Orodispersible and transmucosal alternative medications for symptom control in adults

BACKGROUND: Paediatric palliative care makes frequent use of orodispersible and transmucosal drug delivery routes. The limited published experience of this practice suggests that it enables the delivery of needle-free symptom relief, with the potential to train family carers to administer anticipatory medications without reliance on trained health professionals. AIMS: To identify orodispersible and potential transmucosal alternatives that may be used in adults in the event of a patient having no oral or intravenous route and no access to subcutaneous injections. METHODS: The author panel identified medications through review of multiple drug formularies, review of the published evidence and their experience. Where possible, licensed alternatives were identified and any 'off label' or unlicensed medications clearly highlighted. RESULTS: A list of 27 medications is provided, which could be used either via the orodispersible or transmucosal alternative route for healthcare professionals delivering end of life care to consider when the licensed alternative routes are unavailable. All users of this guide are encouraged to use their professional judgement whenever selecting a medication for a patient, recognising that this review is neither a guideline nor a systematic review, and taking account of licensing considerations, adverse effects, potential unpredictability of time to effect and contraindications. CONCLUSION: Should it be necessary to use these orodispersible or transmucosal alternatives then any experience gained should be reported in the literature. Combined with further research, this experience offers the possibility of reducing injection frequency and inherent delays in medication administration, particularly in the community setting during the COVID-19 pandemic

Fluctuating Cu-O-Cu Bond model of high temperature superconductivity in cuprates

Twenty years of extensive research has yet to produce a general consensus on the origin of high temperature superconductivity (HTS). However, several generic characteristics of the cuprate superconductors have emerged as the essential ingredients of and/or constraints on any viable microscopic model of HTS. Besides a Tc of order 100K, the most prominent on the list include a d-wave superconducting gap with Fermi liquid nodal excitations, a d-wave pseudogap with the characteristic temperature scale T*, an anomalous doping-dependent oxygen isotope shift, nanometer-scale gap inhomogeneity, etc.. The key role of planar oxygen vibrations implied by the isotope shift and other evidence, in the context of CuO2 plane symmetry and charge constraints from the strong intra-3d Coulomb repulsion U, enforces an anharmonic mechanism in which the oxygen vibrational amplitude modulates the strength of the in-plane Cu-Cu bond. We show, within a Fermi liquid framework, that this mechanism can lead to strong d-wave pairing and to a natural explanation of the salient features of HTS

Nodal Quasiparticle Dispersion in Strongly Correlated d-wave Superconductors

We analyze the effects of a momentum-dependent self-energy on the photoemission momentum distribution curve (MDC) lineshape, dispersion and linewidth. We illustrate this general analysis by a detailed examination of nodal quasiparticles in high Tc cuprates. We use variational results for the nodal quasiparticle weight Z (which varies rapidly with hole doping x) and the low energy Fermi velocity $v_F^{low}$ (which is independent of x), to show that the high energy MDC dispersion $v_{high} = v_F^{low}/Z$, so that it is much larger than the bare (band structure) velocity and also increases strongly with underdoping. We also present arguments for why the low energy Fermi velocity and the high energy dispersion are independent of the bare band structure at small x. All of these results are in good agreement with earlier and recent photoemission data [Zhou et al, Nature 423, 398 (2003)].Comment: 4 pages, 3 eps fig

Predicting the transition from acute to persistent low back pain

Background Most people experience low back pain (LBP) at least once in their lifetime. Only a minority of them go on to develop persistent LBP. However, the socioeconomic costs of persistent LBP significantly exceed the costs of the initial acute LBP episode. Aims To identify factors that influence the progression of acute LBP to the persistent state at an early stage. Methods Prospective inception cohort study of patients attending a health practitioner for their first episode of acute LBP or recurrent LBP after a pain free period of at least 6 months. Patients were assessed at baseline addressing occupational and psychological factors as well as pain, disability, quality of life and physical activity and followed up at 3, 6, 12 weeks and 6 months. Variables were combined to the three indices ‘working condition', ‘depression and maladaptive cognitions' and ‘pain and quality of life'. Results The index ‘depression and maladaptive cognitions' was found to be a significant baseline predictor for persistent LBP up to 6 months (OR 5.1; 95% CI: 1.04-25.1). Overall predictive accuracy of the model was 81%. Conclusions In this study of patients with acute LBP in a primary care setting psychological factors at baseline correlated with a progression to persistent LBP up to 6 months. The benefit of including factors such as ‘depression and maladaptive cognition' in screening tools is that these factors can be addressed in primary and secondary preventio

Carrier concentrations in Bi_{2}Sr_{2-z}La_{z}CuO_{6+\delta} single crystals and their relation to Hall coefficient and thermopower

We measured the thermopower S and the Hall coefficients R_H of Bi_{2}Sr_{2-z}La_{z}CuO_{6+\delta} (BSLCO) single crystals in a wide doping range, in an effort to identify the actual hole concentrations per Cu, p, in this system. It is found that the "universal" relation between the room-temperature thermopower and T_c does not hold in the BSLCO system. Instead, comparison of the temperature-dependent R_H data with other cuprate systems is used as a tool to identify the actual p value. To justify this approach, we compare normalized R_H(T) data of BSLCO, La_{2-x}Sr_{x}CuO_{4} (LSCO), YBa_{2}Cu_{3}O_{y}, and Tl_{2}Ba_{2}CuO_{6+\delta}, and demonstrate that the R_H(T) data of the LSCO system can be used as a template for the estimation of p. The resulting phase diagram of p vs T_c for BSLCO suggests that T_c is anomalously suppressed in the underdoped samples, becoming zero at around p ~ 0.10, while the optimum T_c is achieved at p ~ 0.16 as expected.Comment: 4 pages including 5 figures, accepted for publication in Phys. Rev. B, Rapid Communication

Implications of the isotope effects on the magnetization, magnetic torque and susceptibility

We analyze the magnetization, magnetic torque and susceptibility data of La2-xSrxCu(16,18)O4 and YBa2(63,65)CuO7-x near Tc in terms of the universal 3D-XY scaling relations. It is shown that the isotope effect on Tc mirrors that on the anisotropy. Invoking the generic behavior of the anisotropy the doping dependence of the isotope effects on the critical properties, including Tc, correlation lengths and magnetic penetration depths are traced back to a change of the mobile carrier concentration.Comment: 5 pages, 3 figure

Unusual T_c variation with hole concentration in Bi_2Sr_{2-x}La_xCuO_{6+\delta}

We have investigated the $T_c$ variation with the hole concentration $p$ in the La-doped Bi 2201 system, Bi$_2$Sr$_{2-x}$La$_x$CuO$_{6+\delta}$. It is found that the Bi 2201 system does not follow the systematics in $T_c$ and $p$ observed in other high-$T_c$ cuprate superconductors (HTSC's). The $T_c$ vs $p$ characteristics are quite similar to what observed in Zn-doped HTSC's. An exceptionally large residual resistivity component in the inplane resistivity indicates that strong potential scatterers of charge carriers reside in CuO$_2$ planes and are responsible for the unusual $T_c$ variation with $p$, as in the Zn-doped systems. However, contrary to the Zn-doped HTSC's, the strong scatter in the Bi 2201 system is possibly a vacancy in the Cu site.Comment: RevTeX, 3 figures, to be published in the Physical Review

Association of a genetic polymorphism (-44 C/G SNP) in the human DEFB1 gene with expression and inducibility of multiple β-defensins in gingival keratinocytes

BACKGROUND: Human β-defensins (hBDs) are antimicrobial peptides with a role in innate immune defense. Our laboratory previously showed that a single nucleotide polymorphism (SNP) in the 5' untranslated region of the hBD1 gene (DEFB1), denoted -44 (rs1800972), is correlated with protection from oral Candida. Because this SNP alters the putative mRNA structure, we hypothesized that it alters hBD1 expression. METHODS: Transfection of reporter constructs and evaluation of antimicrobial activity and mRNA expression levels in keratinocytes from multiple donors were used to evaluate the effect of this SNP on constitutive and induced levels of expression. RESULTS: Transfection of CAT reporter constructs containing the 5' untranslated region showed that the -44 G allele yielded a 2-fold increase in CAT protein compared to other common haplotypes suggesting a cis effect on transcription or translation. The constitutive hBD1 mRNA level in human oral keratinocytes was significantly greater in cells from donors with the -44 GG genotype compared to those with the common CC genotype. Surprisingly, the hBD3 mRNA level as well as antimicrobial activity of keratinocyte extracts also correlated with the -44 G allele. Induced levels of hBD1, hBD2, and hBD3 mRNA were evaluated in keratinocytes challenged with Toll-like receptor 2 and 4 ligands, interleukin-1β, TNFα, and interferon-γ (IFNγ). In contrast to constitutive expression levels, IFNγ-induced keratinocyte hBD1 and hBD3 mRNA expression was significantly greater in cells with the common CC genotype, but there was no clear correlation of genotype with hBD2 expression. CONCLUSION: The DEFB1 -44 G allele is associated with an increase in overall constitutive antimicrobial activity and expression of hBD1 and hBD3 in a manner that is consistent with protection from candidiasis, while the more common C allele is associated with IFNγ inducibility of these β-defensins and is likely to be more protective in conditions that enhance IFNγ expression such as chronic periodontitis. These results suggest a complex relationship between genetics and defensin expression that may influence periodontal health and innate immune responses

Identification of prognostic factors for chronicity in patients with low back pain: a review of screening instruments

Low back pain (LBP) is currently the most prevalent and costly musculoskeletal problem in modern societies. Screening instruments for the identification of prognostic factors in LBP may help to identify patients with an unfavourable outcome. In this systematic review screening instruments published between 1970 and 2007 were identified by a literature search. Nine different instruments were analysed and their different items grouped into ten structures. Finally, the predictive effectiveness of these structures was examined for the dependent variables including "work status", "functional limitation”, and "pain". The strongest predictors for "work status” were psychosocial and occupational structures, whereas for "functional limitation” and "pain” psychological structures were dominating. Psychological and occupational factors show a high reliability for the prognosis of patients with LBP. Screening instruments for the identification of prognostic factors in patients with LBP should include these factors as a minimum core se