Systemic anticancer therapy for urothelial carcinoma: UK oncologists' perspective.

Urothelial carcinoma (UC) is a common cancer associated with a poor prognosis in patients with advanced disease. Platinum-based chemotherapy has remained the cornerstone of systemic anticancer treatment for many years, and recent developments in the treatment landscape have improved outcomes. In this review, we provide an overview of systemic treatment for UC, including clinical data supporting the current standard of care at each point in the treatment pathway and author interpretations from a UK perspective. Neoadjuvant cisplatin-based chemotherapy is recommended for eligible patients with muscle-invasive bladder cancer and is preferable to adjuvant treatment. For first-line treatment of advanced UC, platinum-eligible patients should receive cisplatin- or carboplatin-based chemotherapy, followed by avelumab maintenance in those without disease progression. Among patients unable to receive platinum-based chemotherapy, immune checkpoint inhibitor (ICI) treatment is an option for those with programmed death ligand 1 (PD-L1)-positive tumours. Second-line or later treatment options depend on prior treatment, and enfortumab vedotin is preferred after prior ICI and chemotherapy, although availability varies between countries. Additional options include rechallenge with platinum-based chemotherapy, an ICI, or non-platinum-based chemotherapy. Areas of uncertainty include the optimal number of first-line chemotherapy cycles for advanced UC and the value of PD-L1 testing for UC.

Using Infrared Photothermal Heterodyne Imaging to Characterize Micro- and Nanoplastics in Complex Environmental Matrices.

A key challenge for addressing micro- and nanoplastics (MNPs) in the environment is being able to characterize their chemical properties, morphologies, and quantities in complex matrices. Current techniques, such as Fourier transform infrared spectroscopy, provide these broad characterizations but are unsuitable for studying MNPs in spectrally congested or complex chemical environments. Here, we introduce a new, super-resolution infrared absorption technique to characterize MNPs, called infrared photothermal heterodyne imaging (IR-PHI). IR-PHI has a spatial resolution of ∼300 nm and can determine the chemical identity, morphology, and quantity of MNPs in a single analysis with high sensitivity. Specimens are supported on CaF2 coverslips under ambient conditions from where we (1) quantify MNPs from nylon tea bags after steeping in ultrapure water at 25 and 95 °C, (2) identify MNP chemical or morphological changes after steeping at 95 °C, and (3) chemically identify MNPs in sieved road dust. In all cases, no special sample preparation was required. MNPs released from nylon tea bags at 25 °C were fiber-like and had characteristic IR frequencies corresponding to thermally extruded nylon. At 95 °C, degradation of the nylon chemical structure was observed via the disappearance of amide group IR frequencies, indicating chain scission of the nylon backbone. This degradation was also observed through morphological changes, where MNPs altered shape from fiber-like to quasi-spherical. In road dust, IR-PHI analysis reveals the presence of numerous aggregate and single-particle (<3 µm) MNPs composed of rubber and nylon.

Deep image restoration for infrared photothermal heterodyne imaging.

Infrared photothermal heterodyne imaging (IR-PHI) is an all-optical table top approach that enables super-resolution mid-infrared microscopy and spectroscopy. The underlying principle behind IR-PHI is the detection of photothermal changes to specimens induced by their absorption of infrared radiation. Because detection of resulting refractive index and scattering cross section changes is done using a visible (probe) laser, IR-PHI exhibits a spatial resolution of ∼300 nm. This is significantly below the mid-infrared diffraction limit and is unlike conventional infrared absorption microscopy where spatial resolution is of order ∼5µm. Despite having achieved mid-infrared super-resolution, IR-PHI's spatial resolution is ultimately limited by the visible probe laser's diffraction limit. This hinders immediate application to studying samples residing in spatially congested environments. To circumvent this, we demonstrate further enhancements to IR-PHI's spatial resolution using a deep learning network that addresses the Abbe diffraction limit as well as background artifacts, introduced by experimental raster scanning. What results is a twofold improvement in feature resolution from 300 to ∼150 nm.

Examining the Need to Standardize Implanted Stimulator Connectors: NANS Survey Results.

INTRODUCTION: Connectors between implanted stimulator electrodes and pulse generators allow revisions, including battery changes or generator upgrades, to proceed without disturbing uninvolved components, such as the electrode. As new devices are introduced, however, connector incompatibility, even with updated hardware from the same manufacturer, can lead to additional procedures, expense, and morbidity. MATERIALS AND METHODS: Following the example of the cardiac pacemaker/defibrillator industry, the Institute of Neuromodulation (IoN) met to explore the possibility of creating connector standards for implanted neurostimulation devices. At a subsequent meeting of the Association for the Advancement of Medical Instrumentation, which coordinates the development of such standards, industry representatives asked for data defining the need for a new standard. Accordingly, IoN prepared an online survey to be sent to the North American Neuromodulation Society mailing list regarding experience with the connectivity of spinal cord stimulation (SCS) generators and electrodes. RESULTS: The 87 respondents of 9657 surveyed included 77 clinicians, who reported a total of 42,572 SCS implants and revisions. More than a quarter of revisions (2741 of 9935) required the interconnection of devices made by separate manufacturers, in most cases (n = 1528) to take advantage of a new feature (e.g., rechargeability, new waveform) or because an original component could not be replaced (n = 642). Connector adapters provided by manufacturers were used in less than half (n = 1246) of these cases. Nearly all (94%) of the clinicians agreed that standardized connectors should be developed for SCS, and 86% opined that standardized connectors should be developed for other neurostimulation therapies. CONCLUSION: Those who responded to our survey support the development of standard connectors for implanted stimulators, with voluntary compliance by manufacturers, to mitigate the need for adapters and facilitate interchanging components when appropriate. Other advantages to patients and manufacturers might accrue from the adoption of standards, as technology evolves and diversifies.

Assessing Patient Experience and Healthcare Quality of Dental Care Using Patient Online Reviews in the United States: Mixed Methods Study.

BACKGROUND: Over the last two decades, patient review websites have emerged as an essential online platform for doctor ratings and reviews. Recent studies suggested the significance of such websites as a data source for patients to choose doctors for healthcare providers to learn and improve from patient feedback and to foster a culture of trust and transparency between patients and healthcare providers. However, as compared to other medical specialties, studies of online patient reviews that focus on dentists in the United States remain absent. OBJECTIVE: This study sought to understand to what extent online patient reviews can provide performance feedbacks that reflect dental care quality and patient experience. METHODS: Using mixed informatics methods incorporating statistics, natural language processing, and domain expert evaluation, we analyzed the online patient reviews of 204,751 dentists extracted from HealthGrades with two specific aims. First, we examined the associations between patient ratings and a variety of dentist characteristics. Second, we identified topics from patient reviews that can be mapped to the national assessment of dental patient experience measured by the Patient Experience Measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Dental Plan Survey. RESULTS: Higher ratings were associated with female dentists (t71881=2.45, P<.01, g=0.01), dentists at a younger age (F7, 107128=246.97, P<.001, g=0.11), and those whose patients experienced a short wait time (F4, 150055=10417.77, P<0.001, g=0.18). We also identified several topics that corresponded to CAHPS measures, including discomfort (eg, painful/painless root canal or deep cleaning), and ethics (eg, high-pressure sales, and unnecessary dental work). CONCLUSIONS: These findings suggest that online patient reviews could be used as a data source for understanding the patient experience and healthcare quality in dentistry.

Separation of overlapping sources in bioacoustic mixtures.

Source separation is an important step to study signals that are not easy or possible to record individually. Common methods such as deep clustering, however, cannot be applied to signals of an unknown number of sources and/or signals that overlap in time and/or frequency-a common problem in bioacoustic recordings. This work presents an approach, using a supervised learning framework, to parse individual sources from a spectrogram of a mixture that contains a variable number of overlapping sources. This method isolates individual sources in the time-frequency domain using only one function but in two separate steps, one for the detection of the number of sources and corresponding bounding boxes, and a second step for the segmentation in which masks of individual sounds are extracted. This approach handles the full separation of overlapping sources in both time and frequency using deep neural networks in an applicable manner to other tasks such as bird audio detection. This paper presents method and reports on its performance to parse individual bat signals from recordings containing hundreds of overlapping bat echolocation signals. This method can be extended to other bioacoustic recordings with a variable number of sources and signals that overlap in time and/or frequency.

Impairment of wound healing by reactive skin decontamination lotion (RSDL®) in a Göttingen minipig® model.

Reactive Skin Decontamination Lotion (RSDL®) is an FDA-approved skin decontamination kit carried by service members for removal and neutralisation of vesicants and nerve agents. The RSDL kit, comprised of a lotion-impregnated sponge, was shown to be the superior medical decontamination device for chemical warfare agent (CWA) exposure on intact skin. In the event of a chemical exposure situation (i.e. terrorism, battlefield) physical injuries are probable, and preservation of life will outweigh the risk associated with application of RSDL to compromised skin. The purpose of this study was to quantify the rate and quality of wound healing in epidermal skin wounds treated with RSDL in a porcine model. Degree of wound healing was assessed using bioengineering methods to include ballistometry, colorimetry, evaporimetry, and high-frequency ultrasonography. Clinical observation, histopathology and immunohistochemistry were also utilised. All pigs received four bilateral superficial abdominal wounds via a pneumatic dermatome on their ventral abdomen, then were treated with the following dressings over a seven-day period: RSDL sponge, petroleum based Xeroform® gauze, 3 M™ Tegaderm™ Film, and 3 M™ Tegaderm™ Foam. Two additional non-wounded sites on the flank were used as controls. Two groups of pigs were then evaluated for a 21- or 56-day time period, representing short- and long-term wound-healing progression. Our findings indicated RSDL had a negative impact on wound-healing progression at both 21 and 56 days post-injury. Wounds receiving RSDL demonstrated a decreased skin elasticity, significant transepidermal water loss, and altered skin colouration and thickness. In addition, the rate of wound healing was delayed, and return to a functional skin barrier was altered when compared to non-RSDL-treated wounds. In conclusion, wound management care and clinical therapeutic intervention plans should be established to account for a prolonged duration of healing in patients with RSDL-contaminated wounds.

Changing healthcare provider and parent behaviors in the pediatric post-anesthesia-care-unit to reduce child pain: Nurse and parent training in postoperative stress.

BACKGROUND: Children who undergo surgery experience significant pain in the post anesthesia care unit. Nurse and parent behaviors in the post anesthesia care unit directly impact child postoperative pain. Therefore, we have developed and evaluated (Phase 1) and then tested (Phase 2) the feasibility of a new intervention (Nurse and Parent Training in Postoperative Stress) to alter parent and nurse behaviors in a way consistent with reducing child postoperative pain. METHODS: In Phase 1, a multidisciplinary team of experts (physicians, nurses, and psychologists) developed an empirically-based intervention which was then evaluated by experienced nurses (N = 8) and parents (N = 9) during focus groups. After revising the intervention based on focus group feedback, it was tested in Phase 2 using a pre-post study design. Nurses (N = 23) who worked in the recovery room were recruited to be part of both pre- and post-intervention data collection periods. Parents were recruited to be part of either the pre- (N = 52) or post-intervention (N = 60) data collection periods. Nurses and parent-child dyads were recorded in the post anesthesia care unit and videos were coded for the desired (ie, behaviors that may decrease child pain) and non-desired (ie, behaviors that may increase child pain) behaviors. Pain data was collected from the children's medical records to assess pain after surgery. The intervention was given to the nurses and parents in the post-intervention data collection period. RESULTS: Nurses significantly increased their rate of desired behaviors by 231% (P = 0.001; Somer's D = 1) and significantly decreased their rate of non-desired behaviors by 62% (P = 0.004, Somer's D = -0.88, 95% CI [-1.74, -0.03]). Parents significantly increased their rate of desired behaviors by 124% (P = 0.033). Moreover, the intervention significantly decreased child pain in the post anesthesia care unit (b = -2.19, SE = 0.63, z = -3.46, P = 0.001, 95%CI [-3.43, -0.95]). CONCLUSION: The intervention was effective in changing nurse and parent behaviors as well as child pain after surgery.

An evaluation of preoperative anxiety in Spanish-speaking and Latino children in the United States.

BACKGROUND: There is a large body of literature examining factors associated with children's preoperative anxiety; however, cultural variables such as ethnicity and language have not been included. AIMS: The purpose of this investigation was to examine the role of Latino ethnicity and Spanish-speaking families in pediatric preoperative anxiety. METHODS: Participants were 294 children aged 2-15 years of age undergoing outpatient, elective tonsillectomy and/or adenoidectomy surgery and general anesthesia. Participants were recruited and categorized into 3 groups: English-speaking non-Latino White (n = 139), English-speaking Latino (n = 88), and Spanish-speaking Latino (n = 67). Children's anxiety was rated at 2 time points before surgery: the time the child entered the threshold of the operating room (Induction 1) and the time when the anesthesia mask was placed (Induction 2). RESULTS: Results from separate linear regression models at Induction 1 and Induction 2, respectively, showed that being from a Spanish-speaking Latino family was associated with higher levels of preoperative anxiety compared with being from an English-speaking family. In addition, young age and low sociability was associated with higher preoperative anxiety in children. CONCLUSION: Clinicians should be aware that younger, less sociable children of Spanish-speaking Latino parents are at higher risk of developing preoperative anxiety and manage these children based on this increased risk.

Parental satisfaction of child's perioperative care.

BACKGROUND: Satisfaction in the hospital setting is an important component of both hospital funding and patient experience. When it comes to a child's hospital experience, parent satisfaction of their child's perioperative care is also necessary to understand. However, little research has been conducted on the predictors of this outcome. Therefore, the purpose of this current study was to validate a priori selected predictors for parental satisfaction in their child's perioperative process. METHODS: Eight hundred and ten pediatric patients who underwent tonsillectomy and adenoidectomy surgery and their parents were included in this study. The primary outcome was assessed using a 21-item parent satisfaction questionnaire resulting in three satisfaction scores: overall care satisfaction, OR/induction satisfaction, and total satisfaction. RESULTS: Descriptive statistics and correlational analysis found that sedative-premedication, parental presence at anesthesia induction, child social functioning, parental anxiety, and language were all significant predictors of various components of the satisfaction score. Regression models, however, revealed that only parent anxiety and child social functioning remained significant predictors such that parents who reported lower state anxiety (OR/induction satisfaction: OR = 0.975, 95% CI [0.957, 0.994]; total satisfaction: OR = 0.968, 95% CI [0.943, 0.993]) and who had higher socially functioning children (overall care satisfaction: OR = 1.019, 95% CI [1.005, 1.033]; OR/induction satisfaction: OR = 1.011, 95% CI [1.000, 1.022]) were significantly more satisfied with the perioperative care they received. CONCLUSION: Lower parent anxiety and higher child social functioning were predictive of higher parental satisfaction scores.

Adaptive whitening of ambient ocean noise with narrowband signal preservation.

Passive underwater listening devices are often deployed to listen for narrowband signals of interest in time-varying background ocean noise. Such tonals are generated mechanically by ships, submarines, and machines, or acoustically by aquatic wildlife. Quantization of the sensor data for storage or low bit-rate transmission adds white noise which can overwhelm weak narrowband signals if the background noise is sufficiently colored. Whitening the background noise prior to quantization can reduce the detrimental effects, but the whitening process must preserve any tonals in the signal for maximum effectiveness. Existing adaptive whitening techniques make no effort to avoid suppressing tonals in the whitening process, while existing spectral separation methods fail to whiten background noise. The proposed methods perform adaptive whitening of background ambient noise while preserving narrowband tones at their original signal-to-noise ratios. The proposed methods are shown to outperform combinations of existing partial solutions both subjectively and by evaluating the objective criteria introduced. The stability and convergence properties of the proposed algorithms match or surpass those of existing well-known adaptive algorithms.

Revisiting a measure of child postoperative recovery: development of the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery.

BACKGROUND: The Post Hospitalization Behavior Questionnaire (PHBQ) was designed for assessing children's posthospitalization and postoperative new-onset behavioral changes. However, the psychometric properties of the scale have not been re-evaluated in the past five decades despite substantial changes in the practice of surgery and anesthesia. In this investigation, we examined the psychometric properties of the PHBQ to potentially increase the efficacy and relevance of the instrument in current perioperative settings. METHOD: This study used principal components analysis, a panel of experts, Cronbach's alpha, and correlations to examine the current subscale structure of the PHBQ and eliminate items to create the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS). Data from previous investigations (N = 1064, Mage  = 5.88) which utilized the PHBQ were combined for the purposes of this paper. RESULTS: A principal components analysis revealed that the original subscale structure of the PHBQ could not be replicated. Subsequently, a battery reduction, which utilized principal components analysis and a panel of experts, was used to eliminate the subscale structure of the scale and reduce the number of items from 27 to 11, creating the PHBQ-AS. The PHBQ-AS demonstrated good internal consistency reliability and concurrent validity with another measure of children's psychosocial and physical functioning. CONCLUSION: Revising the former subscale structure and reducing the number of items in the PHBQ to create the PHBQ-AS may provide a means for reducing the burden of postoperative behavioral assessment through decreasing time of administration and eliminating redundancy of items and allow for more accurate measurement of child postoperative behavioral changes.

Pain management at home in children with cancer: a daily diary study.

BACKGROUND: With the transition of care of cancer patients from the hospital to the home setting, parents are largely responsible for children's pain management. Children's cancer pain is undermanaged, yet, there is little empirical data on the occurrence and management of cancer pain in the home setting. The purpose of the present study, therefore, was to employ a daily diary protocol to examine barriers to pain management of children's cancer pain by parents at home. PROCEDURE: Parent-child dyads were recruited from the Cancer Institute at a major children's hospital in Southern California. A total of 45 patient/parent pairs completed baseline data on demographic and personality characteristics, children's quality of life, and parental beliefs regarding analgesic use for children and then completed daily diaries of pain and analgesic administration for 14 consecutive days. RESULTS: Most children were reported to experience chronic pain while undergoing treatment for cancer, yet overall analgesic administration at home was low. Parents who reported misconceptions regarding analgesic use for children were less likely to administer pain medication to children. Children who were less shy, more social, or had lower quality of life were more likely to receive analgesics. CONCLUSIONS: A significant proportion of children receiving outpatient treatment for cancer were rated as experiencing chronic pain and pain was not optimally managed in the home setting. Further understanding and addressing barriers to children's cancer pain management in the home setting will aid in alleviating unnecessary pain in this vulnerable patient population.

Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service.

OBJECTIVE: To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service. METHODS: Five cases with secondary findings were reviewed. RESULTS: In Case 1, NIPT revealed a large duplication in chromosome 18p, which was supported by arrayCGH of amniocyte DNA, with final karyotype showing mosaic tetrasomy 18p. In Case 2, a deletion in the proximal long arm of chromosome 18 of maternal origin was suspected and confirmed by arrayCGH of maternal white cell DNA. In Case 3, NIPT was negative for trisomies 21 and 18. In-depth analysis for deletions/duplications was requested when fetal structural anomalies were detected at routine scan. A deletion in the proximal long arm of chromosome 3 was found and confirmed by karyotyping. In Case 4, NIPT correctly predicted confined placental mosaicism with triple trisomy involving chromosomes X, 7 and 21. In Case 5, NIPT correctly detected a previously unknown maternal mosaicism for 45X. CONCLUSION: Non-invasive prenatal testing is able to detect a wide range of fetal, placental and maternal chromosomal abnormalities. This has important implications on patient counseling when an abnormality is detected by NIPT.

Sphingid caterpillars conspicuous patches do not function as distractive marks or warning against predators.

To avoid predation by visual predators, caterpillars can be cryptic to decrease detectability or aposematic to warn predators of potential unpalatability. However, for some species, it is not clear if conspicuous patches are selected to avoid predation. For example, Pandora sphinx (Eumorpha pandorus, Lepidoptera: Sphingidae) caterpillars are assumed to be palatable and have both cryptic (green, brown) and conspicuous (orange, red) color morphs. Five lateral, off-white to yellow patches on either side may serve as a warning for predators or to draw attention away from the caterpillar's form to function as distractive marks. We conducted a field study in three temperate fragmented forests in Massachusetts to investigate the potential utility of E. pandorus coloration and conspicuous patches. Using four plasticine caterpillar prey model treatments, green and red with and without lateral conspicuous patches, we tested the effects of color, patch patterning, and seasonality on attack rates by a variety of taxa. We found that 43% of the prey models (n = 964) had bite marks by an array of predators including arthropods (67.5%), birds (18.2%), rodents (11.5%), and large mammals (2.8%). Arthropods as dominant predators align with conclusions from previous studies of prey models placed near ground level. Attack rates peaked for arthropods in late August and early September but were more constant across trials for vertebrates. Arthropods, a heterogeneous group, as indicated by the variety of bite marks, showed significantly higher attack rates on green colored prey models and a tendency of higher attack on solid (non-patch patterned) prey models. Vertebrates, more visually oriented predators, had significantly higher attack rates on red colored prey models and patch patterned prey models. Thus, our results did not suggest that conspicuous patch patterning reduced predation and therefore, we did not find support for the distractive mark hypothesis or warning hypothesis. Further, our study shows clear contrasting interpretations by different predators regarding visual defensive strategies.

Cabazitaxel versus docetaxel for treatment of metastatic castrate refractory prostate cancer.

Objectives: To assess cabazitaxel versus docetaxel re-challenge for the treatment of metastatic castrate refractory prostate cancer (CRPC) patients previously treated with docetaxel at inception of primary hormone therapy. Patients and Methods: The CANTATA trial was a prospective, two-arm, open-label, phase II study conducted in eight UK centres. Patients over the age of 18, with histologically proven, metastatic prostate cancer who had been previously treated with up to 6 cycles of docetaxel as part of the STAMPEDE trial (or treated with the same drug outside of the trial at primary diagnosis) and had a performance status (PS) of 0-2, were eligible. Patients who progressed during primary treatment with docetaxel or had received prior systemic chemotherapy were excluded. Cabazitaxel (25 mg/m2) or docetaxel (75 mg/m2) was administered via intravenous infusion every 3 weeks with oral prednisolone (10 mg) for up to 10 cycles, until disease progression, death or unacceptable toxicity. The primary outcome was clinical progression-free survival (PFS) as defined by either date of pain progression, date of a cancer-related skeletal-related event, or date of death from any cause. Analyses were by intention to treat. EudraCT number: 2012-003835-40. Results: Between 7 March 2013 and 4 January 2016, 15 patients with a median age of 70 years (range 54-76) were recruited; seven received cabazitaxel, eight docetaxel. The study was halted due to slow accrual. The median clinical PFS time in the cabazitaxel group was 6.2 months compared with 8.4 for the docetaxel group (95% confidence intervals were not reached due to the small number of patients). A total of 13 serious adverse events were reported. Conclusion: Due to the low number of patients recruited, meaningful comparisons could not be made. However, toxicity was in line with known outcomes for these agents, demonstrating it is feasible and safe to deliver chemotherapy to men relapsing with CRPC after upfront chemotherapy.

Synthesis, structure and spectroscopic properties of calix[4]phloroglucinarene dodecamethyl ether and its trifluoroacetic acid complex.

The action of trifluoroacetic acid (TFA) on 2,4,6-trimethoxybenzyl alcohol 3 affords the title tetrameric compound in high yield as a maroon TFA complex, 4; trituration of which with acetone gives the free, colorless, calix[4]phloroglucinarene (5) that can also be directly isolated by treating the reaction mixture with base. The novelty of compounds 4 and 5 is that they possess four additional methoxy groups, which occupy the cavity of the known calix[4]resorcinarene octamethyl ether (2). Ultraviolet-visible spectroscopic analysis shows that TFA-complex 4 exhibits transannular charge-transfer interactions between the opposite aromatic rings. The (1)H-NMR spectrum of the TFA-complex 4 does not change over a wide temperature range, strongly suggesting that it adopts a saddle (1,3-alternate) structure. The conformation of the free phloroglucinarene 5 is temperature-dependent, as determined by variable temperature (1)H NMR spectroscopy. Tetramer 5 adopts a partial cone conformation at low temperatures, but at elevated temperatures is similar to that of the TFA complex 4 (saddle). Tetramer 5 is conformationally mobile at ambient temperature, but generally has a flattened cone (boat) conformation. The ΔG(≠) for inversion in 5 between partial cone and boat conformation is 12.5 Kcal mol(-1), while that between boat and saddle conformation is 14.3 Kcal mol(-1). Conformational changes are also dependant on pH.

Spirocyclic systems derived from pyroglutamic acid.

The synthesis and likely conformational structure of rigid spirocyclic bislactams and lactam-lactones derived from pyroglutamic acid, and their suitability as lead structures for applications in drug development programmes using cheminformatic analysis, has been investgated.