Will (or can) people pay for headache care in a poor country?

We asked whether attempts to introduce headache services in poor countries would be futile on grounds of cost and unsustainability. Using data from a population-based survey in the Republic of Georgia, an exemplary poor country with limited health care, and against the background of headache-attributed burden, we report on willingness to pay (WTP) for effective headache treatment. Consecutive households were visited in areas of Tbilisi (urban) and Kakheti (rural), together representative of Georgian habitation. Biologically unrelated adults were interviewed by medical residents using a structured ICHD-II-based diagnostic questionnaire, the MIDAS questionnaire and SF-36. The bidding-game method was employed to assess WTP. Of 1,145 respondents, 50.0% had episodic headache (migraine and/or tension-type headache) and 7.6% had headache on ≥15 days/month, which was not further diagnosed. MIDAS scores were higher in people with headache on ≥15 days/month (mean 11.2) than in those with episodic headache (mean 7.0; P = 0.004). People with headache had worse scores in all SF-36 sub-scales than those without, but no differences were found between headache types. Almost all (93%) respondents with headache reported WTP averaging USD 8 per month for effective headache treatment. WTP did not correlate with headache type or frequency, or with MIDAS or SF-36 scores. Headache is common and headache-attributed burden is high in Georgia, with a profound impact on HRQoL. Even those less affected indicated WTP for effective treatment, if it were available, that would on average cover costs, which locally are low. Headache services in a poor country are potentially sustainable.

Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of cisplatin-induced neuropathy.

BACKGROUND: Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG) cells leading to sensory polyneuropathy (PNP). We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO) protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden. RESULTS: A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s +/- 1,68 m/s; cisplatin + rhEPO 49,66 m/s +/- 1,26 m/s; control 55,01 m/s +/- 1,88 m/s; p < 0,001). The co-application of rhEPO, however, did not alter the level of unrepaired cisplatin-DNA lesions accumulating in DRG target cells. Micro-morphological analyses of the sciatic nerve from cisplatin-exposed mice showed damaged myelin sheaths and mitochondria. Co-administered rhEPO inhibited myelin sheaths from structural injuries and resulted in an increased number of intact mitochondria. CONCLUSION: The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.

Repair capacity for platinum-DNA adducts determines the severity of cisplatin-induced peripheral neuropathy.

The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine-guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies. Comparison of the adduct kinetics in cisplatin-injected mice either proficient or deficient for nucleotide excision repair (NER) functions revealed the essential role of this DNA repair pathway in protecting differentiated cells of the nervous system from excessive formation of such lesions. Hence, chronic exposure to cisplatin resulted in an accelerated accumulation of unrepaired intrastrand cross-links in neuronal cells of mice with dysfunctional NER. The augmented adduct levels in dorsal root ganglion (DRG) cells of those animals coincided with an earlier onset of PNP-like functional disturbance of their sensory nervous system. Independently from the respective repair phenotype, the amount of persisting DNA cross-links in DRG neurons at a given cumulative dose was significantly correlated to the degree of sensory impairment as measured by electroneurography. Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP.

A pilot methodological validation study for a population-based survey of the prevalences of migraine, tension-type headache and chronic daily headache in the country of Georgia.

We report the methodology of an epidemiological survey of the prevalences of migraine, tension-type headache and chronic daily headache in Georgia. Medical residents visited adjacent households in Tbilisi to interview a pre-defined target of 100 biologically unrelated subjects. All respondents reporting headache in the previous year, as well as random 20 non-headache controls, were examined by a neurologist. The response rate was 70%. Of 156 respondents, 93 were biologically unrelated and 45 (48%) reported headache in the previous year. Eight subjects fulfilled all IHS criteria for migraine (1-year prevalence 8.6% [95% CI: 2.9-14.3%]), and 13 had probable migraine, meeting all but the criterion for duration. Nineteen had tension-type headache (20.4% [95% CI: 12.2-28.6%]) and five had chronic daily headache (5.4% [95% CI: 1-10.0%]). In comparisons of diagnoses by questionnaire and neurologist (considered the gold standard), sensitivities for the questionnaire of 89% for migraine and 67% for tension-type headache were calculated (overall kappa=0.74).

Validation of a Georgian language headache questionnaire in a population-based sample.

In a pilot phase of a survey of the prevalence of primary headache disorders in the Republic of Georgia, we validated a Georgian language questionnaire for migraine (MIG), tension-type headache (TTH), MIG+TTH and trigeminal autonomic cephalalgias (TAC). A population-based sample of 186 people with headache completed the questionnaire and were blindly examined by one of two headache experts. The questionnaire diagnoses were: MIG 49, TTH 76, MIG+TTH 45 and TAC 16. The physicians' diagnoses were: MIG 59, TTH 77, MIG+TTH 34, TAC 2 and "symptomatic headache" in 14 subjects. Sensitivity and specificity for MIG were 0.75 and 0.96, for TTH 0.79 and 0.86, and for MIG+TTH 0.61 and 0.84 respectively. Of 16 TAC diagnoses, the physicians confirmed cluster headache in two patients only. The questionnaire can be utilised to investigate the prevalence of MIG and of TTH. It offers preliminary screening only for TAC, which should be confirmed during a face to face examination.