the source. Various algorithms are being developed for such purposes including via Bayesian analysis  (assumininferred . Ultimat