PAM-flexible Engineered FnCas9 variants for robust and ultra-precise genome editing and diagnostics.

The clinical success of CRISPR therapies hinges on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) is highly precise, with a negligible affinity for mismatched substrates, but its low cellular targeting efficiency limits therapeutic use. Here, we rationally engineer the protein to develop enhanced FnCas9 (enFnCas9) variants and broaden their accessibility across human genomic sites by ~3.5-fold. The enFnCas9 proteins with single mismatch specificity expanded the target range of FnCas9-based CRISPR diagnostics to detect the pathogenic DNA signatures. They outperform Streptococcus pyogenes Cas9 (SpCas9) and its engineered derivatives in on-target editing efficiency, knock-in rates, and off-target specificity. enFnCas9 can be combined with extended gRNAs for robust base editing at sites which are inaccessible to PAM-constrained canonical base editors. Finally, we demonstrate an RPE65 mutation correction in a Leber congenital amaurosis 2 (LCA2) patient-specific iPSC line using enFnCas9 adenine base editor, highlighting its therapeutic utility.

The investigation of diesel soot emission using instrument combination of multi-wavelength photoacoustic spectroscopy and scanning mobility particle sizer.

The parallel measurements of wavelength dependent optical absorption, particle number size distribution have made by a multi wavelength photoacoustic spectrometer (4λ-PAS) and scanning mobility particle sizer (SMPS) respectively at different modes of a diesel engine using two different types of fuel. The thermal evolution of the emission was also investigated using posterior temperature treatment of emission. The bimodal size distribution of emitted particles at a set reference temperature has been observed regardless of the applied fuel at idle. However, the emitted particulate assembly had lognormal size distribution falls into the accumulation mode at all other defined engine modes and both fuel types. The total number- and volume concentration (TNC and TVC) showed retrograde tendency with the increasing torque and rpm independently of the applied fuel types. The TNC values decreased up to 50% for both fuels with engine operation changes from idle engine mode(em#1) to low engine mode(em#2). With further increase in torque and rpm of engine, the change in TNC is negligible. On the other hand, the TVC remains more or less the same for idle to low engine mode transition and increased more than 60% for high mode (em#3) transition. The Optical Absorption Coefficient (OAC) values measured at the operational wavelengths of the 4λ-PAS instrument decreased at all wavelengths with increasing rpm and torque. The wavelength dependency quantified by Aerosol Ängström Exponent (AAE) was applied here for qualitative analysis of the carbonaceous emission and showed decreased values towards the higher engine speed and torque output of the engine. The proposed technique can be used as real-time, precise and accurate measurement of light absorption by DPM aerosols, which opens up novel possibilities for the volatility and thermal evolution investigation of diesel emissions.

Tetrahydrobenzothiophene derivatives ameliorate Mia PaCa-2 cell progression and induces apoptosis via inhibiting EGFR2 tyrosine kinase signal.

A series of new thiophene analogues with acarbonitrile-basedmoiety were designed and synthesized via structural optimization. The conjugates were assessed for their in-vitro cytotoxic activity against a human pancreatic cancer cell line (Mia PaCa-2) and among them compound 5b showed IC50 value of 13.37 ± 2.37 µM. The compounds 5b (20 µM & 25 µM) and 7c (30 & 35 µM) also showed reduced clonogenicity, enhanced ROS and decreased mitochondrial membrane potential in Mia PaCa-2 cells. Treatment with these compounds also increased apoptotic population as evident with the double staining assay. Among the evaluated series, compounds 5b, 5g, 7c, and 9a attained a greater inhibitory potency than first generation's reversible EGFR inhibitor, Gefitinib. EGFR2 enzyme inhibitory studies revealed that 5b efficiently and arbitrarily suppressed the development of EGFR2 dependent cells and inhibited the enzymatic activity with an IC50 value of 0.68 µM; interestingly, the most effective molecule 5b with N-methyl piperazine substitution, has 1.29-fold greater potency than well-known EGFR inhibitor Gefitinib and increased Gefitinib's anti-growth impact with 2.04 folds greater against Mia PaCa-2. The in-vitro studies were validated with in-silico docking studies wherein compounds 5b and 7c exhibited binding energies of -8.2 and -7.4 Kcal/mol respectively. The present study reveals that tetrahydrobenzothiophene based analogues could be a promising lead for the evolution of potent chemo preventives over pancreatic cancer.

Pre-treatment inflammatory and immune system parameters predicting cervical cancer metastasis.

Objective: This study aimed to evaluate the relationship between mannose-binding lectin-associated serine protease-2 as an immune system parameter and neutrophil lymphocyte ratio (NLR) as an inflammatory parameter to predict cervical cancer metastasis. Materials and Methods: This cross-sectional study included 70 patients diagnosed with cervical cancer between January 2022 and February 2023 at Dr. Wahidin Sudirohusodo Hospital, Hasanuddin University Hospital, and Ibnu Sina Hospital, Makassar, Indonesia. Blood samples taken before therapy as well as clinical and histological data were gathered and examined. MASP-2 levels and NLR were measured by ELISA and flow cytometry respectively. Results: The median age of the patients was 46 years (range, 24-72 years), with the majority of patients aged between 41 and 52 years. Statistical analysis showed that MASP-2 was associated with cervical cancer stage (p≤0.000), organ metastasis (p=0.011), and lymphovascular invasion (p=0.036). In addition, NLR was associated with cervical cancer stage (p=0.004), histopathology type (p=0.031), tumor size (p=0.019), and organ metastasis (p=0.013). Conclusion: Pretreatment with MASP-2 as an immune system parameter and NLR as an inflammatory parameter is associated with cervical cancer metastasis. The NLR indicator can be applied in clinical practice because it is simple and reasonably priced.

Seroprevalence and haemato-biochemical effects of bovine leucosis in buffalo, Punjab, Pakistan.

Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a Deltaretrovirus belonging to the family Retroviridae. BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association (P < 0.05) of age with BLV infection. Furthermore, milk yield and pregnancy had a significant association with the seroprevalence of BLV infection in buffalo whereas no significant association was found with sex, breeding, and health status. Biochemical and oxidative stress markers revealed a significant decrease in liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in seropositive animals as compared to healthy animals. It is concluded that BLV has a considerable prevalence in buffalo in Punjab, Pakistan and there is a dire need to investigate the disease epidemiology at both national and international levels and strategies should be developed to implement an effective control program.

Matrix-Metalloproteinase Inhibitory Study of Novel Tetrahydroisoquinoline-4-carboxylates: Design, Synthesis, and Molecular Docking Studies.

The design, molecular docking, synthesis and structure-activity relationship (SAR) of a series of novel methyl 1-oxo-2-(propan-2-yl)-3-(pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylates, were investigated for antiproliferative and cytotoxic studies by screening against cancer cell lines of different origin by MTT, LDH and Trypan Blue Assay. Irrespective of cell lines, among the synthesized nonpeptido-mimetic analogs 5a-e, 5c has executed potent bio-potency with IC50 value of 7.00 to 7.21 µM, which further expressed in-vivo anti-tumor activity against murine T-cell lymphoma cell lines (Daltons Lymphoma-DLA) by regressing tumor growth. The formation of neovessels from the vasculogenesis was diminished reflecting the antitumor activity. The neovessel formation is directly relied on expression of matrix meteloproteases (MMP's) level which was drastically reduced by 5c treatment as evaluated by immonoblot assays. This is further supported by in-silico ADMET studies performed by ACD I-Lab 2.0 were in agreement with Lipinski rule of five. Reporting results were assessed as a positive parameter for further validation of the compound for therapeutic potential of cancer by 5c for preclinical studies in near future.

Synthesis of Palladium-Catalysed C-C Bond Forming 5-Chloro Quinolines via Suzuki-Miyaura Coupling; Anti-Pancreatic Cancer Screening on PANC-1 Cell Lines.

Pancreatic cancer is the most severe among other cancers due to its late detection and less chance of survivability. Heterocycles are proven ring systems in the treatment of various cancers and this is due to the presence of two biodynamic molecules combined, which have a greater synergistic efficacy in many anticancer drugs. Quinoline and pyridine ring systems are brought together to obtain greater potency and this is achieved by coupling both using Pd-catalyst, and in the present investigation, Suzuki-Miyaura coupling (SMC) reactions are adopted to generate potent molecular entities. Pancreatic cancer is difficult to treat due to overexpression of the VEGFR2 protein. VEGFR2 is targeted to design the molecules of quinoline-coupled pyridine moieties and is docked to evaluate the protein-ligand interaction at the binding site. The binding affinity of conjugates revealed the potency and capability of ligands to inhibit the VEGFR2 pathway. The in-silico ADMET properties determined their inherent pharmacokinetic feasibility. The synthesized conjugates have been evaluated by MTT assay against the human pancreatic cancer cell lines (PANC-1). Among the series, compounds 5d, 5e, and 5h exhibited a greater inhibitory activity against the cell lines with an IC50 value of 82.32±1.38, 54.74±1.18 and 80.35±1.68 µM. In the present exploration, 5e exhibited greater inhibitory activity and it could be a promising lead for the development of new chemotherapeutics against pancreatic cancer.

Nonwoven/Nanomembrane Composite Functional Sweat Pads.

Sweat is a natural body excretion produced by skin glands, and the body cools itself by releasing salty sweat. Wetness in the underarms and feet for long durations causes itchiness and an unpleasant smell. Skin-friendly reusable sweat pads could be used to absorb sweat. Transportation of moisture and functionality is the current challenge that many researchers are working on. This study aims to develop a functional and breathable sweat pad with antimicrobial and quick drying performance. Three layered functional sweat pads (FSP) are prepared in which the inner layer is made of an optimized needle-punched coolmax/polypropylene nonwoven blend. This layer is then dipped in antimicrobial ZnO solution (2, 4, and 6 wt.%), and super absorbent polymer (SAP) is embedded, and this is called a functional nonwoven (FNW1) sheet. Electrospun nanofiber-based nanomembranes of polyamide-6 are optimized for bead-free fibers. They are used as a middle layer to enhance the pad's functionality, and the third layer is again made of needle-punched optimized coolmax/polypropylene nonwoven sheets. A simple nonwoven-based sweat pad (SSP) is also prepared for comparison purposes. Nonwoven sheets are optimized based on better comfort properties, including air/water vapor permeability and moisture management (MMT). Nonwoven webs having a higher proportion of coolmax show better air permeability and moisture transfer from the inner to the outer layer. Antimicrobial activity of the functional nonwoven layer showed 8 mm of bacterial growth, but SSP and FSP showed only 6 mm of growth against Staphylococcus aureus. FSP showed superior comfort and antibacterial properties. This study could be a footstone toward highly functional sweat pads with remarkable comfort properties.

Serum pepsinogen level as a biomarker for atrophy, reflux esophagitis, and gastric cancer screening in Indonesia.

Background: Chronic dyspepsia's symptoms are frequently seen in primary to tertiary healthcare in Indonesia. This study aimed to describe the potential usability of pepsinogen (PG) values in determining gastric mucosal conditions, including superficial gastritis and atrophic gastritis. Materials and Methods: We recruited 646 adult dyspeptic patients and then analyzed PG values (including PGI, PGII, and PGI/II ratio) with endoscopic findings, gastric mucosal damages, and Helicobacter pylori infection. The gastric mucosal damage and H. pylori infection were evaluated using histological examination based on the updated Sydney system. Results: Among 646 enrolled patients, 308 (47.2%), 212 (32.8%), 91 (14.1%), 34 (5.2%), and 1 (0.2%) patient were diagnosed with normal mucosa, gastritis, reflux esophagitis, peptic ulcer disease, and gastric cancer, respectively. Significant differences in PGI, PGII, and PGI/II ratio values were observed among ethnic groups (all P < 0.01). The PGI and PGII levels were significantly higher and PGI/II was significantly lower in H. pylori-infected patients than in uninfected ones (all P < 0.001). The optimal cutoff value for PGII and PGI/II was 12.45 ng/mL with an area under the curve (AUC) value of 0.755 (0.702-0.811), sensitivity 59.3%, and specificity 77.1%; and 4.75 with AUC value of 0.821 (0.763-0.855), sensitivity 81.5%, and specificity 78.7%, respectively, to determine moderate-severe atrophy. Conclusion: Serum PG levels, a useful biomarker, represent the endoscopic findings, especially for reflux esophagitis. In addition, the benefits of PG values detecting atrophic gastritis were limited to moderate-severe atrophic gastritis. This usefulness requires careful attention for several ethnic groups in Indonesia.

Synthesis of novel nicotinamide susbstituted phthalocyanine and photodynamic antomicrobial chemotherapy evaluation potentiated by potassium iodide against the gram positive S. aureus and gram negative E. coli.

In the present work, we propose the synthesis of novel nicotinamide subsituted phthlocyanine photosensitizer (PS) and characterized by FTIR, UV-visible, H-NMR and MALDI Toff spectroscopy. Nicotinamide plays a vital rule in the central nervous system and its potential as a therapeutic for neurodegenerative disease. Nicotinamide substituted PS (3) efficiently produced ROS via type-1 process as measured by DCF assay. We observed that our PS after red light illumination (22 J/cm2) killed gram positive S. aureus upto 3 log reduction. Furher the addition of Potassium Iodide (100 mM) significantly potentiated PS at lower concentrations and enhanced the bacterial killing upto 6 log reduction against the S. aureus. We further found that the synergistic effect of PS and KI also eradicated the gram negative E. coli strain at lower concentraion of PS and found to killed E. coli upto 5 log reduction under the red light illumination at 22 J/cm2 of light dose. The conjugation of such biologically important form of vitamin B3 with PS would be a great addition and could pav the way for the novel photodynamic agent in the treatement of cancer and infectious diseases. A new symmetrical Nicotinamide tetrasubstituted zinc phthalocyanine (3) was synthesized. Upon addition of potassium Iodide with PS, the PS exhibited significant photodynamic activity with 5-6 logs reduction in bacterial load was achieved.

Fast Enantio- and Chemoselective Arylation of Ketones with Organoboronic Esters Enabled by Nickel/N-Heterocyclic Carbene Catalysis.

A general, efficient, highly enantio- and chemoselective N-heterocyclic carbene (NHC)/Ni-catalyzed addition of readily available and stable arylboronic esters to ketones is reported. This protocol provides unexpectedly fast access (usually 10 min) to various chiral tertiary alcohols with exceptionally broad substrate scope and excellent functional group tolerance (76 examples, up to 98 % ee). This process is orthogonal to other known Ni-mediated Suzuki-Miyaura couplings, as it tolerates aryl chlorides, fluorides, ethers, esters, amides, nitriles, and alkyl chlorides. The reaction is applied to late-stage modifications of various densely functionalized medicinally relevant molecules. Preliminary mechanistic studies suggest that a rare enantioselective η2 -coordinating activation of ketone carbonyls is involved. This cross-coupling-like mechanism is expected to enable other challenging transformations of ketones.

Systematical study of multi-walled carbon nanotube nanofluids based disposed transformer oil.

In this paper, the electrical, dielectric, Raman and small angle X-ray scattering (SAXS) structure behavior of disposed transformer oil in the presence of multi-walled carbon nanotube (MWCNT) were systematically tested to verify their versatility for preparing better alternative transformer oil in future. MWCNT nanofluids are prepared using a two-step method with concentrations ranging from 0.00 to 0.02 g/L. The test results reveal that 0.005 g/L concentration possesses the most optimum performance based on the electrical (AC breakdown and lightning impulse) and dielectric (permittivity, dissipation factor and resistivity) behavior. According to the trend of AC breakdown strength and lightning impulse pattern, there were 212.58% and 40.01% enhancement indicated for 0.005 g/L concentration compared to the disposed transformer oil. The presence of MWCNT also yielding to the decrement of dissipation factor, increased on permittivity and resistivity behavior of disposed transformer oil which reflected to the performance of electrical properties. Furthermore, it is found that these features correlated to the structural properties as systematically verify by Raman and SAXS analysis study.

Pyriform sinus perforation during nasotracheal intubation: a case report.

INTRODUCTION: Endotracheal intubation is the gold standard to protect the airway during general anesthesia. It is the commonest technique in medical practice with a low complication rate. PRESENTATION OF CASE: We report a case of left pyriform fossa perforation in a child after apparently uneventful nasotracheal intubation for tonsillectomy. DISCUSSION: This is a rare complication. Physicians performing endotracheal intubation or dealing with intubated patients should be aware of the clinical symptoms of such complications. A rational management approach has been discussed. CONCLUSIONS: Early diagnosis is the mainstay to improve the outcome and avoid the morbidity and potentially life-threatening course of such trauma.

Analysis of risks of gastric cancer by gastric mucosa among Indonesian ethnic groups.

Indonesia is a big country with multiethnic populations whose gastric cancer risks have not been elucidated. We performed a nationwide survey and obtained histological specimens from 1053 individuals in 19 cities across the country. We examined the gastric mucosa, the topography, the atrophic gastritis risk factors, and the gastric cancer risk scores. Almost half (46.1%) of the patients with dyspeptic symptoms had histological abnormalities; chronic (36.3%) and atrophic gastritis (28.9%) being the most frequent. Individuals of the Timor ethnicity had the highest prevalence of acute (52.6%) and chronic gastritis (68.4%), even those negative for H. pylori. Our topographic analysis showed the majority of patients had predominantly antral acute and chronic gastritis. A multivariate logistic regression model showed age (Odds ratio [OR], 1.107), Timor ethnicity (OR, 8.531), and H. pylori infection (OR, 22.643) as independent risk factors for presence of atrophic gastritis. In addition, the gastric cancer risk score was highest in those from Timor, Papuan, and Bugis ethnic populations. Overall, Indonesia is a low-risk gastric cancer country. However, several ethnic groups displayed severe gastric mucosa symptoms suggesting policy makers should focus on those ethnic groups to perform gastric cancer screenings and to eradicate H. pylori.

All-cause and cause-specific mortality rates of patients treated for alcohol use disorders: A meta-analysis.

BACKGROUND: Although alcohol use disorders (AUDs) are known to increase the relative risk of all-cause and some cause-specific mortality, the absolute mortality rates of the AUD population are unknown. Such knowledge would benefit planners of the provision of services for this population, including in prioritizing the identification and/or treatment of diseases likely to cause their death. METHODS: We conducted a systematic review of studies in English, reporting the cause-specific mortality rates among people treated for AUDs. Number of deaths by cause and total person-years of follow-up were extracted. All-cause and cause-specific mortality rates per 1000 person-years were meta-analyzed assuming random effects. RESULTS: Thirty-one studies were included. Participants were mainly middle-aged males. The quality of studies was generally good. A total of 6768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients) were recorded, and the pooled all-cause mortality rate was 27.67/1000 person-years (py) (95% confidence interval [CI]: 23.9, 32.04). The most common cause of death in the AUD population was cardiovascular disease (CVD) (6.9/1000 py; 95% CI: 5.61, 8.49), followed by gastrointestinal deaths (5.63/1000 py; 95% CI: 4.1, 7.74), unnatural deaths (4.95/1000 py; 95% CI: 4.01, 6.09)), neoplasms, respiratory diseases, and substance use disorders. CONCLUSIONS: Patients with AUDs have increased rates of all-cause and cause-specific mortality compared with the general population. Like the general population, they are most likely to die of CVD. In contrast to the general population, gastrointestinal and unnatural deaths are the next most common causes of death. We believe these facts should be considered when planning health care services for patients with AUDs.

Systemic and coronary levels of CRP, MPO, sCD40L and PlGF in patients with coronary artery disease.

BACKGROUND: Biomarkers play a pivotal role in the diagnosis and management of patients with acute coronary syndrome. This study aimed to investigate the differences in level of several biomarkers, i.e. C-reactive protein, myeloperoxidase, soluble CD40 ligand and placental growth factor, between acute coronary syndrome and chronic stable angina patients. The relationship between these biomarkers in the coronary circulation and systemic circulation was also investigated. METHODS: A total of 79 patients were recruited in this study. The coronary blood was sampled from occluded coronary artery, while the peripheral venous blood was withdrawn from antecubital fossa. The serum concentrations of C-reactive protein, soluble CD40 ligand and placental growth factor and plasma concentration of myeloperoxidase were measured using ELISA method. RESULTS: The systemic level of the markers measured in the peripheral venous blood was significantly increased in acute coronary syndrome compared to chronic stable angina patients. The concentrations of the C-reactive protein, myeloperoxidase and soluble CD40 ligand taken from peripheral vein were closely similar to the concentration found in coronary blood of ACS patients. The level of placental growth factor was significantly higher in coronary circulation than its systemic level. CONCLUSION: The concentration of these C-reactive protein, myeloperoxidase, soluble CD40 ligand and placental growth factor were significantly increased in acute coronary syndrome patients. The concentration of the markers measured in the systemic circulation directly reflected those in the local coronary circulation. Thus, these markers have potential to become a useful tool in predicting plaque vulnerability in the future.

Chemotherapy Induced Acute Pericarditis in a Child.

A9 years boy diagnosed with nasopharyngeal carcinoma was started on chemotherapy protocol including 5-fluorouracil. After 90 hours of 5-fluorouracil infusion, he developed severe retrosternal chest pain. Electrocardiography showed signs of acute pericarditis and was managed with ibuprofen and 5-fluorouracil was discontinued. The 5-fluorouracil rarely causes cardiac complications such as angina pectoris and pericarditis in adult patients. We report acute myopericarditis in a child caused by 5-fluorouracil, which is a very rare complication of 5-fluorouracil in pediatric age group.

The efficacy of dexamethasone on reduction in the reoperation rate of chronic subdural hematoma--the DRESH study: straightforward study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural hematoma (cSDH) is a common neurosurgical disease. It is often considered to be a rather benign entity. In spite of well established surgical procedures cSDH is complicated by a recurrence rate up to 30%. Since glucocorticoids have been used for treatment of cSDH in 1962 their role is still discussed controversially in lack of evident data. On the basis of the ascertained inflammation cycle in cSDH dexamethasone will be an ideal substance for a short lasting, concomitant treatment protocol. OBJECTIVE: to test the efficacy of dexamethasone on reduction inthe reoperation rate of cSDH. METHODS/DESIGN: The study is designed as a double-blind randomized placebo-controlled trial 820 patients who are operated for cSDH and from the age of 25 years are included after obtaining informed consent. They are randomized for administration of dexamethasone (16-16-12-12-8-4 mg/d) or placebo (maltodextrin) during the first 48 hours after surgery. The type I error is 5% and the type II error is 20%. The primary endpoint is the reoperation within 12 weeks postoperative. DISCUSSION: This study tests whether dexamethasone administered over 6 days is a safe and potent agent in relapse prevention for evacuated cSDH. TRIAL REGISTRATION: EudraCT 201100354442.

Patient initiated clinics for patients with chronic or recurrent conditions managed in secondary care: a systematic review of patient reported outcomes and patient and clinician satisfaction.

BACKGROUND: The cost to the NHS of missed or inappropriate hospital appointments is considerable. Alternative methods of appointment scheduling might be more flexible to patients' needs without jeopardising health and service quality. The objective was to systematically review evidence of patient initiated clinics in secondary care on patient reported outcomes among patients with chronic/recurrent conditions. METHODS: Seven databases were searched from inception to June 2013. Hand searching of included studies references was also conducted. Studies comparing the effects of patient initiated clinics with traditional consultant led clinics in secondary care for patients with long term chronic or recurrent diseases on health related quality of life and/or patient satisfaction were included. Data was extracted by one reviewer and checked by a second. Results were synthesised narratively. RESULTS: Seven studies were included in the review, these covered a total of 1,655 participants across three conditions: breast cancer, inflammatory bowel disease and rheumatoid arthritis. Quality of reporting was variable. Results showed no significant differences between the intervention and control groups for psychological and health related quality of life outcomes indicating no evidence of harm. Some patients reported significantly more satisfaction using patient-initiated clinics than usual care (p < 0.001). CONCLUSIONS: The results show potential for patient initiated clinics to result in greater patient and clinician satisfaction. The patient-consultant relationship appeared to play an important part in patient satisfaction and should be considered an important area of future research as should the presence or absence of a guidebook to aid self-management. Patient initiated clinics fit the models of care suggested by policy makers and so further research into long term outcomes for patients and service use in this area of practice is both relevant and timely.