Improved adherence and growth outcomes with jet-delivered growth hormone.

Background We previously reported improved persistence and adherence to daily recombinant growth hormone (rGH) in children using jet transjection delivery compared to using needle-based devices. This study examines the relationship between improved adherence and medium-term growth outcomes in children receiving jet-delivered rGH (JrGH) at a single centre. Methods This was a retrospective longitudinal follow-up study of children (<16 years) treated with daily JrGH (somatropin; Ferring Pharmaceuticals) in the form of Zomacton® with the Zomajet® device. Delivery schedules of home distribution services were utilised to calculate adherence, quantified as the proportion of days covered (PDC) index (PDC > 0.8 adherent, PDC ≤ 0.8 less adherent). Demography, patient history, height standard deviation scores (HTSDS) and difference from mid-parental height SDS (MPHSDS - HTSDS) were extracted from hospital records for up to 3 years of treatment. Results Of 75 patients eligible for JrGH, 52 had PDC treatment and height data for at least 1 year and 22 for 3 years. A greater proportion of patients were classified as adherent in both 1- and 3-year treated cohorts (adherent 30 [57.7%] and 14 [63.6%], less adherent 22 [42.3%] and 8 [36.4%]). After 1 year of JrGH treatment, HTSDS was not significantly different in either adherence group. After 3 years, only adherent patients demonstrated sustained year-on-year increments in HTSDS and significant improvement in target HTSDS positions (by 1.32 SDS) compared to baseline (p = 0.0008). MPHSDS - HTSDS showed a similar significant improvement at 3 years in adherent patients only (p = 0.0043). Conclusions Patients adherent to JrGH demonstrate significant growth improvement compared to baseline over 3 years.

Association of influenza outbreaks with advanced pediatric medical support.

Retrospective data evaluated increases in advanced medical support for children with medically attended acute respiratory illness (MAARI) during influenza outbreak periods (IOP). Advanced support included hospitalisation, intensive care unit admission, or mechanical ventilation, for children aged 0-17 years hospitalised in Maryland's 50 acute-care hospitals over 12 influenza seasons. Weekly numbers of positive influenza tests in the Maryland area defined IOP for each season as the fewest consecutive weeks, including the peak week containing at least 85% of positive tests with a 2-week buffer on either side of the IOP. Peak IOP (PIOP) was defined as four consecutive weeks containing the peak week with the most number of positive influenza tests. Off-PIOP was defined as the 'shoulder' weeks during each IOP. Non-influenza season (NIS) was the remaining weeks of that study season. Rate ratios of mean daily MAARI-related admissions resulting in advanced medical support outcomes during PIOP or Off-PIOP were compared with the NIS and were significantly elevated for all 12 study seasons combined. The results suggest that influenza outbreaks are associated with increased advanced medical support utilisation by children with MAARI. We feel that this data may help preparedness for severe influenza epidemics or pandemic.

A questionnaire-based audit to assess overall experience and convenience among patients using vaginal progesterone tablets (Lutigest®) for luteal phase support during IVF treatment.

PURPOSE: The aim of this audit was to assess the overall experience and patient convenience of vaginal progesterone tablets (Lutigest®, marketed as Endometrin® in the USA) used for luteal phase support (LPS) during in vitro fertilization (IVF) treatment. PATIENTS AND METHODS: This questionnaire-based audit included responses from 100 patients undergoing IVF treatment at six IVF clinics in the UK from September 2015 to November 2016. Fourteen days after starting progesterone supplementation for LPS during their IVF treatment, patients rated overall experience and perceived convenience of the prescribed progesterone by completing a questionnaire. RESULTS: Of the 100 patients included, 96 received vaginal progesterone tablets for LPS. Overall, 53.1% (51/96) indicated that the progesterone tablets were "very easy" to use; 42.7% (41/96) and 44.8% (43/96) found it "very convenient" or "neither convenient or inconvenient" to administer the tablet, respectively. Overall experience with using progesterone tablets was rated as "very comfortable" by 34.4% (33/96) and "neither comfortable or uncomfortable" by 56.3% (54/96) of patients. The applicator was used by 93.8% (90/96) of patients to administer the tablet, and 86.5% (83/96) indicated that the applicator was easy to clean for repeated use. A total of 33 patients had a previous IVF cycle during which they were prescribed vaginal progesterone pessaries for LPS. Compared with progesterone pessaries, the majority found treatment with progesterone tablets to be more comfortable (60.6%; 20/33) and more convenient (57.6%; 19/33) and indicated that the progesterone tablet was their preferred progesterone formulation for LPS (60.6%; 20/33). CONCLUSION: These findings offer insights into real-world patient experiences with the progesterone vaginal tablet formulation. The results suggest overall patient convenience, ease, and comfort with using progesterone vaginal tablets for LPS. The majority of patients found progesterone vaginal tablets more convenient and comfortable to use compared with progesterone pessaries.

Maintaining persistence and adherence with subcutaneous growth-hormone therapy in children: comparing jet-delivery and needle-based devices.

PURPOSE: Persistence and adherence with subcutaneous growth hormone (GH; somatropin) therapy in children is widely acknowledged to be suboptimal. This study aimed to investigate how the use of a jet-delivery device, ZomaJet(®), impacts on medication-taking behaviors compared to needle-based devices. MATERIALS AND METHODS: A retrospective cohort study of children aged ≤18 years was conducted using a UK-based, nationwide database of GH home-delivery schedules. Data were evaluated for the period between January 2010 and December 2012 for 6,061 children receiving either Zomacton(®) (somatropin) via the ZomaJet jet-delivery device or one of six brands of GH all administered via needle-based devices. Persistence was analyzed for patients with appropriate data, measured as the time interval between first and last home deliveries. An analysis of adherence was conducted only for patients using ZomaJet who had appropriate data, measured by proportion of days covered. Brand switches were identified for all patients. RESULTS: Persistence with GH therapy was significantly longer in patients using ZomaJet compared to needle-based devices (599 days versus 535 days, respectively, n=4,093; P<0.001); this association was observed in both sexes and across age subgroups (≤10 and 11-16 years). The majority (58%) of patients using ZomaJet were classed as adherent (n=728). Only 297 patients (5%) switched GH brand (n=6,061), and patients tended to use ZomaJet for longer than other devices before switching. CONCLUSION: It appears important that the choice of a jet-delivery device is offered to children prescribed daily GH therapy. These devices may represent a much-needed effective strategy for maintaining persistence with subcutaneous GH administration in children, potentially offering better clinical outcomes and greater cost-efficiency.

Health related quality of life and quantitative pain measurement in females with chronic non-malignant pain.

The aim of the present study was to assess, compare, and correlate the pain response to an experimental pain stimulus (hyperalgesia to pressure pain threshold (PPT) measured from different body sites), the pain intensity (VAS) of the habitual pain, and quality of life parameters (SF-36) in groups of females with chronic non-malignant pain syndromes. Forty female pain patients with fibromyalgia/whiplash (n = 10), endometriosis (n = 10), low back pain (n = 10), or rheumatoid arthritis (n = 10), as well as 41 age-matched healthy female controls participated in the study. The fibromyalgia/whiplash patients scored significantly higher (p < 0.04) VAS ratings (median rating = 7.0) than the endometriosis (6.0), low back pain (6.0), and rheumatoid arthritis (3.5) patients. All fours patient groups had significantly lower PPTs at all sites as compared with controls. The fibromyalgia/whiplash patients experienced the highest influence of pain on their overall health status, particularly vitality, social function, emotional problems, and mental health. A significant negative correlation was found between VAS rating and quality of life (p < 0.04). Significant correlation (p < 0.05) was found between pressure hyperalgesia measured at lowest PPT sites and the impairment of SF-36 physical function as well as mental health parameters. This study demonstrates significant generalised pressure hyperalgesia in four groups of chronic pain patients, correlations between degree of pressure hyperalgesia and impairment of some quality of life parameters, and increased pain intensity of the ongoing pain is associated with decreased quality of life.

Visceral pain: gender differences in response to experimental and clinical pain.

Gender differences in response to visceral pain have important implications for experimental studies and when evaluating clinical pain. Few studies have in details explored specific gender differences in response to experimental stimulation of selected visceral organs or specific visceral diseases. Lower pain threshold to e.g. oesophageal distension has however been shown in females. The effect of female sex hormones on visceral function and pain is studied in greater details in both experimental and clinical studies. Pronounced differences in pain sensitivity are found across the menstrual phases. This may also interact with pharmacological interventions. For clinicians assessing the pain level of female patients in the reproductive age group should take into consideration the physiological and clinical effects of the menstrual cycle and the somatic segmental sites related to the uterus and cervix when clinically evaluating the pain and assessing for disease activity.

Endometriosis is associated with central sensitization: a psychophysical controlled study.

Endometriosis is a pain syndrome representing a major cause of pelvic pain in women of reproductive age. The aim of this study was to test the hypothesis that persistent nociceptive input from endometriotic tissues leads to central sensitization manifested by somatic hyperalgesia and increased referred pain areas to experimental saline-induced muscle pain in patients with endometriosis, compared to healthy control subjects. Ten women with laparoscopically confirmed endometriosis and 10 healthy, age-matched women participated in the study. Hypertonic saline (0.5 mL, 5.8%) was injected intramuscularly, in random succession, into 1 site of menstrual pain referral (the multifidus muscle at the low back) and into 1 non-pain control site (first dorsal interosseous muscle [FDI] of the hand). The post-saline pain intensity and pain areas at the FDI were significantly greater in patients with endometriosis than in control subjects (P <.05) but were not different between the groups for the back. An absence of enhancement of post-saline pain responses at the back in the endometriosis group suggests that saline-induced pain at the back appears to activate segmental inhibitory systems in patients with endometriosis. Manifestation of central sensitization in women with endometriosis is demonstrated by increased muscle nociceptor input in the form of increased post-saline pain intensity, pain areas at the FDI, and hypersensitivity to pressure stimulation. These findings provide new insights into the complex pain mechanisms associated with endometriosis.

Controlled dilatation of the uterine cervix--an experimental visceral pain model.

Pain originating from the female reproductive organs is a substantial clinical problem to treat. Experimental models may be a tool for the study of visceral pain mechanisms and hence provide information to aid in formulating new treatment strategies. The aim was to develop and evaluate the performance and safety of a model for nociceptive stimulation of the uterine cervix by balloon dilatation using impedance planimetry. Three consecutive (repeated) dilatations at 1 ml/min, an isovolumetric and a fast dilatation at 2 ml/min were performed. Pilot studies were conducted in vitro on hysterectomy specimens, followed by application of the model in 14 healthy females. Subjects indicated the quality of perception and pain during dilatations by verbal reports and the McGill Pain Questionnaire (MPQ), and the intensity by a continuous electronic visual analog scale. The pain location was marked on an anatomical map. The balloon cross-sectional area (CSA) was measured simultaneously. The experimental procedure was atraumatic. Pain was evoked in all subjects, with referral to the hypogastric and low back regions. The word descriptors on the MPQ and the areas of referred sensations were similar to that seen clinically in abortion, labor and menstrual pain. The pain intensity correlated with balloon CSA (r=0.9, P<0.001). No significant differences were found for the balloon volumes (4.2, 3.8 and 3.9 ml) or CSA (163, 122 and 123 mm(2)) to pain threshold (PT) for repeated dilatations, suggesting the reliability of the model. There was significant correlation between the balloon volume and CSA to reach the PT for single and repeated cervical dilatations. During isovolumetric distension, greater overall pain intensity was demonstrated for the prolonged as compared to the shorter duration cervical stimulation. In conclusion, this is the first human experimental pain model for dilatation of the uterine cervix, providing a safe, controlled, quantifiable stimulus that evoked reliable pain scores. The model thus provides a new possibility to study gynecological pain and may lead to better characterization and treatment of female visceral pain syndromes.

A comparison of modality-specific somatosensory changes during menstruation in dysmenorrheic and nondysmenorrheic women.

OBJECTIVE: The objective was to evaluate somatosensory thresholds to a multimodality stimulation regimen applied both within and outside areas of referred menstrual pain in dysmenorrheic women, over four phases of confirmed ovulatory cycles, and to compare them with thresholds in nondysmenorrheic women during menstruation. DESIGN: Twenty dysmenorrheic women with menstrual pain scoring 5.45 +/- 0.39 cm (mean +/- standard error of mean) on a visual analog scale (10 cm) participated. Fifteen nondysmenorrheic women with a menstrual pain score of 0.4 +/- 0.2 cm participated as controls. Ovulation was confirmed by an enzyme-multiplied immunoassay technique. Menstrual pain was described with the McGill Pain Questionnaire. Areas within menstrual pain referral were two abdominal sites and the midline of the low back, and the arm and thigh were the control areas. The pressure pain threshold (PPT) and pinch pain threshold were determined by a hand-held electronic pressure algometer, the heat pain threshold (HPT) by a contact thermode, and the tactile threshold with von Frey hairs. RESULTS: In dysmenorrheic women the McGill Pain Questionnaire showed a larger sensory and affective component of pain than the evaluative and miscellaneous groups. The HPT and PPT were lower in the menstrual phase than in the ovulatory, luteal, and premenstrual phases, both within and outside areas of referred menstrual pain (p <0.01), with a more pronounced decrease at the referral pain areas. The pinch pain threshold was lower in the menstrual phase than in the ovulatory phase (p <0.02), and the tactile threshold did not differ significantly across the menstrual phases or within any site. Dysmenorrheic women had a lower HPT at the control sites and a lower PPT at the abdomen, back, and control sites, than in those of nondysmenorrheic women in the menstrual phase. CONCLUSIONS: The results show reduced somatosensory pain thresholds during menstruation to heat and pressure stimulation, both within and outside areas of referred menstrual pain in dysmenorrheic women. Dysmenorrheic women showed a lower HPT at the control sites and a lower PPT at all the sites than those for nondysmenorrheic women in the menstrual phase. The altered somatosensory thresholds may be dependent on a spinal mechanism of central hyperexcitability, induced by recurrent moderate to severe menstrual pain.

Antenatal women with or without pelvic pain can be characterized by generalized or segmental hypoalgesia in late pregnancy.

The aims of the present study were to determine the influence of pregnancy on somatosensory responses in women with or without pelvic/lumbosacral pain. Thirty pregnant women participated and were divided into pain (n = 12) and nonpain (n = 18) groups on the basis of pain complaints and positive pain-provoking tests associated with pelvic or lumbosacral pain during the current pregnancy. In the pain group, 9 reported initial pain in trimester 1, 2 in trimester 2, and 1 in trimester 3. Quantitative sensory testing with pressure pain threshold (PPT), heat pain threshold (HPT), and tactile threshold (TT) was performed once during each of the 3 trimesters at referred pain sites (sacrum, back, and pubis) and no pain control sites (thigh, arm, and sternum). All subjects in the pain group reported back pain, and 91% also had pain at the sacrum and pubis. The pain group exhibited significantly greater pain sensitivity than the nonpain group. The HPT and PPT were higher in trimester 3 as compared to trimesters 1 and 2 (P < .012). The increase in thresholds, or hypoalgesia, was generalized and present at both referred pain and control sites in the pain group. In the nonpain group hypoalgesia was localized to the presumed referred pain sites at the back and sacrum. There were no significant variations in the TT in any trimester. The study demonstrates for the first time that hypoalgesia in late pregnancy is generalized in women with pelvic pain and localized in women without pelvic pain. This suggests that the descending noxious inhibitory system is activated in late pregnancy and is probably more intense and generally activated in women with pelvic pain and only segmentally activated in women without pain.

Osteoarthritis and its association with muscle hyperalgesia: an experimental controlled study.

Hypertonic saline effectively excites muscle nociceptors. Muscle hyperalgesia was assessed in osteoarthritis (OA) by intramuscular infusion of 0.5 ml hypertonic saline (6%) into the tibialis anterior muscle in humans. Patients (n=14) with OA in the lower extremities were compared with an equal number of age- and sex-matched healthy controls. Ten of the 14 OA patients had pain in the knee joint as the most common presenting complaint. Visual analogue scale (VAS) pain intensity and assessment of pain areas were recorded before infusion and immediately, 2, 5, 10 and 20 min after infusion, and then every 10 min, until the pain vanished. The mean pain offset time in OA patients (11.3+/-7.9 min) was larger as compared with the control subjects (6.04+/-2.1 min) (P=0.025). OA patients had increased pain intensity VAS after the infusion in the right leg compared with controls (P<0.05). Referred and radiating pain areas at 2 min post-infusion increased in OA patients and not in controls as compared with the local pain areas (P<0.05). It is concluded that muscle hyperalgesia and extended pain areas might be due to central sensitization caused by painful osteoarthritis.